query: what are the initial symptoms of Covid-19?

positive: The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned? OBJECTIVES: To provide an overview of the three major deadly coronaviruses and identify areas for improvement of future preparedness plans, as well as provide a critical assessment of the risk factors and actionable items for stopping their spread, utilizing lessons learned from the first two deadly coronavirus outbreaks, as well as initial reports from the current novel coronavirus (COVID-19) epidemic in Wuhan, China. METHODS: Utilizing the Centers for Disease Control and Prevention (CDC, USA) website, and a comprehensive review of PubMed literature, we obtained information regarding clinical signs and symptoms, treatment and diagnosis, transmission methods, protection methods and risk factors for Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS) and COVID-19. Comparisons between the viruses were made. RESULTS: Inadequate risk assessment regarding the urgency of the situation, and limited reporting on the virus within China has, in part, led to the rapid spread of COVID-19 throughout mainland China and into proximal and distant countries. Compared with SARS and MERS, COVID-19 has spread more rapidly, due in part to increased globalization and the focus of the epidemic. Wuhan, China is a large hub connecting the North, South, East and West of China via railways and a major international airport. The availability of connecting flights, the timing of the outbreak during the Chinese (Lunar) New Year, and the massive rail transit hub located in Wuhan has enabled the virus to perforate throughout China, and eventually, globally. CONCLUSIONS: We conclude that we did not learn from the two prior epidemics of coronavirus and were ill-prepared to deal with the challenges the COVID-19 epidemic has posed. Future research should attempt to address the uses and implications of internet of things (IoT) technologies for mapping the spread of infection.

positive: Evaluation of the clinical characteristics of suspected or confirmed cases of COVID-19 during home care with isolation: A new retrospective analysis based on O2O Summary Background The recent outbreak of the novel coronavirus in December 2019 (COVID-19) has activated top-level response nationwide. We developed a new treatment model based on the online-to-offline (O2O) model for the home isolated patients, because in the early stages the medical staff were insufficient to cope with so many patients. Methods In this single-centered, retrospective study, we enrolled 48 confirmed/suspected COVID-19 patients who underwent home isolation in Wuhan between January 6 and January 31, 2020. By WeChat and online document editing all patients were treated with medical observation scale. The clinical indications such as Fever, Muscle soreness, Dyspnea and Lack of strength were collected with this system led by medical staff in management, medicine, nursing, rehabilitation and psychology. Findings The mean(SD) age of 48 patients was 39.08(13.88) years, 35(72.9%) were women. Compared with non-hospitalized patients, inpatients were older(≥8805;70years, 2.4% vs 33.3%, P<0.04). All inpatients had fever, 50% inpatients had coughs and showed infiltration in both lungs at the time of diagnosis. 33.3% inpatients exhibited negative changes in their CT results at initial diagnosis. The body temperature of non-hospitalized patients with mild symptoms returned to normal by day 4-5. While dyspnea peaked on day 6 for non-hospitalized patients with mild symptoms, it persisted in hospitalized patients and exacerbated over time. The lack of strength and muscle soreness were both back to normal by day 4 for non-hospitalized patients. Interpretation Monitoring the trends of symptoms is more important for identifying severe cases. Excessive laboratory data and physical examination are not necessary for the evaluation of patients with mild symptoms. The system we developed is the first to convert the subjective symptoms of patients into objective scores. This type of O2O, subjective-to-objective strategy may be used in regions with similar highly infectious diseases to minimize the possibility of infection among medical staff.

positive: [SARS-CoV-2 infection with gastrointestinal symptoms as the first manifestation in a neonate]. Since December 2019, the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has occurred in Wuhan, Hubei Province, China. The infected cases were noted mostly in adults, but rarely reported in children, especially neonates. Most children with SARS-CoV-2 infection present mainly with respiratory symptoms, but less commonly with gastrointestinal symptoms, and tend to have mild clinical symptoms. A neonate with SARS-CoV-2 infection, who had vomiting and milk refusal as the first symptom, was recently admitted to Wuhan Children's Hospital. After two weeks of treatment, the patient recovered gradually and was discharged. Here, this case is reported to improve the understanding of SARS-CoV-2 infection in neonates.

positive: Loss of Taste and Smell as Distinguishing Symptoms of COVID-19 Olfactory and taste dysfunctions have emerged as symptoms of COVID-19. Among individuals with COVID-19 enrolled in a household study, loss of taste and/or smell was the fourth most commonly reported symptom (26/42; 62%), and among household contacts, it had the highest positive predictive value (83%; 95% CI: 55-95%) for COVID-19. These findings support consideration of loss of taste and/or smell in possible case identification and testing prioritization for COVID-19.

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

positive: Follow-up of asymptomatic patients with SARS-CoV-2 infection

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: Clinical features of 30 cases with novel coronavirus pneumonia/ 中华传染病杂志 Objective@#To analyze the epidemiological and clinical characteristics of patients with 2019 novel coronavirus (2019-nCoV) infection in Shenyang.@*Methods@#The epidemiological and clinical characteristics of 30 patients diagnosed with 2019-nCoV infection admitted to Shenyang sixth people's hospital on January 22, 2020 and February 8, 2020 were retrospectively analyzed.@*Results@#Among the 30 cases, 21 were imported, including 17 from Hubei Province and four from other provinces. Nine cases were local infections. There were 18 men and 12 women, aging from 21 to 72 years with the median of 43 years. Eight cases had underlying diseases including hypertension, diabetes, coronary heart disease and bronchitis. On admission, two (7%) cases were mild, 19 (63%) cases were ordinary, eight (27%) cases were severe, and one (3%) case was critical. Clinical manifestations mainly include fever, with or without upper respiratory tract symptoms, normal, decreased or slightly increased white blood cell counts, mainly decreased lymphocyte counts, normal or increased c-reactive protein, and normal procalcitonin. The computed tomography (CT) of the early stage of the lungs showed that multiple patchy ground glass shadows were mainly accompanied by consolidation, which often involved both lungs or multiple lobes of one lung. At the moment, the clinical treatment mainly included respiratory support, symptomatic treatment, antiviral treatment adn anti-bacterial treatment. By February 15, a total of nine cases were cured and discharged, including one mild case, six ordinary cases, and two severe cases. In the comparisons between mild/ordinary patients and severe/critical patients, the fever duration in the severe/critical group (median 11.5 d) was significantly longer than that in the light/normal group (median 2 d) (Z=-2.292, P=0.022), and the laboratory tests indicated elevated d-dimer levels (Z=-2.669, P=0.008) and more cases with neutrophilic/lymphocyte ratio > 3 (Z=-4.071, P<0.01).@*Conclusions@#In Shenyang, the early cases with 2019-nCoV infection are mainly imported cases, and expanding local infections gradually develop. Clinical manifestations are mainly characterized by fever and cough. Lung CT performance shows multiple ground glass shadows, mainly accompanied by consolidation. CT changes in the lungs should be closely monitored during the treatment, and CT findings in the lungs may change earlier than the clinical manifestations. Prolonged fever duration, elevated d-dimer level and neutrophil/lymphocyte ratio >3 could be used as early warning indicators for severe cases.

positive: Characteristic Temporary Loss of Taste and Olfactory Senses in SARS-CoV-2-positive-Individuals with Mild Symptoms

positive: COVID-19: A New Virus as a Potential Rapidly Spreading in the Worldwide Covid-19 is a novel virus with high affinity to spread in the community In December 2019, it was first identified in Wuhan, China The symptoms are non-specific, so fever, cough, dyspnea, are prominent features Respiratory failure and mortality have also been reported The most common lung CT scan findings are bilateral ground glass opacities

positive: Clinical Characteristics of COVID-19 Patients With Gastrointestinal Symptoms: An Analysis of Seven Patients in China Objectives: Patients with novel coronavirus disease 2019 (COVID-19) can present with gastrointestinal symptoms as their initial symptoms or as the main manifestations during disease progression, but the clinical characteristics of these patients are still unknown. Methods: We identified COVID-19 patients who admitted to Xiangyang No. 1 People's Hospital and presented with gastrointestinal symptoms as their initial or main symptoms. Their medical records were reviewed by two independent clinical scientists. The epidemiological and clinical characteristics as well as the clinical outcomes were analyzed. Results: Among 142 confirmed COVID-19 cases, 7 (4.9%) of them presented with gastrointestinal symptoms. Three patients had gastrointestinal symptoms as the initial symptoms and chief complaints, and 4 patients as the main symptoms during disease progression. Six patients had symptoms of diarrhea (3–16 days), 7 with anorexia (7–22 days), 6 with upper abdominal discomfort (1–7 days), and 4 with nausea (1–7 days), 1 with heartburn lasting 2 days, and 2 with vomiting symptoms (1 day). The chest CT scan showed typical COVID-19 imaging features, and associated with the progression of the disease. During treatment, 2 patients died due to organ failure. Discussion: COVID-19 patients with gastrointestinal symptoms are relatively rare and might be misdiagnosed. The clinical features include watery stools, anorexia, and upper abdominal discomfort. These patients may have severe disease and be associated with a poor prognosis. The underlying mechanisms of SARS-CoV-2 related gastrointestinal symptoms need to clarify in future studies.

positive: Clinical features of pediatric patients with COVID-19: a report of two family cluster cases BACKGROUND: Coronovirus disease 2019 (COVID-19) has spread rapidly across the globe. People of all ages are susceptible to COVID-19. However, literature reports on pediatric patients are limited. METHODS: To improve the recognition of COVID-19 infection in children, we retrospectively reviewed two confirmed pediatric cases from two family clusters. Both clinical features and laboratory examination results of the children and their family members were described. RESULTS: The two confirmed children only presented with mild respiratory or gastrointestinal symptoms. Both of them had normal chest CT images. After general and symptomatic treatments, both children recovered quickly. Both families had travel histories to Hubei Province. CONCLUSIONS: Pediatric patients with COVID-19 are mostly owing to family cluster or with a close contact history. Infected children have relatively milder clinical symptoms than infected adults. We should attach importance to early recognition, early diagnosis, and early treatment of infected children.

positive: 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.

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

positive: Clinical Progression of COVID-19 Patient with Extended Incubation Period, Delayed RT-PCR Time-to-positivity, and Potential Role of Chest CT-scan Coronavirus Disease 2019 (COVID-19), previously called 2019-nCoV, is a novel disease caused by SARS- CoV-2 which was first identified as outbreak of unknown respiratory illness in Wuhan, China. COVID- 19 was declared as global health emergency by WHO on March 11, 2020 and quickly elevated to global pandemic on 11 March 2020. COVID-19 symptom is highly various in each patient, with fever, fatigue, shortness of breath, and cough as the main presenting symptoms. Patient with COVID-19 may shows severe symptom with severe pneumonia and ARDS, mild symptom resembling simple upper respiration tract infection, or even completely asymptomatic. Approximately 80% of cases is mild. However the number may changes as more people are getting tested. Some experts are estimating that up to 50% of all cases may be asymptomatic carrier.

positive: Investigation of three clusters of COVID-19 in Singapore: implications for surveillance and response measures BACKGROUND: Three clusters of coronavirus disease 2019 (COVID-19) linked to a tour group from China, a company conference, and a church were identified in Singapore in February, 2020. METHODS: We gathered epidemiological and clinical data from individuals with confirmed COVID-19, via interviews and inpatient medical records, and we did field investigations to assess interactions and possible modes of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Open source reports were obtained for overseas cases. We reported the median (IQR) incubation period of SARS-CoV-2. FINDINGS: As of Feb 15, 2020, 36 cases of COVID-19 were linked epidemiologically to the first three clusters of circumscribed local transmission in Singapore. 425 close contacts were quarantined. Direct or prolonged close contact was reported among affected individuals, although indirect transmission (eg, via fomites and shared food) could not be excluded. The median incubation period of SARS-CoV-2 was 4 days (IQR 3–6). The serial interval between transmission pairs ranged between 3 days and 8 days. INTERPRETATION: SARS-CoV-2 is transmissible in community settings, and local clusters of COVID-19 are expected in countries with high travel volume from China before the lockdown of Wuhan and institution of travel restrictions. Enhanced surveillance and contact tracing is essential to minimise the risk of widespread transmission in the community. FUNDING: None.

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

positive: Clinical aspects of virus/immune myocarditis Although a cause-and-effect relationship between viral infection and myocarditis remains inferential, two distinct clinical syndromes can be identified. During the early viral phase, the cardiac manifestations emerge while the symptoms of active viral infection are also present. During the chronic phase, symptoms of the viral infection may be remote or nonexistent, and identification of active myocarditis is contingent upon an aggressive diagnostic approach with endomyocardial biopsy and gallium 67 imaging. The exact incidence of myocarditis in patients with heart failure of unknown cause is unclear due to lack of standardization of histologic parameters. There are no other clinical clues to the presence of myocarditis in those patients presenting with cardiomyopathy or ventricular arrhythmia. For further clarification of the incidence and various presentations of myocarditis a large multi-center trial is necessary.

positive: COVID-19 in Post-Operative Patients: Imaging Findings. Background: Coronavirus 2019 (COVID-19) in the post-operative period is challenging. Its clinical manifestations may have similarities to other septic, thoracic, or gastrointestinal post-surgical complications. Additionally, the post-operative period may be a time of increased risk for severe manifestations of COVID-19. We sought to evaluate the frequency of COVID-19 in a cohort of patients who had recently had operations who were undergoing imaging for acute symptoms and the role of chest computed tomography (CT) in this setting. Patients and Methods: We included all patients who had chest CT for acute symptoms in the 15 days after a surgical procedure between March 1 and 31, 2020. Results: Of 46 patients with acute post-operative symptoms requiring chest imaging, eight (17%) were ultimately diagnosed with COVID-19. Among them, five (62%) required mechanical ventilation and two (25%) died. All had abnormal chest CT with typical findings of COVID-19 in 87%. Computed tomography provided an alternate diagnosis in 53% of patients who did not have COVID-19. The average time between a COVID-19-positive chest CT and the polymerase chain reaction (PCR) confirmation was 1.2 days (range, 0-4 days). Conclusion: COVID-19 is a serious post-operative condition associated with significant morbidity and mortality. Chest CT provides prompt diagnosis of COVID-19. In centers with a high prevalence of COVID-19, chest acquisition should be included in CT scans done for acute post-operative symptoms.

positive: Clinical Features and Chest CT Manifestations of Coronavirus Disease 2019 (COVID-19) in a Single-Center Study in Shanghai, China. OBJECTIVE. Confronting the new coronavirus infection known as coronavirus disease 2019 (COVID-19) is challenging and requires excluding patients with suspected COVID-19 who actually have other diseases. The purpose of this study was to assess the clinical features and CT manifestations of COVID-19 by comparing patients with COVID-19 pneumonia with patients with non-COVID-19 pneumonia who presented at a fever observation department in Shanghai, China. MATERIALS AND METHODS. Patients were retrospectively enrolled in the study from January 19 through February 6, 2020. All patients underwent real-time reverse transcription-polymerase chain reaction (RT-PCR) testing. RESULTS. Eleven patients had RT-PCR test results that were positive for severe acute respiratory syndrome coronavirus 2, whereas 22 patients had negative results. No statistical difference in clinical features was observed (p > 0.05), with the exception of leukocyte and platelet counts (p < 0.05). The mean (± SD) interval between onset of symptoms and admission to the fever observation department was 4.40 ± 2.00 and 5.52 ± 4.00 days for patients with positive and negative RT-PCR test results, respectively. The frequency of opacifications in patients with positive results and patients with negative results, respectively, was as follows: ground-glass opacities (GGOs), 100.0% versus 90.9%; mixed GGO, 63.6% versus 72.7%; and consolidation, 54.5% versus 77.3%. In patients with positive RT-PCR results, GGOs were the most commonly observed opacification (seen in 100.0% of patients) and were predominantly located in the peripheral zone (100.0% of patients), compared with patients with negative results (31.8%) (p = 0.05). The median number of affected lung lobes and segments was higher in patients with positive RT-PCR results than in those with negative RT-PCR results (five vs 3.5 affected lobes and 15 vs nine affected segments; p < 0.05). Although the air bronchogram reticular pattern was more frequently seen in patients with positive results, centrilobular nodules were less frequently seen in patients with positive results. CONCLUSION. At the point during the COVID-19 outbreak when this study was performed, imaging patterns of multifocal, peripheral, pure GGO, mixed GGO, or consolidation with slight predominance in the lower lung and findings of more extensive GGO than consolidation on chest CT scans obtained during the first week of illness were considered findings highly suspicious of 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: Extrapulmonary manifestations of COVID-19: Radiologic and clinical overview COVID-19 is principally a respiratory illness and pulmonary manifestations constitute main presentations of the disease. According to the reported studies, SARS-CoV-2 infection is not limited to the respiratory system and other organs can be also affected. Renal dysfunction, gastrointestinal complications, liver dysfunction, cardiac manifestations, mediastinal findings, neurological abnormalities, and hematological manifestations are among the reported extrapulmonary features. Considering the broad spectrum of clinical manifestations and the increasing worldwide burden of the disease, there is an urgent need to rapidly scale up the diagnostic capacity to detect COVID-19 and its complications. This paper focuses on the most common extrapulmonary manifestations in patients with COVID-19 pneumonia. Further studies are needed to elaborate and confirm the causative relationship between SARS-CoV-2 and the reported extrapulmonary manifestations of COVID-19.

positive: Clinical characteristics of asymptomatic and symptomatic patients with mild COVID-19 OBJECTIVES: Detailed knowledge on the prevalence of asymptomatic cases of coronavirus disease 2019 (COVID-19) and the clinical characteristics of mild COVID-19 is essential for effective control of the COVID-19 pandemic. We determined the prevalence of asymptomatic cases of COVID-19 and characterized the symptoms of patients with mild COVID-19. METHODS: Study participants were recruited from a community facility designated for the isolation of patients without moderate-to-severe symptoms of COVID-19 in South Korea. The prevalence of asymptomatic patients at admission and the detailed symptoms of mild COVID-19 were evaluated through a questionnaire-based survey. Diagnosis of COVID-19 was confirmed by real-time RT-PCR. RESULTS: Of the 213 individuals with COVID-19, 41 (19.2%) were asymptomatic until admission. Among the remaining patients with mild COVID-19, the most common symptom was cough (40.1%; 69/172), followed by hyposmia (39.5%; 68/172) and sputum (39.5%; 68/172). Of the 68 individuals with hyposmia, 61 (90%) had accompanying symptoms such as hypogeusia, nasal congestion or rhinorrhoea. Fever (>37.5°C) was only observed in 20 (11.6%) individuals. CONCLUSIONS: As much as one-fifth of individuals with COVID-19 remained asymptomatic from exposure to admission. Hyposmia was quite frequent among individuals with mild COVID-19, but fever was not. Social distancing should be strongly implemented to prevent disease transmission from asymptomatic individuals or those with mild and inconspicuous symptoms.

positive: Gastrointestinal, Hepatobiliary, and Pancreatic Manifestations of COVID-19 Abstract There is an increasing number of confirmed cases and deaths caused by the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contributing to the Coronavirus disease 2019 (COVID-19) pandemic. At this point, the need for further disease characterization is critical. COVID-19 is well established as a respiratory tract pathogen; however, recent studies have shown an increasing number of patients reporting gastrointestinal manifestations such as diarrhea, nausea, vomiting, and abdominal pain. The time from onset of gastrointestinal symptoms to hospital presentation is often delayed compared to that of respiratory symptoms. It has been noted that SARS-CoV-2 RNA can be detected in fecal matter for an extended period of time, even after respiratory samples have tested negative and patients are asymptomatic. In this article, SARS-CoV-2 and its disease COVID-19 will be reviewed with consideration of the latest literature about gastrointestinal symptomatology, the mechanisms by which the virus may inflict damage, and the possibility of viral replication contributing to a fecal-oral route of transmission.

positive: Early CT features and temporal lung changes in COVID-19 pneumonia in Wuhan, China Abstract Purpose To analyse the high-resolution computed tomography (HRCT) early imaging features and the changing trend of coronavirus disease 2019 (COVID-19) pneumonia. Materials and Methods Forty-six patients with COVID-19 pneumonia who had an isolated lesion on the first positive CT were enrolled in this study. The following parameters were recorded for each lesion: sites, sizes, location (peripheral or central), attenuation (ground-glass opacity or consolidation), and other abnormalities (supply pulmonary artery dilation, air bronchogram, interstitial thickening, etc.). The follow-up CT images were compared with the previous CT scans, and the development of the lesions was evaluated. Results The lesions tended to be peripheral and subpleural. All the lesions exhibited ground-glass opacity with or without consolidation. A higher proportion of supply pulmonary artery dilation (89.13% [41/46]) and air bronchogram (69.57% [32/46]) were found. Other ﬁndings included thickening of the intralobular interstitium and a halo sign of ground glass around a solid nodule. Cavitation, calciﬁcation or lymphadelopathy were not observed. The reticular patterns were noted from the 14 days after symptoms onset in 7 of 20 patients (45%). At 22-31 days, the lesions were completely absorbed only in 2 of 7 patients(28.57%). Conclusion The typical early CT features of COVID-19 pneumonia are ground-glass opacity, and located peripheral or subpleural location, and with supply pulmonary artery dilation. Reticulation was evident after the 2nd week and persisted in half of patients evaluated in 4 weeks after the onset. Long-term follow-up is required to determine whether the reticulation represents irreversible ﬁbrosis.

positive: Sequential symptomatic analysis in probable severe acute respiratory syndrome cases() STUDY OBJECTIVE: Previous reports on severe acute respiratory syndrome (SARS) described mainly its symptoms. However, the time sequence of symptom development was rarely discussed. The objective of this study is to chronologically document the time sequence of symptom development in probable SARS cases and compare that of the febrile non-SARS cases, thus providing valuable information for early recognition of the disease. METHODS: This prospective, descriptive, cohort study was conducted in an academic university hospital in Taipei, Taiwan, from March 14 through May 12, 2003. Patients presenting to the emergency department (ED) with a temperature of at least 38.0°C (≥100.3°F) and exposure history were evaluated with a structured protocol. Detailed time sequences of individual symptoms were recorded, and chest radiography and laboratory test results were obtained. Probable SARS cases were determined by the Center of Disease Control Taiwan. Children younger than 15 years and suspected SARS patients with negative polymerase chain reaction results were excluded from final analysis. RESULTS: Seventy-nine SARS and 220 non-SARS cases were analyzed. The major clinical symptoms of SARS patients on ED presentation were myalgia, loose stool or diarrhea, nonproductive cough or dyspnea, headache, and chills. Upper airway symptoms, including rhinorrhea and sore throat, were rarely seen in the SARS patients but were common in the non-SARS group. Characteristic symptom sequence, consisting of initial fever accompanied by diarrhea and myalgia and then progressive respiratory symptoms, was identified in 55 SARS patients (69.6%; 95% confidence interval [CI] 0.60 to 0.80) but only 7 (3.2%; 95% CI 0.008 to 0.05) non-SARS patients. Chest radiographic abnormality may precede lower respiratory tract symptoms in some SARS patients. CONCLUSION: During an outbreak period, recognition of possible SARS cases depends on the heightened awareness of its clinical presentation. Aside from travel and contact history, the time sequence of the accompanying symptoms of SARS should help first-line physicians screen SARS patients at an early stage.

positive: Epidemiology and Clinical Characteristics of COVID-19 Since December 2019, there has been an outbreak of a novel coronavirus (COVID-19) infection in Wuhan, China. Meanwhile, the outbreak also drew attention and concern from the World Health Organization (WHO). COVID-19 is another human infectious disease caused by coronavirus. The transmission of COVID-19 is potent and the infection rate is fast. Since there is no specific drug for COVID-19, the treatment is mainly symptomatic supportive therapy. In addition, it should be pointed out that patients with severe illness need more aggressive treatment and meticulous care. Recently, accurate RNA detection has been decisive for the diagnosis of COVID-19. The development of highly sensitive RT-PCR has facilitated epidemiological studies that provide insight into the prevalence, seasonality, clinical manifestations and course of COVID-19 infection. In this review, we summarize the epidemiology and characteristics of COVID-19.

positive: Type and frequency of ocular and other known symptoms experienced by people who self diagnosed as suffering from COVID-19 in the UK Background: Recent literature suggests that ocular manifestations present in people suffering from COVID-19. However, the prevalence and the type of ocular symptoms varies substantially, and most studies report retrospective data from patients suffering from more serious versions of the disease. Little is known of exactly which ocular symptoms manifest in people with milder forms of COVID-19. Methods: An online questionnaire obtained self-report data from people in the community, who reported to be inflicted with COVID-19. The type and frequency of different symptoms suffered during COVID-19 were obtained. Details of any pre-existing ocular conditions and the duration of symptoms of COVID-19 were ascertained. Results: Data from 132 participants showed that the four most reported COVID-19 symptoms were Dry Cough (63%), Fever (67%), Fatigue (83%), and loss of Smell/Taste (63%). 56% of the participants reported to having experienced an eye symptom, 46% reported to having a new or different eye symptom compared to pre-COVID-19 state. Three ocular symptoms (watery eyes, sore eyes, sensitivity to light) were significantly different from Pre-COVID-19 state (p<0.05). Logistic regression showed a significant association of eye symptoms with Fever (p=0.035). Conclusion: Nearly half of the sample of people studied experienced ocular symptoms. The significant ocular symptoms, indicative of viral conjunctivitis, might have been missed in patients with more serious manifestations of the disease. It is also important to differentiate between the types of ocular manifestation, as symptoms of bacterial conjunctivitis (i.e. mucous discharge, gritty eyes) were not significant. Possible mechanisms for SARS-CoV-2 infection within the eye are discussed.

positive: Clinical characteristics of older patients infected with COVID-19: A descriptive study Abstract Objectives Since the outbreak of 2019 novel coronavirus (COVID-19), which has spread in the world rapidly. Population have a susceptibility to COVID-19, older people were more susceptible to have a variety diseases than younger, including COVID-19 infection with no doubt. This study focused on older patients with COVID-19 infection and analyzed the epidemiological and clinical characteristics of them. Methods We collected information on confirmed older patient transferred by Beijing Emergency Medical Service (EMS) to the designated hospitals from Jan 20 to Feb 29, 2020. The information including demographic, epidemiological, clinical, classification of severity and outcomes. All cases were categorized into three groups and compared the difference between aged 50–64 years, 65–79 years and older than 80 years. Results 56.7 % of elderly confirmed patients were male, fever (78.3 %), cough (56.7 %), dyspnea (30.0 %), and fatigue (23.3 %) were common symptoms of COVID-19 infection. Classification of severity has statistically significant differences between the three groups, compared with middle-aged patients and aged 65–79 years group, older than 80 years group had significant statistical differences in contacted to symptomatic case in 14 days. As of Feb 29, 38.3 % patients had discharged and 53.3 % patients remained in hospital in our study, the fatality of COVID-19 infection in elderly was 8.3 %. Conclusions The COVID-19 infection is generally susceptible with a relatively high fatality rate in older patients, we should pay more attention to the elderly patients with COVID-19 infection.

positive: 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.

positive: A case of COVID-19 patient with the diarrhea as initial symptom and literature review Since Dec 2019, a cluster of pneumonia outbreak in Wuhan, Hubei province, China, and soon spread to all province of China. The pathogen was proved to be a novel betacoronavirus called 2019 novel coronavirus (officially named by the World Health Organization as COVID-19). The typical clinical manifestations were fever, cough, dyspnea, and myalgia or fatigue. Less common symptoms included headache, diarrhea, nausea and vomiting. However diarrhea as the first symptom is rarely reported. Here we reported a case of 2019 novel coronavirus-infected patient (NCIP) with diarrhea as the initial symptom. Image of CT scan and laboratory examination and careful collected as well as detection of viral RNA in pharynx. The case demonstrate that gastrointestinal symptoms ware not rare in NCIP, and diarrhea could be the initial symptom.

positive: [Clinical features of 2019 novel coronavirus pneumonia in the early stage from a fever clinic in Beijing]. Objective: To summarize and analyze the clinical and imaging characteristics of patients with 2019 novel coronavirus pneumonia in the early stage in Beijing. Methods: A retrospective analysis of clinical and imaging data of 9 patients with 2019 novel coronavirus infection diagnosed in one fever clinicic in Beijing from January 18, 2020 to February 3, 2020. Results: 5 male and 4 female was included in those 9 patients, whose median age was 36 years, and the age range from 15 to 49 years. 8 of these patients had no underlying disease and one suffered from diabetes. 7 patients had a history of travel to Wuhan City or Hubei Province, and one patient was a medical staff. Two family clustered was found. The incubation period was 1 to 6 days. The clinical manifestations were fever in 8 cases (8/9) , dry cough in 5 cases (5/9) , pharyngalgia in 4 cases (4/9) , fatigue in 4 cases (4/9) , body soreness in 4 cases (4/9) , and blocked or watery nose in 1 case (1/9) . Six patients (6/9) had abnormal cell peripheral blood, of which 3 (3/9) had an increased monocyte count, 2 (2/9) had a reduced lymphocyte, and 1 (1/9) had an increased leukocyte count, while the 3 patients had normal cell blood routines. The median of CRP was 16.3 mg/L, including 5 patients with slightly elevated (5/9) , 4 patients with normal values (4/9) . the results of procalcitonin test were negative in5 patients. Three patients were examined by chest X-ray examination, one of which was normal, one case showed infiltrates of right upper lung, and another showed in right lower lung. All patients underwent chest HRCT. And 7 cases (7/9) showed multiple ground glass exudation, including 5 cases (5/7) involved bilateral lungs, 2 cases (2/7) involved unilateral lung, 3 cases (3/7) with patchy consolidation, and 2 cases (2/9) showed no abnormality. Conclusions: The patents with 2019 novel coronavirus pneumonia in this study generally have an epidemiological history. The clinical manifestations are fever and cough. Peripheral white blood cell counts were most normal And PCT were all negative. Chest HRCT manifested as multiple ground-glass opacities with partly consolidation. Some patients had normal chest radiographs but HRCT showed pneumonia. Some patients had no pneumonia on chest HRCT.

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

positive: Spectrum of Neuropsychiatric Manifestations in COVID-19 Corona Virus Disease 2019 (COVID-19) emerged in December 2019 from Wuhan, China. It typically presents with mild upper respiratory tract infection symptoms and may have life threatening complications, including acute respiratory distress syndrome, acute stroke, myocardial infarction, kidney failure, shock, and even death. Coronavirus infections are known to have neuroinvasive potential with consequent neuropsychiatric manifestations. We analyzed COVID-19 adult patients in the TriNetX database, which is a global health collaborative clinical research platform collecting real-time electronic medical records data from a network of health care organizations (HCOs) from January 20, 2020 to June 10(th), 2020. 40,469 patients were diagnosed with COVID-19 among whom 9086 (22.5%) patients had neuropsychiatric manifestations. The most common neurologic manifestations included headache (3.7%) and sleep disorders (3.4%), Encephalopathy (2.3%), Stroke and transient ischemic attack (TIA) (1.0%) and 0.6% had seizures. Most common psychiatric manifestations included anxiety and other related disorders (4.6%), mood disorders (3.8%), while 0.2% patients had suicidal ideation. Early recognition and prompt management of neuropsychiatric manifestations in these patients have a potential to decrease overall morbidity and mortality.

positive: 2019 Novel Coronavirus (COVID-19) Pneumonia with Hemoptysis as the Initial Symptom: CT and Clinical Features Recently, some global cases of 2019 novel coronavirus (COVID-19) pneumonia have been caused by second- or third-generation transmission of the viral infection, resulting in no traceable epidemiological history. Owing to the complications of COVID-19 pneumonia, the first symptom and imaging features of patients can be very atypical and early diagnosis of COVID-19 infections remains a challenge. It would aid radiologists and clinicians to be aware of the early atypical symptom and imaging features of the disease and contribute to the prevention of infected patients being missed.

positive: COVID-19 and what pediatric rheumatologists should know: a review from a highly affected country On March 11th, 2020 the World Health Organization declared COVID-19 a global pandemic. The infection, transmitted by 2019 novel coronavirus (2019-nCov), was first discovered in December 2019, in Wuhan, Hubei Province, and then rapidly spread worldwide. Italy was early and severely involved, with a critical spread of the infection and a very high number of victims. Person-to-person spread mainly occurs via respiratory droplets and contact. The median incubation period is 5 days. The spectrum of respiratory symptoms may range from mild to severe, strictly depending on the age of the patient and the underlying comorbidities. In children COVID-19 related disease is less frequent and less aggressive. In Italy 1% of positive cases are under 18 years of age, and no deaths have been recorded before 29 years of age. For patients affected by rheumatic disease, despite the concerns related to the imbalance of their immune response and the effect of immunosuppressive treatments, there are still few data to understand the real consequences of this infection. Major scientific societies have issued recommendations to help rheumatologists in caring their patients. Interestingly, some of the drugs mostly used by rheumatologists appear to be promising in critical COVID-19 infected patients, where the hyperinflammation and cytokine storm seem to drive to the multiorgan failure. Pediatric rheumatologists are expected to play a supporting role in this new front of COVID-19 pandemic, both as general pediatricians treating infected children, and as rheumatologists taking care of their rheumatic patients, as well as offering their experience in the possible alternative use of immunomodulatory drugs.

positive: Gastrointestinal symptoms as the first, atypical indication of SARS-CoV-2 infection.

positive: Clinical Presentation of COVID-19: A Systematic Review Focusing on Upper Airway Symptoms AIM: Pharyngodynia, nasal congestion, rhinorrhea, smell, and taste dysfunctions could be the presenting symptoms of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2. The aim was to perform a systematic review of current evidences on clinical presentation of COVID-19, focusing on upper airway symptoms in order to help otolaryngologists identifying suspected cases. METHODS: We searched PubMed and Web of Science electronic databases. RESULTS: We included 5 retrospective clinical studies for a total of 1556 hospitalized patients with COVID-19, 57.5% were male and mean age was 49.1 years. Pooled data revealed that pharyngodynia was present in 12.4% of patients, nasal congestion in 3.7%, and rhinorrhea was rare. No reports on COVID-19 and olfactory/gustative disorders matched inclusion criteria but preliminary evidences suggested they could be present. Common symptoms were fever (85.6%), cough (68.7%), and fatigue (39.4%). Frequent comorbidities were hypertension (17.4%), diabetes (3.8%), and coronary heart disease (3.8%); 83% of patients had alterations on chest computed tomography that were bilateral in 89.5% of cases. Ground-glass opacity was the most common finding (50%). Lymphopenia (77.2%) and leucopenia (30.1%) were common. Critical cases with complications were 9%, intensive care unit admission was required in 7.3%, invasive ventilation in 3.4%, and mortality was 2.4%. CONCLUSION: Otolaryngologists should know that pharyngodynia, nasal congestion, olfactory, and gustative disorders could be the presenting symptoms of COVID-19. Clinical presentation together with radiological and laboratory findings could help to identify suspected cases.

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

positive: A case of COVID-19 patient with the diarrhea as initial symptom and literature review Summary Since Dec 2019, a cluster of pneumonia outbreak in Wuhan, Hubei province, China, and soon spread to all province of China. The pathogen was proved to be a novel betacoronavirus called 2019 novel coronavirus (officially named by the World Health Organization as COVID-19). The typical clinical manifestations were fever, cough, dyspnea, and myalgia or fatigue. Less common symptoms included headache, diarrhea, nausea and vomiting. However diarrhea as the first symptom is rarely reported. Here we reported a case of 2019 novel coronavirus-infected patient (NCIP) with diarrhea as the initial symptom. Image of CT scan and laboratory examination and careful collected as well as detection of viral RNA in pharynx. The case demonstrate that gastrointestinal symptoms ware not rare in NCIP, and diarrhea could be the initial symptom.

positive: Chest computed tomography findings of coronavirus disease 2019 (COVID-19) pneumonia OBJECTIVE: To retrospectively analyze the chest computed tomography (CT) features in patients with coronavirus disease 2019 (COVID-19) pneumonia. METHODS: From January 9, 2020, to February 26, 2020, totally 56 laboratory-confirmed patients with COVID-19 underwent chest CT. For 40 patients, follow-up CT scans were obtained. The CT images were evaluated for the number, type and distribution of the opacity, and the affected lung lobes. Furthermore, the initial CT scan and the follow-up CT scans were compared. RESULTS: Forty patients (83.6%) had two or more opacities in the lung. Eighteen (32.7%) patients had only ground-glass opacities; twenty-nine patients (52.7%) had ground-glass and consolidative opacities; and eight patients (14.5%) had only consolidation. A total of 43 patients (78.2%) showed two or more lobes involved. The opacities tended to be both in peripheral and central (30/55, 54.5%) or purely peripheral distribution (25/55, 45.5%). Fifty patients (90.9%) had the lower lobe involved. The first follow-up CT scans showed that twelve patients (30%) had improvement, 26 (65%) patients had mild-moderate progression, and two patients (5%) had severe progression with “white lungs.” The second follow-up CT showed that 22 patients (71%) showed improvement compared with the first follow-up CT, four patients (12.9%) had aggravated progression, and five patients (16.1%) showed unchanged radiographic appearance. CONCLUSIONS: The common CT features of COVID-19 pneumonia are multiple lung opacities, multiple types of the opacity (ground-glass, ground-glass and consolidation, and consolidation alone), and multiple lobes especially the lower lobe involved. Follow-up CT could demonstrate the rapid progression of COVID-19 pneumonia (either in aggravation or absorption). KEY POINTS: • The predominant CT features of COVID-19 pneumonia are multiple ground-glass opacities with or without consolidation and, with both lungs, multiple lobes and especially the lower lobe affected. • CT plays a crucial role in early diagnosis and assessment of COVID-19 pneumonia progression. • CT findings of COVID-19 pneumonia may not be consistent with the clinical symptoms or the initial RT-PCR test results.

positive: [Retracted: Clinical and epidemiological characteristics of 34 children with 2019 novel coronavirus infection in Shenzhen] Objective: To describe the characteristics of clinical manifestations and epidemiology of children with 2019 novel coronavirus (2019-nCoV) infection. Methods: All 34 children with laboratory-confirmed 2019-nCoV infection by quantitative real-time reverse transcription-PCR through nasopharyngeal swab specimens were admitted to the Third People's Hospital of Shenzhen from January 19 to Febuary 7, 2020. Clinical data and epidemiological history of these patients were retrospectively collected and analyzed. Results: Among the 34 cases, 14 were males, and 20 were females. The median age was 8 years and 11 months. No patients had underlying diseases. There were 28 children (82%) related with a family cluster outbreak. There were 26 children (76%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 22 (65%) common cases, 9 (26%) mild cases and 3 (8.8%) asymptomatic cases. No severe or critical cases were identified. The most common symptoms were fever (17 cases, 50%) and cough (13 cases, 38% ). In the 34 cases, the white blood cell counts of 28 cases (82%) were normal. Five cases had white blood cell counts more than 10×10(9)/L. One case had white blood cell counts less than 4×10(9)/L. Neutropenia and lymphopenia was found in one case, respectively. C-reactive protein levels and erythrocyte sedimentation rates were elevated in 1 and 5 case, respectively. Elevated procalcitonin was found in 1 case and D-Dimer in 3 cases. The levels of lactic dehydrogenase (LDH) were more than 400 U/L in 10 cases. The CT images of these patients showed bilateral multiple patchy or nodular ground-glass opacities and/or infiltrating shadows in middle and outer zone of the lung or under the pleura. Twenty patients were treated with lopinavir and ritonavir. Glucocorticoids and immunoglobulin were not used in any cases. All the cases improved and were discharged from hospital. Further following up was need. Conclusions: The clinical manifestations in children with 2019-nCoV infection are non-specific and are milder than that in adults. Chest CT scanning is heplful for early diagnosis. Children's infection is mainly caused by family cluster outbreak and imported cases. Family daily prevention is the main way to prevent 2019-nCoV infection.

positive: High-Resolution Computed Tomography Manifestations of 5 Pediatric Patients With 2019 Novel Coronavirus We present clinical and chest computed tomography (CT) features of 5 cases of pediatric patients with 2019 novel coronavirus. Two patients had fever and dry cough, whereas the rest of 3 patients were asymptomatic. Three patients had unilateral ground glass opacities with or without consolidation in the subpleural region on high-resolution chest CT, 1 patient had bilateral ground glass opacities, and 1 patient was negative for CT. We note that up to 66.7% asymptomatic patients had pulmonary lesions, so the asymptomatic children with Wuhan contact are recommended to do a 2019 novel coronavirus real-time fluorescence polymerase chain reaction screening. Unlike adult patients, only a small amount of patients had multilobes affected, so we speculate that the pediatric patients generally have milder CT findings than adults.

positive: Analysis clinical features of COVID-19 infection in secondary epidemic area and report potential biomarkers in evaluation Objective: Based on the clinical characteristics of infected patients with novel coronavirus in secondary epidemic areas,we aimed to identify potential biomarkers for the evaluation of novel coronavirus-infected patients,guide the diagnosis and treatment of this disease in secondary epidemic areas and provide a reference for the clinical prevention and control of this epidemic situation. Methods: The clinical data of 33 patients with respiratory symptoms caused by the novel coronavirus in Wenzhou city from January 15 to February 12,2020,were thoroughly reviewed. At the onset of the disease,we found that the primary symptoms were fever,cough,fatigue,chest tightness,chest pain and specific blood test results. According to the patients'histories,the patients were divided into two groups: those who spent time in the main epidemic area and those who did not spend time in the main epidemic area. The differences in the clinical manifestations between these two groups were analyzed. Results: The main clinical symptoms of patients infected with novel coronavirus in the secondary epidemic area were respiratory tract ailments and systemic symptoms. After grouping patients based on the presence or absence of residency in or travel history to the main epidemic area, there was no significant difference between the baseline data of these two groups, and there were no significant differences in symptoms and signs between the two groups (P>0.05). Some patients had abnormally increased serum amyloid protein A (SAA). There were statistically significant differences in the leukocyte count/C-reactive protein,monocyte ratio/C-reactive protein,neutrophil count/C-reactive protein,monocyte count/C-reactive protein and hemoglobin/C-reactive protein values between the two groups (P < 0.05). Conclusion: Respiratory tract ailments and systemic symptoms were the primary symptoms of novel coronavirus infection in the secondary epidemic area; these symptoms are not typical. The abnormal increase in serum amyloid protein (SAA) may be used as an auxiliary index for diagnosis and treatment. CRP changes before other blood parameters and thus may be an effective evaluation index for patients with COVID-19 infection.

positive: Potential neurological symptoms of COVID-19

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

positive: Early Insights into Immune Responses during COVID-19. Coronavirus disease-2019 (COVID-19) is caused by the newly emerged virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was recently declared as a pandemic by the World Health Organization. In its severe form, the disease is characterized by acute respiratory distress syndrome, and there are no targeted intervention strategies to treat or prevent it. The immune response is thought to both contribute to the pathogenesis of disease and provide protection during its resolution. Thus, understanding the immune response to SARS-CoV-2 is of the utmost importance for developing and testing vaccines and therapeutics. In this review, we discuss the earliest knowledge and hypotheses of the mechanisms of immune pathology in the lung during acute infection as well at the later stages of disease resolution, recovery, and immune memory formation.

positive: Olfactory and taste disorder: The first and only sign in a patient with SARS-CoV-2 pneumonia

positive: Early clinical manifestations and pulmonary imaging analysis of patients with Novel coronavirus pneumonia/ 中华急诊医学杂志 Objective To investigate the early clinical characteristics and radiographic changes in confirmed Novel coronavirus pneumonia (NCP) and excluded NCP patients. Methods Twenty-four patients with suspected NCP admitted to Shanghai Jiao Tong University Affiliated Sixth People’s Hospital and Jinshan Branch Hospital between January and February, 2020 were chosen as our research subjects. Early clinical features and radiographic changes were analyzed in 10 patients of confirmed NCP and 14 patients of excluded NCP. Results In the early stage, all 24 suspected patients were mild, and had normal blood gas analysis. Of 10 diagnosed patients, 50% were male. All the 10 patients had fever and fatigue, with body temperature between 37.5℃ and 38.5℃. Only 1 patient had dry cough. 2 patients had no clear epidemiological exposure history, the other 8 had a clear epidemiological exposure, with a possible incubation period of 1-10 days. From CT imaging, lesions were characterized as ground glass shadow ( n =9), which could be unilateral ( n =1) or bilateral ( n =9), and were mainly close to the pleura ( n =9), with nodule shadow ( n =1) and without focal necrosis, and could combined with pleural effusion ( n =1. Among patients excluded NCP, all 14 patients had a clear history of epidemic exposure, with an onset time of 1 to 13 days. 12 patients had fever , including 4 with temperature > 38.5°C, 8 with temperature 37.3-38.5°C, and 2 without fever. All patients had fatigue , 7 patients had dry cough and 2 patients had chest pain. From CT imaging, ground glass shadow appeared in 4 patients , lesions were unilateral in 10 patients and bilateral in 4 patients , and the lesions were relatively sporadic, without necrosis or pleural effusion. Conclusion 1．Not all patients with NCP have a direct history of epidemiology exposure, some patients may be infected unknowingly. 2. According to CT imaging, NCP seems to have no special manifestations different from other viral pneumonia. 3. NCP is more common among middle-aged people.

positive: Epidemiologic and clinical characteristics of 10 children with coronavirus disease 2019 in Changsha, China BACKGROUND: The outbreak of a new coronavirus, first reported in Wuhan, China, is spreading around the world. Information on the characteristics of children with Coronavirus Disease 2019 (COVID-19) is limited. METHODS: In this retrospective study, we recruited 10 children infected with SARS-COV-2 from January 27 to March 10, 2020, in Changsha, China. We report the epidemiological, clinical, laboratory, and high-resolution CT findings for these children. Qualitative descriptive analysis was used to describe the key results. RESULTS: Ten children were included. Three were male and seven were female. Three were from Wuhan, Hubei Province, and seven were from Changsha. All had a history of close contact with adults with COVID-19 before the onset of disease. Clinical manifestations included fever in four cases, respiratory symptoms in three cases, febrile convulsions in one case, vomiting in one case, abdominal pain in one case, and asymptomatic infection in two cases. All the children tested positive for nucleic acid in throat swabs at admission. Stool swabs of three cases were positive for nucleic acid after several days of fever. In nine children, blood routine results were normal, whereas in one case the white blood cell count was elevated. In four cases, CT findings of the lungs showed light ground-glass opacities, one case showed changes similar to bronchopneumonia, and the remaining cases were normal. All were treated with symptomatic support without complications. CONCLUSION: Our findings indicate that intrafamily transmission may be the main form of transmission of COVID-19 in children, and persistent intestinal excretion of virus is another characteristic among children. The results of stool swab tests should be considered for discharge and release from isolation.

positive: 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.

positive: Temporal Correlation Between Neurological and Gastrointestinal Symptoms of SARS-CoV-2 Severe Acute Respiratory Syndrome Coronavirus-2 (SAR-CoV-2) has been shown to invade brain tissue. Based on the evolutionary similarity with SARS-CoV, researchers propose that SARS-CoV-2 can invade the olfactory bulb and gastrointestinal (GI) system through angiotensin-converting enzyme 2. However, how SARS-CoV-2 causes neurological or GI symptoms is not clear. Many suggested intestinal and neural inflammations, caused by viral invasion, as the most likely reason for the GI and neurological symptoms; however, the patients with coronavirus disease 2019 (COVID-19) without neurological or GI symptoms indicate that this is not the case. The gut-brain axis could explain the reason for why some with COVID-19 do not have these symptoms. COVID-19 patients mostly show respiratory distress first, then diarrhea, anorexia, stroke, or loss of consciousness comes into view. Obviously, GI invasion is a mechanical process that begins with oral invasion and, therefore, most probably exists before the brain invasion, as indicated in case reports. However, when the GI tract is invaded, the virus may enter the central nervous system through vascular and lymphatic systems or the vagal nerve. SARS-CoV-2 can infect leukocytes and migrate with them into the brain, or the viral particles can be directly transported across the blood-brain barrier to the brain. Also, more recent research has revealed that SARS-CoV-2 can invade the peripheral lymphatic vessels connecting with the glymphatic system of the brain. The temporal correlation between neurological and gastrointestinal symptoms suggests the lymph vessels around the GI tract, the vascular system, or the gut-brain axis (enteric nervous system) as the most likely entry route for SARS-CoV-2 to the brain.

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: Epidemiological and initial clinical characteristics of patients with family aggregation of COVID-19 BACKGROUND: Since December 2019, a new outbreak of the coronavirus disease 2019 (COVID-19) in Wuhan (Hubei, China) and rapidly spread throughout China, however, confirmed cases are still increasing worldwide. OBJECTIVES: To investigate the epidemiological history and initial clinical characteristics of 10 patients with family aggregation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Western Chongqing, China. STUDY DESIGN: Ten patients positive for SARS-CoV-2 nucleic acid detection by real time Reverse Transcription-Polymerase Chain Reaction (RT-PCR), were collected from The People's Hospital of Dazu District, Chongqing. Epidemiological data and laboratory and imaging results were collected on the first day of admission, and analyzed based on the Diagnosis and Treatment Guideline for COVID-19 (5th edition, China). RESULTS: Of the 10 cases, case A had a history of a temporary stay in Wuhan and transmitted the virus to the others through family gathering, living together, and sharing vehicles. The average age was 56.5 years (± 11.16), six patients were males, and the incubation period was 2-14 days. Dry cough was the main symptom, followed by fever and fatigue. Most patients were clinically classified as ordinary-type, with three cases being severe-type. Chest computed tomography results were nonspecific, mainly with ground-glass attenuation and/or shadow images. Extensive lesion distribution was seen in severe cases. CD4+ lymphocyte counts were 61, 180, and 348 cells/uL in severe-type patients, respectively. Notably, viral nucleic acid values in nasopharyngeal swabs were lower (19, 25, and 26) than those of ordinary-type patients, suggesting a higher viral load. Neutrophil-lymphocyte ratio (NLR) was also higher in severe-type patients CONCLUSIONS: Initial examination results of lower CD4+ lymphocyte counts and RT-PCR-CT values coupled with higher NLR may indicate the severity of COVID-19 infection for these family clusters.

positive: Clinical features of imported cases of coronavirus disease 2019 in Tibetan patients in the Plateau area Abstract Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has rapidly spread throughout China, but the clinical characteristics of Tibetan patients living in the Qinghai-Tibetan plateau are unknown. We aimed to investigate the epidemiological, clinical, laboratory and radiological characteristics of these patients. We included 67 Tibetan patients with confirmed SARS-CoV-2 infection. The patients were divided into two groups based on the presence of clinical symptoms at admission, with 31 and 36 patients in the symptomatic and asymptomatic groups, respectively. The epidemiological, clinical, laboratory and radiological characteristics were extracted and analysed. No patient had a history of exposure to COVID-19 patients from Wuhan or had travelled to Wuhan. The mean age of Tibetan patients was 39.3 years and 59% of the patients were male. Seven patients presented with fever on admission and lymphocytopenia was present in 20 patients. 47 patients had abnormal chest CTs at admission instead of stating that 20 were unchanged. Lactate dehydrogenase levels were increased in 31 patients. Seven patients progressed to severe COVID-19; however, after treatment, their condition was stable. No patients died. Of the 36 asymptomatic patients, the mean age was younger than the symptomatic group (34.4vs 44.9 years, P=0.02). Lymphocyte count and prealbumin levels were higher in the asymptomatic group than the group with clinical symptoms (1.6 vs 1.3 and 241.8 vs 191.9, respectively; P<0.05). Imported cases of COVID-19 in Tibetan patients were generally mild in this high-altitude area. Absence of fever or radiologic abnormalities on initial presentation were common

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

positive: CT imaging features of 34 patients infected with COVID-19 OBJECTIVE: To retrospectively analyze the CT findings in patients infected with Coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: The thirty-four cases, 15 females and 19 males, with an age ranging from 7 to 88 years old, confirmed by real-time reverse-transcriptase-polymerase chain reaction (RT-PCR), were used for our study. All thin-section CT scans of the lungs were performed in all of patients. The clinical, laboratory and CT imaging were available to evaluate in all patients. RESULTS: The patients present with fever (85.29%, n = 29), cough (67.65%, n = 23), fatigue or myalgia (26.47%, n = 9), and pharyngalgia (8.82%, n = 3). The 4 patients (11.76%) with no symptoms were identified during screening for close contacts, who had typical CT findings. On initial CT scans, the bilateral lung involved was shown in 24 cases (70.59%), while 29 (82.35%) cases were distributed in peripheral. The pure ground glass opacity (GGO) was shown in 18 cases (52.94%), the GGO with consolidation was in 12 cases (35.29%), and full consolidation only in 3 cases. The lesion with air bronchogram was seen in 14 (41.18%) cases, with enlarged blood vessel in 17 (50.00%) cases, with crazy-paving pattern in 8 (23.53%) cases, with fine reticular pattern in 4 (11.77%) cases, and with intralesional vacuole sign in 6 (17.65%) cases. The pleural effusion was seen in one patient. Follow-up imaging in 19 patients during the study time window demonstrated mild, moderate or severe progression of disease, as manifested by increasing extent and density of lung opacities. CONCLUSIONS: The bilateral GGO with air bronchogram, enlarged blood vessel, fine reticular pattern, and peripheral distribution are the early CT findings of COVID-19. The crazy-paving pattern and intralesional vacuole sign are the features of progressive stage.

positive: Clinical and Imaging features of COVID-19 Patients: Analysis of Data from High-Altitude Areas

positive: 2019 Novel coronavirus infection and gastrointestinal tract Since end of December 2019, a cluster of patients with pneumonia of unknown origin was reported from Wuhan, Hubei province, China. As of Feb 17th, 2020, statistical data show that the outbreak constitutes an epidemic threat in China, where the exponential increase in patients has reached 75114 confirmed cases, with 2239 deaths. Different from SARS-CoV (severe acute respiratory syndrome coronavirus) and MERS-CoV (Middle East respiratory syndrome coronavirus) infection, the initial presentations or the chief complain of some patients with the 2019 novel coronavirus (COVID-19) were gastrointestinal symptoms. So we call upon all the first-line medical staff to be cautious and pay more attention to those untypical patients especially from the epidemic area. Besides, as the viral nucleic acids could be found in the fecal samples and anal swabs of some patients with COVID-19 infection, the possibility of fecal-oral transmission need to be took into account. Based on the previously and recently studies, we speculate that COVID-19 may have some relationship with the gut microbiota through angiotensin-converting enzyme 2 (ACE2) receptor, thus targeting gut microbiota might be a new therapeutic option for the treatment of virus-related pneumonia. This article is protected by copyright. All rights reserved.

positive: Periorbital Erythema as a Presenting Sign of Covid-19

positive: Alteration of Consciousness as Initial Presentation in COVID-19: Observation

positive: Clinical characteristics of COVID-19 in 104 people with SARS-CoV-2 infection on the Diamond Princess cruise ship: a retrospective analysis BACKGROUND: The ongoing COVID-19 pandemic is a global threat. Identification of markers for symptom onset and disease progression is a pressing issue. We described the clinical features of people infected on board the Diamond Princess cruise ship who were diagnosed with asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or mild or severe COVID-19, on admission to the Self-Defense Forces Central Hospital (Tokyo, Japan) and at the end of observation. METHODS: This retrospective, single-centre study included participants with laboratory-detected SARS-CoV-2 infection who were admitted to the Self-Defense Forces Central Hospital from Feb 11 to Feb 25, 2020. Clinical records, laboratory data, and radiological findings were analysed. Clinical outcomes were followed up until discharge or Feb 26, 2020, whichever came first. We defined asymptomatic infection as SARS-CoV-2 infection with no history of clinical signs and symptoms, severe COVID-19 as clinical symptoms of pneumonia (dyspnoea, tachypnoea, peripheral capillary oxygen saturation <93%, and need for oxygen therapy), and mild COVID-19 as all other symptoms. Clinical features on admission were compared among patients with different disease severity, including asymptomatic infection, at the end of observation. We used univariable analysis to identify factors associated with symptomatic illness among asymptomatic people infected with SARS-CoV-2 and disease progression in patients with COVID-19. FINDINGS: Among the 104 participants included in the final analysis, the median age was 68 years (IQR 47-75) and 54 (52%) were male. On admission, 43 (41%) participants were classified as asymptomatic, 41 (39%) as having mild COVID-10, and 20 (19%) as having severe COVID-19. At the end of observation, 33 (32%) participants were confirmed as being asymptomatic, 43 (41%) as having mild COVID-19, and 28 (27%) as having severe COVID-19. Serum lactate hydrogenase concentrations were significantly higher in the ten participants who were asymptomatic on admission but developed symptomatic COVID-19 compared with the 33 participants who remained asymptomatic throughout the observation period (five [50%] vs four [12%] participants; odds ratio 7·25, 95% CI 1·43-36·70; p=0·020). Compared with patients with mild disease at the end of observation, patients with severe COVID-19 were older (median age 73 years [IQR 55-77] vs 60 years [40-71]; p=0·028) and had more frequent consolidation on chest CT (13 [46%] of 28 vs nine [21%] of 43; p=0·035) and lymphopenia (16 [57%] vs ten [23%]; p=0·0055) on admission. INTERPRETATION: Older age, consolidation on chest CT images, and lymphopenia might be risk factors for disease progression of COVID-19 and contribute to improved clinical management. FUNDING: None.

positive: Could sudden sensorineural hearing loss be the sole manifestation of COVID-19? An investigation into SARS-COV-2 in the etiology of sudden sensorineural hearing loss Abstract Objective The aim of this study is to investigate the presence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in patients presenting with only sudden sensorineural hearing loss (SSNHL) during the pandemic. Methods The study included 5 male patients who presented with the sole complaint of unilateral SSNHL to the otolaryngology outpatient clinic between April 3 and April 12, 2020. The patients were referred to the infectious diseases clinic to be evaluated for SARS-CoV-2 by using real time polymerase chain reaction (RT-PCR) testing. Results RT-PCR testing for SARS-CoV-2 were positive in one of the patient and negative in rest four patients. We also noted positive response to Coronavirus Disease-19 (COVID-19) specific treatment in SARS-CoV-2 positive SSNHL patient. Conclusion It should be kept in mind that non-specific symptoms such as SSNHL could be the only sign to recognize a COVID-19 case. Awareness of such a non-specific presentation of COVID-19 patients is crucial during this pandemic period for the prevention of infectious spread through isolation and early initiation of COVID-19 targeted treatment.

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: Symptom clusters in Covid19: A potential clinical prediction tool from the COVID Symptom study app As no one symptom can predict disease severity or the need for dedicated medical support in COVID-19, we asked if documenting symptom time series over the first few days informs outcome. Unsupervised time series clustering over symptom presentation was performed on data collected from a training dataset of completed cases enlisted early from the COVID Symptom Study Smartphone application, yielding six distinct symptom presentations. Clustering was validated on an independent replication dataset between May 1- May 28th, 2020. Using the first 5 days of symptom logging, the ROC-AUC of need for respiratory support was 78.8%, substantially outperforming personal characteristics alone (ROC-AUC 69.5%). Such an approach could be used to monitor at-risk patients and predict medical resource requirements days before they are required.

positive: The outbreak of Coronavirus Disease 2019 (COVID-19)—An emerging global health threat Abstract The outbreak of Coronavirus Disease 2019 (COVID-19) causing novel coronavirus-infected pneumonia (NCIP), has affected the lives of 71,429 people globally. Originating in China, the disease has a rapid progression to other countries. Research suggests remarkable genomic resemblance of 2019-nCoV with Severe Acute Respiratory Syndrome (SARS) which has a history of a pandemic in 2002. With evidence of nosocomial spread, a number of diligent measures are being employed to constrain its propagation. Hence, the Public Health Emergency of International Concern (PHEIC) has been established by the World Health Organization (WHO) with strategic objectives for public health to curtail its impact on global health and economy.

positive: Acute encephalopathy with elevated CSF inflammatory markers as the initial presentation of COVID-19 BACKGROUND: COVID-19 is caused by the severe acute respiratory syndrome virus SARS-CoV-2. It is widely recognized as a respiratory pathogen, but neurologic complications can be the presenting manifestation in a subset of infected patients. CASE PRESENTATION: We describe a 78-year old immunocompromised woman who presented with altered mental status after witnessed seizure-like activity at home. She was found to have SARS-CoV-2 infection and associated neuroinflammation. In this case, we undertake the first detailed analysis of cerebrospinal fluid (CSF) cytokines during COVID-19 infection and find a unique pattern of inflammation in CSF, but no evidence of viral neuroinvasion. CONCLUSION: Our findings suggest that neurologic symptoms such as encephalopathy and seizures may be the initial presentation of COVID-19. Central nervous system inflammation may associate with neurologic manifestations of disease.

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

positive: Canadian Geriatrics Society COVID-19 Recommendations for Older Adults. What Do Older Adults Need To Know?

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

positive: Probability of symptoms and critical disease after SARS-CoV-2 infection We quantified the probability of developing symptoms (respiratory or fever \geq 37.5 {\deg}C) and critical disease (requiring intensive care or resulting in death) of SARS-CoV-2 positive subjects. 5,484 contacts of SARS-CoV-2 index cases detected in Lombardy, Italy were analyzed, and positive subjects were ascertained via nasal swabs and serological assays. 73.9% of all infected individuals aged less than 60 years did not develop symptoms (95% confidence interval: 71.8-75.9%). The risk of symptoms increased with age. 6.6% of infected subjects older than 60 years had critical disease, with males at significantly higher risk.

positive: The neurology of COVID-19 revisited: A proposal from the Environmental Neurology Specialty Group of the World Federation of Neurology to implement international neurological registries A comprehensive review of the neurological disorders reported during the current COVID-19 pandemic demonstrates that infection with SARS-CoV-2 affects the central nervous system (CNS), the peripheral nervous system (PNS) and the muscle. CNS manifestations include: headache and decreased responsiveness considered initial indicators of potential neurological involvement; anosmia, hyposmia, hypogeusia, and dysgeusia are frequent early symptoms of coronavirus infection. Respiratory failure, the lethal manifestation of COVID-19, responsible for 215,461 deaths worldwide, is probably neurogenic in origin and may result from the viral invasion of cranial nerve I, progressing into rhinencephalon and brainstem respiratory centers. Cerebrovascular disease, in particular large-vessel ischemic strokes, and less frequently cerebral venous thrombosis, intracerebral hemorrhage and subarachnoid hemorrhage, usually occur as part of a thrombotic state induced by viral attachment to ACE2 receptors in endothelium causing widespread endotheliitis, coagulopathy, arterial and venous thromboses. Acute hemorrhagic necrotizing encephalopathy is associated to the cytokine storm. A frontal hypoperfusion syndrome has been identified. There are isolated reports of seizures, encephalopathy, meningitis, encephalitis, and myelitis. The neurological diseases affecting the PNS and muscle in COVID-19 are less frequent and include Guillain-Barré syndrome; Miller Fisher syndrome; polyneuritis cranialis; and rare instances of viral myopathy with rhabdomyolysis. The main conclusion of this review is the pressing need to define the neurology of COVID-19, its frequency, manifestations, neuropathology and pathogenesis. On behalf of the World Federation of Neurology we invite national and regional neurological associations to create local databases to report cases with neurological manifestations observed during the on-going pandemic. International neuroepidemiological collaboration may help define the natural history of this worldwide problem.

positive: CT Scans Obtained for Nonpulmonary Indications: Associated Respiratory Findings of COVID-19. Background Atypical manifestations of COVID-19 are being encountered as the pandemic unfolds, leading to non-chest CT scans that may uncover unsuspected pulmonary disease. Purpose To investigate patients with primary non-respiratory symptoms who underwent abdomen/pelvis or cervical spine/neck CT with unsuspected findings highly suspicious for pulmonary COVID-19. Materials and Methods This retrospective study from March 10, 2020 to April 6, 2020 involved three institutions, two in a region considered a hotspot (area of high prevalence) for COVID-19. Patients without known COVID-19 were included who presented to the emergency room (ER) with primary non-respiratory [gastrointestinal (GI) or neurological] symptoms, had lung parenchymal findings suspicious for COVID-19 on a non-chest CT but no concurrent chest CT and had COVID-19 testing in the ER. Group 1 patients had RT PCR obtained pre-CT read (COVID-19 suspected on presentation); Group 2 had RT PCR obtained post-CT read (COVID-19 not suspected). Presentation and imaging findings were compared and outcomes were evaluated. Descriptive statistics and Fisher exact tests were used for analysis. Results Group 1 comprised 62 patients [31 men, 31 women, mean age 67(SD ±17) years] and group 2 comprised 57 patients [28 men, 29 women, mean age 63(SD ± 16) years). Cough and fever were more common in group 1 (37/62, 60%, 29/62, 47%) than group 2 (9/57, 16%, 12/57, 21%) respectively, with no significant difference in the remaining symptoms. There were 101 abdomen/pelvis and 18 cervical spine/neck CTs. In Group 1, non-chest CT findings provided the initial evidence of COVID-19 related pneumonia in 32/62 (52%); for Group 2, it was 44/57 (77%). Overall, the most common CT findings were ground glass opacity (114/119, 96%) and consolidation (47/119,40%). 29/119 (24%) patients required major interventions (vasopressor medication or intubation) and 27/119 (23%) died. Patients who underwent cervical spine/neck CT had worse outcomes than those with abdominal/pelvic CT (p =0.01). Conclusion In a substantial percentage of patients with primary non-respiratory symptoms who underwent non-chest CT, the CT provided the first evidence of COVID-19 related pneumonia.

positive: Rapidly Progressive COVID-19 Pneumonia: What Radiologists Should Do

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

positive: Clinical Characteristics of COVID-19 Infection in Newborns and Pediatrics: A Systematic Review INTRODUCTION: World Health Organization has declared COVID-19 a pandemic and a global health emergency. Thus, it is necessary to clearly characterize clinical manifestations and management of COVID-19 infection in children to provide accurate information for healthcare workers. Accordingly, the present study was designed to review articles published on clinical manifestations and characteristics of children and infants with COVID-19. METHODS: In this systematic review, medical databases including Cochrane Library, Web of Science, Embase, Scopus, SID, Medline, WHO and LitCovid were searched using English and Persian keywords including COVID-19, Pediatrics, Newborn, Coronavirus 2019, 2019-nCoV, SARS-CoV-2. Finally, data of 14 related articles were included in the study. RESULTS: A total of 2228 children, newborns and infants were studied. Clinical manifestation in children may be mild (72%), moderate (22%) or severe (6%), and the most common symptoms include dry cough (91%) and fever (96%). According to the included articles, two children had died, one of which was a 14-year-old boy and his exposure history and underlying disease were unclear, and the other was a male newborn with gestational age of 35 weeks and 5 days, birth weight of 2200, Apgar score of 8, 8 (1 min and 5 min) and his first symptom was increased heart rate. No differences were found between male and female children regarding infection with COVID-19. CONCLUSION: Most pediatrics were infected with COVID-19 due to family cluster or history of close contact. Infected children have relatively milder clinical symptoms compared to infected adults. We should pay special attention to early diagnosis and early treatment in children infected with COVID-19.

positive: [Clinical features of 2019 novel coronavirus pneumonia in the early stage from a fever clinic in Beijing] Objective: To summarize and analyze the clinical and imaging characteristics of patients with 2019 novel coronavirus pneumonia in the early stage in Beijing. Methods: A retrospective analysis of clinical and imaging data of 9 patients with 2019 novel coronavirus infection diagnosed in one fever clinicic in Beijing from January 18, 2020 to February 3, 2020. Results: 5 male and 4 female was included in those 9 patients, whose median age was 36 years, and the age range from 15 to 49 years. 8 of these patients had no underlying disease and one suffered from diabetes. 7 patients had a history of travel to Wuhan City or Hubei Province, and one patient was a medical staff. Two family clustered was found. The incubation period was 1 to 6 days. The clinical manifestations were fever in 8 cases (8/9) , dry cough in 5 cases (5/9) , pharyngalgia in 4 cases (4/9) , fatigue in 4 cases (4/9) , body soreness in 4 cases (4/9) , and blocked or watery nose in 1 case (1/9) . Six patients (6/9) had abnormal cell peripheral blood, of which 3 (3/9) had an increased monocyte count, 2 (2/9) had a reduced lymphocyte , and 1 (1/9) had an increased leukocyte count, while the 3 patients had normal cell blood routines. The median of CRP was 16.3 mg/L, including 5 patients with slightly elevated (5/9) , 4 patients with normal values (4/9) . the results of procalcitonin test were negative in5 patients. Three patients were examined by chest X-ray examination, one of which was normal, one case showed infiltrates of right upper lung, and another showed in right lower lung. All patients underwent chest HRCT. And 7 cases (7/9) showed multiple ground glass exudation, including 5 cases (5/7) involved bilateral lungs, 2 cases (2/7) involved unilateral lung, 3 cases (3/7) with patchy consolidation, and 2 cases (2/9) showed no abnormality. Conclusions: The patents with 2019 novel coronavirus pneumonia in this study generally have an epidemiological history. The clinical manifestations are fever and cough. Peripheral white blood cell counts were most normal And PCT were all negative. Chest HRCT manifested as multiple ground-glass opacities with partly consolidation. Some patients had normal chest radiographs but HRCT showed pneumonia. Some patients had no pneumonia on chest HRCT.

positive: COVID-19 in Iran, a comprehensive investigation from exposure to treatment outcomes Purpose There is a growing need for information regarding the recent coronavirus disease of 2019 (Covid-19). We present a comprehensive report of Covid-19 patients in Iran. Methods One hundred hospitalized patients with Covid-19 were studied. Data on potential source of exposure, demographic, clinical, and paraclinical features, therapy outcome, and post-discharge follow-up were analyzed. Results The median age of the patients was 58 years, and the majority of the patients (72.7%) were above 50 years of age. Fever was present in 45.2% of the patients on admission. The most common clinical symptoms were shortness of breath (74%) and cough (68%). Most patients had elevated C-reactive protein (92.3%), elevated erythrocyte sedimentation rate (82.9%), lymphocytopenia (74.2 %) on admission. Lower lobes of the lung were most commonly involved, and ground-glass opacity (81.8%) was the most frequent finding in CT scans. The administration of hydroxychloroquine improved the clinical outcome of the patients. Lopinavir/ritonavir was efficacious at younger ages. Of the 70 discharged patients, 40% had symptom relapse, (8.6%) were readmitted to the hospital, and 3 patients (4.3%) died. Conclusion This report demonstrates a heterogeneous nature of clinical manifestations in patients affected with Covid-19. The most common presenting symptoms are non-specific, so attention should be made on broader testing, especially in age groups with the greatest risk and younger individuals who can serve as carriers of the disease. Hydroxychloroquine and lopinavir/ritonavir (in younger age group) can be potential treatment options. Finally, patients discharged from the hospital should be followed up because of potential symptom relapse.

positive: The Role of Chest Computed Tomography in Asymptomatic Patients of Positive Coronavirus Disease 2019: A Case and Literature Review Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing global health emergency. At present, patients are the primary source of infection. A randomly diagnosed confirmed case of COVID-19 highlights the importance of computerized tomography of thorax in diagnosing asymptomatic patients. In the early phase of COVID-19, routine screenings miss patients who are virus carriers, and tracking travel history is of paramount importance to early detection and isolation of SARS-CoV-2 cases.

positive: Clinical course of coronavirus disease 2019 in 11 patients after thoracic surgery and challenges in diagnosis OBJECTIVES: To illustrate the clinical course and difficulties in early diagnosis of coronavirus disease 2019 (COVID-19) in patients after thoracic surgery. METHODS: We retrospectively analyzed the clinical course of the first 11 patients diagnosed with COVID-19 after thoracic surgery in early January 2020. Postoperative clinical, laboratory, and radiologic records and the time line of clinical course were summarized. Potential prognostic factors were evaluated. RESULTS: In the 11 confirmed cases (3 female, 8 male), median days from symptom onset to case detection was 8. Insidious symptom onset and misinterpreted postoperative changes on chest computed tomography (CT) resulted in delay in diagnosis. There were 3 fatalities due to respiratory failure, whereas 4 severe and 4 mild cases recovered and were discharged. All patients had once experienced leukocytosis and eosinopenia. Remittent fever and resected lung segments ≥5 were associated with fatality. CONCLUSIONS: The case fatality rate of postsurgical patients subsequently diagnosed with COVID-19 was 27.3%. Insidious symptom onset, postoperative leukocytosis with lymphopenia, and postsurgical CT changes overshadowed the early signs of viral pneumonia. Dynamic symptom monitoring, serial chest CTs, and tests for viral RNA and serum antibody improve the chance for prompt detection of COVID-19. Consideration should be given to preadmission and preoperative screening and strict contact isolation during the postoperative period.

positive: Does the Clinical Spectrum of Coronavirus Disease 2019 (COVID-19) Show Regional Differences?

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

positive: Case of COVID-19 presenting with gastrointestinal symptoms. Patients with coronavirus disease 2019 (COVID-19) predominantly present with the pulmonary symptoms such as fever, cough, and shortness of breath. We present a case of an 83 years old patient with COVID-19 who presented with only gastrointestinal symptoms without respiratory complaints. Our case raises the concern regarding our current lack of understanding of extrapulmonary manifestations of COVID-19. Given genetic homology between 2019 severe acute respiratory syndrome coronavirus (SARS-CoV) 2 and SARS-CoV, our case underscores the urgent need for further studies to understand the role of the gastrointestinal system in 2019 SARS-CoV-2 transmission and COVID-19 pathogenesis.

positive: Prevalence and Clinical Presentation of Health Care Workers With Symptoms of Coronavirus Disease 2019 in 2 Dutch Hospitals During an Early Phase of the Pandemic IMPORTANCE: On February 27, 2020, the first patient with coronavirus disease 2019 (COVID-19) was reported in the Netherlands. During the following weeks, at 2 Dutch teaching hospitals, 9 health care workers (HCWs) received a diagnosis of COVID-19, 8 of whom had no history of travel to China or northern Italy, raising the question of whether undetected community circulation was occurring. OBJECTIVE: To determine the prevalence and clinical presentation of COVID-19 among HCWs with self-reported fever or respiratory symptoms. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was performed in 2 teaching hospitals in the southern part of the Netherlands in March 2020, during the early phase of the COVID-19 pandemic. Health care workers employed in the participating hospitals who experienced fever or respiratory symptoms were asked to voluntarily participate in a screening for infection with the severe acute respiratory syndrome coronavirus 2. Data analysis was performed in March 2020. MAIN OUTCOMES AND MEASURES: The prevalence of severe acute respiratory syndrome coronavirus 2 infection was determined by semiquantitative real-time reverse transcriptase–polymerase chain reaction on oropharyngeal samples. Structured interviews were conducted to document symptoms for all HCWs with confirmed COVID-19. RESULTS: Of 9705 HCWs employed (1722 male [18%]), 1353 (14%) reported fever or respiratory symptoms and were tested. Of those, 86 HCWs (6%) were infected with severe acute respiratory syndrome coronavirus 2 (median age, 49 years [range, 22-66 years]; 15 [17%] male), representing 1% of all HCWs employed. Most HCWs experienced mild disease, and only 46 (53%) reported fever. Eighty HCWs (93%) met a case definition of fever and/or coughing and/or shortness of breath. Only 3 (3%) of the HCWs identified through the screening had a history of travel to China or northern Italy, and 3 (3%) reported having been exposed to an inpatient with a known diagnosis of COVID-19 before the onset of symptoms. CONCLUSIONS AND RELEVANCE: Within 2 weeks after the first Dutch case was detected, a substantial proportion of HCWs with self-reported fever or respiratory symptoms were infected with severe acute respiratory syndrome coronavirus 2, likely as a result of acquisition of the virus in the community during the early phase of local spread. The high prevalence of mild clinical presentations, frequently not including fever, suggests that the currently recommended case definition for suspected COVID-19 should be used less stringently.

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: [Anosmia and ageusia as primary symptoms of COVID-19] This case report describes a physician in the early 30ies with subjective anosmia and ageusia as the major presenting symptoms of COVID-19. Apart from a week of slightly runny nose when coming from cold to warm air, the only symptom was a sudden onset of persistent anosmia and ageusia. Two weeks after normalisation of the mild sino-nasal symptoms, the patient was tested positive for SARS-CoV-2, and anosmia was verified with Sniffin' Sticks tests. Hypogeusia was verified with taste screening and two validated taste tests. Olfactory and gustatory loss may be underestimated symptoms of COVID-19.

positive: Early neurological manifestations of hospitalized COVID-19 patients INTRODUCTION: Neurological manifestations can occur during coronavirus disease 19 (COVID-19). Several pathogenic mechanisms have been hypothesized, without conclusive results. In this study, we evaluated the most frequent neurological symptoms in a cohort of hospitalized COVID-19 patients, and also investigated the possible relationship between plasmatic inflammatory indices and olfactory disorders (ODs) and between muscle pain and creatine kinase (CK). METHODS: We consecutively enrolled hospitalized COVID-19 patients. A structured questionnaire concerning typical and neurological symptoms, focusing on headache, dizziness, ODs, taste disorders (TDs), and muscle pain, was administrated by telephone interviews. RESULTS: Common neurological symptoms were reported in the early phase of the disease, with a median onset ranging from 1 to 3 days. Headache showed tension-type features and was more frequently associated with a history of headache. Patients with ODs less frequently needed oxygen therapy. Inflammatory indices did not significantly differ between patients with and without ODs. Muscle pain did not show any association with CK level but was more frequently associated with arthralgia and headache. CONCLUSION: In our cohort, ODs were an early symptom of COVID-19, more frequently reported by patients with milder forms of disease. Headache in association with arthralgia and muscle pain seems to reflect the common symptoms of the flu-like syndrome, and not COVID-19 infection-specific.

positive: Familial cluster of COVID-19 infection from an asymptomatic

positive: What should a cardiologist know about coronavirus disease 2019? Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is the cause of coronavirus disease 2019 (COVID‑19). The most common symptoms of COVID‑19 are: fever (81.8%-100%), cough (46.3%-86.2%), myalgia and fatigue (11%-50%), expectoration (4.4%-72%), and dyspnea (18.6%-59%). The most common laboratory abnormalities in COVID‑19 include decreased lymphocyte count (35%-82.1%), thrombocytopenia (17%-36.2%), elevated serum C‑reactive protein (60.7%-93%), lactate dehydrogenase (41%-76%), and D‑dimer concentrations (36%-46.4%). Among comorbidities in patients with COVID‑19, cardiovascular disease is most commonly found. In addition, patients with concomitant cardiovascular diseases have worse prognosis and more often require admission to the intensive care unit (ICU), compared with patients without such comorbidities. It is estimated that about 20% of patients with COVID‑19 develop cardiac injury. Cardiac injury is more prevalent among patients with COVID‑19 who require ICU care. In a group of critically ill patients, 27.5% had an elevated N‑terminal pro-B‑type natriuretic peptide concentration, and increased cardiac troponin level was found in 10% of patients. One of the life‑threatening cardiac manifestations is coronavirus fulminant myocarditis, which may also occur without accompanying symptoms of pulmonary involvement. Early recognition and treatment is crucial in these cases. So far, data on the incidence of arrhythmias in patients with COVID‑19 are limited. Coronavirus disease 2019 impacts patients with cardiovascular comorbidities and affects daily practice of cardiologists. Thus, it is important to know typical COVID‑19 symptoms, possible clinical manifestations, complications, and recommended treatment.

positive: Early Epidemiological and Clinical Characteristics of 28 Cases of Coronavirus Disease in South Korea OBJECTIVES: The first confirmed case of coronavirus disease 2019 (COVID-19) in South Korea was reported in January 2020, with 28 confirmed cases reported as of February 14(th), 2020. The epidemiological and clinical characteristics of all 28 cases were analyzed in response to this disease. METHODS: The epidemiological characteristics and early clinical features of the 28 patients from Korea with confirmed COVID-19 were analyzed using COVID-19 reporting and surveillance data and the epidemiological investigation reports prepared by the rapid response team. RESULTS: There were 16 patients that entered Korea from foreign countries: Wuhan, China (11 patients), Zhuhai, China, (1 patient), Singapore (2 patients), Japan (1 patient), and Thailand (1 patient). The early symptoms were fever, sore throat, cough or sputum production, chills, and muscle ache. Three patients were asymptomatic, however, 18 developed pneumonia. Of the 28 cases, 16 were index cases imported from abroad, with 10 cases of secondary infection originating in Korea, and the route of transmission still under investigation for 2 patients. The 10 patients with secondary infection were infected from contact with family members or acquaintances of primary patients, and the suspected sites of transmission were mostly at home. CONCLUSION: COVID-19 in Korea was spread by 16 infected individuals traveling from other countries, leading to second-generation cases. The initial symptoms were mostly minor, but the disease was infectious at this stage, resulting from close contact, particularly at home. Establishing an early detection strategy for COVID-19 is crucial for managing the transmission of the disease.

positive: Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19):A multi-center study in Wenzhou city, Zhejiang, China Abstract Background Little is known about COVID-19 outside Hubei. The aim of this paper was to describe the clinical characteristics and imaging manifestations of hospitalized patients with confirmed COVID-19 infection in Wenzhou, Zhejiang, China. Methods In this retrospective cohort study, 149 RT-PCR confirmed positive patients were consecutively enrolled from January 17th to February 10th, 2020 in three tertiary hospitals of Wenzhou. Outcomes were followed up until Feb 15th, 2020. Findings A total of 85 patients had Hubei travel/residence history, while another 49 had contact with people from Hubei and 15 had no traceable exposure history to Hubei. Fever, cough and expectoration were the most common symptoms, 14 patients had decreased oxygen saturation, 33 had leukopenia, 53 had lymphopenia, and 82 had elevated C-reactive protein. On chest computed tomography (CT), lung segments 6 and 10 were mostly involved. A total of 287 segments presented ground glass opacity, 637 presented mixed opacity and 170 presented consolidation. Lesions were more localized in the peripheral lung with a patchy form. No significant difference was found between patients with or without Hubei exposure history. Seventeen patients had normal CT on admission of these, 12 had negative findings even10 days later. Interpretation Most patients presented with a mild infection in our study. The imaging pattern of multifocal peripheral ground glass or mixed opacity with predominance in the lower lung is highly suspicious of COVID-19 in the first week of disease onset. Nevetheless, some patients can present with a normal chest finding despite testing positive for COVID-19. Funding: We did not receive any fundings.

positive: Sniffing out the evidence; It's now time for public health bodies recognize the link between COVID-19 and smell and taste disturbance Since the outbreak of the pandemic, anecdotal observations have been accumulating rapidly that sudden anosmia and dysgeusia are peculiar symptoms associated with the COVID-19 infection. Prof C. Hopkins, as President of British Rhinological Society, published a letter describing "the loss of sense of smell as a marker of COVID-19 infection" and proposed that adults presenting with anosmia but no other symptoms should self-isolate for seven days. The Hopkins team published the first case report and case series as well as other evidence that isolated sudden onset anosmia (ISOA), should be considered highly suspicious for SARS-CoV-2(1). Subsequently, a larger series of 2428 patients presenting with new onset anosmia during the COVID-19 pandemic has been reported, of whom 16% report loss of sense of smell as an isolated symptom. Only 51% reported the recognized symptoms of cough or fever. A major limitation of this series however, was a lack of access to testing to confirm the COVID-19 status of the patients(2); in the 80 who had been tested 74% were positive. In the same way, the American Academy of Otolaryngology-head and neck surgery (AA0-HNS) proposed "that anosmia could be added to the list of screening tools for possible COVID-19 infection. More, they warrant serious consideration for self-isolation and testing those patients".

positive: SARS-CoV-2 IgG Antibody Responses in New York City Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a strain of coronavirus that causes coronavirus disease 2019 (Covid-19) and has been declared a global pandemic by the World Health Organization. Total cases of SARS-CoV-2 worldwide exceed 4.8 million, with over 320,000 deaths recorded. Little is known about the body's immune response to SARS-CoV-2 infection. In this paper, we describe SARS-CoV-2 IgG antibody responses in 11,092 patients from the New York City metropolitan area and report a SARS-CoV-2 IgG positivity rate of nearly 50%, indicating the widespread nature of the pandemic in the city and state of New York. Additionally, we report on the correlation between SARS-CoV-2 patient symptom severity and level of SARS-CoV-2 IgG antibody found in the patient sample.

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

positive: Viral Dynamics Matter in COVID-19 Pneumonia: the success of early treatment with hydroxychloroquine and azithromycin in Lebanon. Background: We share our experience in COVID-19 pneumonia management at Saint George Hospital University Medical Center (SGHUMC) in Lebanon. In the absence of a standard of care, early diagnosis and opt-in therapy with Hydroxychloroquine and Azithromycin were offered. Methods: We reviewed records of COVID-19 pneumonia patients from March 16-April 26 2020. Based on NEWS score, we stratified patients as A: low B: medium, and C: high clinical severity and obtained pharmacotherapy data. Chest-CT-severity-score (CTSS) was used. We defined clinical cure as resolution of symptoms and biomarkers and virologic cure as a PCR above 35 cycles(Ct). Results: We recorded 21 COVID-19 pneumonia patients of whom 19 opted for treatment. Clinical symptoms and laboratory markers at presentation did not significantly correlate with severity. Lower initial viral load significantly correlated with lower levels of clinical and radiological severity (p=0.038). Virologic cure, Ct>35, by day 10, was only 33% in high severity significantly less than categories A and B. We observed 100% clinical cure at day 10 in Category-A, 67% in B, and 33% in C(p<0.05). Patients with the lowest severity had the fastest virologic cure in a mean of 5.8 days from diagnosis, shortest hospitalization and earlier radiological improvement(p<0.005). Ultimately, 18 patients were discharged home in good condition and one remains in the ICU. Conclusion: Viral dynamics matter in COVID-19 pneumonia. An early control of replication may be crucial in averting complications. Early administration of Hydroxychloroquine and Azithromycin potentially explains our 94.7% success rate in treating a fairly complex cohort of COVID-19 pneumonia.

positive: Gustatory Dysfunction as an Early Symptom in COVID-19 Screening. The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from Wuhan, China in December 2019 leads to the present coronavirus disease 2019 (COVID-19) pandemic. The various symptoms identified for COVID-19 are fever, dry cough, sore throat, dyspnea, fatigue, myalgia, and headache. Olfactory and gustatory dysfunctions are emerging as a new symptom more in the European patients. Taste disturbances are common in various oral and systemic diseases. Varying severity and onset of taste disturbances are reported in COVID-19 positive patients in this pandemic. But a sudden onset of taste disturbances without an established and recognized cause should raise suspicion of COVID-19. This article will analyze the various studies focusing on taste disturbances as a reliable early symptom for COVID-19 screening.

positive: Clinical Insights into the Gastrointestinal Manifestations of COVID-19 The month of December 2019 became a critical part of the time of humanity when the first case of coronavirus disease 2019 (COVID-19) was reported in the Wuhan, Hubei Province in China. As of April 13th, 2020, there have been approximately 1.9 million cases and 199,000 deaths across the world, which were associated with COVID-19. The COVID-19 is the seventh coronavirus to be identified to infect humans. In the past, Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome were the two coronaviruses that infected humans with a high fatality, particularly among the elderly. Fatalities due to COVID-19 are higher in patients older than 50 years of age or those with multimorbid conditions. The COVID-19 is mainly transmitted through respiratory droplets, with the most common symptoms being high fever, cough, myalgia, atypical symptoms included sputum production, headache, hemoptysis and diarrhea. However, the incubation period can range from 2 to 14 days without any symptoms. It is particularly true with gastrointestinal (GI) symptoms in which patients can still shed the virus even after pulmonary symptoms have resolved. Given the high percentage of COVID-19 patients that present with GI symptoms (e.g., nausea and diarrhea), screening patients for GI symptoms remain essential. Recently, cases of fecal-oral transmission of COVID-19 have been confirmed in the USA and China, indicating that the virus can replicate in both the respiratory and digestive tract. Moreover, the epidemiology, clinical characteristics, diagnostic procedures, treatments and prevention of the gastrointestinal manifestations of COVID-19 remain to be elucidated.

positive: Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity The novel coronavirus (2019-nCoV) infection caused pneumonia. we retrospectively analyzed the virus presence in the pharyngeal swab, blood, and the anal swab detected by real-time PCR in the clinical lab. Unexpectedly, the 2109-nCoV RNA was readily detected in the blood (6 of 57 patients) and the anal swabs (11 of 28 patients). Importantly, all of the 6 patients with detectable viral RNA in the blood cohort progressed to severe symptom stage, indicating a strong correlation of serum viral RNA with the disease severity (p-value = 0.0001). Meanwhile, 8 of the 11 patients with annal swab virus-positive was in severe clinical stage. However, the concentration of viral RNA in the anal swab (Ct value = 24 + 39) was higher than in the blood (Ct value = 34 + 39) from patient 2, suggesting that the virus might replicate in the digestive tract. Altogether, our results confirmed the presence of virus RNA in extra-pulmonary sites.

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

positive: Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province BACKGROUND: The 2019 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 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.

positive: New emerging dermatological symptoms in coronavirus pandemic COVID‐19 (Coronavirus Disease 2019) is a fatal disease that could lead to a serious respiratory illness. It is caused by SARS‐CoV‐2 virus. In December 2019, the first of human cases were identified in China and the infection spread quickly around the world. The World Health Organisation (WHO) declared the disease, a global pandemic on 11 March 2020, even as COVID‐19 rapidly spread across the world. According to clinical reports, fever, headache, cough and myalgia are common clinical symptoms. Many symptoms also occur, such as sputum formation, haemoptysis and diarrhea.

positive: Novel coronavirus pneumonia combined with viral conjunctivitis: three cases report/ 中华实验眼科杂志 Since January 2020, as ophthalmologists working at the center of the novel coronavirus pneumonia (NCP) outbreak in Wuhan, China, we found 3 cases in 30 NCP patients with binocular conjunctivitis. Of them, one case visited for conjunctivitis as a first symptom and then diagnosed as NCP, and two cases visited for binocular conjunctivitis during the NCP onset. In 3 patients, conjunctivitis was manifested as signs of viral conjunctivitis from mild to moderate. Their symptoms of two patients disappeared after treatment with antiviral eyedrops for 7 to 10 days and another patient died of NCP. Interestingly,although we detected positive viral nucleic acid in the conjunctiva sacs of 2 of other 27 NCP patients by using swabs and RT-PCR technology, no conjunctivitis occurred in these two patients.

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: Cutaneous signs in COVID-19 patients: A review Coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily affects the epithelium of the airways. With the increasing involvement of dermatologist in management of this crisis, cutaneous symptoms gained more and more attention. In this review, we will describe cutaneous symptoms of patients of all ages in association with COVID-19. We will focus on such disorders that are caused by direct action of SARS-CoV-2 on tissues, complement, and coagulation system and on nonspecific eruption of the systemic viral infection. Drug-induced reactions are only mentioned in the differential diagnoses. Although more systematic investigations are warranted, it becomes clear that some symptoms are clinical signs of a milder COVID-19 course, while others are a red flag for a more severe course. Knowledge of the cutaneous manifestations of COVID-19 may help in early diagnosis, triage of patients, and risk stratification.

positive: [Clinical analysis of 23 patients with coronavirus disease 2019 in Xinyang City of Henan Province] OBJECTIVE: To analyze the epidemiological characteristics and clinical features of the patients with coronavirus disease 2019 (COVID-19), so as to provide basis for clinical diagnosis. METHODS: The epidemiology, clinical symptoms, laboratory and radiologic data of 23 patients with COVID-19 admitted to the Fifth People's Hospital of Xinyang City from January 22nd to January 29th, 2020 were retrospectively analyzed. RESULTS: There was 23 patients with COVID-19, with 15 men and 8 women, and the median age was 46.0 (40.5, 52.0) years old (ranged from 27 years old to 80 years old). Nine patients had basic disease (39.1%), including hypertension (17.4%), cardiovascular diseases (17.4%), diabetes (8.7%), hypothyroidism (4.3%) and past history of tuberculosis (4.3%). All the 23 patients had contact history in Wuhan area or with confirmed cases. Clinical symptoms included fever (100%), cough (69.6%), expectoration (43.5%), myalgia (26.1%), headache (17.4%) and dyspnea (17.4%), and the less common symptom was diarrhea (4.3%). Blood routine tests showed leukocytopenia in 11 patients (47.8%), normal leukocyte counts in 10 patients (43.5%), and leukocytosis in 2 patients (8.7%); lymphopenia was found in 13 patients (56.5%). All 23 patients had different degrees of infective lesions in chest CT, with 7 patients (30.4%) on one side and 16 patients (69.6%) on both sides. There were 19 mild patients, 4 severe patients, and no critical or death case. Complications included acute respiratory distress syndrome (17.4%). No patient was reported with liver, kidney or heart dysfunction or secondary infection. CONCLUSIONS: Epidemic history of contact, fever, pneumonia signs of chest CT, normal or decreased count of leukocyte and lymphopenia are the clinical basis for diagnosis of COVID-19. However, at present, the treatment of patients has not been completed, and the effective treatment strategy and final prognosis are unclear.

positive: Enteric involvement in hospitalised patients with COVID-19 outside Wuhan

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

positive: AGA Institute Rapid Review of the GI and Liver Manifestations of COVID-19, Meta-Analysis of International Data, and Recommendations for the Consultative Management of Patients with COVID-19 Abstract Background Multiple gastrointestinal (GI) symptoms including diarrhea, nausea/vomiting, and abdominal pain, as well liver enzyme abnormalities have been variably reported in patients with COVID-19. The AGA) Institute Clinical Guideline Committee and Clinical Practice Updates Committee performed a systematic review and meta-analysis of international data on GI and liver manifestations of COVID-19. Methods We performed a systematic literature search to identify published and unpublished studies using OVID Medline and pre-print servers (medRxiv, LitCovid, and SSRN) up until April 5 2020; major journal sites were monitored for US publications until April 19 2020. We analyzed the prevalence of diarrhea, nausea, vomiting, and abdominal pain as well as LFT abnormalities using a fixed effect model and assessed the certainty of evidence using GRADE. Results We identified 118 studies and used a hierarchal study selection process to identify unique cohorts. We performed a meta-analysis of 47 studies including 10,890 unique patients. Pooled prevalence estimates of GI symptoms was diarrhea 7.7% (95% CI 7.2-8.2), nausea/vomiting 7.8% (95% CI 7.1-8.5), abdominal pain 2.7% (95% CI 2.0-3.4). Most studies reported on hospitalized patients. The pooled prevalence of elevated liver abnormalities was: AST 15.0% (13.6 to 16.5) and ALT 15.0% (13.6 to 16.4). When analyzed comparing data from China to studies from countries other than China, diarrhea, nausea/vomiting, liver abnormalities were more prevalent outside of China with diarrhea reported in 18.3% (16.6 to 20.1). Isolated GI symptoms were rarely reported. We also summarized of the Gl and liver adverse effects of the most commonly utilized medications for COVID19 Conclusions GI symptoms are associated with COVID-19 in less than 10% of patients. In studies outside of China, estimates are higher. Further studies are needed with standardized GI symptoms questionnaires and LFT checks on admission to better quantify and qualify the association of these symptoms with COVID-19. Based on findings from our meta-anlaysis, we make several Best Practice Statements for the consultative management of COVID-19.

positive: Clinical and epidemiological characteristics of 1420 European patients with mild-to-moderate coronavirus disease 2019 BACKGROUND: The clinical presentation of European patients with mild-to-moderate COVID-19 infection is still unknown. OBJECTIVE: To study the clinical presentation of COVID-19 in Europe. METHODS: Patients with positive diagnosis of COVID-19 were recruited from 18 European hospitals. Epidemiological and clinical data were obtained through a standardized questionnaire. Bayesian analysis was used for analysing the relationship between outcomes. RESULTS: A total of 1,420 patients completed the study (962 females, 30.7% of healthcare workers). The mean age of patients was 39.17 ± 12.09 years. The most common symptoms were headache (70.3%), loss of smell (70.2%), nasal obstruction (67.8%), cough (63.2%), asthenia (63.3%), myalgia (62.5%), rhinorrhea (60.1%), gustatory dysfunction (54.2%) and sore throat (52.9%). Fever was reported by 45.4%. The mean duration of COVID-19 symptoms of mild-to-moderate cured patients was 11.5 ± 5.7 days. The prevalence of symptoms significantly varied according to age and sex. Young patients more frequently had ear, nose and throat complaints, whereas elderly individuals often presented fever, fatigue and loss of appetite. Loss of smell, headache, nasal obstruction and fatigue were more prevalent in female patients. The loss of smell was a key symptom of mild-to-moderate COVID-19 patients and was not associated with nasal obstruction and rhinorrhea. Loss of smell persisted at least 7 days after the disease in 37.5% of cured patients. CONCLUSION: The clinical presentation of mild-to-moderate COVID-19 substantially varies according to the age and the sex characteristics of patients. Olfactory dysfunction seems to be an important underestimated symptom of mild-to-moderate COVID-19 that needs to be recognized as such by the WHO.

positive: A COVID-19 outbreak in a rheumatology department upon the early days of the pandemic Objectives: To describe our experience with a coronavirus disease 2019 (COVID-19) outbreak within a large rheumatology department, early in the pandemic. Methods: Symptomatic and asymptomatic healthcare workers (HCWs) had a naso-oropharyngeal swab for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and were followed clinically. Reverse transcription polymerase-chain reaction (RT-PCR) was repeated to document cure, and serological response was assessed. Patients with risk contacts within the department in the 14 days preceding the outbreak were screened for COVID-19 symptoms. Results: 14/34 HCWs (41%; 40{+/-}14 years, 71% female) tested positive for SARS-CoV-2, and 11/34 (32%) developed symptoms but were RT-PCR-negative. Half of RT-PCR-positive HCWs did not report fever, cough, or dyspnoea before testing, which were absent in 3/14 cases (21%). Mild disease prevailed (79%), but 3 HCWs had moderate disease requiring further assessment, which excluded severe complications. Nevertheless, symptom duration (28{+/-}18 days), viral shedding (31{+/-}10 days post-symptom onset, range 15-51) and work absence (29{+/-}28 days) were prolonged. 13/14 (93%) of RT-PCR-positive and none of the RT-PCR-negative HCWs had a positive humoral response, with higher IgG-index in individuals over 50 years (14.5{+/-}7.7 vs 5.0{+/-}4.4, p=0.012). Of 617 rheumatic patients, 8 (1.3%) developed COVID-19 symptoms (1/8 hospitalisation, 8/8 complete recovery), following a consultation/procedure with an asymptomatic (7/8) or mildly-symptomatic (1/8) HCW. Conclusions: A COVID-19 outbreak can occur among HCWs and rheumatic patients, swiftly spreading over the presymptomatic stage. Mild disease without typical symptoms should be recognised, and may evolve with delayed viral shedding, prolonged recovery, and adequate immune response in most individuals.

positive: 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.

positive: [Analysis of gastrointestinal symptoms in 80 patients with coronavirus disease 2019] OBJECTIVE: To investigate the clinical characteristics of gastrointestinal symptoms in patients with coronavirus disease 2019 (COVID-19) during the whole disease process, and provide reference for etiological diagnosis and treatment. METHODS: The clinical data of patients with COVID-19 admitted in the Infectious Diseases Branch of the First Affiliated Hospital of University of Science and Technology of China from January 22nd, 2020 to March 8th, 2020 were analyzed retrospectively. According to whether there were gastrointestinal symptoms (poor appetite, nausea/vomiting and diarrhea), all patients were divided into gastrointestinal symptom group and asymptomatic group. The characteristics of gastrointestinal symptoms, such as poor appetite, nausea, vomiting and diarrhea were counted and analyzed, and the correlation between gastrointestinal symptoms and gender, age, basic diseases, disease severity, laboratory examination and drug treatment were analyzed. RESULTS: A total of 80 COVID-19 patients were involved, 43 cases (53.8%) presented with poor appetite, 17 cases (21.3%) had nausea and vomiting, and 33 cases (41.3%) had diarrhea. Among them, 5 cases, 1 case and 4 cases respectively preformed poor appetite, nausea/vomiting and diarrhea before admission, while the others experienced gastrointestinal symptoms within 48 hours after admission. Duration of poor appetite, nausea/vomiting and diarrhea (days) of all patients were 5.3±2.1, 2.2±1.0 and 1.4±0.9, respectively. The patients with poor appetite were older than those without symptoms (years old: 48.2±17.6 vs. 39.3±15.1), albumin (Alb) level and the lymphocytes ratio were lower than those in asymptomatic group [Alb (g/L): 39.8 (35.7, 45.1) vs. 46.1 (42.6, 49.4), lymphocytes ratio: 0.19 (0.09, 0.28) vs. 0.28 (0.17, 0.35)], while the neutrophil ratio, the levels of C-reactive protein (CRP), D-dimer, and lactate dehydrogenase (LDH) were higher than those in asymptomatic group [the neutrophil ratio: 0.74 (0.61, 0.85) vs. 0.64 (0.52, 0.76), CRP (mg/L): 21.4 (3.9, 52.9) vs. 5.6 (2.4, 14.0), D-dimer (mg/L): 0.2 (0.2, 0.5) vs. 0.2 (0.1, 0.3), LDH (µmol×s-1×L-1): 4.49 (3.59, 5.19) vs. 3.12 (2.77, 4.90)]; at the same time, more traditional Chinese medicine was used in the patients with gastrointestinal symptoms [65.1% (28/43) vs. 40.5% (15/37), all P < 0.05]. In addition, 14 cases of 18 patients with cardiovascular diseases presented with poor appetite, 7 patients had nausea and vomiting symptoms. All of the 3 patients with chronic kidney disease presented with poor appetite, nausea and vomiting, and 2 of them had diarrhea. CONCLUSIONS: The gastrointestinal symptoms in patients with COVID-19 are common. Whether it is caused by the virus or related drugs, diet and mental conditions, clinicians should analyze the causes of these symptoms timely, and then provide a better treatment for patients with COVID-19.

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

positive: 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.

positive: Clinical features of pediatric patients with coronavirus disease (COVID-19) Abstract Background Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has spread around the world, and reports of children with COVID-19 are increasing. Objectives To assess clinical profiles of pediatric COVID-19. Study design A retrospective analysis was undertaken using clinical data of sixteen children (11 months-14 years) diagnosed with COVID-19 between January 1, 2020 and March 17, 2020 at Xiangyang Central Hospital, Hubei province, China. Results All children had positive epidemiologic histories, 12 (12/16, 75 %) involving family units. The illnesses were either mild (5/16, 31.3 %) or ordinary (11/16, 68.8 %), presenting as follows: asymptomatic (8/16, 50 %), fever and/or cough (8/16, 50 %). Four asymptomatic patients (4/16, 25 %) in ordinary cases had chest computed tomography (CT) abnormalities. Leukocyte counts were normal in 14 cases(88 %), but 2 patients (12.5 %) had leukopenia, and 1 (6.3 %) was lymphopenic. There were 11 patients with chest CT abnormalities, some nodular, others small patchy and others ground-glass opacities. In asymptomatic children, the median time to SRAS-CoV-2 nucleic acid test(NAT) positivity once exposed to a family member with confirmed infection was 15.5 days (range, 10–26 days). The median time to first NAT-negative conversion was 5.5 days (range, 1–23 days). Conclusions COVID-19 in children of Xiangyang city is often family acquired and not serious, with favorable outcomes. Asymptomatic children can be diagnosed as pneumonia because of chest CT abnormalities. It is essential to actively screen this segment of the population.

positive: 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.

positive: [Using the big data ofinternet to understand coronavirus disease 2019's symptom characteristics: a big data study]. Objective: Analyzing the symptom characteristics of Coronavirus Disease 2019(COVID-19) to improve its prevention. Methods: Using Baidu Index Platform (http://index.baidu.com) and the website of Chinese Center for Disease Control and Prevention as data resources to obtain the search volume (SV) of keywords for symptoms associated with COVID-19 from January 1 to February 20 in each year from 2017 to 2020, in Hubei province and other top 10 impacted provinces in China and the epidemic data. Data of 2020 were compared with the previous three years. Data of Hubei province were compared with confirmed cases. The differences and characteristics of the SV of COVID-19-related symptoms, and the correlation between the SV of COVID-19 and new confirmed or suspected cases were analyzed and the hysteresis effects were discussed. Results: Compared the data from January 1 to February 20, 2020, with the SV for the same period of previous three years, Hubei's SV for cough, fever, diarrhea, chest tightness, dyspnea and other symptoms were significantly increased. The total SV of lower respiratory symptoms was significantly higher than that of upper respiratory symptoms (P<0.001). The SV of COVID-19 in Hubei province was significantly correlated with new confirmed or suspected cases (R(confirmed) = 0.723, R(suspected) = 0.863, all P < 0.001). The results of the distributed lag model suggested that the patients who retrieved relevant symptoms on the Internet may begin to see a doctor in 2-3 days later and be diagnosed in 3-4 days later. Conclusions: The total SV of lower respiratory symptoms is higher than that of upper respiratory symptoms, and the SV of diarrhea also increased significantly. It warns us to pay attention to not only the symptoms of lower respiratory tract, but also the gastrointestinal symptoms, especially diarrhea in patients with COVID-19. There is a relationship between Internet retrieval behavior and the number of new confirmed or suspected cases. Big data has a certain role in the early warning of infectious diseases.

positive: Association of Digestive Symptoms and Hospitalization in Patients With SARS-CoV-2 Infection INTRODUCTION: High rates of concurrent gastrointestinal manifestations have been noted in patients with corona virus disease 2019 (COVID-19); however, the association between these digestive manifestations and need for hospitalization has not been established. METHODS: This is a retrospective review of consecutive patients diagnosed with COVID-19. A total of 207 patients were identified; 34.5% of patients noted concurrent gastrointestinal symptoms, with 90% of gastrointestinal symptoms being mild. RESULTS: In a multivariate regression model controlled for demographics and disease severity, an increased risk of hospitalization was noted in patients with any digestive symptom (adjusted odds ratio 4.84, 95% confidence interval: 1.68-13.94). DISCUSSION: The presence of digestive symptoms in COVID-19 is associated with a need for hospitalization.

positive: Diagnostic and clinical significance of "atypical" symptoms in coronavirus disease 2019.

positive: Time from Symptom Onset to Hospitalisation of Coronavirus Disease 2019 (COVID-19) Cases: Implications for the Proportion of Transmissions from Infectors with Few Symptoms Interventions targeting symptomatic hosts and their contacts were successful in bringing the 2003 SARS pandemic under control. In contrast, the COVID-19 pandemic has been harder to contain, partly because of its wide spectrum of symptoms in infectious hosts. Current evidence suggests that individuals can transmit the novel coronavirus while displaying few symptoms. Here, we show that the proportion of infections arising from hosts with few symptoms at the start of an outbreak can, in combination with the basic reproduction number, indicate whether or not interventions targeting symptomatic hosts are likely to be effective. However, as an outbreak continues, the proportion of infections arising from hosts with few symptoms changes in response to control measures. A high proportion of infections from hosts with few symptoms after the initial stages of an outbreak is only problematic if the rate of new infections remains high. Otherwise, it can simply indicate that symptomatic transmissions are being prevented successfully. This should be considered when interpreting estimates of the extent of transmission from hosts with few COVID-19 symptoms.

positive: Comment on "Cutaneous manifestations in COVID-19: a first perspective " by Recalcati S Since the coronavirus disease 2019 (COVID 19) outbreak was first reported in the Chinese city of Wuhan on December 31, 2019, it has stricken more than 1,000,000 persons worldwide, of whom over 50,000 have died (1). Having been infected by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), patients with COVID-19 mainly present with fever and respiratory symptoms (2). Isolated sudden onset anosmia has also frequently been reported (3). Less frequently, rhinorrhea, diarrhoea and dysgeusia may be associated. While only a few reports have evoked cutaneous manifestations (4), we read with interest an initial study on the topic entitled "Cutaneous manifestations in COVID-19: a first perspective " by Recalcati S. (5).

positive: 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.

positive: Clinical characteristics and drug therapies in patients with the common-type coronavirus disease 2019 in Hunan, China Background Clinical characteristics of patients with the coronavirus disease 2019 (COVID-19) may present differently within and outside the epicenter of Wuhan, China. More clinical investigations are needed. Objective The study was aimed to describe the clinical characteristics, laboratory parameters, and therapeutic methods of COVID-19 patients in Hunan, China. Setting The First Hospital of Changsha, First People's Hospital of Huaihua, and the Central Hospital of Loudi, Hunan province, China. Methods This was a retrospective multi-center case-series analysis. Patients with confirmed COVID-19 diagnosis hospitalized at the study centers from January 17 to February 10, 2020, were included. The following data were obtained from electronic medical records: demographics, medical history, exposure history, underlying comorbidities, symptoms, signs, laboratory findings, computer tomography scans, and treatment measures. Main outcome measure Epidemiological, clinical, laboratory, and radiological characteristics and treatments. Results A total of 54 patients were included (51 had the common-type COVID-19, three had the severe-type), the median age was 41, and 52% of them were men. The median time from the first symptoms to hospital admission was seven days. Among patients with the common-type COVID-19, the median length of stay was nine days, and 21 days among patients with severe COVID-19. The most common symptoms at the onset of illness were fever (74.5%), cough (56.9%), and fatigue (43.1%) among patients in the common-type group. Fourteen patients (37.8%) had a reduced WBC count, 23 (62.2%) had reduced eosinophil ratio, and 21 (56.76%) had decreased eosinophil count. The most common patterns on chest-computed tomography were ground-glass opacity (52.2%) and patchy bilateral shadowing (73.9%). Pharmacotherapy included recombinant human interferon α2b, lopinavir/ritonavir, novaferon, antibiotics, systematic corticosteroids and traditional Chinese medicine prescription. The outcome of treatment indicated that in patients with the common-type COVID-19, interferon-α2b, but not novaferon, had some benefits, antibiotics treatment was not needed, and corticosteroids should be used cautiously. Conclusion As of February 10, 2020, the symptoms of COVID-19 patients in Hunan province were relatively mild comparing to patients in Wuhan, the epicenter. We observed some treatment benefits with interferon-α2b and corticosteroid therapies but not with novaferon and antibiotic treatment in our study population.

positive: Comparative Analysis of Early-Stage Clinical Features Between COVID-19 and Influenza A H1N1 Virus Pneumonia Introduction: Influenza virus pneumonia and COVID-19 are two different types of respiratory viral pneumonia but with very similar clinical manifestations. The aim of the present study was to help clinicians gain a better understanding about differences between Influenza virus pneumonia and COVID-19 by comparative analysis of the early-stage clinical features. Methods: Clinical data of patients with confirmed diagnosis of COVID-19 and influenza A pneumonia identified in our hospital were collected and analyzed retrospectively to identify the clinical features that could differentiate between the two types of viral pneumonia. Results: The two types of viral pneumonia mainly affected adults, especially people over 50 years, with no gender difference between them. Fever, cough, sputum and muscle soreness were the most common symptoms of COVID-19. Some patients with COVID-19 may also exhibit digestive tract symptoms. Elevation of C-reactive protein (CRP) was a more common phenomenon in patients with COVID-19 than that in patients with influenza A H1N1 virus pneumonia. In addition, eosinophil count was decreased and the monocyte percentage was increased in COVID-19 patients. The grid-form shadow was a typical presentation of COVID-19 on the lung CT image, and the disease usually progressed quickly within a week. Conclusion: Influenza pneumonia and COVID-19 are two different types of respiratory viral pneumonia with very similar clinical manifestations. The percentage of monocytes is increased and the eosinophil count is decreased in COVID-19. Glass-ground density exudation shadow located peripherally is the typical sign of COVID-19 on the lung CT image, and the shadow often with grid-form sign. These features may not be typically observed in patients with influenza pneumonia. Chest CT scan combined with nucleic acid detection is an effective and accurate method for diagnosing COVID-19. Blood routine test has a limited diagnostic value in differentiating the two forms of pneumonia.

positive: 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.

positive: Central nervous system manifestations of COVID-19: A systematic review Abstract Objective In this systematic review, we will discuss the evidence on the occurrence of central nervous system (CNS) involvement and neurological manifestations in patients with COVID-19. Methods MEDLINE (accessed from PubMed) and Scopus from December 01, 2019 to March 26, 2020 were systematically searched for related published articles. In both electronic databases, the following search strategy was implemented and these key words (in the title/abstract) were used: “COVID 19” OR “coronavirus” AND “brain” OR “CNS” OR “neurologic”. Results Through the search strategy, we could identify two articles about neurological involvement by COVID-19. One of these publications was a narrative review and the other one was a viewpoint. However, the authors scanned the reference lists of the included studies and could identify multiple references. One study, specifically investigated the neurological manifestations of COVID-19 and could document CNS manifestations in 25% of the patients. Most of the studies investigated the manifestations of COVID-19 in general. Conclusion While neurological manifestations of COVID-19 have not been studied appropriately, it is highly likely that some of these patients, particularly those who suffer from a severe illness, have CNS involvement and neurological manifestations. Precise and targeted documentation of neurological symptoms, detailed clinical, neurological, and electrophysiological investigations of the patients, attempts to isolate SARS-CoV-2 from cerebrospinal fluid, and autopsies of the COVID-19 victims may clarify the role played by this virus in causing neurological manifestations.

positive: CT features of novel coronavirus pneumonia (COVID-19) in children ABSTRACT: A serious epidemic of COVID-19 broke out in Wuhan, Hubei Province, China, and spread to other Chinese cities and several countries now. As the majority of patients infected with COVID-19 had chest CT abnormality, chest CT has become an important tool for early diagnosis of COVID-19 and monitoring disease progression. There is growing evidence that children are also susceptible to COVID-19 and have atypical presentations compared with adults. This review is mainly about the differences in clinical symptom spectrum, diagnosis of COVID-19, and CT imaging findings between adults and children, while highlighting the value of radiology in prevention and control of COVID-19 in pediatric patients. KEY POINTS: • Compared with adults, pediatric patients with COVID-19 have the characteristics of lower incidence, slighter clinical symptoms, shorter course of disease, and fewer severe cases. • The chest CT characteristics of COVID-19 in pediatric patients were atypical, with more localized GGO extent, lower GGO attenuation, and relatively rare interlobular septal thickening. • Chest CT should be used with more caution in pediatric patients with COVID-19 to protect this vulnerable population from risking radiation.

positive: The implications of preliminary screening and diagnosis: Clinical characteristics of 33 mild patients with SARS-CoV-2 infection in Hunan, China BACKGROUND: In December 2019, coronavirus Disease 2019 (COVID-19) occurred in Wuhan, Hubei Province, China. The disease has rapidly spread from Wuhan to other regions. OBJECTIVES: To describe the clinical manifestations and epidemiological characteristics of patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in Hunan Province in 2020. STUDY DESIGN: From January 19 to February 7, 2020, 33 patients with positive in nucleic acid test of pharyngeal swab were retrospectively collected and analyzed. RESULTS: There are 33 COVID-19 patients (16 male, 17 female), and the median age was 46 years. Nineteen patients (48 %) were associated with a family cluster outbreak. Seventeen patients (52 %) had traveled or lived in Hubei Province. These patients are early mild cases, most common symptoms are fever [23 (70 %)] and cough [13 (39 %)]. Most patients' white blood cell counts are normal, while they manifest as significant reduction in lymphocytes [17/28 (61 %)]. The levels of c-reactive protein and erythrocyte sedimentation rate suggest a typical viral infection. Procalcitonin did not increase and D-dimer increased slightly. Lactate dehydrogenase (LDH) levels have elevated in most patients. CT images of these patients showed bilateral multiple plaques or nodular ground-glass opacities (68.4 %). Fecal nucleic acid results were positive in eight COVID-19 patients accompanied with diarrhea. Tear nucleic acid results were negative in six COVID-19 patients. And four asymptomatic patients were infected with SARS-CoV-2. CONCLUSIONS: The clinical symptoms, laboratory results and imaging reports of patients with COVID-19 in Hunan area are significantly different from those in Wuhan area. For non-Wuhan epidemic areas, more attention should be paid to nucleic acid test results of throat swabs and stools, and it is not easily to diagnose based on clinical symptoms and CT results. Reduced whole blood lymph count can be used as an adjuvant diagnosis of early SARS-CoV-2 infection. Attention should be paid to asymptomatic carriers, which is of great significance for the control of the global epidemic.

positive: Abdominal and testicular pain: An atypical presentation of COVID-19

positive: Key Considerations for Radiologists When Diagnosing the Novel Coronavirus Disease (COVID-19)

positive: Clinical manifestations of children with COVID‐19: A systematic review BACKGROUND: The coronavirus disease 2019 (COVID‐19) outbreak is an unprecedented global public health challenge, leading to thousands of deaths every day worldwide. Despite the epidemiological importance, clinical patterns of children with COVID‐19 remain unclear. The aim of this study was to describe the clinical, laboratorial, and radiological characteristics of children with COVID‐19. METHODS: The Medline database was searched between December 1st 2019 and April 6th 2020. No language restrictions were applied. Inclusion criteria were (a) studied patients younger than 18 years old; (b) presented original data from cases of COVID‐19 confirmed by reverse‐transcription polymerase chain reaction; and (c) contained descriptions of clinical manifestations, laboratory tests, or radiological examinations. RESULTS: A total of 38 studies (1124 cases) were included. From all the cases, 1117 had their severity classified: 14.2% were asymptomatic, 36.3% were mild, 46.0% were moderate, 2.1% were severe, and 1.2% were critical. The most prevalent symptom was fever (47.5%), followed by cough (41.5%), nasal symptoms (11.2%), diarrhea (8.1%), and nausea/vomiting (7.1%). One hundred forty‐five (36.9%) children were diagnosed with pneumonia and 43 (10.9%) upper airway infections were reported. Reduced lymphocyte count was reported in 12.9% of cases. Abnormalities in computed tomography were reported in 63.0% of cases. The most prevalent abnormalities reported were ground‐glass opacities, patchy shadows, and consolidations. Only one death was reported. CONCLUSIONS: Clinical manifestations of children with COVID‐19 differ widely from adult cases. Fever and respiratory symptoms should not be considered a hallmark of COVID‐19 in children.

positive: Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial Abstract Background Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients. We evaluate the role of hydroxychloroquine on respiratory viral loads. Patients and methods French Confirmed COVID-19 patients were included in a single arm protocol from early March to March 16th, to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. Presence and absence of virus at Day6-post inclusion was considered the end point. Results Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms. Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported of untreated patients in the literature. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination. Conclusion Despite its small sample size our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.

positive: Updates on What ACS Reported: Emerging Evidences of COVID-19 with Nervous System Involvement With the ongoing pandemic of coronavirus disease (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), our knowledge of the pathogenesis of COVID-19 is still in its infancy. Almost every aspect of the pathogen remains largely unknown, ranging from mechanisms involved in infection transmission, interplay with the human immune system, and covert mechanisms of end-organ damage. COVID-19 has manifested itself worldwide with a syndromic appearance that is dominated by respiratory dysregulations. While clinicians are focused on correcting respiratory homeostasis, echoing the original SARS, SARS-CoV-2 is also invading other end-organs, which may not exhibit overt clinical features. Nervous system involvement was not initially considered to play a significant role in patients with COVID-19. However, since this viewpoint was initially published, multiple studies have been released regarding the possible neurovirulence of SARS-CoV-2. In our previous viewpoint, we implored our colleagues to recognize the covert tactics of SARS-CoV-2 and emphasized that symptoms like anosmia, dysgeusia, ataxia, and altered mental status could be early signs of the neurotropic potential of this virus. The past few weeks, after the viewpoint surfaced, it was noticed that it has enabled clinicians and healthcare professionals to compute the neurovirulence associated with SARS-CoV-2 in COVID-19 patients, as evidenced by very recently reported studies.

positive: Gastrointestinal Symptoms and outcomes in hospitalized COVID-19 patients. INTRODUCTION Gastrointestinal (GI) symptoms are increasingly being recognized in coronavirus disease 2019 (COVID-19). It is unclear if the presence of GI symptoms is associated with poor outcomes in COVID-19. We aim to assess if GI symptoms could be used for prognostication in hospitalized patients with COVID-19. METHODS We retrospectively analyzed patients admitted to a tertiary medical center in Brooklyn, NY, from March 18, 2020, to March 31, 2020, with COVID-19. The patients' medical charts were reviewed for the presence of GI symptoms at admission, including nausea, vomiting, diarrhea, and abdominal pain. COVID-19 patients with GI symptoms (cases) were compared with COVID-19 patients without GI symptoms (control). RESULTS A total of 150 hospitalized COVID-19 patients were included, of which 31 (20.6%) patients had at least one or more of the GI symptoms (cases). They were compared with the 119 COVID-19 patients without GI symptoms (controls). The average age among cases was 57.6 years (SD 17.2) and, control was 63.3 years (SD 14.6). No statistically significant difference was noted in comorbidities and laboratory findings. The primary outcome was mortality, which did not differ between cases and controls (41.9% vs. 37.8%, p=0.68). No statistically significant differences were noted in secondary outcomes, including the length of stay (LOS, 7.8 days vs. 7.9 days, p=0.87) and need for mechanical ventilation (29% vs. 26.9%, p=0.82). DISCUSSION In our study, the presence of GI manifestations in COVID-19 at the time of admission was not associated with increased mortality, LOS, or mechanical ventilation.

positive: Characterization and Clinical Course of 1000 Patients with COVID-19 in New York: retrospective case series Objective: To characterize patients with coronavirus disease 2019 (COVID-19) in a large New York City (NYC) medical center and describe their clinical course across the emergency department (ED), inpatient floors, and intensive care units (ICUs). Design: Retrospective manual medical record review. Setting: NewYork-Presbyterian/Columbia University Irving Medical Center (NYP/CUIMC), a quaternary care academic medical center in NYC. Participants: The first 1000 consecutive patients with laboratory-confirmed COVID-19. Methods: We identified patients with a positive RT-SARS-CoV-2 PCR receiving care at NYP/CUIMC from March 1 through April 15. Patient data was manually abstracted from the electronic medical record. Main outcome measures: We describe patient characteristics including demographics, presenting symptoms, comorbidities on presentation, hospital course, time to intubation, complications, outcomes, and disposition. Results: Among the first 1000 patients with confirmed COVID-19, 151 patients were discharged from or died in the ED, 618 were admitted to the floor, and 231 were admitted or transferred to the ICU; 195 remained hospitalized and 172 had died in the hospital. The most common presenting symptoms were cough (73.2%), fever (72.8%), and dyspnea (62.9%). Compared to Chinese and Italian cohorts, hospitalized patients and ICU patients in particular had more baseline comorbidities including hypertension, diabetes, and obesity and higher rates of acute kidney injury (AKI) and dialysis. ICU patients were older and predominantly male (67.5%); 75.3% developed AKI and 31.2% required dialysis. Notably, of patients who required mechanical ventilation, only 5.9% were first intubated more than 14 days after symptom onset. Time to intubation from symptom onset had a bimodal distribution, with modes at 3-4 and 9 days. Conclusions: Hospitalized patients with COVID-19 illness at this medical center faced significant morbidity and mortality, with high rates of AKI, dialysis, and a bimodal distribution in time to intubation from symptom onset. Patients in this large sample have more baseline comorbidities and more complications than previous Italian and Chinese cohorts.

positive: Patients with respiratory symptoms are at greater risk of COVID-19 transmission

positive: Imaging manifestations and diagnostic value of chest CT of coronavirus disease 2019 (COVID-19) in the Xiaogan area AIM To report the epidemiological, clinical, and radiological characteristics of patients with COVID-19 in Xiaogan, Hubei, China. MATERIALS AND METHODS The complete clinical and imaging data of 114 confirmed COVID-19 patients treated in Xiaogan Hospital were analysed retrospectively. Data were gathered regarding the presence of chest computed tomography (CT) abnormalities; the distribution, morphology, density, location, and stage of abnormal shadows on chest CT; and observing the correlation between the severity of chest infection and lymphocyte ratio and blood oxygen saturation (SPO2) in patients. RESULTS Chest CT revealed abnormal lung shadows in 110 patients. Regarding lesion distribution, multi-lobe lesions in both lungs were present in most patients (80 cases; 72.7%). Lesions most frequently involved both the peripheral zone and the central zone (62 cases; 56.4%). Regarding lesion morphology, 56 cases (50.1%) demonstrated patchy shadows that were partially fused into large areas. Thirty cases showed ground-glass opacity (27.3%), 30 cases showed the consolidation change (27.3%), and the remaining 50 cases showed both types of changes (45.4%). The progressing stage was the most common stage (54 cases; 49.1%). CT results showed a negative correlation with SPO2 and lymphocyte numbers (p<0.05), with r-values of −0.446 and −0.780, respectively. CONCLUSION Spiral CT is a sensitive examination method, which can be applied to make an early diagnosis and for evaluation of progression, with a diagnostic sensitivity and accuracy better than that of nucleic acid detection.

positive: CT manifestations and clinical characteristics of 1115 patients with coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis Abstract Rationale and objectives: We aimed to assess the prevalence of significant computed tomographic(CT) manifestations and describe some notable features based on chest CT images, as well as the main clinical features of patients with coronavirus disease 2019(COVID-19). Materials and methods: A systematic literature search of PubMed, EMBASE, the Cochrane Library, and Web of Science was performed to identify studies assessing CT features, clinical and laboratory results of COVID-19 patients. A single-arm meta-analysis was conducted to obtain the pooled prevalence and 95% confidence interval(95%CI). Results: A total of 14 articles(including 1115 patients) based on chest CT images were retrieved. In the lesion patterns on chest CTs, we found that pure ground-glass opacities(GGO)(69%, 95%CI 58–80%), consolidation(47%, 35–60%) and “air bronchogram sign”(46%,25–66%) were more common than the atypical lesion of “crazy-paving pattern”(15%, 8–22%). With regard to disease extent and involvement, 70%(95%CI 46–95%) of cases showed a location preference for the right lower lobe, 65%(58–73%) of patients presented with ≥3 lobes involvement, and meanwhile, 42%(32–53%) of patients had involvement of all five lobes, while 67%(55–78%) of patients showed a predominant peripheral distribution. An understanding of some important CT features might be helpful for medical surveillance and management. In terms of clinical features, muscle soreness(21%, 95%CI 15–26%) and diarrhea(7%, 4–10%) were minor symptoms compared with fever(80%, 74–87%) and cough(53%, 33–72%). Conclusion: Chest CT manifestations in patients with COVID-19, as well as its main clinical characteristics, might be helpful in disease evolution and management.

positive: Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been widely spread. We aim to investigate the clinical characteristic and allergy status of patients infected with SARS-CoV-2. METHODS: Electronic medical records including demographics, clinical manifestation, comorbidities, laboratory data, and radiological materials of 140 hospitalized COVID-19 patients, with confirmed result of SARS-CoV-2 viral infection, were extracted and analyzed. RESULTS: An approximately 1:1 ratio of male (50.7%) and female COVID-19 patients was found, with an overall median age of 57.0years. All patients were community-acquired cases. Fever (91.7%), cough (75.0%), fatigue (75.0%), and gastrointestinal symptoms (39.6%) were the most common clinical manifestations, whereas hypertension (30.0%) and diabetes mellitus (12.1%) were the most common comorbidities. Drug hypersensitivity (11.4%) and urticaria (1.4%) were self-reported by several patients. Asthma or other allergic diseases were not reported by any of the patients. Chronic obstructive pulmonary disease (COPD, 1.4%) patients and current smokers (1.4%) were rare. Bilateral ground-glass or patchy opacity (89.6%) was the most common sign of radiological finding. Lymphopenia (75.4%) and eosinopenia (52.9%) were observed in most patients. Blood eosinophil counts correlate positively with lymphocyte counts in severe (r=.486, P<.001) and nonsevere (r=.469, P<.001) patients after hospital admission. Significantly higher levels of D-dimer, C-reactive protein, and procalcitonin were associated with severe patients compared to nonsevere patients (all P<.001). CONCLUSION: Detailed clinical investigation of 140 hospitalized COVID-19 cases suggests eosinopenia together with lymphopenia may be a potential indicator for diagnosis. Allergic diseases, asthma, and COPD are not risk factors for SARS-CoV-2 infection. Older age, high number of comorbidities, and more prominent laboratory abnormalities were associated with severe patients.

positive: Ocular manifestations and clinical characteristics of 534 cases of COVID-19 in China: A cross-sectional study Objective: The novel coronavirus disease (COVID-19) was first reported in Wuhan, China in December 2019 and is now pandemic all over the world. Previous study has reported several COVID-19 cases with conjunctivitis. However, the complete profiling of COVID-19 related ocular symptoms and diseases are still missing. We aim to investigate the ocular manifestations and clinical characteristics of COVID-19 patients. Methods: A total of five hundred and thirty-four patients were recruited at Mobile Cabin Hospital and Tongji Hospital. We collected information on demographic characteristics, exposure history, ocular symptoms, systemic concomitant symptoms, eye drop medication, eye protections, radiologic findings, and SARS-CoV-2 detection in nasopharyngeal swabs by RT-PCR from questionnaires and electronic medical records. Results: The median age of patients was 40 and 50 years at Mobile Cabin Hospital and Tongji Hospital, respectively. Of 534 COVID-19 patients, 25 patients (4.68%) presented with conjunctival congestion and 3 patients had conjunctival congestion as the initial symptom. The average duration of conjunctival congestion was 4.9 {+/-} 2.6 days (mean [SD]), ranging from 2 to 10 days. Dry eye (112, 20.97%), blurred vision (68, 12.73%), and foreign body sensation (63, 11.80%) ranked as the top three COVID-19 related ocular symptoms. Notably, a total of 332 COVID-19 patients (62%) had a hand-eye contact history. We also found that some COVID-19 patients had a history of eye disease, including conjunctivitis (33, 6.18%), dry eye (24, 4.49%), keratitis (14, 2.62%), cataract (9, 1.69%), and diabetic retinopathy (5, 0.94%). In consistent with previous studies, the most common clinical symptoms were fever, cough, and fatigue. Patients, 60.5% in Mobile Cabin Hospital and 67.5% in Tongji Hospital, respectively were confirmed with positive SARS-CoV-2 detection. Conclusions: Conjunctival congestion was one of the COVID-19 related ocular symptoms, which may have clinical diagnostic significance. It is essential to provide eye-care equipment and strengthen education on eye protection, as dirty hand-eye contact might be a high risk factor of COVID-19. Further detailed and comprehensive ophthalmological guidance is needed for COVID-19 control.

positive: Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series OBJECTIVE: To study the clinical characteristics of patients in Zhejiang province, China, infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) responsible for coronavirus disease 2019 (covid-2019). DESIGN: Retrospective case series. SETTING: Seven hospitals in Zhejiang province, China. PARTICIPANTS: 62 patients admitted to hospital with laboratory confirmed SARS-Cov-2 infection. Data were collected from 10 January 2020 to 26 January 2020. MAIN OUTCOME MEASURES: Clinical data, collected using a standardised case report form, such as temperature, history of exposure, incubation period. If information was not clear, the working group in Hangzhou contacted the doctor responsible for treating the patient for clarification. RESULTS: Of the 62 patients studied (median age 41 years), only one was admitted to an intensive care unit, and no patients died during the study. According to research, none of the infected patients in Zhejiang province were ever exposed to the Huanan seafood market, the original source of the virus; all studied cases were infected by human to human transmission. The most common symptoms at onset of illness were fever in 48 (77%) patients, cough in 50 (81%), expectoration in 35 (56%), headache in 21 (34%), myalgia or fatigue in 32 (52%), diarrhoea in 3 (8%), and haemoptysis in 2 (3%). Only two patients (3%) developed shortness of breath on admission. The median time from exposure to onset of illness was 4 days (interquartile range 3-5 days), and from onset of symptoms to first hospital admission was 2 (1-4) days. CONCLUSION: As of early February 2020, compared with patients initially infected with SARS-Cov-2 in Wuhan, the symptoms of patients in Zhejiang province are relatively mild.

positive: Can COVID-19 present unusual GI symptoms?

positive: The Early Natural History of SARS-CoV-2 Infection: Clinical Observations From an Urban, Ambulatory COVID-19 Clinic

positive: Olfactory and rhinological evaluations in SARS-CoV-2 patients complaining of olfactory loss. Since December 2019, a novel coronavirus SARS-CoV-2 (Covid-19) outbreak emerged in China and spread rapidly in several countries. As of April 5, 2020, 1.218.474 cases were confirmed with 65.884 deaths worldwide (1). The clinical manifestations of Covid-19 range from asymptomatic carrier status to severe pneumonia. In a study of 7,736 Covid-19 patients in China, of all the clinical symptoms, hyposmia was not reported in any patient(2). Anyway, it is now clear that olfactory dysfunction may also be present in these patients(3) as the only or prevalent manifestation(4).

positive: Clinical Characteristics and Risk factors for developed COVID-19 patients transferring to designated hospital from Jianghan Fangcang shelter Hospital: a retrospective, observational study Background The outbreak of coronavirus disease 2019 (COVID-19) has become a world-wide emergency. Fangcang shelter hospitals have been applied in COVID-19 to ease ongoing shortage of medical resources in Wuhan since February 2020. Methods This study enrolled all cases (no=1848) with mild or moderate type of COVID-19 in Fangcang shelter hospital of Jianghan in Wuhan from Feb 5th to Mar 9th, 2020. Diagnosis of COVID-19 was based on the National health commission of China. Epidemiological history, comorbidity, vital signs, symptoms and signs were recorded in detail. Laboratory tests included biochemical indicators and nucleic acid tests by throat swabs have been performed as well. Findings A total of 1327 patients reached the criteria of isolation release. Meanwhile, 521 patients have been transferred to the designated hospitals for further treatment, including severe type, fever more than 3 days, and severe comorbidity. The case-severity rate (rate of mild or moderate type transforming to severe type) was 3.0% in the shelter hospital. The patients from mild or moderate type to severe type showed the following clinical characteristics: the median incubation (onset to shelter) period was 10 days; they were all symptomatic at admission; fever, cough, and fatigue were the most common symptoms; hypertension, diabetes and coronary heart diseases were common co-morbidities; most of the patients had elevated levels of CRP at ill onset with 33.3% over 10 mg per L; bilateral distribution and ground-glass opacity were the most common manifestations in chest CT. Interpretation The potential risk factors of fever, fatigue, high level of C-reactive protein were the risk factors to identify the progression of COVID-19 patients with mild or moderate type. Fangcang shelter hospitals have substantially reduced the time from the onset of severe symptoms transfer to a designated hospital. Early application of the Fangcang shelter hospital may contribute to decrease the ratio of mild transforming to severe patients. Funding No specific grant from any funding was applied to this research.

positive: COVID-19: Focus on the lungs but do not forget the gastrointestinal tract The coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was declared in the last weeks as global pandemic. Currently affecting more than 5 000 000 individuals worldwide, COVID-19 is most commonly associated with symptoms caused by the acute respiratory distress syndrome (ARDS). As the number of infected individuals increases, we are learning that not only lungs, but also other organs can be affected by the virus. The gastrointestinal symptoms, for example diarrhoea, vomiting, nausea or abdominal pain, are frequent in patients with COVID-19. Moreover, alimentary tract symptoms may precede the respiratory presentation of SARS-CoV-2 infection. This can lead to delayed diagnosis and inappropriate management of infected patients. In addition, SARS-CoV-2 nucleic acid can be detected in faeces of infected patients and rectal swabs are even reported to remain positive for a longer period of time than nasopharyngeal swabs. Here, we aim to provide an update on the gastrointestinal involvement of COVID-19 presenting the symptoms that can be encountered in infected patients. We address the role of angiotensin-converting enzyme 2 (ACE2), as a functional receptor for SARS-CoV-2, which also was found in the gastrointestinal tract. Finally, we briefly discuss faecal shedding of SARS-CoV-2 and its potential role in the pathogenesis of the disease.

positive: SARS-CoV-2 infection in 86 healthcare workers in two Dutch hospitals in March 2020 Background On February 27, 2020, the first patient with COVID-19 was reported in the Netherlands. During the following weeks, nine healthcare workers (HCWs) were diagnosed with COVID-19 in two Dutch teaching hospitals, eight of whom had no history of travel to China or Northern-Italy. A low-threshold screening regimen was implemented to determine the prevalence and clinical presentation of COVID-19 among HCWs in these two hospitals. Methods HCWs who suffered from fever or respiratory symptoms were voluntarily tested for SARS-CoV-2 by real-time reverse-transcriptase PCR on oropharyngeal samples. Structured interviews were conducted to document symptoms for all HCWs with confirmed COVID-19. Findings Thirteen-hundred fifty-three (14%) of 9,705 HCWs employed were tested, 86 (6%) of whom were infected with SARS-CoV-2. Most HCWs suffered from relatively mild disease and only 46 (53%) reported fever. Seventy-nine (92%) HCWs met a case definition of fever and/or coughing and/or shortness of breath. None of the HCWs identified through the screening reported a travel history to China or Northern Italy, and 3 (3%) reported to have been exposed to an inpatient known with COVID-19 prior to the onset of symptoms. Interpretation Within two weeks after the first Dutch case was detected, a substantial proportion of HCWs with fever or respiratory symptoms were infected with SARS-CoV-2, probably caused by acquisition of the virus in the community during the early phase of local spread. The high prevalence of mild clinical presentations, frequently not including fever, asks for less stringent use of the currently recommended case-definition for suspected COVID-19.

positive: Acute encephalopathy with elevated CSF inflammatory markers as the initial presentation of COVID-19. BACKGROUND: COVID-19 is caused by the severe acute respiratory syndrome virus SARS-CoV-2. It is widely recognized as a respiratory pathogen, but neurologic complications can be the presenting manifestation in a subset of infected patients. CASE PRESENTATION: We describe a 78-year old immunocompromised woman who presented with altered mental status after witnessed seizure-like activity at home. She was found to have SARS-CoV-2 infection and associated neuroinflammation. In this case, we undertake the first detailed analysis of cerebrospinal fluid (CSF) cytokines during COVID-19 infection and find a unique pattern of inflammation in CSF, but no evidence of viral neuroinvasion. CONCLUSION: Our findings suggest that neurologic symptoms such as encephalopathy and seizures may be the initial presentation of COVID-19. Central nervous system inflammation may associate with neurologic manifestations of disease.

positive: SARS-CoV-2-Induced Vomiting as Onset Symptom in a Patient with COVID-19

positive: 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.

positive: [Anosmia and ageusia as primary symptoms of COVID-19]. This case report describes a physician in the early 30ies with subjective anosmia and ageusia as the major presenting symptoms of COVID-19. Apart from a week of slightly runny nose when coming from cold to warm air, the only symptom was a sudden onset of persistent anosmia and ageusia. Two weeks after normalisation of the mild sino-nasal symptoms, the patient was tested positive for SARS-CoV-2, and anosmia was verified with Sniffin' Sticks tests. Hypogeusia was verified with taste screening and two validated taste tests. Olfactory and gustatory loss may be underestimated symptoms of COVID-19.

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

positive: A report of clinical diagnosis and treatment of nine cases of coronavirus disease 2019 Coronavirus disease 2019 (COVID‐19) caused by the severe acute respiratory syndrome coronavirus 2 has become an important public health issue in the world. More than 118 000 cases were confirmed around the world. The main clinical manifestations were respiratory symptoms and occasional gastrointestinal symptoms. However, there is no unified standard for the diagnosis and treatment of COVID‐19. In the retrospective analysis, we report nine cases of COVID‐19, describe the history of contact, clinical manifestations, the course of diagnosis and clinical treatment before, during and after treatment.

positive: CT Scans of Patients with 2019 Novel Coronavirus (COVID-19) Pneumonia Rationale: The increasing speed of confirmed 2019 novel coronavirus (COVID-19) cases is striking in China. The purpose of this study is to summarize the outcomes of patients with novel COVID-19 pneumonia (NCP) at our institution. Methods: In this single-center study, we retrospectively included 118 cases of NCP, from January 16, 2020 to February 4, 2020. The clinical outcomes were monitored up to February 11, 2020. The outcomes of NCP patients were phase summarized at our institution. Three kinds of responses to clinical treatment were defined and evaluated: 1) good, symptoms continually improved; 2) fair, symptoms not improved or relapsed; 3) poor, symptoms aggravated. The risk factors, including basal clinical characteristics, CT imaging features, and follow-up CT changes (no change, progress, and improvement) related to poor/fair outcomes, were also investigated. Results: Six patients were improved to no-emergency type, 2 remained the same, and 2 progressed to fatal type. Besides, 13 patients progressed from the common type group to the emergency group (3 in fatal type and 10 in severe type). Forty-two (35.6%) patients were discharged with a median hospital stay of 9.5 days (range, 4.0-15.0 days). Thus, the numbers in different responses were, 73 patients in good response group (4 emergency cases, 69 no-emergency cases), 28 in fair response group (3 emergency cases, 25 no-emergency cases), and 17 in poor response group (3 emergency cases, 14 no-emergency cases). No patient has died in our hospital to date. The median duration of progress observed from CT scans was 6 days (range, 2-14 days). The progression in abnormal imaging findings indicate a poor/fair response, whereas the alleviated symptoms seen from CT suggest a good response. Conclusion: Most cases are no-emergency type and have a favorable response to clinical treatment. Follow-up CT changes during the treatment can help evaluate the treatment response of patients with NCP.

positive: The Many Faces and Fangs of COVID-19: An Editorial

positive: The clinical characteristics of COVID-19: a retrospective analysis of 104 patients from the outbreak on board the Diamond Princess cruise ship in Japan Background: The ongoing outbreak of the coronavirus disease 2019 (COVID-19) is a global threat. Identification of markers for symptom onset and disease progression is a pressing issue. We compared the clinical features on admission among patients who were diagnosed with asymptomatic, mild, and severe COVID-19 at the end of observation. Methods: This retrospective, single-center study included 104 patients with laboratory-confirmed COVID-19 from the mass infection on the Diamond Princess cruise ship from February 11 to February 25, 2020. Clinical records, laboratory data, and radiological findings were analyzed. Clinical outcomes were followed up until February 26, 2020. Clinical features on admission were compared among those with different disease severity at the end of observation. Univariate analysis identified factors associated with symptom onset and disease progression. Findings: The median age was 68 years, and 54 patients were male. Briefly, 43, 41, and 20 patients on admission and 33, 43, and 28 patients at the end of observation had asymptomatic, mild, and severe COVID-19, respectively. Serum lactate hydrogenase levels were significantly higher in 10 patients who were asymptomatic on admission but developed symptomatic COVID-19 compared with 33 patients who remained asymptomatic throughout the observation period. Older age, consolidation on chest computed tomography, and lymphopenia on admission were more frequent in patients with severe COVID-19 than those with mild COVID-19 at the end of observation. Interpretation: Lactate dehydrogenase level is a potential predictor of symptom onset in COVID-19. Older age, consolidation on chest CT images, and lymphopenia might be risk factors for disease progression of COVID-19 and contribute to the clinical management. Funding: Not applicable.

positive: Medically unexplained symptoms in the times of Covid-19 pandemic: a case-report Abstract In early 2020, a novel coronavirus (SARS-CoV-2) leading to a potentially fatal condition was discovered. Since then, the 2019 coronavirus disease (COVID-19) has spread worldwide becoming a pandemic. Beyond the risks strictly related to the infection, concerns have been expressed for the psychological impact that COVID-19 may have, especially on vulnerable individuals with pre-existing mental health conditions. Somatic symptom disorder (SSD) is characterized by a dysfunctional preoccupation with physical symptoms leading to excessive and unnecessary healthcare utilization. Despite being quite common, such condition remains underrecognized. We report a detailed clinical case of a 16 years old adolescent, who presented with a history suggestive of COVID-19 infection and associated psychological distress. Despite testing negative for the presence of SARS-CoV-2, his extreme and persisting health preoccupations required an inpatient admission to the Child and Adolescent Neuropsychiatric Unit. He responded rapidly to a low dose of antipsychotic and an antidepressant. Based on his medical history and current presentation, he received a diagnosis of SSD. When COVID-19-like symptoms occur, we highlight the importance of differentially diagnosing a possible exacerbation of a pre-existing SSD, triggered by fear of being infected. This may help preventing further burden to the healthcare system.

positive: 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).

positive: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection During Pregnancy In China: A Retrospective Cohort Study Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as the cause of the ongoing worldwide epidemic of Coronavirus Disease 2019 (COVID-19) in China and worldwide. However, there were few studies about the effects of SARS-CoV-2 infection on pregnant women. Methods In this retrospective cohort study, we enrolled 31 pregnant women and 35 non-pregnant women from Jan 28 to Feb 28, 2020 to evaluate the effects of SARS-CoV-2 infection during pregnancy. Inflammatory indices were used to assess the severity of COVID-19. Evidence of vertical transmission was determined by laboratory confirmation of SARS-CoV-2 in amniotic fluid, placenta, neonatal throat and anal swab and breastmilk samples. Findings Compared with non-pregnant women, pregnant women had a significantly lower proportion of fever (54.8% vs. 87.5%, p= 0.006), a shorter average interval from onset to hospitalization, and a higher proportion of severe or critical COVID-19 (32.3% vs. 11.4%, p=0.039). Neutrophil-to-lymphocyte ratio (NLR) and systematic immune-inflammation-based prognostic index (SII) were significantly higher on admission in severe/critical pneumonia group than moderate pneumonia group. We could not detect the presence of SARS-CoV-2 by RT-PCR in amniotic fluid, placenta, neonatal throat and anal swab and breastmilk samples. Conclusions The clinical symptoms of COVID-19 in pregnant women were insidious and atypical, compared with those in non-pregnant patients. SII and NLR could be a useful marker to evaluate the severity of COVID-19. There was no evidence of vertical transmission during pregnancy with SARS-CoV-2 infection.

positive: Sniffing out the evidence; It's now time for public health bodies recognize the link between COVID-19 and smell and taste disturbance. Since the outbreak of the pandemic, anecdotal observations have been accumulating rapidly that sudden anosmia and dysgeusia are peculiar symptoms associated with the COVID-19 infection. Prof C. Hopkins, as President of British Rhinological Society, published a letter describing "the loss of sense of smell as a marker of COVID-19 infection" and proposed that adults presenting with anosmia but no other symptoms should self-isolate for seven days. The Hopkins team published the first case report and case series as well as other evidence that isolated sudden onset anosmia (ISOA), should be considered highly suspicious for SARS-CoV-2(1). Subsequently, a larger series of 2428 patients presenting with new onset anosmia during the COVID-19 pandemic has been reported, of whom 16% report loss of sense of smell as an isolated symptom. Only 51% reported the recognized symptoms of cough or fever. A major limitation of this series however, was a lack of access to testing to confirm the COVID-19 status of the patients(2); in the 80 who had been tested 74% were positive. In the same way, the American Academy of Otolaryngology-head and neck surgery (AA0-HNS) proposed "that anosmia could be added to the list of screening tools for possible COVID-19 infection. More, they warrant serious consideration for self-isolation and testing those patients".

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

positive: COVID-19 diagnosis prediction by symptoms of tested individuals: a machine learning approach Effective screening of SARS-CoV-2 enables quick and efficient diagnosis of COVID-19 and can mitigate the burden on healthcare systems. Prediction models that combine several features to estimate the risk of infection have been developed in hopes of assisting medical staff worldwide in triaging patients when allocating limited healthcare resources. We established a machine learning approach that trained on records from 51,831 tested individuals (of whom 4,769 were confirmed COVID-19 cases) while the test set contained data from the following week (47,401 tested individuals of whom 3,624 were confirmed COVID-19 cases). Our model predicts COVID-19 test results with high accuracy using only 8 features: gender, whether the age is above 60, information about close contact with an infected individual, and 5 initial clinical symptoms. Overall, using nationwide data representing the general population, we developed a model that enables screening suspected COVID-19 patients according to simple features accessed by asking them basic questions. Our model can be used, among other considerations, to prioritize testing for COVID-19 when allocating limited testing resources.

positive: Urticaria (angioedema) and COVID‐ 19 infection The novel coronavirus, otherwise known as COVID‐19 has fast become a major health concern.(1 2) It has been reported that in addition to the conventional respiratory symptoms, patients also display skin manifestations such as Urticaria and angioedema.(3) Here we present a case study of an elderly man who first presented with generalised pruritic hives ranging from 1.5 to 8.0 cm in diameter on the 5(th) of March 2020. The patient was investigated for another differential diagnosis of Urticaria such as parasitic and bacterial infection, for which negative results were found. On the 5th of March 2020 the patient‐reported these symptoms plus general malaise, fatigue, 37.9⁰C temperature and sore throat. Initial biochemical tests showed that the patient presented with low numbers of white blood cells (WBC) (WBC=2.75x10(3)).

positive: Epidemiological and clinical characteristics analysis of COVID-19 in the surrounding areas of Wuhan, Hubei Province in 2020 AIM: Since December 2019, new COVID-19 outbreaks have occurred and spread around the world. However, the clinical characteristics of patients in other areas around Wuhan, Hubei Province are still unclear. In this study, we performed epidemiological and clinical characteristics analysis on these regional cases. METHODS: We retrospectively investigated COVID-19 patients positively confirmed by nucleic acid Q-PCR at Taihe Hospital from January 16 to February 4, 2020. Their epidemiological, clinical manifestations, and imaging characteristics were analysed. RESULTS: Among the 73 patients studied, 12.3 % developed symptoms after returning to Shiyan from Wuhan, and 71.2 % had a history of close contact with Wuhan personnel or confirmed cases. Among these patients, 9 cases were associated with family clustering. The first main symptoms presented by these patients were fever (84.9 %) and cough (21.9 %). The longest incubation period was 26 days, and the median interval from the first symptoms to admission was 5 days. Of the patients, 67.1 % were originally healthy people with no underlying diseases, others mostly had common comorbidities including hypertension (12.3 %) and diabetes (5.5 %), 10.9 % were current smokers, 30.1 % had low white blood cell counts and 45.2 % showed decreased lymphocytes at the first time of diagnosis. CT scans showed that multiple patchy ground glass shadows outside of the patient lungs were commonly observed, and a single sub-pleural sheet of ground glass shadow with enhanced vascular bundles was also found located under the pleura. Patient follow-up to February 14 presented 38.4 % severe cases and 2.7 % critical cases. After follow-up, the parameter of lymphocyte counts below 0.8 × 10(9)/L cannot be used to predict severe and critical groups from the ordinary group, and a lower proportion of smokers and higher proportion of diabetes patients occur in the poor outcome group. Other co-morbidities are observed but did not lead to poor outcomes. CONCLUSION: The epidemiological characteristics of patients in the area around Wuhan, such as Shiyan, at first diagnosis are described as follows: Patients had histories of Wuhan residences in the early stage and family clustering in the later period. The incubation period was relatively long, and the incidence was relatively hidden, but the virulence was relatively low. The initial diagnosis of the patients was mostly ordinary, and the percentage of critical patients who evolved into the ICU during follow-up is 2.7 %, which is lower than the 26.1 % reported by Wuhan city. According to the Shiyan experience, early diagnosis with multiple swaps of the Q-PCR test and timely treatment can reduce the death rate. Diabetes could be one of the risk factors for progression to severe/critical outcomes. No evidence exists that smoking protects COVID-19 patients from developing to severe/critical cases, and the absolute number of lymphocytes at initial diagnosis could not predict the progression risk from severe to critical condition. Multivariate regression analysis should be used to further guide the allocation of clinical resources.

positive: Clinical and epidemiological characteristics of 34 children with 2019 novel coronavirus infection in Shenzhen/ 中华儿科杂志 Objective@#To describe the characteristics of clinical manifestations and epidemiology of children with 2019 novel coronavirus (2019-nCoV) infection.@*Methods@#All 34 children with laboratory-confirmed 2019-nCoV infection by quantitative real-time reverse transcription-PCR through nasopharyngeal swab specimens were admitted to the Third People’s Hospital of Shenzhen from January 19 to Febuary 7, 2020. Clinical data and epidemiological history of these patients were retrospectively collected and analyzed.@*Results@#Among the 34 cases, 14 were males, and 20 were females. The median age was 8 years and 11 months. No patients had underlying diseases. There were 28 children (82%) related with a family cluster outbreak. There were 26 children (76%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 22 (65%) common cases, 9 (26%) mild cases and 3 (8.8%) asymptomatic cases. No severe or critical cases were identified. The most common symptoms were fever (17 cases, 50%) and cough (13 cases, 38% ). In the 34 cases, the white blood cell counts of 28 cases (82%) were normal. Five cases had white blood cell counts more than 10×109/L. One case had white blood cell counts less than 4×109/L. Neutropenia and lymphopenia was found in one case, respectively. C-reactive protein levels and erythrocyte sedimentation rates were elevated in 1 and 5 case, respectively. Elevated procalcitonin was found in 1 case and D-Dimer in 3 cases. The levels of lactic dehydrogenase (LDH) were more than 400 U/L in 10 cases. The CT images of these patients showed bilateral multiple patchy or nodular ground-glass opacities and/or infiltrating shadows in middle and outer zone of the lung or under the pleura. Twenty patients were treated with lopinavir and ritonavir. Glucocorticoids and immunoglobulin were not used in any cases. All the cases improved and were discharged from hospital. Further following up was need.@*Conclusions@#The clinical manifestations in children with 2019-nCoV infection are non-specific and are milder than that in adults. Chest CT scanning is heplful for early diagnosis. Children's infection is mainly caused by family cluster outbreak and imported cases. Family daily prevention is the main way to prevent 2019-nCoV infection.

positive: 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.

positive: Chest CT imaging features and clinical outcome of coronavirus disease 2019 (COVID-19): A single-center case study in Ningbo, China OBJECTIVE: The purpose of this study was to investigate the chest CT imaging features and clinical outcome of coronavirus disease 2019 (COVID-19) in Ningbo, China. METHODS: In this retrospective study, twenty-eight confirmed and seven highly suspected cases of COVID-19 were enrolled in Ningbo first hospital from January 26, 2020 to March 5, 2020. Cases were confirmed by real-time polymerase chain reaction (RT-PCR). The initial and follow-up chest CT imaging features, epidemiological history, and outcome were analyzed. RESULTS: The average age of the patients was 57.3 ± 15.3 years (range: 27–96 years), including 25 females and 10 males. On CT images, 89.3% (25/28) confirmed and 100% (7/7) suspected patients had ground-glass opacities (GGOs), and GGOs with mixed consolidations were observed in 35.7% (10/28) confirmed and 42.9% (3/7) suspected cases, most of these lesions were distributed under the peripheral of both lungs. 17 confirmed and 4 suspected cases had a history of participating in Ningbo Tian-tong Temple rituals and all had GGOs in their lungs during the initial CT scan. As of March 25, 2020, the lung lesions of our cases were significantly resolved and all patients have been discharged from the hospital. CONCLUSION: The most common chest CT features are multiple bilateral and peripheral GGOs with mixed consolidations or not in the lungs of patients with COVID-19. Chest CT plays an important role in the diagnosis and monitoring treatment response of this disease. There was no reported death in our cases.

positive: Altered Mental Status as a Novel Initial Clinical Presentation for COVID-19 Infection in the Elderly The coronavirus disease of 2019 or COVID-19 was first identified in Hubei Province in China in November of 2019 and quickly spread to become a global pandemic. The virus, SARS-Coronavirus-2 (2-SARS-CoV-2), is particularly virulent in the elderly who can develop symptoms and become mortally ill within days of contracting the virus. The virus is easily transmitted by droplets (e.g., sneezing, coughing) and communal living settings such as personal care homes can be vulnerable to the spread of the virus. Identifying patients early in the disease process is important to providing appropriate medical interventions. To date, most of the medical literature, including Center for Disease Control guidelines, has relied on three necessary symptoms in making the diagnosis of COVID-19: fever, cough and shortness of breath. We present four cases of elderly patients who developed altered mental status as their presenting symptom without associated fever or respiratory symptoms.

positive: Beware: Gastrointestinal symptoms can be a manifestation of COVID-19 Abstract Background There is a growing number of reports of COVID-19 cases presenting gastrointestinal (GI) symptoms. Aims To review studies reporting GI symptoms among COVID-19 patients. Results Fifteen papers (2800 patients) were identified. Frequency of GI symptoms varied from 3.0% to 39.6%, including diarrhea: 7.5%, nausea: 4.5%, anorexia: 4.4%, vomiting: 1.3%, abdominal pain: 0.5%, belching/reflux: 0.3%. These may be the first manifestation of COVID-19, however, there is controversy whether these reflect better or worst prognosis. Finally, the potential relationship with the angiotensin converting enzyme 2 (ACE2) cell receptor in the digestive tract as the virus entry route, is discussed. Conclusions GI symptoms may be common in COVID-19 may be the first manifestation before fever and respiratory symptoms. Therefore, clinicians and gastroenterologists need to be aware of these atypical cases during the current pandemic and of the fecal–oral transmission, and preventive measures may be implemented.

positive: Extrapulmonary Gastrointestinal Presentation of Coronavirus (COVID-19): A Case Report and Review of Literature Coronavirus disease 2019 (COVID-19) is currently the causative agent for a global health emergency and is predominantly associated with respiratory symptoms. In this case, a patient presented to the emergency department with gastrointestinal symptomatology without associated respiratory findings and was subsequently diagnosed with COVID-19 based on incidental findings from an abdominal computed tomography (CT) study. Given the patient’s lack of respiratory symptoms, diagnosis and treatment were ultimately delayed. During this global health crisis, an improved understanding of the various presentations of COVID-19 is paramount in an effort to initiate immediate treatment and prevent further transmission.

positive: COVID-19: Importance of the Awareness of the Clinical Syndrome by Urologists

positive: Cerebral Venous Thrombosis: Atypical Presentation of COVID-19 in the Young Abstract Objective Identify clinical and radiographic features of venous infarct as a presenting feature of COVID-19 in the young. Background SARS-CoV-2 infection causes hypercoagulability and inflammation leading to venous thrombotic events (VTE). Although elderly patients with comorbidities are at higher risk, COVID-19 may also cause VTE in a broader patient population without these risks. Neurologic complications and manifestations of COVID-19, including neuropathies, seizures, strokes and encephalopathy usually occur in severe established cases of COVID-19 infection who primarily present with respiratory distress. Case description : Case report of a 29-year-old woman, with no significant past medical history or comorbidities, presenting with new onset seizures. Further questioning revealed a one-week history of headaches, low-grade fever, mild cough and shortness of breath, diagnosed as COVID-19. Imaging revealed a left temporoparietal hemorrhagic venous infarction with left transverse and sigmoid sinus thrombosis treated with full dose anticoagulation and antiepileptics. Conclusion Although elderly patients with comorbidities are considered highest risk for COVID-19 neurologic complications, usually when systemic symptoms are severe, this case report emphasizes that young individuals are at risk for VTE with neurologic complications even when systemic symptoms are mild, likely induced by COVID-19 associated hypercoagulable state.

positive: The Clinical Manifestations and Chest Computed Tomography Findings of Coronavirus Disease 2019 (COVID-19) Patients in China: A Proportion Meta-Analysis OBJECTIVES: The objectives of this study were to identify the clinical features and chest computed tomography (CT) findings of coronavirus disease 2019 (COVID-19) patients and to compare the characteristics of patients diagnosed in Wuhan and in other areas of China by integrating the findings reported in previous studies. METHODS: We conducted a proportion meta-analysis to integrate the results of previous studies identified in online databases, and subsequently compared the overlapping of 95% confidence intervals (CIs) between locations of diagnosis. The heterogeneity of the results of the included studies was also demonstrated. RESULTS: Nine studies with level IV evidence were considered to be eligible for the meta-analysis, and a comparative analysis was only possible between patients diagnosed in Wuhan and outside of Wuhan in China. Fever (84.8%; 95% CI, 78.5% to 90.1%) was identified as the most common clinical manifestation in all COVID-19 patients, and signs of respiratory infection were also frequently present in these patients. When comparing the clinical features according to the location of diagnosis, fever and dyspnea were less frequent in patients diagnosed outside of Wuhan (fever: 78.1%; 95% CI, 73.2% to 82.7%; dyspnea: 3.80%; 95% CI, 0.13% to 12.22%) than in patients diagnosed in Wuhan (fever: 91.7%; 95% CI, 88.0% to 94.8%; dyspnea: 21.1%; 95% CI, 13.2% to 30.3%). The chest CT findings exhibited no significant differences between the groups. CONCLUSION: Fever was found to be the most common symptom in COVID-19, and respiratory infection signs were also commonly present. Fever and dyspnea were less frequently observed in the patients diagnosed outside of Wuhan, which should be considered in COVID-19 screening programs. These results may be attributable to the earlier diagnosis of the disease and the younger age of patients outside of Wuhan although further analysis is needed. The role of chest CT in COVID-19 diagnosis is inconclusive based on this study.

positive: COVID-19 infection among asymptomatic and symptomatic pregnant women: Two weeks of confirmed presentations to an affiliated pair of New York City hospitals The novel coronavirus 2019, or COVID-19, infection has rapidly spread through the New York metropolitan area since the first reported case in the state on March 1, 2020. New York currently represents an epicenter for COVID-19 infection in the United States, with 84,735 cases reported as of April 2, 2020. We previously presented an early experience with seven COVID-positive patients in pregnancy, including two women who were diagnosed with COVID-19 following an asymptomatic initial presentation. We now describe a series of 43 test-confirmed cases of COVID-19 presenting to a pair of affiliated New York City hospitals over two weeks from March 13 to 27, 2020. Fourteen (32.6%) patients presented without any COVID-associated viral symptoms, and were identified either after developing symptoms during admission or following the implementation of universal testing for all obstetrical admissions on March 22. Of these, 10/14 (71.4%) developed symptoms or signs of COVID-19 infection over the course of their delivery admission or early after postpartum discharge. Of the other 29 (67.4%) patients who presented with symptomatic COVID-19 infection, three women ultimately required antenatal admission for viral symptoms, and an additional patient represented six days postpartum after a successful labor induction with worsening respiratory status that required oxygen supplementation. There were no confirmed cases of COVID-19 detected in neonates upon initial testing on the first day of life. Applying COVID-19 disease severity characteristics as described by Wu et al, 37 (86%) women possessed mild disease, four (9.3%) exhibited severe disease, and two (4.7%) developed critical disease; these percentages are similar to those described for non-pregnant adults with COVID-19 infections (about 80% mild, 15% severe, and 5% critical disease).

positive: Treatment of Acute Ischemic Stroke due to Large Vessel Occlusion With COVID-19: Experience From Paris BACKGROUND AND PURPOSE: Higher rates of strokes have been observed in patients with coronavirus disease 2019 (COVID-19), but data regarding the outcomes of COVID-19 patients suffering from acute ischemic stroke due to large vessel occlusion (LVO) are lacking. We report our initial experience in the treatment of acute ischemic stroke with LVO in patients with COVID-19. METHODS: All consecutive patients with COVID-19 with acute ischemic stroke due to LVO treated in our institution during the 6 first weeks of the COVID-19 outbreak were included. Baseline clinical and radiological findings, treatment, and short-term outcomes are reported. RESULTS: We identified 10 patients with confirmed COVID-19 treated for an acute ischemic stroke due to LVO. Eight were men, with a median age of 59.5 years. Seven had none or mild symptoms of COVID-19 at stroke onset. Median time from COVID-19 symptoms to stroke onset was 6 days. All patients had brain imaging within 3 hours from symptoms onset. Five patients had multi-territory LVO. Five received intravenous alteplase. All patients had mechanical thrombectomy. Nine patients achieved successful recanalization (mTICI2B-3), none experienced early neurological improvement, 4 had early cerebral reocclusion, and a total of 6 patients (60%) died in the hospital. CONCLUSIONS: Best medical care including early intravenous thrombolysis, and successful and prompt recanalization achieved with mechanical thrombectomy, resulted in poor outcomes in patients with COVID-19. Although our results require further confirmation, a different pharmacological approach (antiplatelet or other) should be investigated to take in account inflammatory and coagulation disorders associated with COVID-19.

positive: The clinical characteristics of pneumonia patients coinfected with 2019 novel coronavirus and influenza virus in Wuhan, China The outbreak of 2019 novel coronavirus (COVID‐19) infection emerged in Wuhan, China, in December 2019. Since then the novel coronavirus pneumonia disease has been spreading quickly and many countries and territories have been affected, with major outbreaks in China, South Korea, Italy, and Iran. Influenza virus has been known as a common pathogen in winter and it can cause pneumonia. It was found clinically that very few patients were diagnosed with both COVID‐19 and influenza virus. A total of 5 of the 115 patients confirmed with COVID‐19 were also diagnosed with influenza virus infection, with three cases being influenza A and two cases being influenza B. In this study, we describe the clinical characteristics of those patients who got infected with COVID‐19 as well as influenza virus. Common symptoms at onset of illness included fever (five [100%] patients), cough (five [100%] patients), shortness of breath (five [100%] patients), nasal tampon (three [60%] patients), pharyngalgia (three [60%] patients), myalgia (two [40%] patients), fatigue (two [40%] patients), headache (two [40%] patients), and expectoration (two [40%] patients). The laboratory results showed that compared to the normal values, the patients' lymphocytes were reduced (four [80%] patients), and liver functions alanine aminotransferase and aspartate aminotransferase (two [40%] patients and two [40%] patients) and C‐reactive protein (four [80%] patients) were increased when admitted to hospital. They stayed in the hospital for 14, 30, 17, 12, and 19 days (28.4 ± 7.02), respectively. The main complications for the patients were acute respiratory distress syndrome (one [20%] patients), acute liver injury (three [60%] patients), and diarrhea (two [40%] patients). All patients were given antiviral therapy (including oseltamivir), oxygen inhalation, and antibiotics. Three patients were treated with glucocorticoids including two treated with oral glucocorticoids. One of the five patients had transient hemostatic medication for hemoptysis. Fortunately, all patients did not need intensive care unit and were discharged from the hospital without death. In conclusion, those patients with both COVID‐19 and influenza virus infection did not appear to show a more severe condition because based on the laboratory findings, imaging studies, and patient prognosis, they showed similar clinical characteristics as those patients with COVID‐19 infection only. However, it is worth noting that the symptoms of nasal tampon and pharyngalgia may be more prone to appear for those coinfection patients.

positive: Improved Early Recognition of Coronavirus Disease-2019 (COVID-19): Single-Center Data from a Shanghai Screening Hospital. BACKGROUND In December 2019, an outbreak of a novel coronavirus disease (COVID-19; previously known as 2019-nCoV) was reported in Wuhan, Hubei province, China, which has subsequently affected more than 200 countries worldwide including Europe, North America, Oceania, Africa and other places. The number of infected people is rapidly increasing, while the diagnostic method of COVID-19 is only by nucleic acid testing. OBJECTIVE To explain the epidemiological characteristics, clinical features, imaging manifestations and to judge diagnostic value of COVID-19 by analyzing the clinical data of COVID-19 suspected and confirmed patients in a non-outbreak, Shanghai, China. To clarify the early epidemiology and clinical characteristics about COVID-19. METHODS Cross-sectional, single-center case reports of the 86 patients screened at Zhoupu Hospital in Pudong New District, Shanghai, China, from January 23 to February 16, 2020. Epidemiology, demography, clinical, laboratory and chest CTs were collected and analyzed. The screened patients were divided into COVID-19 and non-COVID-19 based on nucleic acid test results. RESULTS Of the 86 screened patients, 11 were confirmed (12.8%) by nucleic acid testing (mean age 40.73 ± 11.32, 5 males). No significant differences were found in clinical symptoms including fever, cough, dyspnea, sore throat, and fatigue (P > 0.05). No statistical difference was observed in plasma C-reactive protein (CRP) between the two groups (COVID-19 and non-COVID-19 ) of patients (P = 0.402), while the white blood cell count and lymphocyte count of the confirmed patients were slightly lower than those of the suspected patients (P < 0.05). Some non-COVID-19 chest CTs also showed subpleural lesions, such as ground-glass opacities (GGO) combined with bronchiectasis; or halo nodules distributed under the pleura with focal GGO; consolidation of subpleural distribution or combined with air bronchi sign and vascular bundle sign, etc. CONCLUSION The early clinical manifestations and imaging findings of COVID-19 are not characteristic in non-outbreak areas. Etiological testing should be performed as early as possible for clinically suspected patients.

positive: Neurologic manifestations in hospitalized patients with COVID-19: The ALBACOVID registry. OBJECTIVE The coronavirus disease 2019 (COVID-19) has spread worldwide since December 2019. Neurological symptoms have been reported as part of the clinical spectrum of the disease. We aim to determine whether neurological manifestations are common in hospitalized COVID-19 patients and to describe their main characteristics. METHODS We systematically review all patients diagnosed with COVID-19 admitted to hospital in a Spanish population during March 2020. Demographic characteristics, systemic and neurological clinical manifestations, and complementary tests were analyzed. RESULTS Of 841 patients hospitalized with COVID-19 (mean age 66.4 years, 56.2% men) 57.4% developed some form of neurological symptom. Nonspecific symptoms such as myalgias (17.2%), headache (14.1%), and dizziness (6.1%) were present mostly in the early stages of infection. Anosmia (4.9%) and dysgeusia (6.2%) tended to occur early (60% as the first clinical manifestation) and were more frequent in less severe cases. Disorders of consciousness occurred commonly (19.6%), mostly in older patients and in severe and advanced COVID-19 stages. Myopathy (3.1%), dysautonomia (2.5%), cerebrovascular diseases (1.7%), seizures (0.7%), movement disorders (0.7%), encephalitis (n=1), Guillain-Barré syndrome (n=1), and optic neuritis (n=1) were also reported, but less frequent. Neurological complications were the main cause of death in 4.1% of all deceased study subjects. CONCLUSIONS Neurological manifestations are common in hospitalized COVID-19 patients. In our series, more than half of patients presented some form of neurological symptom. Clinicians need to maintain close neurological surveillance for prompt recognition of these complications. The investigation of the mechanisms and emerging consequences of SARS-CoV-2 neurological involvement require further studies.

positive: Clinical features of COVID-19 in elderly patients: A comparison with young and middle-aged patients Abstract Background Due to the general susceptibility of new coronaviruses, the clinical characteristics and outcomes of elderly and young patients may be different. Objective To analyze the clinical characteristics of elderly patients with 2019 new-type coronavirus pneumonia (COVID-19). Methods This is a retrospective study of patients with new coronavirus pneumonia (COVID-19) who were hospitalized in Hainan Provincial People's Hospital from January 15, 2020 to February 18, 2020. Compare the clinical characteristics of elderly with Young and Middle-aged patients. Results A total of 56 patients were enrolled 18 elderly patients (32.14%), and 38 young and middle-aged patients (67.86%). The most common symptoms in both groups were fever, followed by cough and sputum. Four patients in the elderly group received negative pressure ICU for mechanical ventilation, and five patients in the young and middle-aged group. One patient died in the elderly group (5.56%), and two patients died in the young and middle-aged group (5.26%). The PSI score of the elderly group was higher than that of the young and middle-aged group (P < 0.001). The proportion of patients with PSI grades IV and V was significantly higher in the elderly group than in the young and middle-aged group (P < 0.05). The proportion of multiple lobe involvement in the elderly group was higher than that in the young and middle-aged group (P < 0.001), and there was no difference in single lobe lesions between the two groups. The proportion of lymphocytes in the elderly group was significantly lower than that in the young and middle-aged group (P < 0.001), and the C-reactive protein was significantly higher in the young group (P < 0.001). The Lopinavir and Ritonavir Tablets, Chinese medicine, oxygen therapy, and mechanical ventilation were statistically different in the elderly group and the young and middle-aged group, and the P values were all <0.05. Interpretation The mortality of elderly patients with COVID-19 is higher than that of young and middle-aged patients, and the proportion of patients with PSI grade IV and V is significantly higher than that of young and middle-aged patients. Elderly patients with COVID-19 are more likely to progress to severe disease.

positive: Coexistence of Covid-19 and Acute Ischemic Stroke Report of Four Cases Abstract Coronaviruses are revealed to target the human respiratory system mainly. However, they also have neuro-invasive abilities and might spread from the respiratory system to the central nervous system. Herein, we report four patients with COVID-19 simultaneously diagnosed with acute ischemic stroke. There were four stroke cases with simultaneously diagnosis of Covid-19 till the April 14, 2020 in the city of Sakarya, Turkey. They were aged between 45 to 77 years. All four cases were likely to have contracted the virus in Sakarya. The patients had all commonly reported symptoms of Covid-19. Three patients have elevated D-dimer levels, and two of them had high C-reactive protein (CRP) levels. They were managed symptomatically for both the infection and the stroke. Our findings suggest that ischemic cerebrovascular diseases may simultaneously develop in the course of Covid-19 independently of the critical disease process. Increased inflammation predicted by CRP and D-dimer levels may play a role in the formation of ischemia. In particular, elder patients with prothrombotic risk factors should also be considered for the signs of cerebrovascular events in addition to infectious symptoms.

positive: EARLY DETECTION OF COVID-19 Since SARS-Cov-2 epidemic appeared in Wuhan China, it became challenge for health authorities to counter Covid-19 epidemic. Early evaluation of suspects, screening for Covid-19 and management posed challenge to health authorities especially in developing countries which were not ready to cope with it. Early mild symptoms appeared during course of disease provide a chance to early detect Covid-19. We use retrospective methodology to collect available data on early sign and symptoms of Covid-19 through accessing World Health Organization (WHO) webpages, New England Journal of Medicine (NEJM), Nature Journal, Journal of American Medical Association (JAMA) network, British Medical Journal (BJM), Lancet and other world renowned journal publications to establish a relationship of early symptoms for detection of Covid-19. Data of 2707 Covid-19 laboratory confirmed cases was collected and analyzed for early signs. Available data was categorized into physical and blood biomarkers. This categorized data was assessed for scoring early detection of Covid-19 by scoring Hashmi-Asif Covid-19 formula. Each characteristic was given a score in Hashmi-Asif Covid-19 chart with maximum score of 28. Scoring 16 on chart means Covid-19 will fully develop in near future. Correlation of each sign and symptoms with development of Covid-19 in formula showed significant correlation assessed by Pearson correlation and Spearman Correlation coefficient (rho) showed significant correlation of development of Covid-19 with fever 64.11% (P=0.001), cough 65% and dry mucus 19.67% equally sensitive (P=0.000), leukopenia 19.06% (P=0.006), lymphopenia 52.93% (P=0.005), thrombopenia 19.1% (P=0.013), elevated Aspartate aminotransferase 12.79% (P=0.007) and elevated Alanine aminotransferase 11.34% (P=0.006). Chart can sense Covid-19 progression 72-96 hours earlier compared to usual course of disease and detection by standard method. Chart for early detection provides early quarantine decision to reduce disease spread and give ample time for intervening disease progression to reduce morbidity time due to Covid-19

positive: Comparison of Epidemiological Variations in COVID-19 Patients Inside and Outside of China—A Meta-Analysis The objective of this study is to compare the epidemiological variations in COVID-19 patients reported in studies from inside and outside of China. We selected COVID-19 observational studies from eight countries, including, China, Italy, Australia, Canada, Korea, Taiwan, Singapore, and the USA, comprising a total of 13 studies and performed a meta-analysis for age, gender, fatality rate, and clinical symptoms of fever, cough, shortness of breath, and diarrhea. The meta-analysis shows that there are differences in symptoms and other characteristics reported by the patients of COVID-19 inside and outside China. Patients in China have a higher proportion of fever, cough, and shortness of breath as compared to patients outside of China. However, we found the opposite results for the gastrointestinal symptoms such as Diarrhea. Patients outside of China have a significantly higher proportion of Diarrhea as compared to patients within China. We also observed gender disparity among our studies, with the male population being more susceptible than the female population. Moreover, the analysis suggests that the fatality rate in China is relatively lower as compared to the fatality rate in other countries. These findings also suggest that the clinical symptoms of COVID-19 should not be generalized to fever, shortness of breath, and cough only but other symptoms such as diarrhea are also prevalent in patients with COVID-19.

positive: Risk factors for disease progression in COVID-19 patients BACKGROUND: Coronavirus disease (COVID-19) is rapidly spreading worldwide. Although 10-20% of patients with COVID-19 have severe symptoms, little is known about the risk factors related to the aggravation of COVID-19 symptoms from asymptomatic or mild to severe disease states. METHODS: This retrospective study included 211 patients who were asymptomatic or with mild presentations of COVID-19. We evaluated the differences in demographic and clinical data between the cured (discharged to home) and transferred (aggravated to severe-stage COVID-19) groups. RESULTS: A multivariate logistic analysis showed that body temperature, chills, initial chest X-ray findings, and the presence of diabetes were significantly associated with predicting the progression to severe stage of COVID-19 (p < 0.05). The odds ratio of transfer in patients with COVID-19 increased by 12.7-fold for abnormal findings such as haziness or consolidation in initial chest X-ray, 6.32-fold for initial symptom of chills, and 64.1-fold for diabetes. CONCLUSIONS: Even if patients are asymptomatic or have mild symptoms, clinicians should closely observe patients with COVID-19 presenting with chills, body temperature > 37.5 °C, findings of pneumonia in chest X-ray, or diabetes.

positive: The importance of olfactory and gustatory disorders as early symptoms of coronavirus disease (COVID-19)

positive: 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.

positive: Loss of smell and taste in combination with other symptoms is a strong predictor of COVID-19 infection Importance: A strategy for preventing further spread of the ongoing COVID-19 epidemic is to detect infections and isolate infected individuals without the need of extensive bio-specimen testing. Objectives: Here we investigate the prevalence of loss of smell and taste among COVID-19 diagnosed individuals and we identify the combination of symptoms, besides loss of smell and taste, most likely to correspond to a positive COVID-19 diagnosis in non-severe cases. Design: Community survey. Setting and Participants: Subscribers of RADAR COVID-19, an app that was launched for use among the UK general population asking about COVID-19 symptoms. Main Exposure: Loss of smell and taste. Main Outcome Measures: COVID-19. Results: Between 24 and 29 March 2020, 1,573,103 individuals reported their symptoms via the app; 26% reported suffering from one or more symptoms of COVID-19. Of those, n=1702 reported having had a RT-PCR COVID-19 test and gave full report on symptoms including loss of smell and taste; 579 were positive and 1123 negative. In this subset, we find that loss of smell and taste were present in 59% of COVID-19 positive individuals compared to 18% of those negative to the test, yielding an odds ratio (OR) of COVID-19 diagnosis of OR[95%CI]=6.59[5.25; 8.27], P= 1.90x10-59 . We also find that a combination of loss of smell and taste, fever, persistent cough, fatigue, diarrhoea, abdominal pain and loss of appetite is predictive of COVID-19 positive test with sensitivity 0.54[0.44; 0.63], specificity 0.86[0.80; 0.90], ROC-AUC 0.77[0.72; 0.82] in the test set, and cross-validation ROC-AUC 0.75[0.72; 0.77]. When applied to the 410,598 individuals reporting symptoms but not formally tested, our model predicted that 13.06%[12.97%;13.15] of these might have been already infected by the virus. Conclusions and Relevance: Our study suggests that loss of taste and smell is a strong predictor of having been infected by the COVID-19 virus. Also, the combination of symptoms that could be used to identify and isolate individuals includes anosmia, fever, persistent cough, diarrhoea, fatigue, abdominal pain and loss of appetite. This is particularly relevant to healthcare and other key workers in constant contact with the public who have not yet been tested for COVID-19.

positive: COVID‐19 and its effects on the digestive system and endoscopy practice The Coronavirus Disease 2019 (COVID‐19) is a respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and has been classified as a pandemic by the World Health Organization in March 2020. Several studies have demonstrated that the gastrointestinal (GI) tract is also a potential route. As the pandemic is continuously evolving, and more data are made available, this article highlights the best evidence and practices regarding the effects of the SARS‐CoV‐2 virus relevant to GI practice. Published clinical studies have supported that SARS‐CoV‐2 affects the GI tract and the liver. The largest published dataset comprised of 4243 patients and showed a pooled prevalence of GI symptoms at 17.6%. GI symptoms varied and usually preceded pulmonary symptoms by 1–2 days. These include anorexia (26.8%), nausea and vomiting (10.2%), diarrhea (12.5%), and abdominal pain (9.2%). Incidence of liver injury ranges from 15 to 53%. Evidence shows that the severity of COVID‐19 infection is compounded by its effects on nutrition, most especially for the critically ill. As such, nutrition societies have recommended optimization of oral diets and oral nutritional supplements followed by early enteral nutrition if nutritional targets are not met, and parenteral nutrition in the distal end of the spectrum. In addition to possible fecal–oral transmission, GI endoscopy procedures, which are considered to be aerosol‐generating procedures, contribute to increased risk to GI health‐care professionals. Infection prevention measures and guidelines are essential in protecting both patients and personnel.

positive: 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.

positive: Clinical and radiological features of novel coronavirus pneumonia Recently, COVID-19 has spread in more than 100 countries and regions around the world, raising grave global concerns. COVID-19 transmits mainly through respiratory droplets and close contacts, causing cluster infections. The symptoms are dominantly fever, fatigue, and dry cough, and can be complicated with tiredness, sore throat, and headache. A few patients have symptoms such as stuffy nose, runny nose, and diarrhea. The severe disease can progress rapidly into the acute respiratory distress syndrome (ARDS). Reverse transcription polymerase chain reaction (RT-PCR) and Next-generation sequencing (NGS) are the gold standard for diagnosing COVID-19. Chest imaging is used for cross validation. Chest CT is highly recommended as the preferred imaging diagnosis method for COVID-19 due to its high density and high spatial resolution. The common CT manifestation of COVID-19 includes multiple segmental ground glass opacities (GGOs) distributed dominantly in extrapulmonary/subpleural zones and along bronchovascular bundles with crazy paving sign and interlobular septal thickening and consolidation. Pleural effusion or mediastinal lymphadenopathy is rarely seen. In CT imaging, COVID-19 manifests differently in its various stages including the early stage, the progression (consolidation) stage, and the absorption stage. In its early stage, it manifests as scattered flaky GGOs in various sizes, dominated by peripheral pulmonary zone/subpleural distributions. In the progression state, GGOs increase in number and/or size, and lung consolidations may become visible. The main manifestation in the absorption stage is interstitial change of both lungs, such as fibrous cords and reticular opacities. Differentiation between COVID-19 pneumonia and other viral pneumonias are also analyzed. Thus, CT examination can help reduce false negatives of nucleic acid tests.

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

positive: Clinical and CT imaging features of the COVID-19 pneumonia: Focus on pregnant women and children Abstract Background The ongoing outbreak of COVID-19 pneumonia is globally concerning. We aimed to investigate the clinical and CT features in the pregnant women and children with this disease, which have not been well reported. Methods Clinical and CT data of 59 patients with COVID-19 from January 27 to February 14, 2020 were retrospectively reviewed, including 14 laboratory-confirmed non-pregnant adults, 16 laboratory-confirmed and 25 clinically-diagnosed pregnant women, and 4 laboratory-confirmed children. The clinical and CT features were analyzed and compared. Findings Compared with the non-pregnant adults group (n = 14), initial normal body temperature (9 [56%] and 16 [64%]), leukocytosis (8 [50%] and 9 [36%]) and elevated neutrophil ratio (14 [88%] and 20 [80%]), and lymphopenia (9 [56%] and 16 [64%]) were more common in the laboratory-confirmed (n = 16) and clinically-diagnosed (n = 25) pregnant groups. Totally 614 lesions were detected with predominantly peripheral and bilateral distributions in 54 (98%) and 37 (67%) patients, respectively. Pure ground-glass opacity (GGO) was the predominant presence in 94/131 (72%) lesions for the non-pregnant adults. Mixed consolidation and complete consolidation were more common in the laboratory-confirmed (70/161 [43%]) and clinically-diagnosed (153/322 [48%]) pregnant groups than 37/131 (28%) in the non-pregnant adults (P = 0·007, P < 0·001). GGO with reticulation was less common in 9/161 (6%) and 16/322 (5%) lesions for the two pregnant groups than 24/131 (18%) for the non-pregnant adults (P = 0·001, P < 0·001). The pulmonary involvement in children with COVID-19 was mild with a focal GGO or consolidation. Twenty-three patients underwent follow-up CT, revealing progression in 9/13 (69%) at 3 days whereas improvement in 8/10 (80%) at 6–9 days after initial CT scans. Interpretation Atypical clinical findings of pregnant women with COVID-19 could increase the difficulty in initial identification. Consolidation was more common in the pregnant groups. The clinically-diagnosed cases were vulnerable to more pulmonary involvement. CT was the modality of choice for early detection, severity assessment, and timely therapeutic effects evaluation for the cases with epidemic and clinical features of COVID-19 with or without laboratory confirmation. The exposure history and clinical symptoms were more helpful for screening in children versus chest CT.

positive: Early Clinical and CT Manifestations of Coronavirus Disease 2019 (COVID-19) Pneumonia. OBJECTIVE. The purpose of this study was to investigate early clinical and CT manifestations of coronavirus disease (COVID-19) pneumonia. MATERIALS AND METHODS. Patients with COVID-19 pneumonia confirmed by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test (reverse transcription-polymerase chain reaction) were enrolled in this retrospective study. The clinical manifestations, laboratory results, and CT findings were evaluated. RESULTS. One hundred eight patients (38 men, 70 women; age range, 21-90 years) were included in the study. The clinical manifestations were fever in 94 of 108 (87%) patients, dry cough in 65 (60%), and fatigue in 42 (39%). The laboratory results were normal WBC count in 97 (90%) patients and normal or reduced lymphocyte count in 65 (60%). High-sensitivity C-reactive protein level was elevated in 107 (99%) patients. The distribution of involved lobes was one lobe in 38 (35%) patients, two or three lobes in 24 (22%), and four or five lobes in 46 (43%). The major involvement was peripheral (97 patients [90%]), and the common lesion shape was patchy (93 patients [86%]). Sixty-five (60%) patients had ground-glass opacity (GGO), and 44 (41%) had GGO with consolidation. The size of lesions varied from smaller than 1 cm (10 patients [9%]) to larger than 3 cm (56 patients [52%]). Vascular thickening (86 patients [80%]), crazy paving pattern (43 patients [40%]), air bronchogram sign (52 patients [48%]), and halo sign (69 [64%]) were also observed in this study. CONCLUSION. The early clinical and laboratory findings of COVID-19 pneumonia are low to midgrade fever, dry cough, and fatigue with normal WBC count, reduced lymphocyte count, and elevated high-sensitivity C-reactive protein level. The early CT findings are patchy GGO with or without consolidation involving multiple lobes, mainly in the peripheral zone, accompanied by halo sign, vascular thickening, crazy paving pattern, or air bronchogram sign.

positive: Clinical characteristics and outcomes of COVID-19 patients with gastrointestinal symptoms admitted to Jianghan Fangcang Shelter Hospital in Wuhan, China OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a health emergency worldwide, and gastrointestinal (GI) symptoms are increasingly reported in COVID-19 patients. However, sample size was small and the incidence of GI symptoms in patients was variable across studies, and the correlation between these symptoms and clinical outcomes remains incompletely understood. The objective of this study is to compare clinical characteristics and outcomes between patients with and without GI symptoms admitted to Jianghan Fangcang Shelter Hospital in Wuhan. METHODS: All patients admitted to Jianghan Fangcang Shelter Hospital were evaluated. Data on epidemiological and clinical characteristics, laboratory findings, treatment procedures, and clinical outcomes were retrieved from electronic medical records. RESULTS: This retrospective study recruited 1320 COVID-19 patients admitted to hospital from February 5, 2020, to March 9, 2020. On the basis of the presence of GI symptoms, the sample was divided into a GI group (n=192) and a non-GI group (n=1128). The most common GI symptoms were diarrhea (8.1%), anorexia (4.7%), and nausea and vomiting (4.3%). The risk of clinical deterioration was significantly higher in the GI group than in the non-GI group (15.6% vs. 10.1%, p=0.032). GI symptoms (p=0.045), male gender (p<0.001), and increased C-reactive protein (p=0.008) were independent risk factors for clinical worsening. CONCLUSION: The risk of clinical deterioration was significantly higher in the GI group. Furthermore, potential risk factors for developing GI symptoms, male gender, and increased C-reactive protein can help clinicians predict clinical outcomes in COVID-19 patients. This article is protected by copyright. All rights reserved.

positive: Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases BACKGROUND: The cutaneous manifestations of COVID-19 disease are poorly characterized. OBJECTIVES: To describe the cutaneous manifestations of COVID-19 disease and to relate them to other clinical findings. METHODS: We carried out a nationwide case collection survey of images and clinical data. Using a consensus we described five clinical patterns. We later described the association of these patterns with patient demographics, the timing in relation to symptoms of the disease, the severity and the prognosis. RESULTS: The lesions may be classified as acral areas of erythema with vesicles or pustules (pseudo-chilblain) (19%), other vesicular eruptions (9%), urticarial lesions (19%), maculopapular eruptions (47%) and livedo or necrosis (6%). Vesicular eruptions appear early in the course of the disease (15% before other symptoms). The pseudo-chilblain pattern frequently appears late in the evolution of the COVID-19 disease (59% after other symptoms), while the rest tend to appear with other symptoms of COVID-19. The severity of COVID-19 shows a gradient from less severe disease in acral lesions to more severe in the latter groups. The results are similar for confirmed and suspected cases, in terms of both clinical and epidemiological findings. Alternative diagnoses are discussed but seem unlikely for the most specific patterns (pseudo-chilblain and vesicular). CONCLUSIONS: We provide a description of the cutaneous manifestations associated with COVID-19 infection. These may help clinicians approach patients with the disease and recognize cases presenting with few symptoms. What is already known about this topic? Previous descriptions of cutaneous manifestations of COVID-19 were case reports and mostly lacked illustrations. What does this study add? We describe a large, representative sample of patients with unexplained skin manifestations and a diagnosis of COVID-19, using a consensus method to define morphological patterns associated with COVID-19. We describe five clinical patterns associated with different patient demographics, timing and prognosis, and provide illustrations of these patterns to allow for easy recognition.

positive: Rapid asymptomatic transmission of COVID-19 during the incubation period demonstrating strong infectivity in a cluster of youngsters aged 16-23 years outside Wuhan and characteristics of young patients with COVID-19: A prospective contact-tracing study Summary Background The outbreak of coronavirus-disease-2019 (COVID-19) has rapidly spread to many places outside Wuhan. Previous studies on COVID-19 mostly included older hospitalized-adults. Little information on infectivity among and characteristics of youngsters with COVID-19 is available. Methods A cluster of 22 close-contacts of a 22-year-old male (Patient-Index) including youngsters with laboratory-confirmed COVID-19 and hospitalized close-contacts testing negative for severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) in Anhui Province, China was prospectively-traced. Results Since January 23, 2020, we enrolled a cluster of eight youngsters with COVID-19 (median age [range], 22 [16–23] years; six males) originating from Patient-Index returning from Wuhan to Hefei on January 19. Patient-Index visited his 16-year-old female cousin in the evening on his return, and met 15 previous classmates in a get-together on January 21. He reported being totally asymptomatic and were described by all his contacts as healthy on January 19-21. His very first symptoms were itchy eyes and fever developed at noon and in the afternoon on January 22, respectively. Seven youngsters (his cousin and six classmates) became infected with COVID-19 after a-few-hour-contact with Patient-Index. None of the patients and contacts had visited Wuhan (except Patient-Index), or had any exposure to wet-markets, wild-animals, or medical-institutes within three months. For affected youngsters, the median incubation-period was 2 days (range, 1–4). The median serial-interval was 1 day (range, 0–4). Half or more of the eight COVID-19-infected youngsters had fever, cough, sputum production, nasal congestion, and fatigue on admission. All patients had mild conditions. Six patients developed pneumonia (all mild; one bilateral) on admission. As of February 20, four patients were discharged. Conclusions SARS-CoV-2-infection presented strong infectivity during the incubation-period with rapid transmission in this cluster of youngsters outside Wuhan. COVID-19 developed in these youngsters had fast onset and various nonspecific atypical manifestations, and were much milder than in older patients as previously reported.

positive: 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/m2 (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/m2 and a known history of type 2 diabetes were independent risk factors of severe illness in patients with COVID-19.

positive: Imaging and clinical features of patients with 2019 novel coronavirus SARS-CoV-2 BACKGROUND: The pneumonia caused by the 2019 novel coronavirus (SARS-CoV-2, also called 2019-nCoV) recently break out in Wuhan, China, and was named as COVID-19. With the spread of the disease, similar cases have also been confirmed in other regions of China. We aimed to report the imaging and clinical characteristics of these patients infected with SARS-CoV-2 in Guangzhou, China. METHODS: All patients with laboratory-identified SARS-CoV-2 infection by real-time polymerase chain reaction (PCR) were collected between January 23, 2020, and February 4, 2020, in a designated hospital (Guangzhou Eighth People’s Hospital). This analysis included 90 patients (39 men and 51 women; median age, 50 years (age range, 18–86 years). All the included SARS-CoV-2-infected patients underwent non-contrast enhanced chest computed tomography (CT). We analyzed the clinical characteristics of the patients, as well as the distribution characteristics, pattern, morphology, and accompanying manifestations of lung lesions. In addition, after 1–6 days (mean 3.5 days), follow-up chest CT images were evaluated to assess radiological evolution. FINDINGS: The majority of infected patients had a history of exposure in Wuhan or to infected patients and mostly presented with fever and cough. More than half of the patients presented bilateral, multifocal lung lesions, with peripheral distribution, and 53 (59%) patients had more than two lobes involved. Of all included patients, COVID-19 pneumonia presented with ground glass opacities in 65 (72%), consolidation in 12 (13%), crazy paving pattern in 11 (12%), interlobular thickening in 33 (37%), adjacent pleura thickening in 50 (56%), and linear opacities combined in 55 (61%). Pleural effusion, pericardial effusion, and lymphadenopathy were uncommon findings. In addition, baseline chest CT did not show any abnormalities in 21 patients (23%), but 3 patients presented bilateral ground glass opacities on the second CT after 3–4 days. CONCLUSION: SARS-CoV-2 infection can be confirmed based on the patient’s history, clinical manifestations, imaging characteristics, and laboratory tests. Chest CT examination plays an important role in the initial diagnosis of the novel coronavirus pneumonia. Multiple patchy ground glass opacities in bilateral multiple lobular with periphery distribution are typical chest CT imaging features of the COVID-19 pneumonia.

positive: Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms OBJECTIVE: The SARS-CoV-2-infected disease (COVID-19) outbreak is a major threat to human beings. Previous studies mainly focused on Wuhan and typical symptoms. We analysed 74 confirmed COVID-19 cases with GI symptoms in the Zhejiang province to determine epidemiological, clinical and virological characteristics. DESIGN: COVID-19 hospital patients were admitted in the Zhejiang province from 17 January 2020 to 8 February 2020. Epidemiological, demographic, clinical, laboratory, management and outcome data of patients with GI symptoms were analysed using multivariate analysis for risk of severe/critical type. Bioinformatics were used to analyse features of SARS-CoV-2 from Zhejiang province. RESULTS: Among enrolled 651 patients, 74 (11.4%) presented with at least one GI symptom (nausea, vomiting or diarrhoea), average age of 46.14 years, 4-day incubation period and 10.8% had pre-existing liver disease. Of patients with COVID-19 with GI symptoms, 17 (22.97%) and 23 (31.08%) had severe/critical types and family clustering, respectively, significantly higher than those without GI symptoms, 47 (8.14%) and 118 (20.45%). Of patients with COVID-19 with GI symptoms, 29 (39.19%), 23 (31.08%), 8 (10.81%) and 16 (21.62%) had significantly higher rates of fever >38.5°C, fatigue, shortness of breath and headache, respectively. Low-dose glucocorticoids and antibiotics were administered to 14.86% and 41.89% of patients, respectively. Sputum production and increased lactate dehydrogenase/glucose levels were risk factors for severe/critical type. Bioinformatics showed sequence mutation of SARS-CoV-2 with m6A methylation and changed binding capacity with ACE2. CONCLUSION: We report COVID-19 cases with GI symptoms with novel features outside Wuhan. Attention to patients with COVID-19 with non-classic symptoms should increase to protect health providers.

positive: Epidemiological and initial clinical characteristics of patients with family aggregation of COVID-19 Abstract Background Since December 2019, a new outbreak of the coronavirus disease 2019 (COVID-19) in Wuhan (Hubei, China) and rapidly spread throughout China, however, confirmed cases are still increasing worldwide. Objectives To investigate the epidemiological history and initial clinical characteristics of 10 patients with family aggregation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Western Chongqing, China. Study design Ten patients positive for SARS-CoV-2 nucleic acid detection by real time Reverse Transcription-Polymerase Chain Reaction (RT-PCR), were collected from The People's Hospital of Dazu District, Chongqing. Epidemiological data and laboratory and imaging results were collected on the first day of admission, and analyzed based on the Diagnosis and Treatment Guideline for COVID-19 (5th edition, China). Results Of the 10 cases, case A had a history of a temporary stay in Wuhan and transmitted the virus to the others through family gathering, living together, and sharing vehicles. The average age was 56.5 years (± 11.16), six patients were males, and the incubation period was 2–14 days. Dry cough was the main symptom, followed by fever and fatigue. Most patients were clinically classified as ordinary-type, with three cases being severe-type. Chest computed tomography results were nonspecific, mainly with ground-glass attenuation and/or shadow images. Extensive lesion distribution was seen in severe cases. CD4+ lymphocyte counts were 61, 180, and 348 cells/uL in severe-type patients, respectively. Notably, viral nucleic acid values in nasopharyngeal swabs were lower (19, 25, and 26) than those of ordinary-type patients, suggesting a higher viral load. Neutrophil-lymphocyte ratio (NLR) was also higher in severe-type patients Conclusions Initial examination results of lower CD4+ lymphocyte counts and RT-PCR-CT values coupled with higher NLR may indicate the severity of COVID-19 infection for these family clusters.

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

positive: Uncommon presentation of COVID-19: Gastrointestinal bleeding The COVID-19 outbreak has become a pandemic that is threatening global health. The typical clinical manifestations were fever, cough, dyspnea, and myalgia or fatigue. Digestive symptoms such as nausea, vomiting, diarrhea, abdominal pain usually accompany respiratory symptoms. However gastrointestinal bleeding as the first symptom is not reported. Here we reported a case of COVID-19 with gastrointestinal bleeding as the initial symptom to the emergency department with a real-time reverse transcriptase polymerase chain reaction test positive, and normal thorax tomography. The case demonstrate that; clinicians should be alerted to patients about COVID-19 when referring to atypical symptoms and every patient undergoing endoscopy should be considered potentially infected or can infect others.

positive: Coronavirus disease 2019 presenting with conjunctivitis as the first symptom

positive: 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.

positive: COVID-19: Epidemiology, Evolution, and Cross-Disciplinary Perspectives The recent outbreak of COVID-19 in Wuhan turned into a public health emergency of international concern. With no antiviral drugs nor vaccines, and the presence of carriers without obvious symptoms, traditional public health intervention measures are significantly less effective. Here, we report the epidemiological and virological characteristics of the COVID-19 outbreak. Originated in bats, 2019-nCoV/ severe acute respiratory syndrome coronavirus (SARS-CoV)-2 likely experienced adaptive evolution in intermediate hosts before transfer to humans at a concentrated source of transmission. Similarities of receptor sequence binding to 2019-nCoV between humans and animals suggest a low species barrier for transmission of the virus to farm animals. We propose, based on the One Health model, that veterinarians and animal specialists should be involved in a cross-disciplinary collaboration in the fight against this epidemic.

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

positive: 2019 Novel Coronavirus (COVID-19) Pneumonia: Serial Computed Tomography Findings From December 2019, Coronavirus disease 2019 (COVID-19) pneumonia (formerly known as the 2019 novel Coronavirus [2019-nCoV]) broke out in Wuhan, China. In this study, we present serial CT findings in a 40-year-old female patient with COVID-19 pneumonia who presented with the symptoms of fever, chest tightness, and fatigue. She was diagnosed with COVID-19 infection confirmed by real-time reverse-transcriptase-polymerase chain reaction. CT showed rapidly progressing peripheral consolidations and ground-glass opacities in both lungs. After treatment, the lesions were shown to be almost absorbed leaving the fibrous lesions.

positive: Urticarial eruption in coronavirus disease 2019 infection: a case report in Tangerang, Indonesia We have read with great interest the articles regarding cutaneous manifestations in Coronavirus Disease 2019 (COVID-19) infection. Studies showed 20.4% of COVID-19 patients developed cutaneous manifestations and might be the only presenting symptom.(1) To date, previous cases reported urticaria as one of the cutaneous manifestations in COVID-19.(2)(1)(3)(4) This atypical symptom might lead to misdiagnosis, delayed diagnosis, and virus transmission, especially in countries where cutaneous manifestation of COVID-19 has not been reported widely such as in Indonesia. We would like to report a case of urticaria in COVID-19-positive non-ICU hospitalized patient from Indonesia to bring awareness to its cutaneous manifestations.

positive: Comment on “Cutaneous manifestations in COVID‐19: a first perspective ” by Recalcati S Since the coronavirus disease 2019 (COVID 19) outbreak was first reported in the Chinese city of Wuhan on December 31, 2019, it has stricken more than 1,000,000 persons worldwide, of whom over 50,000 have died (1). Having been infected by severe acute respiratory syndrome coronavirus 2 (SARS‐COV‐2), patients with COVID‐19 mainly present with fever and respiratory symptoms (2). Isolated sudden onset anosmia has also frequently been reported (3). Less frequently, rhinorrhea, diarrhoea and dysgeusia may be associated. While only a few reports have evoked cutaneous manifestations (4), we read with interest an initial study on the topic entitled “Cutaneous manifestations in COVID‐19: a first perspective ” by Recalcati S. (5).

positive: Clinical analysis of pregnant women with 2019 novel coronavirus pneumonia The aim is to evaluate pregnant women infected with coronavirus disease 2019 (COVID‐19) and provide help for clinical prevention and treatment. All five cases of pregnant women confirmed COVID‐19 were collected among patients who admitted to the Maternal and Child Hospital of Hubei Province between January 20 and February 10, 2020. All patients, aging from 25 to 31 years old, had the gestational week from 38th weeks to 41st weeks. All pregnant women did not have an antepartum fever but developed a low‐grade fever (37.5℃‐38.5℃) within 24 hours after delivery. All patients had normal liver and renal function, two patients had elevated plasma levels of the myocardial enzyme. Unusual chest imaging manifestations, featured with ground‐grass opacity, were frequently observed in bilateral (three cases) or unilateral lobe (two cases) by computed tomography (CT) scan. All labors smoothly processed, the Apgar scores were 10 points 1 and 5 minutes after delivery, no complications were observed in the newborn. Pregnancy and perinatal outcomes of patients with COVID‐19 should receive more attention. It is probable that pregnant women diagnosed with COVID‐19 have no fever before delivery. Their primary initial manifestations were merely low‐grade postpartum fever or mild respiratory symptoms. Therefore, the protective measures are necessary on admission; the instant CT scan and real‐time reverse‐transcriptase polymerase‐chain‐reaction assay should be helpful in early diagnosis and avoid cross‐infection on the occasion that patients have fever and other respiratory signs.

positive: GI symptoms as early signs of COVID-19 in hospitalised Italian patients

positive: Olfactory and Gustatory Dysfunction as an Early Identifier of COVID-19 in Adults and Children: An International Multicenter Study OBJECTIVE: To evaluate the prevalence and characteristics of olfactory or gustatory dysfunction in coronavirus disease 2019 (COVID-19) patients. STUDY DESIGN: Multicenter case series. SETTING: Five tertiary care hospitals (3 in China, 1 in France, 1 in Germany). SUBJECTS AND METHODS: In total, 394 polymerase chain reaction (PCR)–confirmed COVID-19-positive patients were screened, and those with olfactory or gustatory dysfunction were included. Data including demographics, COVID-19 severity, patient outcome, and the incidence and degree of olfactory and/or gustatory dysfunction were collected and analyzed. The Questionnaire of Olfactory Disorders (QOD) and visual analog scale (VAS) were used to quantify olfactory and gustatory dysfunction, respectively. All subjects at 1 hospital (Shanghai) without subjective olfactory complaints underwent objective testing. RESULTS: Of 394 screened subjects, 161 (41%) reported olfactory and/or gustatory dysfunction and were included. Incidence of olfactory and/or gustatory disorders in Chinese (n = 239), German (n = 39), and French (n = 116) cohorts was 32%, 69%, and 49%, respectively. The median age of included subjects was 39 years, 92 of 161 (57%) were male, and 10 of 161 (6%) were children. Of included subjects, 10% had only olfactory or gustatory symptoms, and 19% had olfactory and/or gustatory complaints prior to any other COVID-19 symptom. Of subjects with objective olfactory testing, 10 of 90 demonstrated abnormal chemosensory function despite reporting normal subjective olfaction. Forty-three percent (44/102) of subjects with follow-up showed symptomatic improvement in olfaction or gustation. CONCLUSIONS: Olfactory and/or gustatory disorders may represent early or isolated symptoms of severe acute respiratory syndrome coronavirus 2 infection. They may serve as a useful additional screening criterion, particularly for the identification of patients in the early stages of infection.

positive: Coronavirus disease 2019 in pregnancy: early lessons The worldwide incidence of coronavirus disease 2019 (COVID-19) infection is rapidly increasing, but there exists limited information on coronavirus disease 2019 in pregnancy. Here, we present our experience with 7 confirmed cases of coronavirus disease 2019 in pregnancy presenting to a single large New York City tertiary care hospital. Of the 7 patients, 5 presented with symptoms of coronavirus disease 2019, including cough, myalgias, fevers, chest pain, and headache. Of the 7 patients, 4 were admitted to the hospital, including 2 who required supportive care with intravenous hydration. Of note, the other 2 admitted patients who were asymptomatic on admission to the hospital, presenting instead for obstetrically indicated labor inductions, became symptomatic after delivery, each requiring intensive care unit admission.

positive: [Early detection and disease assessment of patients with novel coronavirus pneumonia] In December 2019, the outbreak of novel coronavirus (2019- nCoV) in wuhan, China, attracting attention worldwidely. The novel coronavirus has the characteristics of rapid transmission, atypical clinical symptoms, and easy to affect both lungs, leading to missed diagnosis and misdiagnosis, as well as difficult to detection and assessment at early stage. Fever, cough, myalgia, weakness, dyspnea and imagings may be helpful for the early detection of novel coronavirus pneumonia. At the same time, the rate of disease progression, fever, CT manifestations, hypoxia degree, age, basic diseases, and laboratory indicators can also be used to evaluate the severity of the novel coronavirus pneumonia.

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: [Clinical characteristics of 30 medical workers infected with new coronavirus pneumonia]. Objective: To investigate the clinical characteristics of medical staff with novel coronavirus pneumonia(NCP). Methods: 30 patients infected with novel coronavirus referred to jianghan university hospital between January 11, 2020 and January 3, 2020 were studied. The data reviewed included those of clinical manifestations, laboratory investigation and Radiographic features. Results: The patients consisted of 10 men and 20 women, including 22 doctors and 8 nurses,aged 21~59 years(mean 35±8 years).They were divided to 26 common type and 4 severe cases, all of whom had close(within 1m) contact with patients infected of novel coronavirus pneumonia. The average contact times were 12 (7,16) and the average cumulative contact time was 2 (1.5,2.7) h.Clinical symptoms of these patients were fever in 23 patients (76.67%) , headache in 16 petients (53.33%) , fatigue or myalgia in 21patients (70%) , nausea, vomiting or diarrhea in 9 petients (30%) , cough in 25 petients (83.33%) , and dyspnea in 14 petients (46.67%) .Routine blood test revealed WBC <4.0×10(9)/L in 8 petients (26.67%) , (4-10) ×10(9)/L in 22 petients (73.33%) , and WBC>4.0×10(9)/L in 4 petients (13.33%) during the disease.Lymphocyte count <1.0×10(9)/L occurred in 12 petients (40%),abnormal liver function in 7 petients (23.33%) ,myocardial damage in 5 petients(16.67%), elevated D-dimer (>0.5mg/l) in 5 patients (16.67%). Compared with normal patients, the average exposure times, cumulative exposure time, BMI, Fever time, white blood cell count, liver enzyme, LDH, myoenzyme and D-dimer were significantly increased in severe patients, while the lymphocyte count and albumin levels in peripheral blood were significantly decreased.Chest CT mainly showed patchy shadows and interstitial changes.According to imaging examination, 11 patients (36.67%) showed Unilateral pneumonia and 19 patients (63.33%) showed bilateral pneumonia,4 patients (13.33%) showed bilateral multiple mottling and ground-glass opacity.Compared with the patients infected in the protected period, the proportion of severe infection and bilateral pneumonia were both increased in the patients infected in unprotected period. Conclusion: Medical staffs are at higher risk of infection.Infection rates are associated with contact time, the amount of suction virus. Severe patients had BMI increased, heating time prolonged , white blood cell count, lymphocyte count, D-dimer and albumin level significantly changed and were prone to be complicated with liver damage and myocardial damage.Strict protection measures is important to prevent infection for medical workers.

positive: Clinical and Laboratory Profiles of 75 Hospitalized Patients with Novel Coronavirus Disease 2019 in Hefei, China The outbreak of the novel coronavirus disease 2019 (COVID-19) infection began in December 2019 in Wuhan, and rapidly spread to many provinces in China. The number of cases has increased markedly in Anhui, but information on the clinical characteristics of patients is limited. We reported 75 patients with COVID-19 in the First Affiliated Hospital of USTC from Jan 21 to Feb 16, 2020, Hefei, Anhui Province, China. COVID-19 infection was confirmed by real-time RT-PCR of respiratory nasopharyngeal swab samples. Epidemiological, clinical and laboratory data were collected and analyzed. Of the 75 patients with COVID-19, 61 (81.33%) had a direct or indirect exposure history to Wuhan. Common symptoms at onset included fever (66 [88.0%] of 75 patients) and dry cough (62 [82.67%]). Of the patients without fever, cough could be the only or primary symptom. The most prominent laboratory abnormalities were lymphopenia, decreased percentage of lymphocytes (LYM%), decreased CD4+ and CD8+ T cell counts, elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH). Patients with elevated interleukin 6 (IL-6) showed significant decreases in the LYM%, CD4+ and CD8+ T cell counts. Besides, the percentage of neutrophils, CRP, LDH and Procalcitonin levels increased significantly. We concluded that COVID-19 could cause different degrees of hematological abnormalities and damage of internal organs. Hematological profiles including LYM, LDH, CRP and IL-6 could be indicators of diseases severity and evaluation of treatment effectiveness. Antiviral treatment requires a comprehensive and supportive approach. Further targeted therapy should be determined based on individual clinical manifestations and laboratory indicators.

positive: Digestive Symptoms in COVID-19 Patients With Mild Disease Severity: Clinical Presentation, Stool Viral RNA Testing, and Outcomes OBJECTIVES: Coronavirus disease 2019 (COVID-19) most commonly presents with respiratory symptoms, including cough, shortness of breath, and sore throat. However, digestive symptoms also occur in patients with COVID-19 and are often described in outpatients with less severe disease. In this study, we sought to describe the clinical characteristics of COVID-19 patients with digestive symptoms and mild disease severity. METHODS: We identified COVID-19 patients with mild disease and one or more digestive symptoms (diarrhea, nausea, and vomiting), with or without respiratory symptoms, and compared them with a group presenting solely with respiratory symptoms. We followed up patients clinically until they tested negative for COVID-19 on at least 2 sequential respiratory tract specimens collected ≥24 hours apart. We then compared the clinical features between those with digestive symptoms and those with respiratory symptoms. RESULTS: There were 206 patients with low severity COVID-19, including 48 presenting with a digestive symptom alone, 69 with both digestive and respiratory symptoms, and 89 with respiratory symptoms alone. Between the 2 groups with digestive symptoms, 67 presented with diarrhea, of whom 19.4% experienced diarrhea as the first symptom in their illness course. The diarrhea lasted from 1 to 14 days, with an average duration of 5.4 ± 3.1 days and a frequency of 4.3 ± 2.2 bowel movements per day. Concurrent fever was found in 62.4% of patients with a digestive symptom. Patients with digestive symptoms presented for care later than those with respiratory symptoms (16.0 ± 7.7 vs 11.6 ± 5.1 days, P < 0.001). Nevertheless, patients with digestive symptoms had a longer duration between symptom onset and viral clearance (P < 0.001) and were more likely to be fecal virus positive (73.3% vs 14.3%, P = 0.033) than those with respiratory symptoms. DISCUSSION: We describe a unique subgroup of COVID-19 patients with mild disease severity marked by the presence of digestive symptoms. These patients are more likely to test positive for viral RNA in stool, to have a longer delay before viral clearance, and to experience delayed diagnosis compared with patients with only respiratory symptoms.

positive: COVID-19: Fever syndrome and neurological symptoms in a neonate

positive: COVID-19 is a Real Headache! After the emergence of a novel coronavirus named SARS-CoV-2, coronavirus disease 2019 (COVID-19) was initially characterized by fever, sore throat, cough, and dyspnea, mainly manifestations of respiratory system. However, other manifestations such as headache, abdominal pain, diarrhea, loss of taste and smell were added to the clinical spectrum, during the course of the COVID-19 pandemic. The reports on the neurological findings are increasing rapidly and headache seems to be the leader on the symptom list. Headache was reported in 11%-34% of the hospitalized COVID-19 patients, but clinical features of these headaches were totally missing in available publications. According to our initial experience, significant features of headache presentation in the symptomatic COVID-19 patients were new-onset, moderate-severe, bilateral headache with pulsating or pressing quality in the temporoparietal, forehead or periorbital region. The most striking features of the headache were sudden to gradual onset and poor response to common analgesics, or high relapse rate, that was limited to the active phase of the COVID-19. Symptomatic COVID-19 patients, around 6%-10%, also reported headache as a presenting symptom. The possible pathophysiological mechanisms of headache include activation of peripheral trigeminal nerve endings by the SARS-CoV-2 directly or through the vasculopathy and/or increased circulating pro-inflammatory cytokines and hypoxia. We concluded that as a common non-respiratory symptom of COVID-19, headache should not be overlooked, and its characteristics should be recorded with scrutiny.

positive: Gastrointestinal and hepatic manifestations of COVID-19: A comprehensive review The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) that causes coronavirus disease-2019 (COVID-19) is a global pandemic, manifested by an infectious pneumonia. Although patients primarily present with fever, cough and dyspnea, some patients also develop gastrointestinal (GI) and hepatic manifestations. The most common GI symptoms reported are diarrhea, nausea, vomiting, and abdominal discomfort. Liver chemistry abnormalities are common and include elevation of aspartate transferase, alanine transferase, and total bilirubin. Studies have shown that SARS-CoV-2 infects the GI tract via its viral receptor angiotensin converting enzyme II, which is expressed on enterocytes of the ileum and colon. Viral RNA has also been isolated from stool specimens of COVID-19 patients, which raised the concern for fecal-oral transmission in addition to droplet transmission. Although indirect evidence has suggested possible fecal-oral transmission of SARS-CoV-2, more effort is needed to establish the role of the fecal-oral transmission route. Further research will help elucidate the association between patients with underlying GI diseases, such as chronic liver disease and inflammatory bowel disease, and severity of COVID-19. In this review, we summarize the data on GI involvement to date, as well as the impact of COVID-19 on underlying GI diseases.

positive: Recommended prophylactic and management strategies for severe acute respiratory syndrome coronavirus 2 infection in transplant recipients Abstract Since December 2019, increasing attention has been paid to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in Wuhan, China. SARS-CoV-2 primarily invades the respiratory tract and lungs, leading to pneumonia and other systemic disorders. The effect of SARS-CoV-2 in transplant recipients has raised significant concerns, especially because there is a large population of transplant recipients in China. Based on the current epidemic situation, this study reviewed publications on this virus and coronavirus disease 2019 (COVID-19), analyzed common features of respiratory viral pneumonias, and presented the currently reported clinical characteristics of COVID-19 in transplant recipients to improve strategies regarding the diagnosis and treatment of COVID-19 in this special population.

positive: Anosmia Is a Key Symptom of COVID-19 Infection and Should Be Used as a Diagnostic Tool. Based on observations described in our letter, we can draw the following conclusions: (1) anosmia must imperatively be added to the list of specific symptoms of COVID-19 infection, (2) anosmia can serve as a free and specific diagnostic tool for developing countries currently affected by the pandemic, (3) the mechanisms of COVID-19 anosmia seem not to directly involve nasal obstruction but rather seem to be related to damage the olfactory neuroepithelium.

positive: Headache as the Presenting Symptom in 2 Patients With COVID-19 and a History of Migraine: 2 Case Reports The coronavirus disease 2019 (COVID-19) pandemic has now affected more than 5 million people globally. Typical symptoms include fever, cough, and shortness of breath. Patients with underlying medical comorbidities such as cardiovascular disease and diabetes are more likely to become severely ill. To date there is limited information on how COVID-19 affects patients with a history migraine. Here, we present the cases of 2 women with a history of migraine whose first symptom of COVID-19 was a severe persistent headache.

positive: First COVID-19 infections in the Philippines: a case report BACKGROUND: The novel coronavirus (COVID-19) is responsible for more fatalities than the SARS coronavirus, despite being in the initial stage of a global pandemic. The first suspected case in the Philippines was investigated on January 22, 2020, and 633 suspected cases were reported as of March 1. We describe the clinical and epidemiological aspects of the first two confirmed COVID-19 cases in the Philippines, both admitted to the national infectious disease referral hospital in Manila. CASE PRESENTATION: Both patients were previously healthy Chinese nationals on vacation in the Philippines travelling as a couple during January 2020. Patient 1, a 39-year-old female, had symptoms of cough and sore throat and was admitted to San Lazaro Hospital in Manila on January 25. Physical examination was unremarkable. Influenza B, human coronavirus 229E, Staphylococcus aureus and Klebsiella pneumoniae were detected by PCR on initial nasopharyngeal/oropharyngeal (NPS/OPS) swabs. On January 30, SARS-CoV-2 viral RNA was reported to be detected by PCR on the initial swabs and she was identified as the first confirmed COVID-19 case in the Philippines. Her symptoms resolved, and she was discharged. Patient 2, a 44-year-old male, had symptoms of fever, cough, and chills. Influenza B and Streptococcus pneumoniae were detected by PCR on initial NPS/OPS swabs. He was treated for community-acquired pneumonia with intravenous antibiotics, but his condition deteriorated and he required intubation. On January 31, SARS-CoV-2 viral RNA was reported to be detected by PCR on the initial swabs, and he was identified as the 2nd confirmed COVID-19 infection in the Philippines. On February 1, the patient’s condition deteriorated, and following a cardiac arrest, it was not possible to revive him. He was thus confirmed as the first COVID-19 death outside of China. CONCLUSIONS: This case report highlights several important clinical and public health issues. Despite both patients being young adults with no significant past medical history, they had very different clinical courses, illustrating how COVID-19 can present with a wide spectrum of disease. As of March 1, there have been three confirmed COVID-19 cases in the Philippines. Continued vigilance is required to identify new cases.

positive: Neurological manifestations of COVID-19 and other coronaviruses: a systematic review OBJECTIVE: To describe the main neurological manifestations related to coronavirus infection in humans. METHODOLOGY: A systematic review was conducted regarding clinical studies on cases that had neurological manifestations associated with COVID-19 and other coronaviruses. The search was carried out in the electronic databases PubMed, Scopus, Embase, and LILACS with the following keywords: “coronavirus” or “Sars-CoV-2” or “COVID-19” and “neurologic manifestations” or “neurological symptoms” or “meningitis” or “encephalitis” or “encephalopathy,” following the Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Seven studies were included. Neurological alterations after CoV infection may vary from 17.3% to 36.4% and, in the pediatric age range, encephalitis may be as frequent as respiratory disorders, affecting 11% and 12% of patients, respectively. The Investigation included 409 patients diagnosed with CoV infection who presented neurological symptoms, with median age range varying from 3 to 62 years. The main neurological alterations were headache (69; 16.8%), dizziness (57, 13.9%), altered consciousness (46; 11.2%), vomiting (26; 6.3%), epileptic crises (7; 1.7%), neuralgia (5; 1.2%), and ataxia (3; 0.7%). The main presumed diagnoses were acute viral meningitis/encephalitis in 25 (6.1%) patients, hypoxic encephalopathy in 23 (5.6%) patients, acute cerebrovascular disease in 6 (1.4%) patients, 1 (0.2%) patient with possible acute disseminated encephalomyelitis, 1 (0.2%) patient with acute necrotizing hemorrhagic encephalopathy, and 2 (1.4%) patients with CoV related to Guillain-Barré syndrome. CONCLUSION: Coronaviruses have important neurotropic potential and they cause neurological alterations that range from mild to severe. The main neurological manifestations found were headache, dizziness and altered consciousness.

positive: Clinical characteristics of 50466 patients with 2019-nCoV infection Objective: We aim to summarize reliable evidences of evidence-based medicine for the treatment and prevention of the 2019 novel coronavirus (2019-nCoV) by analyzing all the published studies on the clinical characteristics of patients with 2019-nCoV. Methods: PubMed, Cochrane Library, Embase, and other databases were searched. Several studies on the clinical characteristics of 2019-nCoV infection were collected for Meta-analysis. Results: Ten studies were included in Meta-analysis, including a total number of 50466 patients with 2019-nCoV infection. Meta-analysis shows that, among these patients, the incidence of fever was 89.1%, the incidence of cough was 72.2%, and the incidence of muscle soreness or fatigue was 42.5%. The incidence of acute respiratory distress syndrome (ARDS) was 14.8%, the incidence of abnormal chest computer tomography (CT) was 96.6%, the percentage of severe cases in all infected cases was 18.1%, and the case fatality rate of patients with 2019-nCoV infection was 4.3%. Conclusion: Fever and cough are the most common symptoms in patients with 2019-nCoV infection, and most of these patients have abnormal chest CT examination. Several people have muscle soreness or fatigue as well as ARDS. Diarrhea, hemoptysis, headache, sore throat, shock, and other symptoms only occur in a small number of patients. The case fatality rate of patients with 2019-nCoV infection is lower than that of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS).

positive: Predictive value of sudden olfactory loss in the diagnosis of COVID-19 Introduction: Recent reports suggest that sudden smell loss might be a symptom of SARS-CoV-2 infection. The aim of this study was to investigate the frequency of olfactory loss in an out-patient population who presented to a coronavirus testing center during a 2-week period and to evaluate the diagnostic value of the symptom sudden smell loss for screening procedures. Methods: In this cross-sectional controlled cohort study, 500 patients who presented with symptoms of a common cold to a corona testing center and fulfilled corona testing criteria, completed a standardized diagnostic questionnaire which included the patients main symptoms, time course and an additional self-assessment of the patients current smell, taste function and nasal breathing compared to the level before onset of symptoms. Results: Out of the 500 patients, 69 presented with olfactory loss. Twenty-two of them subsequently tested positive for SARS-CoV-2. Only twelve out of the patients without olfactory loss tested positive, resulting in a frequency of 64.7% for the symptom sudden smell loss in COVID-19 patients. Compared to COVID-19 patients without smell loss, they were significantly younger and less severely affected. Changes in nasal airflow were significantly more pronounced in SARS-CoV-2 negative patients with olfactory complaints compared to the patients with smell loss who were tested positive for SARS-CoV-2. By excluding patients with a blocked nose, the symptom sudden smell loss can be attested a high specificity (97%) and a sensitivity of 65% with a PPV of 63% and NPV of 97% for COVID-19. Conclusion: Considering the high frequency of smell loss in non-hospitalized COVID-19 patients, acute olfactory impairment should be included in the WHO symptoms list and should be recognized as an early symptom of the disease. In contrast to other acute viral smell impairment, COVID-19 associated smell loss seems to be only rarely accompanied by a severely blocked nose.

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

positive: Clinical and Paraclinical Characteristics of COVID-19 patients: A systematic review and meta-analysis Introduction: Recently, a new strain of coronaviruses, which originated from Wuhan City, Hubei Province, China has been identified. According to the high prevalence of new coronavirus, further investigation on the clinical and paraclinical features of this disease seems essential. Hence, we carried out this systematic review and meta-analysis to figure out the unknown features. Methods: This study was performed using databases of Web of Science, Scopus and PubMed. We considered English cross-sectional and case-series papers which reported clinical, radiological, and laboratory characteristics of patients with COVID-19. We used STATA v.11 and random effect model for data analysis. Results: In the present meta-analysis, 32 papers including 49504 COVID-19 patients were studied. The most common clinical symptoms were fever (84%), cough (65%) and fatigue (42%), respectively. The most common radiological and paraclinical features were bilateral pneumonia (61%), ground-glass opacity (50%), thrombocytopenia (36%) and lymphocytopenia (34%). The study also showed that the frequency of comorbidities and early symptoms was higher in critically severe patients. Moreover, we found the overall mortality rate of three percent. Conclusion: According to that there are many cases without Computed Tomography Scan findings or clear clinical symptoms, it is recommended to use other confirming methods such RNA sequencing in order to identification of suspicious undiagnosed patients. Moreover, while there is no access to clinical and paraclinical facilities in in public places such as airports and border crossings, it is recommended to consider factors such as fever, cough, sputum and fatigue.

positive: PSYCHOTIC SYMPTOMS IN COVID-19 PATIENTS. A RETROSPECTIVE DESCRIPTIVE STUDY. Psychotic symptoms have been related to other coronavirus infections. We conducted a single-centre retrospective and observational study to describe new-onset psychotic episodes in COVID-19 patients. Ten patients infected by the novel coronavirus with psychotic symptoms and no previous history of psychosis were identified by the emergency and liaison psychiatry departments. Nine of the cases presented with psychotic symptoms at least two weeks after the first somatic manifestations attributed to COVID-19 and receiving pharmacological treatment. Structured delusions mixed with confusional features were the most frequent clinical presentations. Hence, COVID-19 patients can develop psychotic symptoms as a consequence of multiple concurrent factors.

positive: Real-time tracking of self-reported symptoms to predict potential COVID-19. A total of 2,618,862 participants reported their potential symptoms of COVID-19 on a smartphone-based app. Among the 18,401 who had undergone a SARS-CoV-2 test, the proportion of participants who reported loss of smell and taste was higher in those with a positive test result (4,668 of 7,178 individuals; 65.03%) than in those with a negative test result (2,436 of 11,223 participants; 21.71%) (odds ratio = 6.74; 95% confidence interval = 6.31-7.21). A model combining symptoms to predict probable infection was applied to the data from all app users who reported symptoms (805,753) and predicted that 140,312 (17.42%) participants are likely to have COVID-19.

positive: Clinical Characteristics of 34 Children with Coronavirus Disease-2019 in the West of China: a Multiple-center Case Series BACKGROUND Up to 9 March, 2020, 109577 patients were diagnosed with coronavirus disease-2019 (COVID-19) globally. The clinical and epidemiological characteristics of adult patients have been revealed recently. However, the information of paediatric patients remains unclear. We describe the clinical and epidemiological characteristics of paediatric patients to provide valuable insight into early diagnosis of COVID-19 in children, as well as epidemic control policy making. METHODS and FINDINGS This retrospective, observational study was a case series performed at 4 hospitals in the west of China. Thirty-four paediatric patients with COVID-19 were included from January 1 to February 25, 2020. And the final follow-up visit was completed by February 28, 2020. Clinical and epidemiological characteristics were analyzed on the basis of demographic data, medical history, laboratory tests, radiological findings, and treatment information. Data analysis was performed on 34 paediatrics patients with COVID-19 aged from 1 to 144 months (median 33.00, IQR 10.00 - 94.25), among whom 14 males (41.18%) were included. 47.60% of patients were noticed without any exposure history. The median incubation period was 10.50 (7.75 - 25.25) days. Infections of other respiratory pathogens were reported in 16 patients (47.06%). The most common initial symptoms were fever (76.47%), cough (58.82%), and expectoration (20.59%). Vomiting (11.76%) and diarrhea (11.76%) were also reported in a considerable portion of cases. A remarkable increase was detected in serum amyloid A for 17 patients (85.00%) and high-sensitivity C-reactive protein for 17 patients (58.62%), while a decrease of prealbumin was noticed in 25 patients (78.13%). In addition, the levels of lactate dehydrogenase was increased significantly in 28 patients (82.35%), as well as α-hydroxybutyrate dehydrogenase in 25 patients (73.53%). Patchy lesions in lobules were detected by chest computed tomographic scans in 28 patients (82.36%). The typical feature of ground-glass opacity for adults was rare in paediatric patients (2.94%). A late-onset pattern of lesions in lobules were also noticed. Stratified analysis of the clinical features were not performed due to relatively limited samples. CONCLUSIONS Our data presented the clinical and epidemiological features of paediatric patients systemically. The findings offer new insight into the early identification and intervention of paediatric patients with COVID-19.

positive: Ocular manifestations and viral shedding in tears of pediatric patients with coronavirus disease 2019: a preliminary report Abstract Purpose To evaluate ocular manifestations and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) prevalence in the tears of children with coronavirus disease 2019 (COVID-19). Methods A total of 27 pediatric patients with confirmed COVID-19 infection hospitalized from March 16 to April 15, 2020, at the Bambino Gesù Children’s Hospital were enrolled in the study. At admission, all patients showed ocular manifestations. Reverse transcriptase–polymerase chain reaction from nasopharyngeal and conjunctival swabs were performed every 2-3 days before discharge. Results Of the 27 patients, 4 (15%) were asymptomatic, 15 (56%) showed respiratory symptoms, and 8 (30%) had gastrointestinal symptoms. At admission, nasopharyngeal swabs were positive for COVID-19 in all patients; on the second swabs, 7 children (26%) tested negative, and 20 remained positive for COVID-19. Ocular manifestations consistent with mild viral conjunctivitis were observed in 4 patients (15%). At first conjunctival swab, 3 patients (11%), 1 symptomatic and 2 asymptomatic for ocular infection, had positive findings for COVID-19; 2 became negative on the second test and 1 on the third. Conclusions In our study cohort, ocular manifestations of COVID-19 seem to have had a milder clinical course in pediatric patients than in adults. Despite the low prevalence and rapid regression of viral presence in the conjunctiva, SARS-CoV-2 transmission through tears may be possible, even in patients without apparent ocular involvement.

positive: Delirium in COVID-19: A case series and exploration of potential mechanisms for central nervous system involvement INTRODUCTION: Neuropsychiatric manifestations of the coronavirus disease 2019 (COVID-19) have been described, including anosmia, ageusia, headache, paresthesia, encephalitis and encephalopathy. Little is known about the mechanisms by which the virus causes central nervous system (CNS) symptoms, and therefore little guidance is available regarding potential workup or management options. CASES: We present a series of four consecutive cases, seen by our psychiatry consultation service over a one-week period, each of which manifested delirium as a result of infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). DISCUSSION: The four cases highlighted here all occurred in older patients with premorbid evidence of cognitive decline. Unique features seen in multiple cases included rigidity, alogia, abulia, and elevated inflammatory markers. In all four cases, a change in mental status was the presenting symptom, and three of the four cases lacked significant respiratory symptoms. In addition to discussing unique features of the cases, we discuss possible pathophysiologic explanations for COVID-19 delirium. CONCLUSIONS: Delirium should be recognized as a potential feature of infection with SARS-CoV-2 and may be the only presenting symptom. Based on the high rates of delirium demonstrated in prior studies, hospitals should consider adding mental status changes to the list of testing criteria. Further research is needed to determine if delirium in COVID-19 represents a primary encephalopathy heralding invasion of the CNS by the virus, or a secondary encephalopathy related to systemic inflammatory response or other factors.

positive: 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.

positive: Clinical characteristics of laboratory confirmed positive cases of SARS-CoV-2 infection in Wuhan, China: A retrospective single center analysis

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: Anosmia: A marker of infection by the new corona virus The diagnosis of Coronavirus Disease 2019 (COVID-19) is based on the identification of common symptoms such as fever, tiredness and dry cough. Anosmia and ageusia are also in fact symptoms of the infection with the new coronavirus and recently were considered as symptoms by the World Health Organization. In this case report we present the new onset anosmia during the COVID-19 pandemic. The patient, 31-year-old, reported olfactory and gustatory dysfunctions as initial symptoms of mild-to-moderate form of the COVID-19. Therefore, chemosensory dysfunctions should serve as a warning to health professionals as a possible marker of infection with the new corona virus.

positive: Frequency of diarrhea in novel coronavirus 2019 infection

positive: Olfactory and rhinological evaluations in SARS-CoV-2 patients complaining of olfactory loss Since December 2019, a novel coronavirus SARS-CoV-2 (Covid-19) outbreak emerged in China and spread rapidly in several countries. As of April 5, 2020, 1.218.474 cases were confirmed with 65.884 deaths worldwide (1). The clinical manifestations of Covid-19 range from asymptomatic carrier status to severe pneumonia. In a study of 7,736 Covid-19 patients in China, of all the clinical symptoms, hyposmia was not reported in any patient(2). Anyway, it is now clear that olfactory dysfunction may also be present in these patients(3) as the only or prevalent manifestation(4).

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

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

positive: Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Jin Yin-tan Hospital of Wuhan, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

positive: Characteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units. Importance The recent and ongoing coronavirus disease 2019 (COVID-19) pandemic has taken an unprecedented toll on adults critically ill with COVID-19 infection. While there is evidence that the burden of COVID-19 infection in hospitalized children is lesser than in their adult counterparts, to date, there are only limited reports describing COVID-19 in pediatric intensive care units (PICUs). Objective To provide an early description and characterization of COVID-19 infection in North American PICUs, focusing on mode of presentation, presence of comorbidities, severity of disease, therapeutic interventions, clinical trajectory, and early outcomes. Design, Setting, and Participants This cross-sectional study included children positive for COVID-19 admitted to 46 North American PICUs between March 14 and April 3, 2020. with follow-up to April 10, 2020. Main Outcomes and Measures Prehospital characteristics, clinical trajectory, and hospital outcomes of children admitted to PICUs with confirmed COVID-19 infection. Results Of the 48 children with COVID-19 admitted to participating PICUs, 25 (52%) were male, and the median (range) age was 13 (4.2-16.6) years. Forty patients (83%) had significant preexisting comorbidities; 35 (73%) presented with respiratory symptoms and 18 (38%) required invasive ventilation. Eleven patients (23%) had failure of 2 or more organ systems. Extracorporeal membrane oxygenation was required for 1 patient (2%). Targeted therapies were used in 28 patients (61%), with hydroxychloroquine being the most commonly used agent either alone (11 patients) or in combination (10 patients). At the completion of the follow-up period, 2 patients (4%) had died and 15 (31%) were still hospitalized, with 3 still requiring ventilatory support and 1 receiving extracorporeal membrane oxygenation. The median (range) PICU and hospital lengths of stay for those who had been discharged were 5 (3-9) days and 7 (4-13) days, respectively. Conclusions and Relevance This early report describes the burden of COVID-19 infection in North American PICUs and confirms that severe illness in children is significant but far less frequent than in adults. Prehospital comorbidities appear to be an important factor in children. These preliminary observations provide an important platform for larger and more extensive studies of children with COVID-19 infection.

positive: Ocular manifestations and clinical characteristics of 535 cases of COVID‐19 in Wuhan, China: a cross‐sectional study PURPOSE: To investigate the ocular manifestations and clinical characteristics of COVID‐19 patients caused by SARS‐CoV‐2 in Wuhan, China. METHODS: A total of 535 COVID‐19 patients were recruited at Mobile Cabin Hospital and Tongji Hospital. Information on demographic characteristics, exposure history, ocular symptoms, eye drop medication, eye protections, chronic eye diseases, systemic concomitant symptoms, radiologic findings and SARS‐CoV‐2 detection in nasopharyngeal swabs by real‐time PCR was collected from questionnaires and electronic medical records. RESULTS: Of 535 patients, 27 patients (5.0%) presented with conjunctival congestion and 4 patients had conjunctival congestion as the initial symptom. The average duration of conjunctival congestion was 5.9 ± 4.5 days (mean [SD]). The other ocular symptoms, including increased conjunctival secretion, ocular pain, photophobia, dry eye and tearing, were also found in patients with conjunctival congestion. Notably, hand–eye contact was independently correlated with conjunctival congestion in COVID‐19 patients. We also found that some COVID‐19 patients had chronic eye diseases, including conjunctivitis (33, 6.2%), xerophthalmia (24, 4.5%) and keratitis (14, 2.6%). Similar to the published studies, the most common clinical symptoms were fever, cough and fatigue. A total of 343 patients (64.1%) had positive SARS‐CoV‐2 detection in nasopharyngeal swabs. CONCLUSIONS: Conjunctival congestion is one of the COVID‐19‐related ocular symptoms, which could occur as the initial symptoms. Frequent hand–eye contact may be the risk factor for conjunctival congestion in COVID‐19 patients. Screening of patients with conjunctival congestion by ophthalmologists is advocated during the outbreak of COVID‐19. It is essential to provide eye‐care equipment and strengthen education on eye protection.

positive: Atypical presentations of coronavirus disease 2019 in a patient with acute obstructive suppurative cholangitis Abstract During the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak in Wuhan, China, we experienced a case of SARS-CoV-2 infection with atypical presentations in a patient with acute obstructive suppurative cholangitis (AOSC), who was initially admitted with jaundice and fever. The patient had no other typical symptoms of COVID-19 such as cough, dyspnea, nausea, vomiting, abdominal pain and diarrhea except for fever, but her epidemiological history was clear. COVID-19 was finally confirmed by repeated viral nucleic acid testing, but her repetitive lungs CT imaging findings had been atypical. After endoscopic-related operations and antiviral treatment, the patient was subsequently recovered and discharged. This particular case is being reported to provide a reference and guidance for the diagnosis and management of COVID-19 in AOSC.

positive: Coronavirus Disease 2019 (COVID-19): Role of Chest CT in Diagnosis and Management. OBJECTIVE. The objective of our study was to determine the misdiagnosis rate of radiologists for coronavirus disease 2019 (COVID-19) and evaluate the performance of chest CT in the diagnosis and management of COVID-19. The CT features of COVID-19 are reported and compared with the CT features of other viruses to familiarize radiologists with possible CT patterns. MATERIALS AND METHODS. This study included the first 51 patients with a diagnosis of COVID-19 infection confirmed by nucleic acid testing (23 women and 28 men; age range, 26-83 years) and two patients with adenovirus (one woman and one man; ages, 58 and 66 years). We reviewed the clinical information, CT images, and corresponding image reports of these 53 patients. The CT images included images from 99 chest CT examinations, including initial and follow-up CT studies. We compared the image reports of the initial CT study with the laboratory test results and identified CT patterns suggestive of viral infection. RESULTS. COVID-19 was misdiagnosed as a common infection at the initial CT study in two inpatients with underlying disease and COVID-19. Viral pneumonia was correctly diagnosed at the initial CT study in the remaining 49 patients with COVID-19 and two patients with adenovirus. These patients were isolated and obtained treatment. Ground-glass opacities (GGOs) and consolidation with or without vascular enlargement, interlobular septal thickening, and air bronchogram sign are common CT features of COVID-19. The The "reversed halo" sign and pulmonary nodules with a halo sign are uncommon CT features. The CT findings of COVID-19 overlap with the CT findings of adenovirus infection. There are differences as well as similarities in the CT features of COVID-19 compared with those of the severe acute respiratory syndrome. CONCLUSION. We found that chest CT had a low rate of missed diagnosis of COVID-19 (3.9%, 2/51) and may be useful as a standard method for the rapid diagnosis of COVID-19 to optimize the management of patients. However, CT is still limited for identifying specific viruses and distinguishing between viruses.

positive: Arthralgia as an initial presentation of COVID-19: observation

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

positive: Neurological manifestations of COVID-19: a review of what we know so far Coronavirus disease 2019 (COVID‐19) has become a pandemic disease globally. While it mostly presents with respiratory symptoms, it has already been found that it could manifest with a series of neurological symptoms as well, either at presentation or during the course of the disease. Symptoms vary from non-specific such as headache or dizziness to more specific such as convulsions and cerebrovascular disease (CVD). This study aims to give an overview of the neurological manifestations of COVID-19 and discuss the potential pathogenetic mechanisms of central nervous system (CNS) involvement. Clinicians and especially internists, neurologists, and infectious disease specialists should be aware of these symptoms and able to recognize them early. Prompt diagnosis and immediate management of the neurological manifestations of the novel coronavirus will not only improve the prognosis of COVID-19 patients but will also prevent the dissemination of the disease due to misdiagnosed cases.

positive: Coronavirus (COVID-19) outbreak: what the department of endoscopy should know Italy recorded its first case of confirmed acute respiratory illness because of coronavirus on February 18, 2020, soon after the initial reports in China. Since that time, Italy and nations throughout the world have adopted very stringent and severe measures to protect populations from spread of infection. Despite these measures, the number of infected people is growing exponentially, with a significant number of patients developing acute respiratory insufficiency. Endoscopy departments face significant risk for diffusion of respiratory diseases that can be spread via an airborne route, including aspiration of oral and fecal material via endoscopes. The purpose of this article is to discuss the measures, with specific focus on personal protection equipment and dress code modalities, implemented in our hospital to prevent further dissemination of COVID-19 infection.

positive: Clinical and immunologic features in severe and moderate forms of Coronavirus Disease 2019 Background Since late December, 2019, an outbreak of pneumonia cases caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and continued to spread throughout China and across the globe. To date, few data on immunologic features of Coronavirus Disease 2019 (COVID-19) have been reported. Methods In this single-centre retrospective study, a total of 21 patients with pneumonia who were laboratory-confirmed to be infected with SARS-CoV-2 in Wuhan Tongji hospital were included from Dec 19, 2019 to Jan 27, 2020. The immunologic characteristics as well as their clinical, laboratory, radiological features were compared between 11 severe cases and 10 moderate cases. Results Of the 21 patients with COVID-19, only 4 (19%) had a history of exposure to the Huanan seafood market. 7 (33.3%) patients had underlying conditions. The average age of severe and moderate cases was 63.9 and 51.4 years, 10 (90.9%) severe cases and 7 (70.0%) moderate cases were male. Common clinical manifestations including fever (100%, 100%), cough (70%, 90%), fatigue (100%, 70%) and myalgia (50%, 30%) in severe cases and moderate cases. PaO2/FiO2 ratio was significantly lower in severe cases (122.9) than moderate cases (366.2). Lymphocyte counts were significantly lower in severe cases (7000 million/L) than moderate cases (11000 million/L). Alanine aminotransferase, lactate dehydrogenase levels, high-sensitivity C-reactive protein and ferritin were significantly higher in severe cases (41.4 U/L, 567.2 U/L, 135.2 mg/L and 1734.4 ug/L) than moderate cases (17.6 U/L, 234.4 U/L, 51.4 mg/L and 880.2 ug /L). IL-2R, TNF-α and IL-10 concentrations on admission were significantly higher in severe cases (1202.4 pg/mL, 10.9 pg/mL and 10.9 pg/mL) than moderate cases (441.7 pg/mL, 7.5 pg/mL and 6.6 pg/mL). Absolute number of total T lymphocytes, CD4+T cells and CD8+T cells decreased in nearly all the patients, and were significantly lower in severe cases (332.5, 185.6 and 124.3 million/L) than moderate cases (676.5, 359.2 and 272.0 million/L). The expressions of IFN-γ by CD4+T cells tended to be lower in severe cases (14.6%) than moderate cases (23.6%). Conclusion The SARS-CoV-2 infection may affect primarily T lymphocytes, particularly CD4+T cells, resulting in significant decrease in number as well as IFN-γ production, which may be associated with disease severity. Together with clinical characteristics, early immunologic indicators including diminished T lymphocytes and elevated cytokines may serve as potential markers for prognosis in COVID-19.

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

positive: Gastrointestinal tract symptoms in coronavirus disease 2019: Analysis of clinical symptoms in adult patients Objective: To investigate the clinical presentation of coronavirus disease 2019 (COVID-19), particularly the incidence of gastrointestinal tract symptoms. Design: We enrolled adult COVID-19 patients from a mobile cabin hospital in Wuhan with a definitive diagnosis by SARS-CoV-2 nucleic acid testing. Face-to-face interviews were conducted in which the patient selected COVID-19-related symptoms and report the time of onset and duration of symptoms. Results: A total of 212 adults were enrolled in this study, of which 127 (59.9%) were females, mean age was 48.50 (range: 17-79) years, and mean disease course was 26.78 (3-60) days. Fever and cough were the most common and earliest clinical symptoms of COVID-19. Diarrhoea occurred in 43.8% (93/212) of patients, of which 86.0% (80/93) had mushy stools. Nausea and vomiting were also common (20.7%). Diarrhoea lasted for 4.00(2.00-8.85) days and mostly occurred 5.00(0.25-11.00) days after the emergence of the first symptoms. Multiple logistic regression analysis found that diarrhoea was significantly correlated with fatigue [OR2.900,95%CI (1.629-5.164), p<0.0001]. Conclusions: Gastrointestinal tract symptoms are common in COVID-19 and most occur during the middle stage of the disease and lasts for a short period of time. Clinicians need to pay greater attention to gastrointestinal tract symptoms of COVID-19.

positive: A comparative study on the clinical features of COVID-19 pneumonia to other pneumonias BACKGROUND: A novel coronavirus (2019-nCoV) has raised world concern since it emerged in Wuhan Hubei China in December, 2019. The infection may result into severe pneumonia with clusters illness onsets. Its impacts on public health make it paramount to clarify the clinical features with other pneumonias. METHODS: Nineteen 2019-nCoV pneumonia (NCOVID-19) and fifteen other pneumonia patients (NON-NCOVID-19) in out of Hubei places were involved in this study. Both NCOVID-19 and NON-NCOVID-19 patients were confirmed to be infected in throat swabs or/and sputa with or without 2019-nCoV by real-time RT-PCR. We analyzed the demographic, epidemiological, clinical, and radiological features from those patients, and compared the difference between NCOVID-19 and NON-NCOVID-19. RESULTS: All patients had a history of exposure to confirmed case of 2019-nCoV or travel to Hubei before illness. The median duration, respectively, was 8 (IQR:6~11) and 5 (IQR:4~11) days from exposure to onset in NCOVID-19 and NON-NCOVID-19. The clinical symptoms were similar between NCOVID-19 and NON-NCOVID-19. The most common symptoms were fever and cough. Fifteen (78.95%) NCOVID-19 but 4 (26.67%) NON-NCOVID-19 patients had bilateral involvement while 17 (89.47%) NCOVID-19 but 1 (6.67%) NON-NCOVID-19 patients had multiple mottling and ground-glass opacity of chest CT images. Compared to NON-NCOVID-19, NCOVID-19 present remarkably more abnormal laboratory tests including AST, ALT, Î³-GT, LDH and α-HBDH. CONCLUSION: The 2019-nCoV infection caused similar onsets to other pneumonias. CT scan may be a reliable test for screening NCOVID-19 cases. Liver function damage is more frequent in NCOVID-19 than NON-NCOVID-19 patients. LDH and α-HBDH may be considerable markers for evaluation of NCOVID-19.

positive: Clinical features, laboratory characteristics, and outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19): Early report from the United States Background Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV2), is an ongoing pandemic that has already affected millions of patients worldwide, and is associated with significant morbidity and mortality burden. Although the clinical and laboratory characteristics of this illness have been reported in patients from China and Europe, data are scant in the United States. Methods We extracted data regarding all patients hospitalized at our hospital with COVID-19 infection between March 1 and April 4, 2020. Presenting signs and symptoms, laboratory and imaging findings, treatment, and complications were recorded from electronic medical records (EMRs). The primary composite endpoint was admission to intensive care unit (ICU), shock, or death. Results We had a total of 43 patients tested for COVID-19 at the emergency room (ER) or during hospitalization, 16 (37%) of whom were admitted with COVID-19 infection. The mean age was 65.5 years and 75% were males. The most common presenting symptoms were fever (94%), cough (88%), and dyspnea (81%). A loss of smell and taste sensations were reported by three (19%) patients. Low oxygen saturation was present in 38% of patients, whilst 31% were hypotensive on admission. Hyponatremia (50%), elevated C-reactive protein (CRP; 100%), and lactate dehydrogenase (LDH; 80%) were common. Acute renal failure, myocardial injury, and elevation in aminotransferases occurred in 69%, 19%, and 38% patients, respectively. The primary composite endpoint occurred in 50% of patients. A total of three patients died; all were aged 70 years or older. Conclusions Laboratory abnormalities and acute renal failure were common in hospitalized patients with SARS-CoV2 infection in our center. Admission to ICU and mechanical ventilation were common.

positive: 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.

positive: SnapShot: COVID-19 Abstract Coronavirus disease 2019 (COVID-19) is a novel respiratory illness caused by SARS-CoV-2. Viral entry is mediated through viral spike protein and host ACE2 enzyme interaction. Most cases are mild; severe disease often involves cytokine storm and organ failure. Therapeutics including antivirals, immunomodulators, and vaccines are in development. To view this SnapShot, open or download the PDF.

positive: 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.

positive: Clinical features of coronavirus disease 2019 (COVID-19) in a cohort of patients with disability due to spinal cord injury STUDY DESIGN: Cohort study of patients with spinal cord injury (SCI). OBJECTIVES: To describe the clinical and analytical features of a coronavirus disease 2019 (Covid-19) infected cohort with SCI to enable accurate diagnosis and to outline prevention measures. SETTING: This study was conducted at the National Hospital for Paraplegics (Toledo, Spain). METHODS: A cohort analysis of seven patients with SCI infected by Covid-19 was performed. Diagnosis was confirmed with reverse transcriptase polymerase chain reaction (RT-PCR) of nasal exudate or sputum samples. Clinical, analytical, and radiographic findings were registered. RESULTS: RT-PCR detected COVID-19 infection in all patients, affecting males and people with a cervical level of injury more often (five out of seven). The average delay for diagnostic confirmation was 4 days (interquartile range, 1–10). Fever was the most frequent symptom (six out of seven). The second most common symptom was asthenia (four out of seven), followed by dyspnea, cough, and expectoration (three out of seven for each symptom). The Modified Early Warning System score for Covid-19 severity rating was classified as severe in five out of seven cases. All but one patient showed radiological alterations evident in chest X-rays at the time of diagnosis. All patients recovered gradually. CONCLUSION: Our patients with SCI and Covid-19 infection exhibited fewer symptoms than the general population. Furthermore, they presented similar or greater clinical severity. The clinical evolution was not as pronounced as had been expected. This study recommends close supervision of the SCI population to detect early compatible signs and symptoms of Covid-19 infection.

positive: Early viral clearance and antibody kinetics of COVID-19 among asymptomatic carriers Background Asymptomatic carriers contribute to the spread of Coronavirus Disease 2019 (COVID-19), but their clinical characteristics, viral kinetics, and antibody responses remain unclear. Methods A total of 56 COVID-19 patients without symptoms at admission and 19 age-matched symptomatic patients were enrolled. RNA of SARS-CoV-2 was tested using transcriptase quantitative PCR, and the total antibodies (Ab), IgG, IgA and IgM against the SARS-CoV-2 were tested using Chemiluminescence Microparticle Immuno Assay. Results Among 56 patients without symptoms at admission, 33 cases displayed symptoms and 23 remained asymptomatic throughout the follow-up period. 43.8% of the asymptomatic carriers were children and none of the asymptomatic cases had recognizable changes in C-reactive protein or interleukin-6, except one 64-year-old patient. The initial threshold cycle value of nasopharyngeal SARS-CoV-2 in asymptomatic carriers was similar to that in pre-symptomatic and symptomatic patients, but the communicable period of asymptomatic carriers (9.63 days) was shorter than pre-symptomatic patients (13.6 days). There was no obvious differences of the seropositive conversion rate of total Ab, IgG, and IgA among the three groups, though the rates of IgM varied largely. The average peak IgG and IgM COI of asymptomatic cases was 3.5 and 0.8, respectively, which is also lower than those in symptomatic patients with peaked IgG and IgM COI of 4.5 and 2.4 (p <0.05). Conclusion Young COVID-19 patients seem to be asymptomatic cases with early clearance of SARS-CoV-2 and low levels of IgM generation but high total Ab, IgG and IgA. Our findings provide empirical information for viral clearance and antibody kinetics of asymptomatic COVID-19 patients.

positive: Cutaneous manifestations in patients with COVID‐19: A preliminary review of an emerging issue BACKGROUND: The infection caused by the recently identified SARS‐CoV‐2, called COronaVIrus Disease‐19 (COVID‐19), has rapidly spread throughout the world. With the exponential increase of patients worldwide, the clinical spectrum of COVID‐19 is being better defined and new symptoms are emerging. Numerous reports are documenting the occurrence of different cutaneous manifestations in COVID‐19 patients. OBJECTIVES: To provide a brief overview of the COVID‐19‐associated cutaneous lesions. METHODS: Literature search was performed in the PubMed, Scopus and Web of Science databases up to 30 April 2020. This narrative review summarizes the available data regarding clinical and histological features of COVID‐19‐associated skin manifestations. RESULTS: Literature reports showed a great heterogeneity in COVID‐19‐associated cutaneous manifestations, as well as in their latency periods and associated extracutaneous symptoms. Pathogenic mechanisms are unknown, although the role of hyperactive immune response, complement activation and microvascular injury has been hypothesized. Based on our experience and the literature data, we subdivided the reported cutaneous lesions into six main clinical patterns: i) urticarial rash, ii) confluent erythematous/maculo‐papular/morbilliform rash, iii) papulovesicular exanthem, iv) chilblain‐like acral pattern, v) livedo reticularis/racemosa‐like pattern, vi) purpuric “vasculitic” pattern. These six patterns can be merged into two main settings: the first one – inflammatory/exanthematous – including the first three groups cited above and the second one including the vasculopathic/vasculitic lesions of the last three aforementioned groups. CONCLUSIONS: The possible presence of cutaneous findings leading to suspect COVID‐19 puts dermatologists in a relevant position. Further studies are needed to delineate the diagnostic and prognostic value of such cutaneous manifestations.

positive: Prevalence and Mortality of COVID-19 patients with Gastrointestinal Symptoms: A Systematic Review and Meta-analysis Abstract Objectives To perform a systematic review and meta-analysis evaluating the prevalence of gastrointestinal (GI) symptoms and mortality in patients diagnosed with coronavirus disease 2019 (COVID-19). Methods A systematic search of MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Scopus was performed from 2019 to May 7th, 2020. Observational studies including adults with COVID-19 infection and reporting GI symptoms were included. Primary outcome was assessing weighted pooled prevalence (WPP) of GI symptoms in patients with COVID-19. Secondary outcomes were WPP of overall mortality, and mortality in COVID-19 patients with GI symptoms. Results A total of 78 studies with 12797 patients were included. Among GI symptoms (at onset of illness in 6, at admission in 17, data given separately for both in 3, data unavailable in 52 studies), WPP of diarrhea was 12% (95% CI, 8%-17%), I 2 =94%, nausea and/or vomiting was 9.0% (95% CI, 5.5%-12.9%). I 2 =93%, loss of appetite was 22.3% (95% CI, 11.2%-34.6%, I 2 =94%, and that of abdominal pain was 6.2% (95% CI, 2.6%-10.3%, I 2 =92%. Mortality among patients with GI symptoms [0.4% (95% CI, 0%-1.1%), I 2 =74%] was similar to overall mortality [2.1% (95% CI, 0.2%-4.7%), I 2 =94%], p=0.15. Majority of studies had high risk of bias and overall quality of evidence was low to very low for all outcomes. Conclusions Gastrointestinal symptoms are seen in up to one in five patients with COVID-19. More high quality evidence is needed to confirm these findings and to explore factors causing mortality in these patients.

positive: Symptom Cluster of ICU Nurses Treating COVID-19 Pneumonia Patients in Wuhan, China BACKGROUND: In treating highly infectious coronavirus disease-19 (COVID-19) pneumonia, intensive care unit (ICU) nurses face a high risk of developing somatic symptom disorder (SSD).The symptom clusters in one population may show overlaps and involvements, a phenomenon that should be deliberately resolved to improve the management efficiency. OBJECTIVES: The present study aims to investigate the symptoms and causes of SSD of ICU nurses treating COVID-19 pneumonia. The research results are expected to provide evidence for the establishment of a better management strategy. METHODS: This study enrolled a total of 140 ICU nurses who were selected by Jiangsu Province Hospital to work in Wuhan (the epicenter of the COVID-19 epidemic in China) on February 3, 2020. A questionnaire, Somatic symptom disorders for ICU nurses in Wuhan No. 1 Hospital, was designed based on the International Classification of Functioning, Disability and Health. Exploratory factor analysis was performed to cluster the symptoms and logistic regression analysis to find the risk factors of the symptoms. RESULTS: Five major symptoms were chest discomfort and palpitation (31.4%), dyspnea (30.7%), nausea (21.4%), headache (19.3%), and dizziness (17.9%). In exploratory factor analysis, the symptoms were classified into three clusters: Cluster A of breathing and sleep disturbances (dizziness, sleepiness, and dyspnea); Cluster B of gastrointestinal complaints and pain (nausea and headache), and Cluster C of general symptoms (xerostomia, fatigue, as well as chest discomfort and palpitation). In Cluster A, urine/feces splash, sex, and sputum splash were independent predictive factors. In Cluster B, fall of protective glasses and urine/feces splash were independent predictive factors. In Cluster C, urine/feces splash and urine/feces clearance were independent predictive factors. CONCLUSION: The ICU nurses in Wuhan showed varying and overlapping SSDs. These SSDs could be classified into three symptom clusters. Based on the characteristics of their SSDs, specific interventions could be implemented to safeguard the health of ICU nurses.

positive: A case of imported COVID-19 diagnosed by PCR-positive lower respiratory specimen but with PCR-negative throat swabs A 35-year-old woman presented with fever and mild diarrhoea without any respiratory symptoms 9 days after travelling to Japan from Wuhan, China. Her computed tomography scan revealed pneumonia. The first polymerase chain reaction (PCR) test on throat swab for the novel corona virus upon admission was negative. Therefore, she was treated for community-acquired pneumonia, but fever persisted. On hospital day 5, PCR test on induced sputum was positive, but a second polymerase chain reaction test on throat swab remained negative. She was discharged, fully recovered, on hospital day 12. A lower respiratory tract specimen should be obtained for better diagnosis of corona virus disease 2019, even in the absence of respiratory symptoms for patients with significant travel or exposure history.

positive: The neurological manifestations of COVID-19: a review article RESULTS: Various neurological manifestations have been reported in the literature associated with COVID-19, which in the current study are classified into Central Nervous System (CNS) related manifestations including headache, dizziness, impaired consciousness, acute cerebrovascular disease, epilepsy, and Peripheral Nervous System (PNS) related manifestations such as hyposmia/anosmia, hypogeusia/ageusia, muscle pain, and Guillain-Barre syndrome. CONCLUSION: During the current context of COVID-19 pandemic, physicians should be aware of wide spectrum of neurological COVID-19 sign and symptoms for early diagnosis and isolation of patients. In this regard, COVID-19 has been associated with many neurological manifestations such as confusion, anosmia, and ageusia. Also, various evidences support the possible CNS roles in the COVID-19 pathophysiology. In this regard, further investigation of CNS involvement of SARS-COV-2 is suggested.

positive: How can we evaluate an interrelation of symptoms? A pandemic of 2019 novel coronavirus (COVID-19) is an international problem and factors associated with increased risk of mortality have been reported. However, there exists limited statistical method to estimate a comprehensive risk for a case in which a patient has several characteristics and symptoms concurrently. We applied Boolean Monte Carlo method (BMCM) to the Novel Corona Virus 2019 Dataset to determine interrelation of patient's characteristics and symptoms. In the analyses, age, fever as an onset symptom, and sex were used as explanatory variables, and death as the objective variable. Among 265 patients included in the analysis, the interrelations for estimating death were determined as age "and" fever "and" sex (p < 0.0001 for both operators). This result indicates that satisfying the three conditions of age, fever, and sex concurrently may be associated with an increased risk of mortality.

positive: Prevalence and clinical features of 2019 novel coronavirus disease (COVID-19) in the Fever Clinic of a teaching hospital in Beijing: a single-center, retrospective study Background With the spread of COVID-19 from Wuhan, Hubei Province to other areas of the country, medical staff in Fever Clinics faced the challenge of identifying suspected cases among patients with respiratory infections manifested with fever. We aimed to describe the prevalence and clinical features of COVID-19 as compared to pneumonias of other etiologies in a Fever Clinic in Beijing. Methods In this single-center, retrospective study, 342 cases of pneumonia were diagnosed in Fever Clinic in Peking University Third Hospital between January 21 to February 15, 2020. From these patients, 88 were reviewed by panel discussion as possible or probable cases of COVID-19, and received 2019-nCoV detection by RT-PCR. COVID-19 was confirmed by positive 2019-nCoV in 19 cases, and by epidemiological, clinical and CT features in 2 cases (the COVID-19 Group, n=21), while the remaining 67 cases served as the non-COVID-19 group. Demographic and epidemiological data, symptoms, laboratory and lung CT findings were collected, and compared between the two groups. Findings The prevalence of COVID-19 in all pneumonia patients during the study period was 6.14% (21/342). Compared with the non-COVID-19 group, more patients with COVID-19 had an identified epidemiological history (90.5% versus 32.8%, P<0.001). The COVID-19 group had lower WBC [5.19×10^9/L (±1.47) versus 7.21×10^9/L (±2.94), P<0.001] and neutrophil counts [3.39×10^9/L (±1.48) versus 5.38×10^9/L (±2.85), P<0.001] in peripheral blood. However, the percentage and count of lymphocytes were not different. On lung CT scans, involvement of 4 or more lobes was more common in the COVID-19 group (45% versus 16.4%, P=0.008). Interpretation In the period of COVID-19 epidemic outside Hubei Province, the prevalence of COVID-19 in patients with pneumonia visiting to our Fever Clinic in Beijing was 6.14%. Epidemiological evidence was important for prompt case finding, and lower blood WBC and neutrophil counts may be useful for differentiation from pneumonia of other etiologies.

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

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

positive: Gastrointestinal Symptoms and COVID-19: Case-Control Study from the United States

positive: ACUTE VISION LOSS IN A PATIENT WITH COVID-19 To date, there have been reports of neurologic manifestations in Covid-19 patients including ischemic strokes, Guillain-Barre Syndrome and anosmia. In this case report, we report a patient who presented with dysosmia, dysgeusia along with monocular peripheral vision loss after being diagnosed with Covid-19.

positive: Coronavirus Infection Among Children and Adolescents Coronavirus infection is a global emergency. Over the past few months, there is a rapid increase in the number of cases and deaths due to coronavirus infection. It has been observed that elderly individuals and those with medical co-morbidities are maximally affected. In children and adolescents, coronavirus infection has low mortality as well as the severity of symptoms are less. Children and adolescents with immunocompromised state, malnutrition, medical co-morbidities and poor hygiene are at higher risk of contracting coronavirus infection. Minimizing this risk factors and adopting appropriate prevention measures will be helpful in limiting the spread of infection as there is no specific treatment and immunization available to date to address this serious issue. This chapter highlights the issues and challenges of coronavirus infection in children and adolescents.

positive: Clinical characteristics of 16 patients with COVID-19 infection outside of Wuhan, China: A retrospective, single-center study Background: Since early December 2019, the 2019 novel coronavirus (COVID-19) has emerged in Wuhan and spread rapidly in China. We aimed to describe the clinical characteristics of hospitalized patients with confirmed COVID-19 infection in Shaoxing, and provide an insight into the treatment of COVID-19 across China and elsewhere. Methods: In this retrospective, single-center, study, we enrolled 16 patients with laboratory-confirmed COVID-19 admitted to the Affiliated Hospital of Shaoxing University between February 24 and January 25, 2020. Epidemiological, demographic, clinical, laboratory, radiological feature, and treatment data were all collected. Outcomes were followed up until March 16, 2020. Results: Among the 16 patients with COVID-19 infection, 11 patients (68.8%) had traveled or lived in Wuhan or surrounding areas, and 2 (12.5%) patients had exposure to patients with confirmed COVID-19 infection. The average age of the patients was 44.1 (16.5) years, and there were 10 women (62.5%) and 6 men (37.5%). More than half had chronic diseases [9 (56.3%)]. The most common symptoms at onset of COVID-19 infection were fever [12 (75%)] and cough [8 (50%)]; 11 (68.8%) patients had lymphopenia, and 12 (75%) had elevated C-reactive protein. On admission, abnormalities in computed tomography (CT) or chest X-ray images were revealed among all patients, and 11 (68.8%) of 16 patients had bilateral involvement. All patients were given psychological counseling, 15 (93.8%) patients were administered with antiviral therapy, 8 (50%) received empirical antibiotic treatment, and 5 (31.3%) patients were given systematic corticosteroids. Complications included acute respiratory distress syndrome (ARDS) requiring non-invasive mechanical ventilation [1 (6.3%)], acute respiratory injury [4 (25%)], acute renal injury [1 (6.3%)], septic shock [1 (6.3%)], liver dysfunction [5 (31.3%)], electrolyte disturbance [8 (50.0%)], and hospital-acquired pneumonia [3 (18.8%)]. None of the 16 patients died of COVID-19 pneumonia. Conclusions: Compared with the symptoms of the initial patients with COVID-19 infection in Wuhan, the symptoms of the patients from Shaoxing city were relatively mild. Currently, there is no effective drug treatment or vaccine for COVID-19, and psychological counseling cannot be ignored. Drugs and vaccines against COVID-19 infection need to be developed as soon as possible.

positive: Neurological manifestations and COVID-19: Experiences from a tertiary care center at the Frontline OBJECTIVE: To report neurological manifestations seen in patients hospitalized with Coronavirus disease 2019 (COVID-19) from a large academic medical center in Chicago, Illinois. METHODS: We retrospectively reviewed data records of 50 patients with COVID-19 who were evaluated by the neurology services from March 1, 2020 - April 30, 2020. Patients were categorized into 2 groups based on timing of developing neurological manifestations: the "Neuro first" group had neurological manifestations upon initial assessment, and the "COVID first" group developed neurological symptoms greater than 24 h after hospitalization. The demographics, comorbidities, disease severity and neurological symptoms and diagnoses of both groups were analyzed. Statistical analysis was performed to compare the two groups. RESULTS: A total of 50 patients (48% African American and 24% Latino) were included in the analysis. Most common neurological manifestations observed were encephalopathy (n = 30), cerebrovascular disease (n = 20), cognitive impairment (n = 13), seizures (n = 13), hypoxic brain injury (n = 7), dysgeusia (n = 5), and extraocular movement abnormalities (n = 5). The "COVID-19 first" group had more evidence of physiologic disturbances on arrival with a more severe/critical disease course (83.3% vs 53.8%, p 0.025). CONCLUSION: Neurologic manifestations of COVID-19 are highly variable and can occur prior to the diagnosis of or as a complication of the viral infection. Despite similar baseline comorbidities and demographics, the COVID-19 patients who developed neurologic symptoms later in hospitalization had more severe disease courses. Differently from previous studies, we noted a high percentage of African American and Latino individuals in both groups.

positive: Command Suicidal Hallucination as Initial Presentation of Coronavirus Disease 2019 (COVID-19): A Case Report INTRODUCTION: Presently the COVID-19 pandemic is raging through the United States and worldwide. This enigmatic virus characteristically affects the respiratory system. Atypical presentations, such as gastrointestinal symptoms, and cases of encephalopathy have also been reported. However, psychiatric symptoms as the initial presenting feature is novel. We describe one such case. CASE PRESENTATION: 53-year-old man with no prior psychiatric or significant medical history was brought to the emergency department after ingesting bleach in an apparent suicide attempt. On initial presentation, the patient was uncooperative and withdrawn, though alert and oriented. He subsequently developed fever, tachycardia, elevated blood urea nitrogen and transaminases. SARS CoV-2 was confirmed on RT-PCR. Neurological examination was non-contributory. As his clinical condition improved, the patient reported that his initial symptom was an auditory hallucination telling him to jump from a bridge or ingest bleach. He reported that the increasing intensity of his auditory hallucinations led him to act upon it. He denied mood symptoms or suicidal ideation. The hallucinations did not recur during the hospital course, but he required 3 doses of antipsychotic medication for agitation. After improvement of his SARS CoV-2 infection, he was free of psychiatric symptoms and was discharged to a subacute rehabilitation center. CONCLUSION: This case indicates that what appears as a sudden onset of a psychiatric illness in the current context may be an initial manifestation of a developing COVID illness.

positive: Self‐reported olfactory loss associates with outpatient clinical course in Covid‐19 BACKGROUND: : Rapid spread of the SARS‐CoV‐2 virus has left many health systems around the world overwhelmed, forcing triaging of scarce medical resources. Identifying indicators of hospital admission for Covid‐19 patients early in the disease course could aid the efficient allocation of medical interventions. Self‐reported olfactory impairment has recently been recognized as a hallmark of Covid‐19 and may be an important predictor of clinical outcome. METHODS: : A retrospective review of all patients presenting to a San Diego Hospital system with laboratory‐confirmed positive Covid‐19 infection was conducted with evaluation of olfactory and gustatory function and clinical disease course. Univariable and multivariable logistic regression were performed to identify risk factors for hospital admission and anosmia. RESULTS: : A total of 169 patients tested positive for Covid‐19 disease between March 3 and April 8, 2020. Olfactory and gustatory data were obtained for 128/169 (75.7%) subjects of which 26/128 (20.1%) required hospitalization. Admission for Covid‐19 was associated with intact sense of smell and taste, increased age, diabetes, as well as subjective and objective parameters associated with respiratory failure. On adjusted analysis, anosmia was strongly and independently associated with outpatient care (aOR 0.09 95% CI: 0.01‐0.74) while positive findings of pulmonary infiltrates and/or pleural effusion on chest radiograph (aOR 8.01 95% CI: 1.12‐57.49) was strongly and independently associated with admission. CONCLUSIONS: : Normosmia is an independent predictor of admission in Covid‐19 cases. Smell loss in Covid‐19 may associate with a milder clinical course. This article is protected by copyright. All rights reserved

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: Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection OBJECTIVE: To study the GI symptoms in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. DESIGN: We analysed epidemiological, demographic, clinical and laboratory data of 95 cases with SARS-CoV-2 caused coronavirus disease 2019. Real-time reverse transcriptase PCR was used to detect the presence of SARS-CoV-2 in faeces and GI tissues. RESULTS: Among the 95 patients, 58 cases exhibited GI symptoms of which 11 (11.6%) occurred on admission and 47 (49.5%) developed during hospitalisation. Diarrhoea (24.2%), anorexia (17.9%) and nausea (17.9%) were the main symptoms with five (5.3%), five (5.3%) and three (3.2%) cases occurred on the illness onset, respectively. A substantial proportion of patients developed diarrhoea during hospitalisation, potentially aggravated by various drugs including antibiotics. Faecal samples of 65 hospitalised patients were tested for the presence of SARS-CoV-2, including 42 with and 23 without GI symptoms, of which 22 (52.4%) and 9 (39.1%) were positive, respectively. Six patients with GI symptoms were subjected to endoscopy, revealing oesophageal bleeding with erosions and ulcers in one severe patient. SARS-CoV-2 RNA was detected in oesophagus, stomach, duodenum and rectum specimens for both two severe patients. In contrast, only duodenum was positive in one of the four non-severe patients. CONCLUSIONS: GI tract may be a potential transmission route and target organ of SARS-CoV-2.

positive: Gustatory Dysfunction as an Early Symptom in COVID-19 Screening The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from Wuhan, China in December 2019 leads to the present coronavirus disease 2019 (COVID-19) pandemic. The various symptoms identified for COVID-19 are fever, dry cough, sore throat, dyspnea, fatigue, myalgia, and headache. Olfactory and gustatory dysfunctions are emerging as a new symptom more in the European patients. Taste disturbances are common in various oral and systemic diseases. Varying severity and onset of taste disturbances are reported in COVID-19 positive patients in this pandemic. But a sudden onset of taste disturbances without an established and recognized cause should raise suspicion of COVID-19. This article will analyze the various studies focusing on taste disturbances as a reliable early symptom for COVID-19 screening.

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

positive: Importance of SARs-Cov-2 anosmia: From phenomenology to neurobiology Anosmia and hypogeusia, the inability or decreased ability to smell and taste, have been reported as common complaints in SARS-CoV-2 patients who were still in an asymptomatic phase. These impairments affect the ability to sense odors in foods and the environment, obviously affecting quality of life, related to social interactions and general well-being. The British Association of Otorhinolaryngology (ENT-UK) considers loss of sense of smell in their list of COVID-19's markers of infection. Here we present two cases in which early manifestations of anosmia and hypogeusia were experienced with psycho-sensorial and atmospheric phenomena. Psychiatrists, neurologists and physicians in general should be aware of this symptom presentation in order to avoid mistreatment, given that persistent olfactory dysfunction might increase the risks of nutritional deficit and lead to development of adjustment disorders. All clinicians should be aware that the presentation of SARS-CoV-2's symptoms goes far beyond respiratory and sensorial dimensions and involves psychosensorial and neurological dimensions; these clinical observations could shed light on the neurobiological substrates involved in COVID-19 disease.

positive: Neutrophil-to-lymphocyte ratio predicts critical illness patients with 2019 coronavirus disease in the early stage BACKGROUND: Patients with critical illness due to infection with the 2019 coronavirus disease (COVID-19) show rapid disease progression to acute respiratory failure. The study aimed to screen the most useful predictive factor for critical illness caused by COVID-19. METHODS: The study prospectively involved 61 patients with COVID-19 infection as a derivation cohort, and 54 patients as a validation cohort. The predictive factor for critical illness was selected using LASSO regression analysis. A nomogram based on non-specific laboratory indicators was built to predict the probability of critical illness. RESULTS: The neutrophil-to-lymphocyte ratio (NLR) was identified as an independent risk factor for critical illness in patients with COVID-19 infection. The NLR had an area under receiver operating characteristic of 0.849 (95% confidence interval [CI], 0.707 to 0.991) in the derivation cohort and 0.867 (95% CI 0.747 to 0.944) in the validation cohort, the calibration curves fitted well, and the decision and clinical impact curves showed that the NLR had high standardized net benefit. In addition, the incidence of critical illness was 9.1% (1/11) for patients aged ≥ 50 and having an NLR < 3.13, and 50% (7/14) patients with age ≥ 50 and NLR ≥ 3.13 were predicted to develop critical illness. Based on the risk stratification of NLR according to age, this study has developed a COVID-19 pneumonia management process. CONCLUSIONS: We found that NLR is a predictive factor for early-stage prediction of patients infected with COVID-19 who are likely to develop critical illness. Patients aged ≥ 50 and having an NLR ≥ 3.13 are predicted to develop critical illness, and they should thus have rapid access to an intensive care unit if necessary.

positive: Epidemiological and clinical characteristics of 136 cases of COVID-19 in main district of Chongqing Background We did a comprehensive exploration of the epidemiological and clinical characteristics of 136 patients with confirmed COVID-19 in main district of Chongqing which was adjacent to the west of Hubei province. Methods This study was conducted on 136 patients with COVID-19 in main district of Chongqing from Jan 25 to Feb 20, 2020. Data of patients included demographic, epidemiological, clinical features, chest radiographs of imported cases, local cases, second-generation cases and third-generation cases. Student's t-test was adopted for quantitative variables while Pearson Chi-squared test or Fisher's exact test for categorical variables. Results The median age was 47 years and common symptoms of illness were cough (50.7%), fever (47.1%) and fatigue (14.0%). The time from contact symptomatic case to illness was 7.7 days, and 88 patients (64.7%) were cluster cases, radiological evidence found bilateral lung involvement was common (57.4%).Compared with the imported cases, the local cases were significantly older, the proportion of men is lower. There was higher proportion of cluster cases in local cases. Unlike imported cases, which fever was the dominant symptom, the local cases have more cough patients, with a significant higher proportion of asymptomatic patients. The third-generation cases have a significant higher proportion of asymptomatic patients. Conclusions We concluded the epidemiological and clinical characteristics of the cases andsuggested to take more comprehensive measures for screening patients, especially for elderly person, avoid family gatherings, and implement more closely surveillance of suspect patients and their close contacts.

positive: [Analysis of gastrointestinal symptoms in 80 patients with coronavirus disease 2019]. OBJECTIVE To investigate the clinical characteristics of gastrointestinal symptoms in patients with coronavirus disease 2019 (COVID-19) during the whole disease process, and provide reference for etiological diagnosis and treatment. METHODS The clinical data of patients with COVID-19 admitted in the Infectious Diseases Branch of the First Affiliated Hospital of University of Science and Technology of China from January 22nd, 2020 to March 8th, 2020 were analyzed retrospectively. According to whether there were gastrointestinal symptoms (poor appetite, nausea/vomiting and diarrhea), all patients were divided into gastrointestinal symptom group and asymptomatic group. The characteristics of gastrointestinal symptoms, such as poor appetite, nausea, vomiting and diarrhea were counted and analyzed, and the correlation between gastrointestinal symptoms and gender, age, basic diseases, disease severity, laboratory examination and drug treatment were analyzed. RESULTS A total of 80 COVID-19 patients were involved, 43 cases (53.8%) presented with poor appetite, 17 cases (21.3%) had nausea and vomiting, and 33 cases (41.3%) had diarrhea. Among them, 5 cases, 1 case and 4 cases respectively preformed poor appetite, nausea/vomiting and diarrhea before admission, while the others experienced gastrointestinal symptoms within 48 hours after admission. Duration of poor appetite, nausea/vomiting and diarrhea (days) of all patients were 5.3±2.1, 2.2±1.0 and 1.4±0.9, respectively. The patients with poor appetite were older than those without symptoms (years old: 48.2±17.6 vs. 39.3±15.1), albumin (Alb) level and the lymphocytes ratio were lower than those in asymptomatic group [Alb (g/L): 39.8 (35.7, 45.1) vs. 46.1 (42.6, 49.4), lymphocytes ratio: 0.19 (0.09, 0.28) vs. 0.28 (0.17, 0.35)], while the neutrophil ratio, the levels of C-reactive protein (CRP), D-dimer, and lactate dehydrogenase (LDH) were higher than those in asymptomatic group [the neutrophil ratio: 0.74 (0.61, 0.85) vs. 0.64 (0.52, 0.76), CRP (mg/L): 21.4 (3.9, 52.9) vs. 5.6 (2.4, 14.0), D-dimer (mg/L): 0.2 (0.2, 0.5) vs. 0.2 (0.1, 0.3), LDH (μmol×s-1×L-1): 4.49 (3.59, 5.19) vs. 3.12 (2.77, 4.90)]; at the same time, more traditional Chinese medicine was used in the patients with gastrointestinal symptoms [65.1% (28/43) vs. 40.5% (15/37), all P < 0.05]. In addition, 14 cases of 18 patients with cardiovascular diseases presented with poor appetite, 7 patients had nausea and vomiting symptoms. All of the 3 patients with chronic kidney disease presented with poor appetite, nausea and vomiting, and 2 of them had diarrhea. CONCLUSIONS The gastrointestinal symptoms in patients with COVID-19 are common. Whether it is caused by the virus or related drugs, diet and mental conditions, clinicians should analyze the causes of these symptoms timely, and then provide a better treatment for patients with COVID-19.

positive: Atypical presentation of SARS-CoV-2 infection: A case report. BACKGROUND The first case of pneumonia subsequently attributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in Wuhan, Hubei Province on December 8, 2019. The symptoms included fever, coughing, and breathing difficulties. A few patients with this infection may only have atypical symptoms, which could lead to a misdiagnosis and subsequently further facilitate the spread of the virus. CASE SUMMARY A 74-year-old female patient complained of severe diarrhea. She did not have fever, coughing, or breathing difficulties. A physical examination revealed no obvious positive signs. The patient had been hypertensive for more than 10 years. Her blood pressure was well controlled. On January 9, 2020, the patient's son visited a colleague who was later confirmed positive for SARS-CoV-2 and his first close contact with our patient was on January 17. The patient was first diagnosed with gastrointestinal dysfunction. However, considering her indirect contact with a SARS-CoV-2-infected individual, we suggested that an atypical pneumonia virus infection should be ruled out. A computed tomography scan was performed on January 26, and showed ground-glass nodules scattered along the two lungs, suggestive of viral pneumonia. Given the clinical characteristics, epidemiological history, and examination, the patient was diagnosed with coronavirus disease-2019 (COVID-19). CONCLUSION Our patient had atypical symptoms of COVID-19. Careful acquisition of an epidemiological history is necessary to make a correct diagnosis and strategize a treatment plan.

positive: Acute‐onset smell and taste disorders in the context of COVID‐19: a pilot multicentre polymerase chain reaction based case–control study BACKGROUND AND PURPOSE: Specific respiratory tract infections, including COVID‐19, may cause smell and/or taste disorders (STDs) with increased frequency. The aim was to determine whether new‐onset STDs are more frequent amongst COVID‐19 patients than influenza patients. METHOD: This was a case–control study including hospitalized patients of two tertiary care centres. Consecutive patients positive for COVID‐19 polymerase chain reaction (cases) and patients positive for influenza polymerase chain reaction (historical control sample) were assessed during specific periods, employing a self‐reported STD questionnaire. RESULTS: Seventy‐nine cases and 40 controls were included. No significant differences were found in basal features between the two groups. New‐onset STDs were significantly more frequent amongst cases (31, 39.2%) than in the control group (5, 12.5 %) [adjusted odds ratio 21.4 (2.77–165.4, P = 0.003)]. COVID‐19 patients with new‐onset STDs were significantly younger than COVID‐19 patients without STDs (52.6 ± 17.2 vs. 67.4 ± 15.1, P < 0.001). Amongst COVID‐19 patients who presented STDs, 22 (70.9%) recalled an acute onset and it was an initial manifestation in 11 (35.5%). Twenty‐five (80.6%) presented smell disorders (mostly anosmia, 14, 45.2%) and 28 (90.3%) taste disorders (mostly ageusia, 14, 45.2%). Only four (12.9 %) reported concomitant nasal obstruction. The mean duration of STD was 7.5 ± 3.2 days and 12 patients (40%) manifested complete recovery after 7.4 ± 2.3 days of onset. CONCLUSION: New‐onset STDs were significantly more frequent amongst COVID‐19 patients than influenza patients; they usually had an acute onset and were commonly an initial manifestation. The use of STD assessment in anamnesis as a hint for COVID‐19 and to support individuals’ self‐isolation in the current epidemic context is suggested.

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: New type of corona virus induced acute otitis media in adult Since late December 2019, a new type of coronavirus (CIVID-19) causing a cluster of respiratory infections was first identified in Wuhan-China. And it disseminated to all countries. Generally, COVID-19 cases have fever, cough, respiratory distress findings (dyspnoea, intercostal retraction, cyanosis etc.). In this paper, we have presented an adult otitis media case whom infected with COVID-19, but she have not any classical COVID-19 symptoms.

positive: Epidemiologic and Clinical Characteristics of 91 Hospitalized Patients with COVID-19 in Zhejiang, China: A retrospective, multi-centre case series BACKGROUND: Recent studies have focused initial clinical and Epidemiologic characteristics on the COVID-19, mainly revealing situation in Wuhan, Hubei. AIM: To reveal more data on the epidemiologic and clinical characteristics of COVID-19 patients outside of Wuhan, in Zhejiang, China. DESIGN: Retrospective case series. METHODS: 88 cases of laboratory-confirmed and 3 cases of clinical-confirmed COVID-19 were admitted to five hospitals in Zhejiang province, China. Data were collected from 20 January 2020 to 11 February 2020. RESULTS: Of all 91 patients, 88 (96.70%) were laboratory-confirmed COVID-19 with throat swab samples that tested positive for SARS-Cov-2 while 3 (3.30%) were clinical-diagnosed COVID-19 cases. The median age of the patients was 50 (36.5-57) years, and female accounted for 59.34%. In this sample 40 (43.96%) patients had contracted the diseases from local cases, 31 (34.07%) patients had been to Wuhan/Hubei, 8 (8.79%) cases had contacted with people from Wuhan, 11 (12.09%) cases were confirmed aircraft transmission. In particular within the city of Ningbo, 60.52% cases can be traced back to an event held in a temple. The most common symptoms were fever (71.43%), cough (60.44%) and fatigue (43.96%). The median of incubation period was 6 (IQR, 3-8) days and the median time from first visit to a doctor to confirmed diagnosis was 1 (1-2) days. According to the Chest computed tomography scans, 67.03% cases had bilateral pneumonia. CONCLUSIONS: Social activity cluster, family cluster and travel by airplane were how COVID-19 patients get transmitted and could be rapidly diagnosed COVID-19 in Zhejiang.

positive: Gastrointestinal Symptoms and outcomes in hospitalized COVID-19 patients INTRODUCTION: Gastrointestinal (GI) symptoms are increasingly being recognized in coronavirus disease 2019 (COVID-19). It is unclear if the presence of GI symptoms is associated with poor outcomes in COVID-19. We aim to assess if GI symptoms could be used for prognostication in hospitalized patients with COVID-19. METHODS: We retrospectively analyzed patients admitted to a tertiary medical center in Brooklyn, NY, from March 18, 2020, to March 31, 2020, with COVID-19. The patients' medical charts were reviewed for the presence of GI symptoms at admission, including nausea, vomiting, diarrhea, and abdominal pain. COVID-19 patients with GI symptoms (cases) were compared with COVID-19 patients without GI symptoms (control). RESULTS: A total of 150 hospitalized COVID-19 patients were included, of which 31 (20.6%) patients had at least one or more of the GI symptoms (cases). They were compared with the 119 COVID-19 patients without GI symptoms (controls). The average age among cases was 57.6 years (SD 17.2) and, control was 63.3 years (SD 14.6). No statistically significant difference was noted in comorbidities and laboratory findings. The primary outcome was mortality, which did not differ between cases and controls (41.9% vs. 37.8%, p=0.68). No statistically significant differences were noted in secondary outcomes, including the length of stay (LOS, 7.8 days vs. 7.9 days, p=0.87) and need for mechanical ventilation (29% vs. 26.9%, p=0.82). DISCUSSION: In our study, the presence of GI manifestations in COVID-19 at the time of admission was not associated with increased mortality, LOS, or mechanical ventilation.

positive: Understanding the neurotropic characteristics of SARS-CoV-2: from neurological manifestations of COVID-19 to potential neurotropic mechanisms Coronavirus disease 2019 (COVID-19), a disease caused by the novel betacoronavirus (SARS-CoV-2), has become a global pandemic threat. The potential involvement of COVID-19 in central nervous system (CNS) has attracted considerable attention due to neurological manifestations presented throughout the disease process. In addition, SARS-CoV-2 is structurally similar to SARS-CoV, and both bind to the angiotensin-converting enzyme 2 (ACE2) receptor to enter human cells. Thus, cells expressing ACE2, such as neurons and glial cells may act as targets and are thus vulnerable to SARS-CoV-2 infection. Here, we have reviewed the neurological characteristics of COVID-19 and summarized possible mechanisms of SARS-CoV-2 invasion of the CNS. COVID-19 patients have presented with a number of different neurological symptoms such as headache, dizziness, hyposmia, and hypogeusia during the course of illness. It has also been reported recently that some cases of COVID-19 have presented with concurrent acute cerebrovascular disease (acute ischemic stroke, cerebral venous sinus thrombosis, cerebral hemorrhage, subarachnoid hemorrhage), meningitis/encephalitis, acute necrotizing hemorrhagic encephalopathy, and acute Guillain–Barré syndrome. Furthermore, SARS-CoV-2 RNA detected in a cerebrospinal fluid specimen of a patient with COVID-19 have provided direct evidence to support the theory of neurotropic involvement of SARS-CoV-2. However, the underlying neurotropic mechanisms of SARS-CoV-2 are yet to be established. SARS-CoV-2 may affect CNS through two direct mechanisms (hematogenous dissemination or neuronal retrograde dissemination) or via indirect routes. The underlying mechanisms require further elucidation in the future.

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

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: What do surgeons need to know about the digestive disorders and paraclinical abnormalities induced by COVID-19? Abstract The symptoms associated with COVID-19 are mainly characterized by a triad composed of fever, dry cough and dyspnea. However, digestive symptoms have also been reported; at first considered as infrequent, they in fact seem to affect (to some extent) more than half of patients. The symptoms are mainly manifested by anorexia, diarrhea, nausea and/or vomiting and abdominal pain. Even though prognosis is associated with lung injury, digestive symptoms seem significantly more frequent in patients presenting with severe COVID-19 infection. Digestive forms, which may be isolated or which can precede pulmonary symptoms, have indeed been reported, with diarrhea as a leading clinical sign. The main biological abnormalities that can suggest COVID-19 infection at an early stage are lymphopenia, elevated CRP and heightened ASAT transaminases. Thoraco-abdominal scan seems useful as a means of on the one hand ruling out digestive pathology not connected with coronavirus and on the other hand searching for pulmonary images compatible with COVID-19 infection. No data exist on the interest of digestive endoscopy in cases of persistent digestive symptoms. Moreover, the endoscopic surgeons may themselves be at significant risk of contamination. Fecal-oral transmission of the infection is possible, especially insofar as viral shedding in stools seems frequent and of longer duration than at the ENT level, including in patients with negative throat swab and without digestive symptoms. In some doubtful cases, virologic assessment of stool samples can yield definitive diagnosis. In the event of prolonged viral shedding in stools, a patient’s persistent contagiousness is conceivable but not conclusively established. Upcoming serology should enable identification of the patients having been infected by the COVID-19 epidemic, particularly among previously undetected pauci-symptomatic members of a health care staff. Resumption of medico-surgical activity should be the object of a dedicated strategy preceding deconfinement.

positive: Case Report on Early Diagnosis of COVID-19 The coronavirus disease 2019 (COVID-19) outbreak in Wuhan, China, spread rapidly throughout China and gradually to some countries abroad. How is the development of an epidemic controlled? Early diagnosis is one of the important contents in prevention and control. COVID-19 patients with early mild pneumonia often lack typical evidence to make a definitive diagnosis. Based on the analysis of the cases of 4 patients, this article finds that early diagnosis requires a combination of epidemiology, clinical manifestations, imaging, and etiology, with particular emphasis on epidemiology history and chest computed tomography (CT) manifestations.

positive: Cardiovascular implications of the COVID-19 pandemic: a global perspective The Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), represents the pandemic of the century, with approximately 3.5 million cases and 250,000 deaths worldwide as of May 2020. Although respiratory symptoms usually dominate the clinical presentation, COVID-19 is now known to also have potentially serious cardiovascular consequences, including myocardial injury, myocarditis, acute coronary syndromes, pulmonary embolism, stroke, arrhythmias, heart failure, and cardiogenic shock. The cardiac manifestations of COVID-19 might be related to the adrenergic drive, systemic inflammatory milieu and cytokine-release syndrome caused by SARS-CoV-2, direct viral infection of myocardial and endothelial cells, hypoxia due to respiratory failure, electrolytic imbalances, fluid overload, and side effects of certain COVID-19 medications. COVID-19 has profoundly reshaped usual care of both ambulatory and acute cardiac patients, by leading to the cancellation of elective procedures and by reducing the efficiency of existing pathways of urgent care, respectively. Decreased utilization of healthcare services for acute conditions by non-COVID-19 patients has also been reported and attributed to concerns about acquiring in-hospital infection. Innovative approaches that leverage modern technologies to tackle the COVID-19 pandemic have been introduced, which include telemedicine, dissemination of educational material over social media, smartphone apps for case tracking, and artificial intelligence for pandemic modelling, among others. This article provides a comprehensive overview of the pathophysiology and cardiovascular implications of COVID-19, its impact on existing pathways of care, the role of modern technologies to tackle the pandemic, and a proposal of novel management algorithms for the most common acute cardiac conditions.

positive: SARS-COV-2 infection (coronavirus disease 2019) for the gastrointestinal consultant The current pandemic due to the severe acute respiratory syndrome coronavirus 2 has caused an extreme burden for health care systems globally, and the number of cases is expected to continue to increase, at least in the immediate future. The virus is estimated to have infected more than 1.5 million individuals. The available reports suggest that gastrointestinal (GI) involvement in coronavirus disease 2019 (COVID-19) is common and in some cases the GI symptoms may precede the respiratory symptoms. In addition to direct effects of severe acute respiratory syndrome coronavirus 2, the infected patients remain at risk for the complications commonly managed by gastroenterology and hepatology consultants. The most commonly reported GI manifestation of COVID-19 is diarrhea, which is reported in a third to up to more than half of the patients. Mild to moderate elevation of the liver enzymes are also common, although no case of acute liver failure has been reported so far. Many of the medications used for treatment of COVID-19 can also be associated with GI symptoms or liver injury and can be included in the differential diagnosis in these patients. Although the diagnosis of the infection is currently based on RNA analysis in respiratory samples, the available literature on fecal shedding of this virus suggests that fecal RNA testing might prove to be a useful diagnostic test. It is reasonable to delay all non-urgent endoscopic procedures during the peak of the pandemic and use additional protective equipment such as N95 respirators during endoscopy while most patients can be considered high risk for having been exposed to the virus.

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: A multinational, multicentre study on the psychological outcomes and associated physical symptoms amongst healthcare workers during COVID-19 outbreak Abstract Objective Since the declaration of the coronavirus 2019 (COVID-19) outbreak as pandemic, there are reports on the increased prevalence of physical symptoms observed in the general population. We investigated the association between psychological outcomes and physical symptoms among healthcare workers. Methods Healthcare workers from 5 major hospitals, involved in the care for COVID-19 patients, in Singapore and India were invited to participate in a study by performing a self-administered questionnaire within the period of February 19 to April 17, 2020. Healthcare workers included doctors, nurses, allied healthcare workers, administrators, clerical staff and maintenance workers. This questionnaire collected information on demographics, medical history, symptom prevalence in the past month, Depression Anxiety Stress Scales (DASS-21) and the Impact of Events Scale-Revised (IES-R) instrument. The prevalence of physical symptoms displayed by healthcare workers and the associations between physical symptoms and psychological outcomes of depression, anxiety, stress, and post-traumatic stress disorder (PTSD) were evaluated. Results Out of the 906 healthcare workers who participated in the survey, 48 (5.3%) screened positive for moderate to very-severe depression, 79 (8.7%) for moderate to extremely-severe anxiety, 20 (2.2%) for moderate to extremely-severe stress, and 34 (3.8%) for moderate to severe levels of psychological distress. The commonest reported symptom was headache (32.3%), with a large number of participants (33.4%) reporting more than four symptoms. Participants who had experienced symptoms in the preceding month were more likely to be older, have pre-existing comorbidities and a positive screen for depression, anxiety, stress, and PTSD. After adjusting for age, gender and comorbidities, it was found that depression (OR 2.79, 95% CI 1.54–5.07, p = 0.001), anxiety (OR 2.18, 95% CI 1.36–3.48, p = 0.001), stress (OR 3.06, 95% CI 1.27–7.41, p = 0.13), and PTSD (OR 2.20, 95% CI 1.12–4.35, p = 0.023) remained significantly associated with the presence of physical symptoms experienced in the preceding month. Linear regression revealed that the presence of physical symptoms was associated with higher mean scores in the IES-R, DASS Anxiety, Stress and Depression subscales. Conclusions Our study demonstrates a significant association between the prevalence of physical symptoms and psychological outcomes among healthcare workers during the COVID-19 outbreak. We postulate that this association may be bi-directional, and that timely psychological interventions for healthcare workers with physical symptoms should be considered once an infection has been excluded.

positive: Association of Digestive Symptoms and Hospitalization in Patients with SARS-CoV-2 Infection Background: High rates of concurrent gastrointestinal manifestations have been noted in patients with COVID- 19, however the association between these digestive manifestations and need for hospitalization has not been established. Methods: Following expedited approval from our Institutional Review Board, we analyzed retrospectively collected data from consecutive patients with confirmed COVID-19 based on a positive polymerase chain reaction testing at our institution from March 03, 2020 to April 7, 2020. Baseline demographic, clinical, laboratory and patient-reported symptom data were collected at presentation in the emergency room. Multivariable logistic regression analyses were performed to evaluate the association between hospitalization and presence of gastrointestinal symptoms. Results: During this study period, we identified 207 consecutive patients with confirmed COVID-19. 34.5% noted concurrent gastrointestinal symptoms; of which 90% of gastrointestinal symptoms were mild. In a multivariate regression model controlled for demographics and disease severity, an increased risk for hospitalization was noted in patients with any gastrointestinal symptom (adjusted OR 4.84 95% CI: 1.68-13.94]. Diarrhea was associated with a seven-fold higher likelihood for hospitalization (adjusted OR=7.58, 95% CI: 2.49-20.02, P <0.001) and nausea or vomiting had a four times higher odds (adjusted OR 4.39, 95% CI: 1.61-11.4, P = 0.005). Conclusion: We demonstrate that a significant portion of COVID19 patients have concurrent mild gastrointestinal symptoms and that the presence of these digestive symptoms is associated with a need for hospitalization. With the current focus on streamlining triaging efforts, first responders and frontline providers should consider assessing for digestive symptoms in their initial clinical evaluation and decision-making.

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

positive: Cluster of COVID-19 in northern France: A retrospective closed cohort study Background: The Oise department in France has been heavily affected by COVID-19 in early 2020. Methods: Between 30 March and 4 April 2020, we conducted a retrospective closed cohort study among pupils, their parents and siblings, as well as teachers and non-teaching staff of a high-school located in Oise. Participants completed a questionnaire that covered history of fever and/or respiratory symptoms since 13 January 2020 and had blood tested for the presence of anti-SARS-CoV-2 antibodies. The infection attack rate (IAR) was defined as the proportion of participants with confirmed SARS-CoV-2 infection based on antibody detection. Blood samples from two blood donor centres collected between 23 and 27 March 2020 in the Oise department were also tested for presence of anti-SARS-CoV-2 antibodies. Findings: Of the 661 participants (median age: 37 years), 171 participants had anti-SARS-CoV-2 antibodies. The overall IAR was 25.9% (95% confidence interval (CI) = 22.6-29.4), and the infection fatality rate was 0% (one-sided 97.5% CI = 0-2.1). Nine of the ten participants hospitalised since mid-January were in the infected group, giving a hospitalisation rate of 5.3% (95% CI = 2.4-9.8). Anosmia and ageusia had high positive predictive values for SARS-CoV-2 infection (84.7% and 88.1%, respectively). Smokers had a lower IAR compared to non-smokers (7.2% versus 28.0%, P <0.001). The proportion of infected individuals who had no symptoms during the study period was 17.0% (95% CI = 11.2-23.4). The proportion of donors with anti-SARS-CoV-2 antibodies in two nearby blood banks of the Oise department was 3.0% (95% CI = 1.1-6.4). Interpretation: The relatively low IAR observed in an area where SARS-CoV-2 actively circulated weeks before confinement measures indicates that establishing herd immunity will take time, and that lifting these measures in France will be long and complex.

positive: Neurological manifestations and COVID-19: Experiences from a tertiary care center at the Frontline. OBJECTIVE To report neurological manifestations seen in patients hospitalized with Coronavirus disease 2019 (COVID-19) from a large academic medical center in Chicago, Illinois. METHODS We retrospectively reviewed data records of 50 patients with COVID-19 who were evaluated by the neurology services from March 1, 2020 - April 30, 2020. Patients were categorized into 2 groups based on timing of developing neurological manifestations: the "Neuro first" group had neurological manifestations upon initial assessment, and the "COVID first" group developed neurological symptoms greater than 24 h after hospitalization. The demographics, comorbidities, disease severity and neurological symptoms and diagnoses of both groups were analyzed. Statistical analysis was performed to compare the two groups. RESULTS A total of 50 patients (48% African American and 24% Latino) were included in the analysis. Most common neurological manifestations observed were encephalopathy (n = 30), cerebrovascular disease (n = 20), cognitive impairment (n = 13), seizures (n = 13), hypoxic brain injury (n = 7), dysgeusia (n = 5), and extraocular movement abnormalities (n = 5). The "COVID-19 first" group had more evidence of physiologic disturbances on arrival with a more severe/critical disease course (83.3% vs 53.8%, p 0.025). CONCLUSION Neurologic manifestations of COVID-19 are highly variable and can occur prior to the diagnosis of or as a complication of the viral infection. Despite similar baseline comorbidities and demographics, the COVID-19 patients who developed neurologic symptoms later in hospitalization had more severe disease courses. Differently from previous studies, we noted a high percentage of African American and Latino individuals in both groups.

positive: The clinical dynamics of 18 cases of COVID-19 outside of Wuhan, China The novel coronavirus can be transmitted from person to person with infection ranging from mild disease to severe pneumonia and radiological abnormalities on chest CT for most patients improved after RT-PCR conversion.

positive: 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.

positive: COVID-19 and Gastrointestinal Symptoms—A Case Report COVID-19, a new illness secondary to a novel Coronavirus emerged in December 2019 in China. Our early understanding of the clinical features of COVID-19 has been based on case series emerging from the first outbreak in Wuhan. These features included fever, a dry cough, myalgia and dyspnea. Gastrointestinal symptoms were rarely reported as a key feature. We present a case report of a 74-year-old male who presented with symptoms of gastroenteritis and subsequently tested positive for COVID-19. This article aims to highlight an uncommon presentation of COVID-19 and that a high index of suspicion is required for COVID-19 in older people given their greater likelihood of presenting atypically.

positive: Clinical Progression of COVID-19 Patient with Extended Incubation Period, Delayed RT-PCR Time-to-positivity, and Potential Role of Chest CT-scan. Coronavirus Disease 2019 (COVID-19), previously called 2019-nCoV, is a novel disease caused by SARS- CoV-2 which was first identified as outbreak of unknown respiratory illness in Wuhan, China. COVID- 19 was declared as global health emergency by WHO on March 11, 2020 and quickly elevated to global pandemic on 11 March 2020. COVID-19 symptom is highly various in each patient, with fever, fatigue, shortness of breath, and cough as the main presenting symptoms. Patient with COVID-19 may shows severe symptom with severe pneumonia and ARDS, mild symptom resembling simple upper respiration tract infection, or even completely asymptomatic. Approximately 80% of cases is mild. However the number may changes as more people are getting tested. Some experts are estimating that up to 50% of all cases may be asymptomatic carrier.

positive: Bariatric Surgical Practice During the Initial Phase of COVID-19 Outbreak There is no data on patients with severe obesity who developed coronavirus disease 2019 (COVID-19) after bariatric surgery. Four gastric bypass operations, performed in a 2-week period between Feb 24 and March 4, 2020, in Tehran, Iran, were complicated with COVID-19. The mean age and body mass index were 46 ± 12 years and 49 ± 3 kg/m(2). Patients developed their symptoms (fever, cough, dyspnea, and fatigue) 1, 2, 4, and 14 days after surgery. One patient had unnoticed anosmia 2 days before surgery. Three patients were readmitted in hospital. All 4 patients were treated with hydroxychloroquine. In two patients who required admission in intensive care unit, other off-label therapies including antiretroviral and immunosuppressive agents were also administered. All patients survived. In conclusion, COVID-19 can complicate the postoperative course of patients after bariatric surgery. Correct diagnosis and management in the postoperative setting would be challenging. Timing of infection after surgery in our series would raise the possibility of hospital transmission of COVID-19: from asymptomatic patients at the time of bariatric surgery to the healthcare workers versus acquiring the COVID-19 infection by non-infected patients in the perioperative period.

positive: Clinical manifestations of children with COVID-19: A systematic review BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak is an unprecedented global public health challenge, leading to thousands of deaths every day worldwide. Despite the epidemiological importance, clinical patterns of children with COVID-19 remain unclear. The aim of this study was to describe the clinical, laboratorial, and radiological characteristics of children with COVID-19. METHODS: The Medline database was searched between December 1st 2019 and April 6th 2020. No language restrictions were applied. Inclusion criteria were (a) studied patients younger than 18 years old; (b) presented original data from cases of COVID-19 confirmed by reverse-transcription polymerase chain reaction; and (c) contained descriptions of clinical manifestations, laboratory tests, or radiological examinations. RESULTS: A total of 38 studies (1124 cases) were included. From all the cases, 1117 had their severity classified: 14.2% were asymptomatic, 36.3% were mild, 46.0% were moderate, 2.1% were severe, and 1.2% were critical. The most prevalent symptom was fever (47.5%), followed by cough (41.5%), nasal symptoms (11.2%), diarrhea (8.1%), and nausea/vomiting (7.1%). One hundred forty-five (36.9%) children were diagnosed with pneumonia and 43 (10.9%) upper airway infections were reported. Reduced lymphocyte count was reported in 12.9% of cases. Abnormalities in computed tomography were reported in 63.0% of cases. The most prevalent abnormalities reported were ground-glass opacities, patchy shadows, and consolidations. Only one death was reported. CONCLUSIONS: Clinical manifestations of children with COVID-19 differ widely from adult cases. Fever and respiratory symptoms should not be considered a hallmark of COVID-19 in children.

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

positive: Gastrointestinal symptoms as Covid-19 onset in hospitalized Italian patients Objective To assess the prevalence of gastrointestinal symptoms and their correlation with need of non-invasive ventilatory support, intensive care unit admission and death in hospitalized SARS-CoV-2 patients. Design Since February 21th 2020, all individuals referred to our emergency department for suspected SARS-CoV-2 underwent a standardized assessment of body temperature and pulse oximetry, hematological screening, chest X-ray and/or computed tomography (CT), and SARS-CoV-2 assay on nasopharyngeal swab. Medical history and GI symptoms including nausea, vomit, diarrhea, and abdominal pain were recorded. Results GI symptoms were the main presentation in 42 (10.2%) of 411 patients, with a mean onset 4.9 +/-... days before admission. In 5 (1.2%) patients GI symptoms have not been associated with respiratory symptoms or fever. We found an inverse trend for ICU admission and death as compared with patients without GI symptoms. Conclusions GI symptoms can be an early and not negligible feature of Covid-19, and might be correlated with a more benign disease course.

positive: 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.

positive: 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.

positive: [Epidemiological characteristics of COVID-19 in Gansu province] Objective: To understand the epidemiological characteristics of COVID-19 cases in different epidemic stages in Gansu province. Methods: Epidemiological investigation was conducted to collect the information of confirmed COVID-19 cases, including demographic, epidemiological and clinical information. Results: As of 25 February 2020, a total of 91 confirmed COVID-19 cases had been reported in Gansu. The epidemic of COVID-19 in Gansu can be divided as three different stages, i.e. imported case stage, imported-case plus indigenous case stage, and indigenous case stage. A total of 63 cases were clustered cases (69.23%), 3 cases were medical staff infected with non-occupational exposure. The initial symptoms included fever (54.95%, 50/91), cough (52.75%, 48/91), or fatigue (28.57%, 26/91), the proportion of each symptom showed a decreasing trend along with the three epidemic stages, but only the differences in proportions of fever (trend χ2=2.20, P<0.05) and fatigue (trend χ2=3.18, P<0.05) among the three epidemic stages were statistically significant. The cases with critical severe symptoms accounted for 42.85% (6/14), 23.73% (14/59) and 16.67% (3/18), respectively, in three epidemic stages, showed a decreasing trend (H=6.45, P<0.05). Also, the incubation period prolonged along with the epidemic stage (F=51.65, P<0.01), but the intervals between disease onset and hospital visit (F=5.32, P<0.01), disease onset and diagnosis (F=5.25, P<0.01) became shorter along with the epidemic stage. Additionally, the basic reproduction number (R0) had decreased from 2.61 in imported case stage to 0.66 in indigenous case stage. Conclusions: The COVID-19 epidemic in Gansu was caused by the imported cases, and about 2/3 cases were clustered ones. No medical worker was observed to be infected by occupational exposure. With the progression of COVID-19 epidemic in Gansu, the change in initial symptom and incubation period suggests, the early screening cannot only depend on body temperature monitoring.

positive: Keratoconjunctivitis as the initial medical presentation of the novel coronavirus disease 2019 (COVID-19) We present a case of coronavirus disease 2019 (COVID-19) with an initial medical presentation of keratoconjunctivitis, the first such reported case in North America. The patient's primary symptom was a red eye with watery discharge, though she did have mild respiratory symptoms, without fever. She was diagnosed with keratoconjunctivitis; evolving corneal findings were characterized through repeat visits to ophthalmology. A conjunctival swab of the affected eye was positive for the SAR-CoV-2 virus. This case emphasizes the importance of ensuring that first-line health care providers, including ophthalmologists, optometrists, emergency physicians, and family physicians, consider COVID-19 on the differential for any patient with recent travel who presents with acute conjunctivitis. Having a high index of suspicion with this presentation would allow for appropriate precautions to be taken to prevent further spread of COVID-19.

positive: An Online Observational Study of Patients With Olfactory and Gustory Alterations Secondary to SARS-CoV-2 Infection Introduction: Since the beginning of the Covid-19 epidemic produced by SARS2-Cov virus, olfactory alterations have been observed at a greater frequency than in other coronavirus epidemics. While olfactory alterations may be observed in patients with rhinovirus, influenza virus, or parainfluenza virus infection, they are typically explained by nasal obstruction with mucus or direct epithelial damage; in the case of SARS-CoV-2, olfactory alterations may present without nasal congestion with mucus. We performed a study of patients presenting olfactory/gustatory alterations in the context of SARS-CoV-2 infection in order to contribute to the understanding of this phenomenon. Material and Methods: We performed a descriptive, cross-sectional, observational study of the clinical characteristics of olfactory/gustatory alterations using a self-administered, anonymous online questionnaire. Results: A total of 909 patients with SARS-CoV-2 infection and olfactory/gustatory alterations responded to the questionnaire in the 4-day data collection period; 824 cases (90.65%) reported simultaneous olfactory and gustatory involvement. Patients' responses to the questionnaire revealed ageusia (581, 64.1% of respondents), hypogeusia (256, 28.2%), dysgeusia (22, 2.4%), anosmia (752 82.8%), hyposmia (142, 15.6%), and dysosmia (8, 0.9%). Fifty-four percent (489) did not report concomitant nasal congestion or mucus. Conclusion: Olfactory alterations are frequent in patients with SARS-CoV-2 infection and is only associated with nasal congestion in half of the cases.

positive: Association of chemosensory dysfunction and COVID-19 in patients presenting with influenza-like symptoms BACKGROUND: Rapid spread of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and concern for viral transmission by ambulatory patients with minimal to no symptoms underline the importance of identifying early or subclinical symptoms of coronavirus disease 2019 (COVID-19) infection. Two such candidate symptoms include anecdotally reported loss of smell and taste. Understanding the timing and association of smell/taste loss in COVID-19 may help facilitate screening and early isolation of cases. METHODS: A single-institution, cross-sectional study evaluating patient-reported symptoms with a focus on smell and taste was conducted using an internet-based platform on adult subjects who underwent testing for COVID-19. Logistic regression was employed to identify symptoms associated with COVID-19 positivity. RESULTS: A total of 1480 patients with influenza-like symptoms underwent COVID-19 testing between March 3, 2020, and March 29, 2020. Our study captured 59 of 102 (58%) COVID-19-positive patients and 203 of 1378 (15%) COVID-19-negative patients. Smell and taste loss were reported in 68% (40/59) and 71% (42/59) of COVID-19-positive subjects, respectively, compared to 16% (33/203) and 17% (35/203) of COVID-19-negative patients (p < 0.001). Smell and taste impairment were independently and strongly associated with COVID-19 positivity (anosmia: adjusted odds ratio [aOR] 10.9; 95% CI, 5.08-23.5; ageusia: aOR 10.2; 95% CI, 4.74-22.1), whereas sore throat was associated with COVID-19 negativity (aOR 0.23; 95% CI, 0.11-0.50). Of patients who reported COVID-19-associated loss of smell, 74% (28/38) reported resolution of anosmia with clinical resolution of illness. CONCLUSION: In ambulatory individuals with influenza-like symptoms, chemosensory dysfunction was strongly associated with COVID-19 infection and should be considered when screening symptoms. Most will recover chemosensory function within weeks, paralleling resolution of other disease-related symptoms.

positive: Understanding the Mosaic of COVID-19: A Review of the Ongoing Crisis In late 2019, a queer type of pneumonia emerged in Wuhan city in the central part of China. On investigation, it was found to be caused by the coronavirus. Human coronaviruses were discovered in the 1960s. There are a total of seven types of coronaviruses that infect humans: 229E and NL63 are the alpha coronaviruses; OC43, HKU1, MERS-CoV, and SARS-CoV are beta coronaviruses, and SARS-CoV-2 or COVID-19 is a novel coronavirus. COVID-19 surfaced in China at the culmination of the year 2019. The pandemic then fanned out rapidly, involving Italy, Japan, South Korea, Iran, and the rest of the world.

positive: Guide to Understanding the 2019 Novel Coronavirus

positive: COVID-19 and anosmia: A review based on up-to-date knowledge The pandemic of Coronavirus Disease 2019 (COVID-19) has caused a vast disaster throughout the world. There is increasing evidence that Olfactory dysfunction can present in COVID-19 patients. Anosmia can occur alone or can be accompanied by other symptoms of COVID-19, such as a dry cough. However, the pathogenic mechanism of olfactory dysfunction and its clinical characteristics in patients with COVID-19 remains unclear. Multiple cross-sectional studies have demonstrated that the incidence rate of Olfactory dysfunction in COVID-19 patients varies from 33.9–68% with female dominance. Anosmia and dysgeusia are often comorbid in COVID-19 patients. Otolaryngologists should be mindful of the symptom of anosmia in outpatients so as not to delay the diagnosis of COVID-19. In this paper, we have reviewed the relevant knowledge based on up-to-date literature.

positive: The epidemic of 2019-novel-coronavirus (2019-nCoV) pneumonia and insights for emerging infectious diseases in the future Abstract At the end of December 2019, a novel coronavirus, 2019-nCoV, caused an outbreak of pneumonia spreading from Wuhan, Hubei province, to the whole country of China, which has posed great threats to public health and attracted enormous attention around the world. To date, there are no clinically approved vaccines or antiviral drugs available for these human coronavirus infections. Intensive research on the novel emerging human infectious coronaviruses is urgently needed to elucidate their route of transmission and pathogenic mechanisms, and to identify potential drug targets, which would promote the development of effective preventive and therapeutic countermeasures. Herein, we describe the epidemic and etiological characteristics of 2019-nCoV, discuss its essential biological features, including tropism and receptor usage, summarize approaches for disease prevention and treatment, and speculate on the transmission route of 2019-nCoV.

positive: Olfactory and Oral Manifestations of COVID-19: Sex-Related Symptoms-A Potential Pathway to Early Diagnosis OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic poses a threat to global health. Early diagnosis is an essential key to limit the outbreak of the virus. STUDY DESIGN: Case series, study conducted between March 25, 2020, and April 15, 2020. SETTING: Ambulatory, nonhospitalized patients who were quarantined in a designated hotel for COVID-19 patients and were recruited by an advertisement at the hotel. SUBJECTS AND METHODS: In total, 140 patients participated in a web-based questionnaire assessing initial symptoms of common viral diseases, olfactory and taste functions, xerostomia, and orofacial pain. RESULTS: A total of 58 men and 70 women participated. Initial symptoms were cough (59.4%), weakness (47.7%), myalgia (46.9%), fever (42.2%), headache (40.6%), impaired sense of smell (38.3%), impaired sense of taste (32.8%), sore throat (26.6%), runny nose (26.6%), and nasal congestion (22.7%). All symptoms were more frequent among women; however, only runny nose was statistically significant (P = .018). The most common combination of symptoms was cough and weakness (37.5%). A total of 25.8% reported olfactory and taste dysfunctions in the absence of other symptoms. In a comparison between the sexes, cough and runny nose were the most common combination in women (P = .018). A total of 38.3% of patients reported olfactory dysfunction as an initial symptom. Anosmia and facial pain were more common among women (P < .001 and P = .01, respectively), and 56% of patients reported xerostomia. CONCLUSION: A considerable number of patients presented with olfactory and oral disorders. Interestingly, women presented with a different cluster of symptoms than men, which may suggest a new clinical approach to diagnosing COVID-19 disease.

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

positive: Clinical Characteristics of COVID-19 Patients With Digestive Symptoms in Hubei, China: A Descriptive, Cross-Sectional, Multicenter Study OBJECTIVE: Since the outbreak of Coronavirus Disease 2019 (COVID-19) in December 2019, various digestive symptoms have been frequently reported in patients infected with the virus. In this study, we aimed to further investigate the prevalence and outcomes of COVID-19 patients with digestive symptoms. METHODS: In this descriptive, cross-sectional, multicenter study, we enrolled confirmed patients with COVID-19 who presented to 3 hospitals from January 18, 2020, to February 28, 2020. All patients were confirmed by real-time polymerase chain reaction and were analyzed for clinical characteristics, laboratory data, and treatment. Data were followed up until March 18, 2020. RESULTS: In the present study, 204 patients with COVID-19 and full laboratory, imaging, and historical data were analyzed. The average age was 52.9 years (SD ± 16), including 107 men and 97 women. Although most patients presented to the hospital with fever or respiratory symptoms, we found that 103 patients (50.5%) reported a digestive symptom, including lack of appetite (81 [78.6%] cases), diarrhea (35 [34%] cases), vomiting (4 [3.9%] cases), and abdominal pain (2 [1.9%] cases). If lack of appetite is excluded from the analysis (because it is less specific for the gastrointestinal tract), there were 38 total cases (18.6%) where patients presented with a gastrointestinal-specific symptom, including diarrhea, vomiting, or abdominal pain. Patients with digestive symptoms had a significantly longer time from onset to admission than patients without digestive symptoms (9.0 days vs 7.3 days). In 6 cases, there were digestive symptoms, but no respiratory symptoms. As the severity of the disease increased, digestive symptoms became more pronounced. Patients with digestive symptoms had higher mean liver enzyme levels, lower monocyte count, longer prothrombin time, and received more antimicrobial treatment than those without digestive symptoms. DISCUSSION: We found that digestive symptoms are common in patients with COVID-19. Moreover, these patients have a longer time from onset to admission, evidence of longer coagulation, and higher liver enzyme levels. Clinicians should recognize that digestive symptoms, such as diarrhea, are commonly among the presenting features of COVID-19 and that the index of suspicion may need to be raised earlier in at-risk patients presenting with digestive symptoms. However, further large sample studies are needed to confirm these findings.

positive: Cutaneous manifestations of COVID-19: Report of three cases and a review of literature BACKGROUND: Various cutaneous manifestations have been observed in patients with COVID-19 infection. However, overall similarities in the clinical presentation of these dermatological manifestations have not yet been summarized. OBJECTIVE: This review aims to provide an overview of various cutaneous manifestations in patients with COVID-19 through three case reports and a literature review. METHODS: A literature search was conducted using PubMed, OVID, and Google search engines for original and review articles. Studies written in the English language that mentioned cutaneous symptoms and COVID-19 were included. RESULTS: Eighteen articles and three additional cases reported in this paper were included in this review. Of these studies, 6 are case series and 12 are case report studies. The most common cutaneous manifestation of COVID-19 was found to be maculopapular exanthem (morbilliform), presenting in 36.1% (26/72) patients. The other cutaneous manifestations included: a papulovesicular rash (34.7%, 25/72), urticaria (9.7%, 7/72), painful acral red purple papules (15.3%, 11/72) of patients, livedo reticularis lesions (2.8%, 2/72) and petechiae (1.4%, 1/72). Majority of lesions were localized on the trunk (66.7%, 50/72), however, 19.4% (14/72) of patients experienced cutaneous manifestations in the hands and feet. Skin lesion development occurred before the onset of respiratory symptoms or COVID-19 diagnosis in 12.5% (9/72) of the patients, and lesions spontaneously healed in all patients within 10 days. Majority of the studies reported no correlation between COVID-19 severity and skin lesions. CONCLUSION: Infection with COVID-19 may result in dermatological manifestations with various clinical presentations, which may aid in the timely diagnosis of this infection.

positive: A review of pathophysiology and neuropsychiatric manifestations of COVID-19 INTRODUCTION: The outbreak of coronavirus disease 2019 (COVID-19) has become one of the most serious pandemics of the recent times. Since this pandemic began, there have been numerous reports about the COVID-19 involvement of the nervous system. There have been reports of both direct and indirect involvement of the central and peripheral nervous system by the virus. OBJECTIVE: To review the neuropsychiatric manifestations along with corresponding pathophysiologic mechanisms of nervous system involvement by the COVID-19. BACKGROUND: Since the beginning of the disease in humans in the later part of 2019, the coronavirus disease 2019 (COVID-19) pandemic has rapidly spread across the world with over 2,719,000 reported cases in over 200 countries [World Health Organization. Coronavirus disease 2019 (COVID-19) situation report-96.,]. While patients typically present with fever, shortness of breath, sore throat, and cough, neurologic manifestations have been reported, as well. These include the ones with both direct and indirect involvement of the nervous system. The reported manifestations include anosmia, ageusia, central respiratory failure, stroke, acute inflammatory demyelinating polyneuropathy (AIDP), acute necrotizing hemorrhagic encephalopathy, toxic–metabolic encephalopathy, headache, myalgia, myelitis, ataxia, and various neuropsychiatric manifestations. These data were derived from the published clinical data in various journals and case reports. CONCLUSION: The neurological manifestations of the COVID-19 are varied and the data about this continue to evolve as the pandemic continues to progress.

positive: An update on COVID-19 for the radiologist - A British society of Thoracic Imaging statement

positive: Analysis of 2019 novel coronavirus infection and clinical characteristics of outpatients: An epidemiological study from a fever clinic in Wuhan, China BACKGROUND: Since the outbreak of 2019 novel coronavirus (SARS‐CoV‐2) pneumonia, thousands of patients with fever or cough were flocked into fever clinic of designated hospitals in Wuhan, China. To date, no data have ever been reported to reflect the prevalence of Corona Virus Disease 2019 (COVID‐19) among these outpatients. Moreover, it is almost unknown to discriminate COVID‐19 and nucleic acid negative patients based on clinical features in the fever clinics. METHODS: The infectious status of SARS‐CoV‐2 was estimated among the outpatients. The epidemiological and clinical characteristics were compared between COVID‐19 and nucleic acid negative patients. RESULTS: The nucleic acid positive rate for SARS‐CoV‐2 in the outpatients from our fever clinic was 67·1%, while the majority of COVID‐19 patients were mild cases. The predominant initial symptom in those COVID‐19 patients was fever (78.2%), followed by cough (15.6%). Very significantly lower number of eosinophils was characterized in COVID‐19 patients as compared to that of nucleic acid negative patients. More importantly, the proportion of subjects with eosinophil counts lower than normal levels in COVID‐19 patients was much higher than that of nucleic acid negative patients. Fever combined with bilateral ground‐glass opacities in CT imaging and eosinophil count below the normal level are probably a valuable indicator of COVID‐19 infection in those outpatients. CONCLUSIONS: Those findings may provide critical information for the regions such as Europe and United States that are facing the same situation as Wuhan experienced, and could be valuable to prevent those nucleic acid negative patients from misdiagnosis before antibody testing. This article is protected by copyright. All rights reserved.

positive: A Web-based, Mobile Responsive Application to Screen Healthcare Workers for COVID Symptoms: Descriptive Study Background: The COVID-19 pandemic has impacted over 1 million people across the globe, with over 330,000 cases in the United States. To help limit the spread in Massachusetts, the Department of Public Health required that all healthcare workers must be screened for symptoms daily - individuals with symptoms may not work. We rapidly created a digital COVID-19 symptom screening tool for a large, academic, integrated healthcare delivery system, Partners HealthCare, in Boston, Massachusetts. Objective: We describe the design and development of the COVID-19 symptom screening application and report on aggregate usage data from the first week of use across the organization. Methods: Using agile principles, we designed, tested and implemented a solution over the span of a week using progressively custom development approaches as the requirements and use case become more solidified. We developed the minimum viable product (MVP) of a mobile responsive, web-based self-service application using REDCap (Research Electronic Data Capture). For employees without access to a computer or mobile device to use the self-service application, we established a manual process where in-person, socially distanced screeners asked employees entering the site if they have symptoms and then manually recorded the responses in an Office 365 Form. A custom .NET Framework application was developed solution as COVID Pass was scaled. We collected log data from the .NET application, REDCap and Office 365 from the first week of full enterprise deployment (March 30, 2020 - April 5, 2020). Aggregate descriptive statistics including overall employee attestations by day and site, employee attestations by application method (COVID Pass automatic screening vs. manual screening), employee attestations by time of day, and percentage of employees reporting COVID-19 symptoms Results: We rapidly created the MVP and gradually deployed it across the hospitals in our organization. By the end of the first week of enterprise deployment, the screening application was being used by over 25,000 employees each weekday. Over the first full week of deployment, 154,730 employee attestation logs were processed across the system. Over this 7-day period, 558 (0.36%) employees reported positive symptoms. In most clinical locations, the majority of employees (~80-90%) used the self-service application, with a smaller percentage (~10-20%) using manual attestation. Hospital staff continued to work around the clock, but as expected, staff attestations peaked during shift changes between 7-8am, 2-3pm, 4-6pm, and 11pm-midnight. Conclusions: Using rapid, agile development, we quickly created and deployed a dedicated employee attestation application that gained widespread adoption and use within our health system. Further, we have identified over 500 symptomatic employees that otherwise would have possibly come to work, potentially putting others at risk. We share the story of our implementation, lessons learned, and source code (via GitHub) for other institutions who may want to implement similar solutions.

positive: Extra-respiratory manifestations of COVID-19 Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global health threat. Although most patients with COVID-19 manifest fever and respiratory tract symptoms, SARS-CoV-2 infection may also involve other organs/systems and present with extra-respiratory manifestations, including cardiac, gastrointestinal, hepatic, renal, neurological, olfactory, gustatory, ocular, cutaneous and haematological symptoms. Occasionally, these extra-respiratory symptoms/signs represent the initial presentation of SARS-CoV-2 infection, prior to fever or respiratory manifestations. Therefore, this comprehensive review of the extra-respiratory manifestations of COVID-19 is intended to help clinicians better understand the range of clinical presentations associated with SARS-CoV-2 infection, allowing the consideration of COVID-19 in differential diagnoses. A screening test for SARS-CoV-2 should be performed when patients have these extra-respiratory manifestations. In addition, clinicians should be alerted to the adverse effects of anti-SARS-CoV-2 agents that can mimic the extra-respiratory manifestations of COVID-19. Moreover, some extra-respiratory manifestations, such as ocular and gastrointestinal involvement, may be caused by direct invasion of SARS-CoV-2. Therefore, protective measures should be taken while managing the associated clinical specimens. Finally, several extra-respiratory manifestations, such as cardiac involvement, acute kidney injury, coagulation disorders and thrombotic complications, could be associated with a poor prognosis.

positive: Patients of COVID-19 may benefit from sustained Lopinavir-combined regimen and the increase of Eosinophil may predict the outcome of COVID-19 progression OBJECTIVES: To explore the epidemiological information, clinical characteristics, therapeutic outcomes and temporal progression of laboratory findings in 2019-coronavirus disease (COVID-19) patients exposed to lopinavir. METHODS: We collected data from ten COVID-19 patients admitted between January 22, 2020 and February 11, 2020 at Xixi hospital in Hangzhou, China. RESULTS: Of ten patients, secondary, tertiary and quartus patients emerged; the incubation period was 3–7 days. Mainly initial symptoms were cough and low fever (37.3–38.0 °C). An asymptomatic case presented normal radiography, the others had ground glass opacities. All cases (three transferred, seven discharged) were exposed to lopinavir on initial hospitalization. Three patients stopped lopinavir because of adverse effects, two of them deteriorated, one was hospitalized longer than others who with sustained lopinavir use. Levels of potassium, albumin, and lymphocytes were low, but increased persistently after treatment. Eosinophil values were low on initial hospitalization, then all returned to normal before discharge. Viral load of SARS-CoV-2, radiography and eosinophil improved continuously in 3–14, 6–8 and 7–9 days, respectively. CONCLUSIONS: Increasing eosinophils may be an indicator of COVID-19 improvement. The COVID-19 patients may benefit from sustained lopinavir use. More research on a larger scale is needed to verify these points.

positive: The Ocular Manifestations and Transmission of COVID-19; Recommendations for Prevention Abstract Background Coronavirus disease-2019 (COVID-19), caused by a novel coronavirus termed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has been linked to ocular signs and symptoms in several case reports. Research has demonstrated that SARS-CoV-2 is spread primarily through close contact via respiratory droplets, but there is the possibility for ocular transmission with the conjunctiva as a conduit as well as a source of infection. Discussion Ocular manifestations of SARS-CoV-2 include follicular conjunctivitis and have been repeatedly noted as an initial or subsequent symptom of COVID-19 positive patients. Particularly in patients with ocular manifestations, there is evidence that the virus may present in tears based on the detection of SARS-CoV-2 in conjunctival swab samples via reverse transcription polymerase chain reaction (RT-PCR). The virus may therefore be transmittable from the ocular surface to a new host via contact with the ocular mucosa, tears, or subsequent fomites. Conclusions All healthcare professionals should ask patients about ocular symptoms consistent with SARS-CoV-2, use eye protection such as goggles or face shields as part of the standard personal protective equipment (PPE) for high-risk patients in addition to wearing of masks both by the patient and provider, and should consider tears to be potentially infectious.

positive: Sudden onset anosmia and dysgeusia in two patients: An early sign of SARS-CoV-2 infection

positive: Lung Base Findings of Coronavirus Disease (COVID-19) on Abdominal CT in Patients With Predominant Gastrointestinal Symptoms OBJECTIVE. This series of patients presented to the emergency department (ED) with abdominal pain, without the respiratory symptoms typical of coronavirus disease (COVID-19), and the abdominal radiologist was the first to suggest COVID-19 infection because of findings in the lung bases on CT of the abdomen. CONCLUSION. COVID-19 infection can present primarily with abdominal symptoms, and the abdominal radiologist must suggest the diagnosis when evaluating the lung bases for typical findings.

positive: Symptoms of COVID-19 Outpatients in the United States BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel pathogen causing the current worldwide coronavirus disease 2019 (COVID-19) pandemic. Due to insufficient diagnostic testing in the United States, there is a need for clinical decision-making algorithms to guide testing prioritization. METHODS: We recruited participants nationwide for a randomized clinical trial. We categorized participants into three groups: 1) those with confirmed SARS-CoV-2 infection, 2) those with probable SARS-CoV-2 infection (pending test or not tested but with a confirmed COVID-19 contact), and 3) those with possible SARS-CoV-2 infection (pending test or not tested and with a contact for whom testing was pending or not performed). We compared the frequency of self-reported symptoms in each group and categorized those reporting symptoms in early infection (0 – 2 days), mid-infection (3 – 5 days), and late infection (>5 days). RESULTS: Among 1,252 symptomatic persons screened, 316 had confirmed, 393 had probable, and 543 had possible SARS-CoV-2 infection. In early infection, those with confirmed and probable SARS-CoV-2 infection shared similar symptom profiles, with fever most likely in confirmed cases (p = 0.002). Confirmed cases did not show any statistically significant differences compared to unconfirmed cases in symptom frequency at any time points. The most commonly reported symptoms in those with confirmed infection were cough (82%), fever (67%), fatigue (62%), and headache (60%), with only 52% reporting both fever and cough. CONCLUSION: Symptomatic persons with probable SARS-CoV-2 infection present similarly to those with confirmed SARS-CoV-2 infection. There was no pattern of symptom frequency over time.

positive: Clinical characteristics of 225 patients with COVID-19 in a tertiary Hospital near Wuhan, China BACKGROUND: The 2019 coronavirus disease (COVID-19) was first identified in Wuhan, Hubei, China in December 2019, caused by a novel coronavirus (SARS-CoV-2). There is a need to study the clinical features of patients in a hospital near Wuhan. OBJECTIVE: To identify clinical features of patients with COVID-19 in a tertiary hospital near Wuhan. STUDY DESIGN: General information, clinical manifestations, laboratory data, and computed tomography (CT) data were collected for 225 patients diagnosed of COVID-19 admitted between January 20 and February 14, 2020, to the Hanchuan City People's Hospital. RESULTS: The patients included 120 male and 105 females who had no connection to the Wuhan Huanan Seafood Market. Their average age was 50â¯±â¯14 years. The major clinical symptoms were fever (84.44% of patients), cough (56.44% of patients), and dyspnea (4.00% of patients); 3.56%-22.67% of subjects suffered from expectoration, fatigue, chills, headache, chest pain, and pharyngalgia. Hypertension was present in 20.89% of patients. The counts of white blood cells (WBCs) and lymphocytes were normal or decreased in 86.67% and 99.11% of patients. CRP was increased in 86.22% of patients, PCT in 10.67%, and ESR in 90.22%. CT showed that 86.22% of patients had multiple patchy glassy shadows in both lungs, particularly in the peripheral area. Thirty-seven (16.44%) patients were diagnosed with severe COVID-19. Methylprednisolone was administered in 44.44% of cases. The mortality among the patients was 0.89%. CONCLUSIONS: Clinical characteristics of COVID-19 patients in the tertiary hospital near Wuhan are very similar to those found in Wuhan, but the lower mortality.

positive: Clinical Characteristics of Re‐hospitalized Patients with COVID‐19 in China BACKGROUND: This study aims to observe the clinical characteristics of recovered patients from Coronavirus Disease 2019 (COVID 19) with positive in RT‐PCR or serum antibody. METHODS: The profile, clinical symptoms, laboratory outcomes and radiologic assessments were extracted on 11 patients, who tested positive for COVID‐19 with RT‐PCR or serum antibody after discharged and was admitted to Hubei No. 3 People's Hospital of Jianghan University for a second treatment in March 2020. RESULTS: The average interval time between the first discharge and the second admission measured 16.00 ± 7.14 days, ranging from 6 to 27 days. In the second hospitalization, 1 patient was positive for RT‐PCR and serum antibody IgM‐IgG, 5 patients were positive for both IgM and IgG but negative for RT‐PCR. 3 patients were positive for both RT‐PCR and IgG but negative for IgM. The main symptoms were cough (54.5%), fever (27.3%) and feeble (27.3%) in the second hospitalization. Compared with the first hospitalization, there were significant decreases in gastrointestinal symptoms (5 vs. 0, P=0.035), elevated levels of both white blood cell count(P=0.036) and lymphocyte count (P=0.002), remarkedly decreases in CRP and SAA (P<0.05) in the second hospitalization. Additionally, 6 patients' chest CT exhibited notable improvements in acute exudative lesions CONCLUSION: There could be the positive results for RT‐PCR analysis or serum IgM‐IgG in discharged patients, even with mild clinical symptoms, however, their laboratory outcomes and chest CT images would not indicate the on‐going development in those patients. This article is protected by copyright. All rights reserved.

positive: 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.

positive: 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.

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: Severe Acute Proximal Pulmonary Embolism and COVID-19: A Word of Caution Abstract Acute pulmonary embolism is an uncharacteristic presentation in patients with COVID-19. Here we describe the case of a young woman presenting with severe pulmonary embolism, without any associated symptoms of infections. A clot in a patent foramen ovale was noted. Despite emergency surgical embolectomy, her clinical conditions continued to deteriorate. She was put on extracorporeal life support and tested positive for COVID-19. She died of multiorgan failure on day 10. COVID-19 may have a thrombogenic effect and it may need to be considered in cases of pulmonary embolism and in absence of any obvious risk factor.

positive: Active or latent tuberculosis increases susceptibility to COVID-19 and disease severity Importance: Risk factors associated with COVID-19, the viral pneumonia originating in Wuhan, China, in Dec 2019, require clarification so that medical resources can be prioritized for those at highest risk of severe COVID-19 complications. Infection with M. tuberculosis (MTB), the pathogen that causes TB and latently infects ~25% of the global population, may be a risk factor for SARS-CoV-2 infection and severe COVID-19 pneumonia. Objective: To determine if latent or active TB increase susceptibility to SARS-COV-19 infection and disease severity, and lead to more rapid development of COVID-19 pneumonia. Design: An observational case-control study of 36 confirmed COVID-19 cases from Shenyang, China, conducted in Feb 2020. Final date of follow-up: Feb 29, 2020. Cases were grouped according to COVID-19 pneumonia severity (mild/moderate, severe/critical), and MTB infection status compared. Comparisons were made with MTB infection data from another case-control study on bacterial/viral pneumonia at Shenyang Chest Hospital. Setting: Multi-center study involving three primary care hospitals in Shenyang, China. Participants: 86 suspected COVID-19 cases from participating primary-care hospitals in Shenyang. All 36 SARS-CoV-2 +ve cases (based on RT-PCR assay) were included. Disease severity was assessed using the Diagnostic and Treatment Guidelines of the National Health Commission of China (v6). Mean age, 47 years (range: 25-79), gender ratio, 1:1. Exposures: Confirmed COVID-19 pneumonia. Interferon-gamma Release Assays (IGRA) were performed using peripheral blood to determine MTB infection. Main Outcome and Measures: Epidemiological, demographic, clinical, radiological, and laboratory data were collected. Comparison of MTB infection status between patients with mild/moderate and severe/critical COVID-19 pneumonia. Results: Mean age of 36 COVID-19 patients: 47 (range: 25-79); M/F: 18/18; Wuhan/Hubei connection: 42%. Mild/moderate cases: 27 (75%); severe/critical: 9 (25%). MTB infection (IGRA+ve): 13 cases (36.11%), including 7 of 9 severe/critical cases. MTB infection rate: higher in COVID-19 (36.11%) than bacterial pneumonia (20%; p=0.0047) and viral pneumonia patients (16.13%; p=0.024). MTB infection more common than other co-morbidities (36.11% vs diabetes: 25%; hypertension: 22.2%; coronary heart disease: 8.33%; COPD: 5.56%). MTB co-infection linked with disease severity (severe/critical 78% vs mild/moderate cases 22%; p=0.0049), and rate of disease progression: infection to development of symptoms (MTB+SARS-CoV-2: 6.5+/-4.2 days vs SARS-COV-2: 8.9+/-5.2 days; p=0.073); from symptom development to diagnosed as severe (MTB+SARS-CoV-2: 3.4+/-2.0 days vs SARS-COV-2: 7.5+/-0.5 days; p=0.075). Conclusions and Relevance: MTB infection likely increases susceptibility to SARS-CoV-2, and increases COVID-19 severity, but this requires validation in a larger study. MTB infection status of COVID-19 patients should be checked routinely at hospital admission.

positive: Clinical characteristics of non-critically ill patients with novel coronavirus infection (COVID-19) in a Fangcang Hospital 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, So2 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.

positive: Asymptomatic infection and atypical manifestations of COVID-19: comparison of viral shedding duration • More than 25% of patients with COVID-19 were asymptomatic. • Among patients with COVID-19, 26.1% presented anosmia, and 22.6% complained of ageusia with median duration of 7 days. • Mean duration of SARS-CoV-2 viral shedding was 24.5 days. • Irrespective of clinical manifestations, all patients with COVID-19 showed prolonged viral shedding.

positive: Novel Coronavirus (2019-nCoV) in Disguise Novel coronavirus (2019-nCoV) pandemic is currently one of the most influential topics as it not only impacts the field of medicine but most importantly, it affects the lives of many individuals throughout the world. We report an interesting 2019-nCoV case in a tertiary community hospital with the initial concern of acute pyelonephritis without respiratory symptoms that ultimately led to the quarantine of a number of healthcare providers. This case emphasizes the importance of radiological evidence in diagnosing 2019-nCoV in the setting of an initial atypical presentation. It also serves as an example of how healthcare providers may need to increase their suspicion for COVID-19 to ensure self-protection and prompt diagnosis in the era of an ongoing pandemic.

positive: Acute Transverse Myelitis Associated with SARS-CoV-2: A Case-Report • The third case of acute transverse myelitis due to SARS-CoV-2 reported in the world; • Possible inflammatory complications affecting the myelin in spinal cord. • We must be vigilant of the critical neurological illnesses associated with COVID-19.

positive: The cross-sectional study of hospitalized coronavirus disease 2019 patients in Xiangyang, Hubei province Summary Objective To describe the epidemiological and clinical characteristics of the Coronavirus Disease 2019 (COVID-19) hospitalized patients and to offer suggestions to the urgent needs of COVID-19 prevention, diagnosis and treatment. Methods We included 102 confirmed COVID-19 cases hospitalized in Xiangyang No.1 peoples hospital, Hubei, China until Feb 9th, 2020. Demographic data, laboratory findings and chest computed tomographic (CT) images were obtained and analyzed. Findings All cases were confirmed by real-time RT-PCR, including 52 males and 50 females with a mean age of 50.38 years (SD 16.86). Incubation time ranged from one to twenty days with a mean period of 8.09 days (SD 4.99). Fever (86[84.3%] of 102 patients), cough (58[57%]), fatigue (28[27%]), shortness of breath (24[23%]), diarrhea (15[15%]), expectoration (13[12%]), inappetence (11[10%]) were common clinical manifestations. We observed a decreased blood leukocyte count and lymphopenia in 21 (20.6%) and 56 (54.9%) patients, respectively. There were 66 (68%) of 97 patients with elevated C-reactive protein levels and 49 (57.6%) of 85 with increased erythrocytes sedimentation rate. Higher levels of procalcitonin and ferritin were observed in 19 (25.3%) of 75 and 12 (92.3%) of 13 patients, respectively. Eight patients were admitted to intensive care unit (ICU), six developed respiratory failure, three had multiple organ failure and three died. The cumulative positivity rate over three rounds of real-time RT-PCR was 96%. One-hundred patients were found with typical radiological abnormalities in two rounds of chest CT scans, indicating a 98% consistency with real-time RT-PCR results. Interpretation Most COVID-19 patients in Xiangyang were secondary cases without sex difference, and the rate of severe cases and death was low. Middle-to-old-age individuals were more susceptible to the virus infection and the subsequent development of severe/fatal consequences. The average incubation period was longer among our patients. We recommend prolonging the quarantine period to three weeks. Three times real-time RT-PCR plus two times CT scans is a practical clinical diagnosis strategy at present and should be used to increase the accuracy of diagnosis, thereby controlling the source of infection more effectively. Key Words SARS-CoV-2; COVID-19; epidemiological and clinical features; diagnosis

positive: Syncope as the presenting symptom of COVID-19 infection

positive: Risk Factors Prediction, Clinical Outcomes, and Mortality of COVID-19 Patients Background: Preventing communicable diseases requires understanding the spread, epidemiology, clinical features, progression, and prognosis of the disease. Early identification of risk factors and clinical outcomes might help to identify critically ill patients, provide proper treatment and prevent mortality. Methods: We conducted a prospective study in patients with flu-like symptoms referred to the imaging department of a tertiary hospital in IRAN between 3 March 2020 and 8 April 2020. Patients with COVID-19 were followed up to check their health condition after two months. The categorical data between groups were analyzed by Fisher exact test and continuous data by Wilcoxon Rank-Sum Test. Findings: 319 patients (mean age 45.48 years, 177 women) were enrolled. Fever, dyspnea, weakness, shivering, C-reactive protein (CRP), fatigue, dry cough, anorexia, anosmia, ageusia, dizziness, sweating and age were the most important symptoms of COVID-19 infection. Traveling in past three months, asthma, taking corticosteroids, liver disease, rheumatological disease, cough with sputum, eczema, conjunctivitis, tobacco use, and chest pain did not have any relationship with COVID-19. Interpretation: Finding clinical symptoms for early diagnosis of COVID-19 is a critical part of prevention. These symptoms can help in the assessment of disease progression. To the best of our knowledge, some of the effective features on the mortality due to COVID-19 are investigated for the first time in this research. Funding: None

positive: Subjective Changes in Smell and Taste During the COVID-19 Pandemic: A National Survey-Preliminary Results. Since the COVID-19 pandemic began, many individuals have noted acute loss of smell and/or taste, although not all patients with these symptoms are tested for COVID-19. To better characterize all patients with these rare symptoms, a national survey was created. Over 13 days in April 2020, a total of 220 people completed the survey in its entirety, representing a wide geographic distribution across the United States. Of the 220 respondents, 93 (42%) were diagnosed with COVID-19, and 127 (58%) were not. A total of 37.7% of respondents reported changes in smell/taste as the initial or sole presentation of their condition. Most but not all patients had other symptoms suggestive of COVID-19 at the time of chemosensory loss. Despite its inclusion as a major symptom of COVID-19 by the CDC (Centers for Disease Control and Prevention), respondents with additional CDC-defined symptoms associated with COVID-19 were statistically more likely to be tested/diagnosed than those without.

positive: Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been widely spread. We aim to investigate the clinical characteristic and allergy status of patients infected with SARS-CoV-2. METHODS: Electronic medical records including demographics, clinical manifestation, comorbidities, laboratory data, and radiological materials of 140 hospitalized COVID-19 patients, with confirmed result of SARS-CoV-2 viral infection, were extracted and analyzed. RESULTS: An approximately 1:1 ratio of male (50.7%) and female COVID-19 patients was found, with an overall median age of 57.0 years. All patients were community-acquired cases. Fever (91.7%), cough (75.0%), fatigue (75.0%), and gastrointestinal symptoms (39.6%) were the most common clinical manifestations, whereas hypertension (30.0%) and diabetes mellitus (12.1%) were the most common comorbidities. Drug hypersensitivity (11.4%) and urticaria (1.4%) were self-reported by several patients. Asthma or other allergic diseases were not reported by any of the patients. Chronic obstructive pulmonary disease (COPD, 1.4%) patients and current smokers (1.4%) were rare. Bilateral ground-glass or patchy opacity (89.6%) was the most common sign of radiological finding. Lymphopenia (75.4%) and eosinopenia (52.9%) were observed in most patients. Blood eosinophil counts correlate positively with lymphocyte counts in severe (r = .486, P < .001) and nonsevere (r = .469, P < .001) patients after hospital admission. Significantly higher levels of D-dimer, C-reactive protein, and procalcitonin were associated with severe patients compared to nonsevere patients (all P < .001). CONCLUSION: Detailed clinical investigation of 140 hospitalized COVID-19 cases suggests eosinopenia together with lymphopenia may be a potential indicator for diagnosis. Allergic diseases, asthma, and COPD are not risk factors for SARS-CoV-2 infection. Older age, high number of comorbidities, and more prominent laboratory abnormalities were associated with severe patients.

positive: Novelty in the gut: a systematic review and meta-analysis of the gastrointestinal manifestations of COVID-19 BACKGROUND: The COVID-19 epidemic has affected over 2.6 million people across 210 countries. Recent studies have shown that patients with COVID-19 experience relevant gastrointestinal (GI) symptoms. We aimed to perform a systematic review and meta-analysis on the GI symptoms of COVID-19. METHODS: A literature search was conducted via electronic databases, including PubMed, Embase, Scopus, and Google Scholar, from inception until 20 March 2020. Data were extracted from relevant studies. A systematic review of GI symptoms and a meta-analysis comparing symptoms in severe and non-severe patients was performed using RevMan V.5.3. RESULTS: Pooled data from 2477 patients with a reverse transcription-PCR-positive COVID-19 infection across 17 studies were analysed. Our study revealed that diarrhoea (7.8%) followed by nausea and/or vomiting (5.5 %) were the most common GI symptoms. We performed a meta-analysis comparing the odds of having GI symptoms in severe versus non-severe COVID-19-positive patients. 4 studies for nausea and/or vomiting, 5 studies for diarrhoea and 3 studies for abdominal pain were used for the analyses. There was no significant difference in the incidence of diarrhoea (OR=1.32, 95% CI 0.8 to 2.18, Z=1.07, p=0.28, I(2)=17%) or nausea and/or vomiting (OR=0.96, 95% CI 0.42 to 2.19, Z=0.10, p=0.92, I(2)=55%) between either group. However, there was seven times higher odds of having abdominal pain in patients with severe illness when compared with non-severe patients (OR=7.17, 95% CI 1.95 to 26.34, Z=2.97, p=0.003, I(2)=0%). CONCLUSION: Our study has reiterated that GI symptoms are an important clinical feature of COVID-19. Patients with severe disease are more likely to have abdominal pain as compared with patients with non-severe disease.

positive: Cutaneous signs in COVID‐19 patients: A review Coronavirus disease (COVID‐19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) primarily affects the epithelium of the airways. With the increasing involvement of dermatologist in management of this crisis, cutaneous symptoms gained more and more attention. In this review, we will describe cutaneous symptoms of patients of all ages in association with COVID‐19. We will focus on such disorders that are caused by direct action of SARS‐CoV‐2 on tissues, complement, and coagulation system and on nonspecific eruption of the systemic viral infection. Drug‐induced reactions are only mentioned in the differential diagnoses. Although more systematic investigations are warranted, it becomes clear that some symptoms are clinical signs of a milder COVID‐19 course, while others are a red flag for a more severe course. Knowledge of the cutaneous manifestations of COVID‐19 may help in early diagnosis, triage of patients, and risk stratification.

positive: 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.

positive: Initial clinical features of suspected coronavirus disease 2019 in two emergency departments outside of Hubei, China With an increasing number of Coronavirus Disease 2019 (COVID‐19) cases outside of Hubei, emergency departments (EDs) and fever clinics are facing challenges posed by the large number of admissions of patients suspected to have COVID‐19. Therefore, it is of crucial importance to study the initial clinical features of patients, to better differentiate between infected and uninfected patients outside Hubei. A total of 116 patients suspected of having COVID‐19 who presented to two emergency departments in Anhui for the first time between 24 January 2020 and 20 February 2020 were enrolled in the study. The initial clinical data of these patients, such as epidemiological features, symptoms, laboratory results, and chest computed tomography (CT) findings were collected using a standard case report form on admission. Thirty‐two patients were diagnosed with COVID‐19; the remaining 84 patients were referred to as negative cases. The median age of the diagnosed patients was 46 years, but only 35 years for negative cases. History of exposure to Wuhan or COVID‐19 patients in the previous 2 weeks was observed in 63% of the diagnosed and 44% of negative cases. Median time from illness onset to ED admission was 5 days for all patients, diagnosed patients, and negative cases, respectively. Fever was observed in 27 (84%) and 57 (68%) diagnosed and negative cases, respectively. Nineteen (59%) diagnosed and 24 (29%) negative cases had lymphopenia on admission in ED. A chest CT scan on admission revealed the presence of pneumonia in the majority of the diagnosed patients (30 out of 32, 94%) and in 56 (67%) negative cases. Bilateral involvement and ground‐glass opacity (GGO) were present in 91% and 47% of the diagnosed patients. Thirty‐two patients were diagnosed with COVID‐19; the remaining 84 patients were referred to as negative cases. The median age of the diagnosed patients was 46 years, but only 35 years for negative cases. History of exposure to Wuhan or COVID‐19 patients in the previous 2 weeks was observed in 63% of the diagnosed and 44% of negative cases. Median time from illness onset to ED admission was 5 days for all patients, diagnosed patients, and negative cases, respectively. Fever was observed in 27 (84%) and 57 (68%) diagnosed and negative cases, respectively. Nineteen (59%) diagnosed and 24 (29%) negative cases had lymphopenia on admission in ED. A chest CT scan on admission revealed the presence of pneumonia in the majority of the diagnosed patients (30 out of 32, 94%) and in 56 (67%) negative cases. Bilateral involvement and GGO were present in 91% and 47% of the diagnosed patients.

positive: ¿Es esperable que haya cuadros neurológicos por la pandemia por SARS-CoV-2?/ ¿Es esperable que haya cuadros neurológicos por la pandemia por SARS-CoV-2?/ Should we expect neurological symptoms in the SARS-CoV-2 epidemic? INTRODUCTION: There is growing evidence that SARS-CoV-2 can gain access to the central nervous system (CNS). We revise the literature on coronavirus infection of the CNS associated with neurological diseases. DEVELOPMENT: Neurological symptoms were rarely reported in the SARS-CoV and MERS-CoV epidemics, although isolated cases were described. There are also reports of cases of neurological symptoms associated with CoV-OC43 and CoV-229E infection. The presence of neurological lesions, especially demyelinating lesions in the mouse hepatitis virus model, may explain the mechanisms by which coronaviruses enter the CNS, particularly those related with the immune response. This may explain the presence of coronavirus in patients with multiple sclerosis. We review the specific characteristics of SARS-CoV-2 and address the question of whether the high number of cases may be associated with greater CNS involvement. CONCLUSION: Although neurological symptoms are not frequent in coronavirus epidemics, the high number of patients with SARS-CoV-2 infection may explain the presence of the virus in the CNS and increase the likelihood of early- or delayed-onset neurological symptoms. Follow-up of patients affected by the SARS-CoV-2 epidemic should include careful assessment of the CNS.

positive: Covid-19 med nedsatt lukte- og smakssans som eneste symptom./ Covid-19 med nedsatt lukte- og smakssans som eneste symptom./ Loss of smell or taste as the only symptom of COVID-19 BACKGROUND: Olfactory and taste disorders (OTDs) have recently been reported among patients with COVID-19, and it has been hypothesised that oral and nasal tissues may contain host cells of SARS-CoV-2. We report on two cases (spouses) with SARS-CoV-2 infection with self-reported OTDs, but otherwise no typical respiratory symptoms of COVID-19. CASE PRESENTATION: A man in his nineties (index patient) had respiratory symptoms and dysgeusia, and was diagnosed with COVID-19. His daughter-in-law and son had no respiratory COVID-19 symptoms. However, they experienced complete loss of smell and taste, respectively, 7 and 10 days after their first close contact with the index patient. Both tested positive for SARS-CoV-2 RNA. INTERPRETATION: Our case histories support recent reports hypothesising that anosmia and ageusia may be the only symptoms of SARS-CoV-2 infection, and that SARS-CoV-2 may infect oral and nasal tissues. Together, these findings may inform future research, diagnosis, prevention and treatment of COVID-19.

positive: Afectación clínica y sintomatológica en pacientes mayores de 65 años por COVID-19

positive: Initial success in the identification and management of the coronavirus disease 2019 (COVID-19) indicates human-to-human transmission in Wuhan, China Coronavirus (CoV) has been one of the major pandemic threats to human health in the last two decades. The human coronavirus was first identified in 1960s. CoVs 229E, NL63, OC43, HKU1, SARS-CoV, and MERS-CoV have caused numerous disasters or human deaths worldwide. Recently, an outbreak of the previously unknown deadly CoV disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome CoV 2 (SARS-CoV-2, early named 2019-nCoV) occurred in Wuhan, China, and it had caused 81238 cases of confirmed infection, including 3250 deaths until March 19, 2020. Its risks and pandemic potential have brought global consideration. We summarized epidemiology, virological characteristics, clinical symptoms, diagnostic methods, clinical treatments, and prevention methods for COVID-19 to present a reference for the future wave of probable CoV outbreaks.

positive: Weakness and elevated creatinine kinase as the initial presentation of coronavirus disease 2019 (COVID-19) COVID-19 is a global public health emergency with more than one million positive cases across the globe. COVID-19 has a multifaceted presentation. We are herein to report two cases of SARS-CoV-2 induced rhabdomyolysis with an initial presentation of weakness and elevated creatinine kinase (CK). Both patients had no respiratory symptoms, they only complained of generalized weakness and were found to have elevated CK. Routine chest X-ray showed bilateral infiltrates in both cases and subsequently reverse-transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2 was positive. To the best of our knowledge, there was only one literature to date documented SARS-CoV-2 induced rhabdomyolysis as a late complication of COVID-19 patient. Our cases showed that elevated CK and rhabdomyolysis can be the sole initial presentation of patients with COVID-19 and total CK should be ordered in every patient on admission.

positive: The role of imaging in 2019 novel coronavirus pneumonia (COVID-19) Almost the entire world, not only China, is currently experiencing the outbreak of a novel coronavirus that causes respiratory disease, severe pneumonia, and even death. The outbreak began in Wuhan, China, in December of 2019 and is currently still ongoing. This novel coronavirus is highly contagious and has resulted in a continuously increasing number of infections and deaths that have already surpassed the SARS-CoV outbreak that occurred in China between 2002 and 2003. It is now officially a pandemic, announced by WHO on the 11th of March. Currently, the 2019 novel coronavirus (SARS-CoV-2) can be identified by virus isolation or viral nucleic acid detection; however, false negatives associated with the nucleic acid detection provide a clinical challenge and thus make the imaging examination crucial. Imaging exams have been a main clinical diagnostic criteria for the 2019 novel coronavirus disease (COVID-19) in China. Imaging features of multiple patchy areas of ground glass opacity and consolidation predominately in the periphery of the lungs are characteristic manifestations on chest CT and extremely helpful in the early detection and diagnosis of this disease, which aids prompt diagnosis and the eventual control of this emerging global health emergency. Key Points • In December 2019, China, an outbreak of pneumonia caused by a novel, highly contagious coronavirus raised grave concerns and posed a huge threat to global public health. • Among the infected patients, characteristic findings on CT imaging include multiple, patchy, ground-glass opacity, crazy-paving pattern, and consolidation shadows, mainly distributed in the peripheral and subpleural areas of both lungs, which are very helpful for the frontline clinicians. • Imaging examination has become the indispensable means not only in the early detection and diagnosis but also in monitoring the clinical course, evaluating the disease severity, and may be presented as an important warning signal preceding the negative RT-PCR test results. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00330-020-06827-4) contains supplementary material, which is available to authorized users.

positive: Human coronavirus NL63 associated with lower respiratory tract symptoms in early life. Coronavirus NL63 has been identified as a new member of the coronavirus genus, but its role as a cause of respiratory disease needs to be established. We studied the first episode of lower respiratory tract symptoms in a cohort of healthy neonates. NL63 was identified in 6 (7%) of 82 cases and was as frequent as other coronaviruses (9%). NL63 was recovered at the onset of symptoms and was cleared within 3 weeks in half of the cases. Our data suggests that coronavirus NL63 causes lower respiratory tract symptoms and is acquired in early life.

positive: Incidental CT findings in the lungs in COVID-19 patients presenting with abdominal pain As the 2019 novel coronavirus disease (COVID-19) continues to spread, some patients are presenting with abdominal symptoms without respiratory complaints. Our case series documents four patients who presented with abdominal symptoms whose abdominopelvic CT revealed incidental pulmonary parenchymal findings in the imaged lung bases and were subsequently confirmed positive for COVID-19 via laboratory testing. It remains to be seen whether these patients will eventually develop respiratory symptoms. While it is possible that the patients' abdominal complaints are coincidental with CT findings, it is interesting that patients can have such extensive incidental disease in the lungs on CT without respiratory symptoms.

positive: A Case of Novel Coronavirus Disease 19 in a Chronic Hemodialysis Patient Presenting with Gastroenteritis and Developing Severe Pulmonary Disease Novel coronavirus disease 2019 (COVID-19) is a highly infectious, rapidly spreading viral disease with an alarming case fatality rate up to 5%. The risk factors for severe presentations are concentrated in patients with chronic kidney disease, particularly patients with end-stage renal disease (ESRD) who are dialysis dependent. We report the first US case of a 56-year-old nondiabetic male with ESRD secondary to IgA nephropathy undergoing thrice-weekly maintenance hemodialysis for 3 years, who developed COVID-19 infection. He has hypertension controlled with angiotensin receptor blocker losartan 100 mg/day and coronary artery disease status-post stent placement. During the first 5 days of his febrile disease, he presented to an urgent care, 3 emergency rooms, 1 cardiology clinic, and 2 dialysis centers in California and Utah. During this interval, he reported nausea, vomiting, diarrhea, and low-grade fevers but was not suspected of COVID-19 infection until he developed respiratory symptoms and was admitted to the hospital. Imaging studies upon admission were consistent with bilateral interstitial pneumonia. He was placed in droplet-eye precautions while awaiting COVID-19 test results. Within the first 24 h, he deteriorated quickly and developed acute respiratory distress syndrome (ARDS), requiring intubation and increasing respiratory support. Losartan was withheld due to hypotension and septic shock. COVID-19 was reported positive on hospital day 3. He remained in critical condition being treated with hydroxychloroquine and tocilizumab in addition to the standard medical management for septic shock and ARDS. Our case is unique in its atypical initial presentation and highlights the importance of early testing.

positive: Clinical characteristics and fecal-oral transmission potential of patients with COVID-19 Background: A significant proportion of patients with COVID-19 generate negative pharyngeal swab viral nucleic acid test results but test positive using fecal samples. However, fecal-oral transmission of COVID-19 has not been established to date. The purpose of this study was to evaluate the duration of fecal swab positivity in COVID-19 patients after pharyngeal swab nucleic acid test turned negative and to explore its potential for fecal-oral transmission. Methods: A retrospective analysis of clinical records, laboratory results, and chest computed tomography (CT) findings of 17 COVID-19 patients confirmed by laboratory tests from January 22 to February 7, 2020 at a tertiary hospital was performed. The potential of fecal-oral transmission was assessed by detecting the presence of SARS-CoV-2 nucleic acid in fecal swab samples. Results: A total of 16 patients (94.1%) had fever; other symptoms included dry cough, dyspnea, nausea, diarrhea, sore throat, fatigue, and muscle pain. Three patients had decreased white blood cell counts, 7 had decreased lymphocyte numbers, and 7 had increased C-reactive protein levels. Fecal samples of 11 patients tested positive for SARS-CoV-2 nucleic acid, of whom the time for the fecal samples to become SARS-CoV-2 nucleic acid-negative was longer in 10 patients than that for pharyngeal swab samples, and only one case exhibited a shorter time for his fecal sample to become SARS-CoV-2 nucleic acid-negative compared to his pharyngeal swab sample. The remaining 6 patients were negative for SARS-CoV-2 nucleic acid in fecal samples. Conclusion: In COVID-19 patients who tested positive for SARS-CoV-2 nucleic acid in both pharyngeal swab and fecal samples, the time for the fecal samples to become SARS-CoV-2 nucleic acid-negative was generally longer than that in pharyngeal swab samples. However, there is currently no evidence demonstrating that the virus can be transmitted through the fecal-oral route.

positive: Concomitant neurological symptoms observed in a patient diagnosed with coronavirus disease 2019 There has been a global outbreak of coronavirus disease 2019 (COVID‐19) since December 2019. In clinical practice, not only fever and respiratory tract symptoms but also multiple organ symptoms are observed in patients diagnosed with COVID‐19. Herein, we report a rare case of a patient diagnosed with COVID‐19 who manifested with concomitant neurological symptoms. The patient developed fever and respiratory symptoms at disease onset, followed by muscle soreness, and subsequently altered consciousness and psychiatric symptoms, with positive signs based on neurological examination. The patient tested positive for the severe acute respiratory syndrome corona virus 2 (SARS‐CoV‐2) nucleic acid (throat swab). Further, chest computed tomography (CT) revealed typical COVID‐19 findings, and head CT did not reveal significant abnormalities. The patient recovered after treatment and was discharged. This rare case indicates that SARS‐CoV‐2 can invade the central nervous system, thus causing neurological symptoms and signs. This article is protected by copyright. All rights reserved.

positive: Clinical Characteristics of 5 COVID-19 Cases With Non-respiratory Symptoms as the First Manifestation in Children An outbreak of the novel coronavirus disease 2019 (COVID-19) occurred in Wuhan, China, in December 2019, which then rapidly spread to more than 80 countries. However, detailed information on the characteristics of COVID-19 in children is still scarce. Five patients with non-respiratory symptoms as the first manifestation were hospitalized from the emergency department, and were later confirmed to have COVID-19, between 23 January and 20 February 2020, at the Wuhan Children's Hospital. SARS-CoV-2 nucleic acid detection was positive for all the patients. Four of the patients were male and one was female, and their ages ranged from 2-months to 5.6 years. All lived in Wuhan. One patient had a clear history of exposure to SARS-CoV-2, one had a suspected history of exposure, while the others had no exposure history. For three of the five patients, the primary onset disease required an emergency operation or treatment, and included intussusception, acute suppurative appendicitis perforation with local peritonitis, and traumatic subdural hemorrhage with convulsion, while for the other two it was acute gastroenteritis (including one patient with hydronephrosis and a stone in his left kidney). During the course of the disease, four of the five patients had a fever, whereas one case had no fever or cough. Two patients had leukopenia, and one also had lymphopenia. In the two cases of severe COVID-19, the levels of CRP, PCT, serum ferritin, IL-6, and IL-10 were significantly increased, whereas the numbers of CD3+, CD4+, CD8+ T lymphocytes, and CD16 + CD56 natural killer cells were decreased. We also found impaired liver, kidney, and myocardial functions; the presence of hypoproteinemia, hyponatremia, and hypocalcemia; and, in one case, abnormal coagulation function. Except for one patient who had a rotavirus infection, all patients tested negative for common pathogens, including the influenza virus, parainfluenza virus, respiratory syncytial virus, adenovirus, enterovirus, mycoplasma, Chlamydia, and Legionella. Chest CT images of all the patients showed patches or ground-glass opacities in the lung periphery or near the pleura, even large consolidations. This case series is the first report to describe the clinical features of COVID-19 with non-respiratory symptoms as the first manifestation in children.

positive: Clinical presentation and course of COVID-19. Information about the clinical presentation and course of COVID-19 is rapidly evolving. Data are emerging from retrospective clinical studies conducted in Wuhan, China, showing the symptoms and characteristics of COVID-19 caused by severe acute respiratory virus coronavirus 2 (SARS-CoV-2) infection, including fever, cough, and shortness of breath. Radiographic data on COVID-19 cases reveal bilateral opacities on chest radiography and ground-glass opacities on computed tomography. Data on laboratory markers and mortality and morbidity are also emerging.

positive: The First Case of 2019 Novel Coronavirus Pneumonia Imported into Korea from Wuhan, China: Implication for Infection Prevention and Control Measures In December 2019, a viral pneumonia outbreak caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV), began in Wuhan, China. We report the epidemiological and clinical features of the first patient with 2019-nCoV pneumonia imported into Korea from Wuhan. This report suggests that in the early phase of 2019-nCoV pneumonia, chest radiography would miss patients with pneumonia and highlights taking travel history is of paramount importance for early detection and isolation of 2019-nCoV cases.

positive: 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.

positive: Neurological Manifestations of COVID-19 (SARS-CoV-2): A Review Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been associated with many neurological symptoms but there is a little evidence-based published material on the neurological manifestations of COVID-19. The purpose of this article is to review the spectrum of the various neurological manifestations and underlying associated pathophysiology in COVID-19 patients. Method: We conducted a review of the various case reports and retrospective clinical studies published on the neurological manifestations, associated literature, and related pathophysiology of COVID-19 using PUBMED and subsequent proceedings. A total of 118 articles were thoroughly reviewed in order to highlight the plausible spectrum of neurological manifestations of COVID 19. Every article was either based on descriptive analysis, clinical scenarios, correspondence, and editorials emphasizing the neurological manifestations either directly or indirectly. We then tried to highlight the significant plausible manifestations and complications that could be related to the pandemic. With little known about the dynamics and the presentation spectrum of the virus apart from the respiratory symptoms, this area needs further consideration. Conclusion: The neurological manifestations associated with COVID-19 such as Encephalitis, Meningitis, acute cerebrovascular disease, and Guillain Barré Syndrome (GBS) are of great concern. But in the presence of life-threatening abnormal vitals in severely ill COVID-19 patients, these are not usually underscored. There is a need to diagnose these manifestations at the earliest to limit long term sequelae. Much research is needed to explore the role of SARS-CoV-2 in causing these neurological manifestations by isolating it either from cerebrospinal fluid or brain tissues of the deceased on autopsy. We also recommend exploring the risk factors that lead to the development of these neurological manifestations.

positive: Diversity of clinical appearance of cutaneous manifestations in the course of COVID‐19 The outbreak of COVID‐19 has stricken more than 203,000 people in Italy up to 30(th) of April 2020, with over 27,000 died according to official estimates(1). While Italy was one of the most affected countries in Europe, the impact of the disease in the southern part of the state was less dramatic than in the north, due to some still not understood reasons. Particularly in Sicily, ‘only’ 3,140 cases have been recorded, of whom 533 encountered in the province of Messina.

positive: Clinical progression of patients with COVID-19 in Shanghai, China Summary Background Studies on the 2019 novel coronavirus disease (COVID-19) have generally been limited to the description of the epidemiology and initial clinical characteristics. We investigated the temporal progression in patients with COVID-19. Methods In this retrospective, single-center study, we included confirmed cases of COVID-19 from Jan 20 to Feb 6, 2020 in Shanghai. Final date of follow-up was February 25, 2020. Results Of the 249 patients enrolled, the median age was 51 years old, and 126 (50.6%) were male. The duration from onset of symptoms to hospitalization was 4(2–7) days in symptomatic patients. Fever was occurred in 235(94.3%) patients. A total of 215 (86.3%) patients had been discharged after 16(12–20) days hospitalization. The estimated median duration of fever in all the patients with fever was 10 days (95 confidential intervals [CIs]: 8–11 days) after onset of symptoms. Patients who were transferred to intensive care units (ICU) had significantly longer duration of fever as compared to those not in ICU (31 days v.s. 9 days after onset of symptoms, respectively, P <0.0001). Radiological aggravation of initial image was observed in 163 (65.7%) patients on day 7 after onset of symptoms. 154(94.5%) of these patients showed radiological improvement on day 14. The median duration to negative reverse-transcriptase PCR tests of upper respiratory tract samples was 11 days (95 CIs: 10–12 days). Viral clearance was more likely to be delayed in patients in ICU than those not in ICU (P <0.0001). In multivariate logistical analysis, age (Odds ratio [OR] = 1.06) and CD4 T cell count (OR = 0.55 per 100 cells/ul increase) were independently associated with ICU admission. Conclusions The majority of COVID-19 cases are mild. The clinical progression pattern suggests that early control of viral replication and application of host-directed therapy in later stage is essential to improve the prognosis of CVOID-19.

positive: Laboratory Findings of COVID-19 Infection are Conflicting in Different Age Groups and Pregnant Women: A Literature Review Coronavirus disease 2019 (COVID-19), a new type and rapidly spread viral pneumonia, is now producing an outbreak of pandemic proportions. The clinical features and laboratory results of different age groups are different due to the general susceptibility of the disease. The laboratory findings of COVID-19 in pregnant women are also conflicting. Para-clinical investigations including laboratory tests and radiologic findings play an important role in early diagnosis and treatment monitoring of severe acute respiratory syndrome and coronavirus-2 (SARS-CoV-2). The majority of previous reports on the SARS-CoV-2 laboratory results were based on data from the general population and limited information is available based on age difference and pregnancy status. This review aimed to describe the COVID-19 laboratory findings in neonates, children, adults, elderly and pregnant women altogether for the first time. The most attracting and reliable markers of COVID-19 in patients were: normal C-reactive protein (CRP) and very different and conflicting laboratory results regardless of clinical symptoms in neonates, normal or temporary elevated CRP, conflicting WBC count results and procalcitonin elevation in children, lymphopenia and elevated lactate dehydrogenase (LDH) in adult patients, lymphopenia and elevated CRP and LDH in the elderly people and high CRP, leukocytosis and elevated neutrophil ratio in pregnant women.

positive: Clinical characteristics of 182 pediatric COVID‐19 patients with different severities and allergic status BACKGROUND: The pandemic of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has made widespread impact recently. We aim to investigate the clinical characteristics of COVID‐19 children with different severities and allergic status. METHODS: Data extracted from the electronical medical records, including demographics, clinical manifestations, comorbidities, laboratory and immunological results and radiological images of 182 hospitalized COVID‐19 children were summarized and analyzed. RESULTS: The median age was 6 years old, ranging from 3 days to 15 years, and there were more boys (male‐female ratio about 2:1) within the studied 182 patients. Most of the children were infected by family members. Fever (43.4%) and dry cough (44.5%) were common symptoms, and gastrointestinal manifestations accounted for 11.0%, including diarrhea, abdominal discomfort and vomiting. 71.4% had abnormal chest computed tomography (CT) scan images, and typical signs of pneumonia were ground‐glass opacity and local patchy shadowing on admission. Laboratory results were mostly within normal ranges, and only a small ratio of lymphopenia (3.9%) and eosinopenia (29.5%) were observed. The majority (97.8%) of infected children were not severe, and 24 (13.2%) of them had asymptomatic infections. Compared to children without pneumonia(manifested as asymptomatic and acute upper respiratory infection), children with pneumonia were associated with higher percentages of the comorbidity history, symptoms of fever and cough, and increased levels of serum procalcitonin, alkaline phosphatase and serum interleukins (IL)‐2, IL‐4, IL‐6, IL‐10 and TNF‐α.There were no differences of treatments, duration of hospitalization, time from first positive to first negative nucleic acid testing and outcomes between children with mild pneumonia and without pneumonia. All the hospitalized COVID‐19 children had recovered except one death due to intussusception and sepsis. In 43 allergic children with COVID‐19, allergic rhinitis (83.7%) was the major disease, followed by drug allergy, atopic dermatitis, food allergy and asthma. Demographics and clinical features were not significantly different between allergic and non‐allergic groups. Allergic patients showed less increase in acute phase reactants, procalcitonin, D‐dimer and aspartate aminotransferase levels compared to all patients. Immunological profiles including circulating T, B and NK lymphocyte subsets, total immunoglobulin and complement levels and serum cytokines did not show any difference in allergic and pneumonia groups. Neither eosinophil counts nor serum total immunoglobulin E (IgE) levels showed a significant correlation with other immunological measures, such as other immunoglobulins, complements, lymphocyte subsets numbers and serum cytokine levels. CONCLUSION: Pediatric COVID‐19 patients tended to have a mild clinical course. Patients with pneumonia had higher proportion of fever and cough and increased inflammatory biomarkers than those without pneumonia. There was no difference between allergic and non‐allergic COVID‐19 children in disease incidence, clinical features, laboratory and immunological findings. Allergy was not a risk factor for developing and severity of SARS‐CoV‐2 infection and hardly influenced the disease course of COVID‐19 in children.

positive: Ocular manifestations and clinical characteristics of 535 cases of COVID-19 in Wuhan, China: a cross-sectional study PURPOSE: To investigate the ocular manifestations and clinical characteristics of COVID-19 patients caused by SARS-CoV-2 in Wuhan, China. METHODS: A total of 535 COVID-19 patients were recruited at Mobile Cabin Hospital and Tongji Hospital. Information on demographic characteristics, exposure history, ocular symptoms, eye drop medication, eye protections, chronic eye diseases, systemic concomitant symptoms, radiologic findings and SARS-CoV-2 detection in nasopharyngeal swabs by real-time PCR was collected from questionnaires and electronic medical records. RESULTS: Of 535 patients, 27 patients (5.0%) presented with conjunctival congestion and 4 patients had conjunctival congestion as the initial symptom. The average duration of conjunctival congestion was 5.9 ± 4.5 days (mean [SD]). The other ocular symptoms, including increased conjunctival secretion, ocular pain, photophobia, dry eye and tearing, were also found in patients with conjunctival congestion. Notably, hand-eye contact was independently correlated with conjunctival congestion in COVID-19 patients. We also found that some COVID-19 patients had chronic eye diseases, including conjunctivitis (33, 6.2%), xerophthalmia (24, 4.5%) and keratitis (14, 2.6%). Similar to the published studies, the most common clinical symptoms were fever, cough and fatigue. A total of 343 patients (64.1%) had positive SARS-CoV-2 detection in nasopharyngeal swabs. CONCLUSIONS: Conjunctival congestion is one of the COVID-19-related ocular symptoms, which could occur as the initial symptoms. Frequent hand-eye contact may be the risk factor for conjunctival congestion in COVID-19 patients. Screening of patients with conjunctival congestion by ophthalmologists is advocated during the outbreak of COVID-19. It is essential to provide eye-care equipment and strengthen education on eye protection.

positive: Clinical Course and Outcomes of Patients with Severe Acute Respiratory Syndrome Coronavirus 2 Infection: a Preliminary Report of the First 28 Patients from the Korean Cohort Study on COVID-19 BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pneumonia emerged in Wuhan, China in December 2019. In this retrospective multicenter study, we investigated the clinical course and outcomes of novel coronavirus disease 2019 (COVID-19) from early cases in Republic of Korea. METHODS: All of the cases confirmed by real time polymerase chain reaction were enrolled from the 1st to the 28th patient nationwide. Clinical data were collected and analyzed for changes in clinical severity including laboratory, radiological, and virologic dynamics during the progression of illness. RESULTS: The median age was 40 years (range, 20-73 years) and 15 (53.6%) patients were male. The most common symptoms were cough (28.6%) and sore throat (28.6%), followed by fever (25.0%). Diarrhea was not common (10.7%). Two patients had no symptoms. Initial chest X-ray (CXR) showed infiltration in 46.4% of the patients, but computed tomography scan confirmed pneumonia in 88.9% (16/18) of the patients. Six patients (21.4%) required supplemental oxygen therapy, but no one needed mechanical ventilation. Lymphopenia was more common in severe cases. Higher level of C-reactive protein and worsening of chest radiographic score was observed during the 5-7 day period after symptom onset. Viral shedding was high from day 1 of illness, especially from the upper respiratory tract (URT). CONCLUSION: The prodromal symptoms of COVID-19 were mild and most patients did not have limitations of daily activity. Viral shedding from URT was high from the prodromal phase. Radiological pneumonia was common from the early days of illness, but it was frequently not evident in simple CXR. These findings could be plausible explanations for the easy and rapid spread of SARS-CoV-2 in the community.

positive: Distinguishing COVID-19 from influenza pneumonia in the early stage through CT imaging and clinical features Purpose: To identify differences in CT imaging and clinical features between COVID-19 and influenza pneumonia in the early stage, and to identify the most valuable features in the differential diagnosis. Materials and Method: A consecutive cohort of 73 COVID-19 and 48 influenza pneumonia patients were retrospectively recruited from five independent institutions. The courses of both diseases were confirmed to be in the early stages (mean 2.66 (SD 2.62) days for COVID-19 and mean 2.19 (SD 2.10) days for influenza pneumonia after onset). The chi-square test, student`s t-test, and Kruskal-Wallis H-test were performed to compare CT imaging and clinical features between the two groups. Spearman or Kendall correlation tests between feature metrics and diagnosis outcomes were also assessed. The diagnostic performance of each feature in differentiating COVID-19 from influenza pneumonia was evaluated with univariate analysis. The corresponding area under the curve (AUC), accuracy, specificity, sensitivity and threshold were reported. Results: The ground-glass opacification (GGO) was the most common imaging feature in COVID-19, including pure-GGO (75.3%) and mixed-GGO (78.1%), mainly in peripheral distribution. For clinical features, most COVID-19 patients presented normal white blood cell (WBC) count (89.04%) and neutrophil count (84.93%). Twenty imaging features and 6 clinical features were identified to be significantly different between the two diseases. The diagnosis outcomes correlated significantly with the WBC count (r=-0.526, P<0.001) and neutrophil count (r=-0.500, P<0.001). Four CT imaging features had absolute correlations coefficients higher than 0.300 (P<0.001), including crazy-paving pattern, mixed-GGO in peripheral area, pleural effusions, and consolidation. Conclusions: Among a total of 1537 lesions and 62 imaging and clinical features, 26 features were demonstrated to be significantly different between COVID-19 and influenza pneumonia. The crazy-paving pattern was recognized as the most powerful imaging feature for the differential diagnosis in the early stage, while WBC count yielded the highest diagnostic efficacy in clinical manifestations.

positive: Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study Summary Background A cluster of patients with coronavirus disease 2019 (COVID-19) pneumonia caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were successively reported in Wuhan, China. We aimed to describe the CT findings across different timepoints throughout the disease course. Methods Patients with COVID-19 pneumonia (confirmed by next-generation sequencing or RT-PCR) who were admitted to one of two hospitals in Wuhan and who underwent serial chest CT scans were retrospectively enrolled. Patients were grouped on the basis of the interval between symptom onset and the first CT scan: group 1 (subclinical patients; scans done before symptom onset), group 2 (scans done ≤1 week after symptom onset), group 3 (>1 week to 2 weeks), and group 4 (>2 weeks to 3 weeks). Imaging features and their distribution were analysed and compared across the four groups. Findings 81 patients admitted to hospital between Dec 20, 2019, and Jan 23, 2020, were retrospectively enrolled. The cohort included 42 (52%) men and 39 (48%) women, and the mean age was 49·5 years (SD 11·0). The mean number of involved lung segments was 10·5 (SD 6·4) overall, 2·8 (3·3) in group 1, 11·1 (5·4) in group 2, 13·0 (5·7) in group 3, and 12·1 (5·9) in group 4. The predominant pattern of abnormality observed was bilateral (64 [79%] patients), peripheral (44 [54%]), ill-defined (66 [81%]), and ground-glass opacification (53 [65%]), mainly involving the right lower lobes (225 [27%] of 849 affected segments). In group 1 (n=15), the predominant pattern was unilateral (nine [60%]) and multifocal (eight [53%]) ground-glass opacities (14 [93%]). Lesions quickly evolved to bilateral (19 [90%]), diffuse (11 [52%]) ground-glass opacity predominance (17 [81%]) in group 2 (n=21). Thereafter, the prevalence of ground-glass opacities continued to decrease (17 [57%] of 30 patients in group 3, and five [33%] of 15 in group 4), and consolidation and mixed patterns became more frequent (12 [40%] in group 3, eight [53%] in group 4). Interpretation COVID-19 pneumonia manifests with chest CT imaging abnormalities, even in asymptomatic patients, with rapid evolution from focal unilateral to diffuse bilateral ground-glass opacities that progressed to or co-existed with consolidations within 1–3 weeks. Combining assessment of imaging features with clinical and laboratory findings could facilitate early diagnosis of COVID-19 pneumonia. Funding None.

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

positive: 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.

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: COVID-19 infection presenting as pancreatitis in a pregnant woman: A case report BACKGROUND: The coronavirus 2019 (COVID-19) pandemic has posed unique challenges in healthcare. In obstetrics, there is little information available to guide practice. As new data emerge, the spectrum of initial presenting symptoms has expanded from fever, cough, and dyspnea to gastrointestinal and other symptoms in both pregnant and non-pregnant patients. CASE: A 36-year-old woman, G4P2, at 33 weeks of gestation presented very early in the COVID-19 course with four days of cough and fever, without recent travel or known exposure. She appeared well, with stable vital signs, and was sent home to self-quarantine after a specimen for COVID-19 testing was collected. Two days later, she presented with nausea, vomiting, and abdominal pain, and was diagnosed with acute pancreatitis. CONCLUSION: To date, no cases of human pancreatitis have been identified as related to a COVID-19 infection, although multiple other gastrointestinal symptoms have been described. Given the lack of other etiology, we consider the possibility that patient's acute pancreatitis could be secondary to COVID-19 infection.

positive: Coronavirus Disease 2019 (COVID-19) Can Masquerade as Acute Postoperative Periprosthetic Joint Infection Fever etiology during the first postoperative days following total knee arthroplasty (TKA) may be challenging to solve. Early periprosthetic joint infection is the main reason; however, other equally important causes must be excluded such as thrombosis, deep venous thrombosis, and chest or urinary tract infections. We report the case of a 70-year-old Caucasian female patient presented with high fever reaching 39°C, fatigue, and myalgia lasting for a week after a fully cemented primary TKA. Symptoms were falsely attributed to the surgical procedure, leading to erroneous early management and a complicated postoperative course. In the era of the severe acute respiratory syndrome coronavirus 2 (SARs-CoV-2) pandemic, a high index of suspicion for coronavirus disease 2019 (COVID-19) symptoms and viral chest infection must be raised, primarily in vulnerable patients.

positive: Clinical characteristics and outcomes of COVID‐19 patients with gastrointestinal symptoms admitted to Jianghan Fangcang Shelter Hospital in Wuhan, China OBJECTIVE: Coronavirus disease 2019 (COVID‐19) is a health emergency worldwide, and gastrointestinal (GI) symptoms are increasingly reported in COVID‐19 patients. However, sample size was small and the incidence of GI symptoms in patients was variable across studies, and the correlation between these symptoms and clinical outcomes remains incompletely understood. The objective of this study is to compare clinical characteristics and outcomes between patients with and without GI symptoms admitted to Jianghan Fangcang Shelter Hospital in Wuhan. METHODS: All patients admitted to Jianghan Fangcang Shelter Hospital were evaluated. Data on epidemiological and clinical characteristics, laboratory findings, treatment procedures, and clinical outcomes were retrieved from electronic medical records. RESULTS: This retrospective study recruited 1320 COVID‐19 patients admitted to hospital from February 5, 2020, to March 9, 2020. On the basis of the presence of GI symptoms, the sample was divided into a GI group (n=192) and a non‐GI group (n=1128). The most common GI symptoms were diarrhea (8.1%), anorexia (4.7%), and nausea and vomiting (4.3%). The risk of clinical deterioration was significantly higher in the GI group than in the non‐GI group (15.6% vs. 10.1%, p=0.032). GI symptoms (p=0.045), male gender (p<0.001), and increased C‐reactive protein (p=0.008) were independent risk factors for clinical worsening. CONCLUSION: The risk of clinical deterioration was significantly higher in the GI group. Furthermore, potential risk factors for developing GI symptoms, male gender, and increased C‐reactive protein can help clinicians predict clinical outcomes in COVID‐19 patients. This article is protected by copyright. All rights reserved.

positive: Clinical Characteristics of COVID-19 Infection in Newborns and Pediatrics: A Systematic Review Introduction: World Health Organization has declared COVID-19 a pandemic and a global health emergency Thus, it is necessary to clearly characterize clinical manifestations and management of COVID-19 infection in children to provide accurate information for healthcare workers Accordingly, the present study was designed to review articles published on clinical manifestations and characteristics of children and infants with COVID-19 Methods: In this systematic review, medical databases including Cochrane Library, Web of Science, Embase, Scopus, SID, Medline, WHO and LitCovid were searched using English and Persian keywords including COVID-19, Pediatrics, Newborn, Coronavirus 2019, 2019-nCoV, SARS-CoV-2 Finally, data of 14 related articles were included in the study Results: A total of 2228 children, newborns and infants were studied Clinical manifestation in children may be mild (72%), moderate (22%) or severe (6%), and the most common symptoms include dry cough (91%) and fever (96%) According to the included articles, two children had died, one of which was a 14-year-old boy and his exposure history and underlying disease were unclear, and the other was a male newborn with gestational age of 35 weeks and 5 days, birth weight of 2200, Apgar score of 8, 8 (1 min and 5 min) and his first symptom was increased heart rate No differences were found between male and female children regarding infection with COVID-19 Conclusion: Most pediatrics were infected with COVID-19 due to family cluster or history of close contact Infected children have relatively milder clinical symptoms compared to infected adults We should pay special attention to early diagnosis and early treatment in children infected with COVID-19

positive: Case Report: Walking Pneumonia in Novel Coronavirus Disease (COVID-19): Mild Symptoms with Marked Abnormalities on Chest Imaging This case report underlines the appearance of a "walking pneumonia" in a novel coronavirus disease (COVID-19) patient, with evidence of progressive lung involvement on chest imaging studies. The patient traveled from Wuhan, Hubei, China, to Thailand in January 2020. One of her family members was diagnosed with COVID-19. She presented to the hospital because of her concern, but she was without fever or any respiratory symptoms. Three days earlier, her nasopharyngeal and throat swabs revealed a negative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Her initial chest radiography was abnormal, and her first sputum SARS-CoV-2 test yielded inconclusive results. A subsequent sputum test was positive for SARS-CoV-2. Diagnosis in this patient was facilitated by chest imaging and repeat viral testing. Thus, chest imaging studies might enhance capabilities for early diagnosis of COVID-19 pneumonia.

positive: Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center's observational study BACKGROUND: An outbreak of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was first detected in Wuhan, Hubei, China. People of all ages are susceptible to SARS-CoV-2 infection. No information on severe pediatric patients with COVID-19 has been reported. We aimed to describe the clinical features of severe pediatric patients with COVID-19. METHODS: We included eight severe or critically ill patients with COVID-19 who were treated at the Intensive Care Unit (ICU), Wuhan Children's Hospital from January 24 to February 24. We collected information including demographic data, symptoms, imaging data, laboratory findings, treatments and clinical outcomes of the patients with severe COVID-19. RESULTS: The onset age of the eight patients ranged from 2 months to 15 years; six were boys. The most common symptoms were polypnea (8/8), followed by fever (6/8) and cough (6/8). Chest imaging showed multiple patch-like shadows in seven patients and ground-glass opacity in six. Laboratory findings revealed normal or increased whole blood counts (7/8), increased C-reactive protein, procalcitonin and lactate dehydrogenase (6/8), and abnormal liver function (4/8). Other findings included decreased CD16 + CD56 (4/8) and Th/Ts*(1/8), increased CD3 (2/8), CD4 (4/8) and CD8 (1/8), IL-6 (2/8), IL-10 (5/8) and IFN-Î³ (2/8). Treatment modalities were focused on symptomatic and respiratory support. Two critically ill patients underwent invasive mechanical ventilation. Up to February 24, 2020, three patients remained under treatment in ICU, the other five recovered and were discharged home. CONCLUSIONS: In this series of severe pediatric patients in Wuhan, polypnea was the most common symptom, followed by fever and cough. Common imaging changes included multiple patch-like shadows and ground-glass opacity; and a cytokine storm was found in these patients, which appeared more serious in critically ill patients.

positive: Dermatological findings in SARS‐CoV‐2 positive patients: An observational study from North India A novel coronavirus (severe acute respiratory syndrome corononavirus‐2; SARS‐CoV‐2) has affected millions of people across the world. The coronavirus disease (COVID‐19) resulting from SARS‐CoV‐2 manifests in variable clinical severity, featuring both respiratory and extra‐respiratory symptoms. Dermatological manifestations of COVID‐19 are sparsely reported. To study the various dermatological findings in SARS‐CoV‐2 positive patients in Indian population. This article is protected by copyright. All rights reserved.

positive: Case Report: Walking Pneumonia in Novel Coronavirus Disease (COVID-19): Mild Symptoms with Marked Abnormalities on Chest Imaging This case report underlines the appearance of a “walking pneumonia” in a novel coronavirus disease (COVID-19) patient, with evidence of progressive lung involvement on chest imaging studies. The patient traveled from Wuhan, Hubei, China, to Thailand in January 2020. One of her family members was diagnosed with COVID-19. She presented to the hospital because of her concern, but she was without fever or any respiratory symptoms. Three days earlier, her nasopharyngeal and throat swabs revealed a negative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Her initial chest radiography was abnormal, and her first sputum SARS-CoV-2 test yielded inconclusive results. A subsequent sputum test was positive for SARS-CoV-2. Diagnosis in this patient was facilitated by chest imaging and repeat viral testing. Thus, chest imaging studies might enhance capabilities for early diagnosis of COVID-19 pneumonia.

positive: Novel coronavirus disease with conjunctivitis and conjunctivitis as first symptom: Two cases report/ 中华实验眼科杂志 As the frontline health care workers at the center of the novel coronavirus disease (COVIN-19) outbreak, we have found many asymptomatic COVIN-19 patients or patients with mild symptoms since December 2019. A number of COVIN-19 cases with conjunctivitis or conjunctivitis as the first symptom have been observed in our clinical work. This paper reports the diagnosis and treatment of one COVIN-19 patient with conjunctivitis as the first symptom and one COVIN-19 patient with conjunctivitis. Case one occurred conjunctivitis at the third day after closely contacted with determined COVID-19 patient and visited to eye doctor, and the symptom of conjunctivitis following the topical administration of anti-virual eyedrops for 1 week, followed by COVID-19. Her 2019-nCoV RNA detection of nasopharynx swab was positive but that of conjunctival sac swab was a negative result. Case two had a positive epidemiological history and simultaneous onset of COVID-19 and conjunctivitis.She presented positive results of 2019-nCoV RNA detection in both nasopharynx and conjunctival sac swabs, and other lab results supported the diagnosis of COVID-19 but she had a normal CT findings of the chest. The ocular symptoms were disappeared after topical administration of anti-virual eyedrops for 1 week.

positive: Urticarial eruption in COVID-19 infection

positive: Subjective neurological symptoms frequently occur in patients with SARS-CoV2 infection OBJECTIVE: Coronavirus disease 2019 (COVID-19) represents a novel pneumonia leading to severe acute respiratory syndrome (SARS). Recent studies documented that SARS-Coronavirus2 (SARS-CoV2), responsible for COVID-19, can affect the nervous system. The aim of the present observational study was to prospectively assess subjective neurological symptoms (sNS) in patients with SARS-CoV2 infection. METHODS: We included patients hospitalized at the University Hospital of Rome Tor Vergata, medical center dedicated to the treatment of patients with COVID-19 diagnosis, who underwent an anamnestic interview about sNS consisting of 13 items, each related to a specific symptom, requiring a dichotomized answer. RESULTS: We included 103 patients with SARS-CoV2 infection. Ninety-four patients (91.3%) reported at least one sNS. Sleep impairment was the most frequent symptom, followed by dysgeusia, headache, hyposmia, and depression. Women more frequently complained hyposmia, dysgeusia, dizziness, numbeness/paresthesias, daytime sleepiness, and muscle ache. Moreover, muscle ache and daytime sleepiness were more frequent in the first 2 days after admission. Conversely, sleep impairment was more frequent in patients with more than 7 days of hospitalization. In these patients we also documented higher white blood cells and lower C-reactive protein levels. These laboratory findings correlated with the occurrence of hyposmia, dysgeusia, headache, daytime sleepiness, and depression. CONCLUSIONS: Patients with SARS-CoV2 infection frequently present with sNS. These symptoms were present from the early phases of the disease. The possibly intrinsic neurotropic properties of SARS-CoV2 may justify the very high frequency of sNS. Further studies targeted at investigating the consequences of SARS-CoV2 infection on the CNS should be planned.

positive: [Clinical analysis of 150 cases of 2019 novel coronavirus infection in Nanyang City, Henan Province]. Objective: To analyze the epidemiological characteristics and clinical features of the patients with 2019-nCoV infection in Nanyang City, so as to provide evidence for clinical diagnosis and treatment. Methods: The epidemiology, clinical symptoms, atory and radiologic data of 150 patients with 2019-nCoV infection admitted to the designated hospitals in Nanyang City from January 24,2020 to February 16, 2020 were retrospectively analyzed. Results: The 150 patients with 2019 nCov infection consisted of 67 men and 83 women, and the median age was 45±16 years; 69 of them were the first generation case,60 of them were the second generation case, 6 of them were the third generation case,the median incubation period of the first generation case was 5.4±2.2 days, and the second generation case was 6.7±3.1 days, and the first-generation cases are the majority in severe patients (69%) . The most common basic disease was hypertension (13 cases, 9%), diabetes (9 cases, 6%), and the most common symptom is fever(142 cases, 95%, 63% showed moderate fever) , cough and sputum(108 cases,72%), fatigue(23 cases,15%), anorexia(20 cases, 13%), headache, diarrhea, muscle soreness, sore throat as the first symptoms. The average time from onset of symptoms to consultation was 4.2±2.2 days for all patients. The changes in peripheral blood cells were mainly lymphonpenia (83 cases, 55%) and eosinophilia (95 cases, 63%), The lymphocyte count of the severe and critically ill patients was more significantly reduced, and some patients had increased myocardial enzymes, mainly LDH (47 cases, 31%), and a few patients had liver function damage, mainly manifested in ALT and AST. High, very few patients have renal impairment. Among the inflammation-related indicators, the main manifestations are increased CRP (66 cases, 43%) and ESR (86 cases, 57%), elevated D-Dimer in 29% of patients. 144 cases have different degrees of infective lesions in chest CT examination, with 30 cases (21%) on one side and 144 cases (79%) on both sides. Morphologically, most of the lesions were patchy ground glass lesions, which could be accompanied by air bronchus signs and some consolidation and paving stone signs. Of the cases showing "white lung", 87% were sever ill or critically ill. After active treatment, 45% of patients were discharged according to discharge standards. 33% of sever and critically ill patients were discharged, 49% of them were degraded hospitalization.The average length of hospitalization was 12±4 days. Conclusion: A history of epidemiological exposure, fever, chest CT with signs of pneumonia, normal or decreased WBC, and lymphocytopenia, eosinophilia are the clinical basis for the diagnosis of this disease, and most of the sever patients were the first generation cases. The degree of lymphocytopenia is related to the severity of the disease.

positive: Medical treatment of 55 patients with COVID-19 from seven cities in northeast China who fully recovered: a single-center, retrospective, observational study Background: COVID-19 is an emerging disease caused by the SARS-CoV-2 virus; no specific medication has been identified to date. We aimed to investigate the administered medications and intervention times for patients who completely recovered from COVID-19. Methods: This single-center, retrospective, and observational study included 55 patients with COVID-19 who were transferred to Shenyang Sixth People's Hospital between January 20 and March 15, 2020. Demographic information, symptoms, laboratory indicators, treatment processes, and clinical outcomes were collected. Administered drugs and intervention times were compared in 47 and eight patients with mild and severe symptoms, respectively. Findings: All 55 patients recovered. Fifty-three patients (96.36%) received antiviral therapy, including 45 in the mild group (median treatment: 14 days; 17 received umifenovir) and all eight severe-group patients (median treatment: 17.5 days; four received lopinavir/ritonavir). Twenty-nine patients (52.72%) were administered antibiotics, including 21 in the mild group (median treatment: 13.5 days; 15 received moxifloxacin) and all eight in the severe group (median treatment: 9 days; two received linezolid). Moreover, seven patients (12.72%) were treated with glucocorticoids and nine (16.36%) with immunomodulators. Interpretation: Given the 100% recovery rate, early administration of antiviral drugs can be considered. Umifenovir may benefit patients with mild symptoms, while lopinavir/ritonavir may benefit those with severe symptoms. Prophylactic administration of common antibiotics may reduce the risk of co-infection. The use of glucocorticoids is usually not necessary.

positive: Digestive Symptoms in COVID-19 Patients With Mild Disease Severity: Clinical Presentation, Stool Viral RNA Testing, and Outcomes OBJECTIVES: Coronavirus disease 2019 (COVID-19) most commonly presents with respiratory symptoms, including cough, shortness of breath, and sore throat. However, digestive symptoms also occur in patients with COVID-19 and are often described in outpatients with less severe disease. In this study, we sought to describe the clinical characteristics of COVID-19 patients with digestive symptoms and mild disease severity. METHODS: We identified COVID-19 patients with mild disease and one or more digestive symptoms (diarrhea, nausea, and vomiting), with or without respiratory symptoms, and compared them with a group presenting solely with respiratory symptoms. We followed up patients clinically until they tested negative for COVID-19 on at least 2 sequential respiratory tract specimens collected ≥24 hours apart. We then compared the clinical features between those with digestive symptoms and those with respiratory symptoms. RESULTS: There were 206 patients with low severity COVID-19, including 48 presenting with a digestive symptom alone, 69 with both digestive and respiratory symptoms, and 89 with respiratory symptoms alone. Between the 2 groups with digestive symptoms, 67 presented with diarrhea, of whom 19.4% experienced diarrhea as the first symptom in their illness course. The diarrhea lasted from 1 to 14 days, with an average duration of 5.4 ± 3.1 days and a frequency of 4.3 ± 2.2 bowel movements per day. Concurrent fever was found in 62.4% of patients with a digestive symptom. Patients with digestive symptoms presented for care later than those with respiratory symptoms (16.0 ± 7.7 vs 11.6 ± 5.1 days, P < 0.001). Nevertheless, patients with digestive symptoms had a longer duration between symptom onset and viral clearance (P < 0.001) and were more likely to be fecal virus positive (73.3% vs 14.3%, P = 0.033) than those with respiratory symptoms. DISCUSSION: We describe a unique subgroup of COVID-19 patients with mild disease severity marked by the presence of digestive symptoms. These patients are more likely to test positive for viral RNA in stool, to have a longer delay before viral clearance, and to experience delayed diagnosis compared with patients with only respiratory symptoms.

positive: COVID-19: gastrointestinal symptoms and potential sources of 2019-nCoV transmission. A new type of coronavirus, i.e. se-vere acute respiratory syndrome coronavirus 2 (SARS-CoV-2; formerly known as 2019-nCoV) appeared in December 2019 in the province of Hubei, China, and over the past four months the number of cases of infection has exceeded 240,000 worldwide, leading to a pandemia [1]. At the genetic level, 2019-nCoV is closely related to the SARS-CoV and, to a lesser extent, to MERS-CoV, which appeared as epidemiological threats in recent years in China and the Middle East, respectively. Infections with the Coronaviridae virus family in a small percentage of patients, especially in those over 60 years of age with a positive clinical history, lead to severe acute respiratory syndrome [2].

positive: Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples from the Hong Kong Cohort and Systematic Review and Meta-analysis Abstract Background & Aims Infection with SARS-CoV-2 causes COVID-19, which has been characterized by fever, respiratory, and gastrointestinal symptoms as well as shedding of virus RNA into feces. We performed a systematic review and meta-analysis of published gastrointestinal symptoms and detection of virus in stool, and also summarized data from a cohort of patients with COVID-19 in Hong Kong. Methods We collected data from the cohort of patients with COVID-19 in Hong Kong (n=59; diagnosis from February 2 through Feb 29, 2020), and searched PubMed, Embase, Cochrane and three Chinese databases through March 11, 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We analyzed pooled data on the prevalence of overall and individual gastrointestinal symptoms (anorexia, nausea, vomiting, diarrhea, and abdominal pain or discomfort) using a random effects model. Results Among the 59 patients with COVID-19 in Hong Kong, 15 patients (25.4%) had gastrointestinal symptoms and 9 patients (15.3%) had stool that tested positive for virus RNA. Stool viral RNA was detected in 38.5% and 8.7% among those with and without diarrhea, respectively (P=.02). The median fecal viral load was 5.1 log10cpm in patients with diarrhea vs 3.9 log10cpm in patients without diarrhea (P=.06). In a meta-analysis of 60 studies, comprising 4243 patients, the pooled prevalence of all gastrointestinal symptoms was 17.6% (95% CI, 12.3%–24.5%); 11.8% of patients with non-severe COVID-19 had gastrointestinal symptoms (95% CI, 4.1%–29.1%) and 17.1% of patients with severe COVID-19 had gastrointestinal symptoms (95% CI, 6.9%–36.7%). In the meta-analysis, the pooled prevalence of stool samples that were positive for virus RNA was 48.1% (95% CI, 38.3%–57.9%); of these samples, 70.3% of those collected after loss of virus from respiratory specimens tested positive for the virus (95% CI, 49.6%–85.1%). Conclusions In an analysis of data from the Hong Kong cohort of patients with COVID-19 and a meta-analysis of findings from publications, we found that 17.6% of patients with COVID-19 had gastrointestinal symptoms. Virus RNA was detected in stool samples from 48.1% patients—even in stool collected after respiratory samples tested negative. Healthcare workers should therefore exercise caution in collecting fecal samples or performing endoscopic procedures in patients with COVID-19—even during patient recovery.

positive: Clinical Characteristics of Imported Cases of COVID-19 in Jiangsu Province: A Multicenter Descriptive Study BACKGROUND: We aimed to report the clinical characteristics of imported coronavirus disease-19 (COVID-19) in Jiangsu Province. METHODS: We retrospectively investigated the clinical, imaging, and laboratory characteristics of confirmed cases of COVID-19 with WHO interim guidance in three Grade ⅢA hospitals of Jiangsu from Jan 22 to Feb 14, 2020. Real time RT-PCR was used to detect the new coronavirus in respiratory samples. RESULTS: Of the 80 patients infected with COVID-19, 41 patients were female, with a median age of 46.1 years. Except for 3 severe patients, the rest of the 77 patients exhibited mild or moderate symptoms. 9 patients were unconfirmed until a third-time nucleic acid test. 38 cases had a history of chronic diseases. The main clinical manifestations of the patients were fever and cough, which accounted for 63 cases (78.75%) and 51 cases (-63.75%) respectively. Only 3 patients (3.75%) showed liver dysfunction. Imaging examination showed that 55 patients (-68.75%) showed abnormal, 25 cases (31.25%) had no abnormal density shadow in the parenchyma of both lungs. Up to now, 21 cases were discharged from the hospital, and no patient died. The average length of stay for discharged patients was 8 days. CONCLUSIONS: Compared with the cases in Wuhan, the cases in Jiangsu exhibited mild or moderate symptoms and no obvious gender susceptivity. The proportion of patients having liver dysfunction and abnormal CT imaging was relatively lower than that of Wuhan. Notably, infected patients may be falsely excluded based on two consecutively negative respiratory pathogenic nucleic acid test results.

positive: Diagnostic value of skin manifestation of SARS-CoV-2 infection SARS-CoV-2 causes multiple immune-related reactions at various stages of the disease. The wide variety of skin presentations has delayed linking these to the virus. Previous studies had attempted to look at the prevalence and timing of SARS-COV-2 rashes but were based on mostly hospitalized severe cases and had little follow up. Using data collected on a subset of 336,847 eligible UK users of the COVID Symptom Study app, we observed that 8.8% of the swab positive cases (total: 2,021 subjects) reported either a body rash or an acral rash, compared to 5.4% of those with a negative swab test (total: 25,136). Together, these two skin presentations showed an odds ratio (OR) of 1.67 (95% confidence interval [CI]: 1.41-1.96) for being swab positive. Skin rashes were also predictive in the larger untested group of symptomatic app users (N=54,652), as 8.2% of those who had reported at least one classical COVID-19 symptom, i.e., fever, persistent cough, and/or anosmia, also reported a rash. Data from an independent online survey of 11,546 respondents with a rash showed that in 17% of swab positive cases, the rash was the initial presentation. Furthermore, in 21%, the rash was the only clinical sign. Skin rashes cluster with other COVID-19 symptoms, are predictive of a positive swab test and occur in a significant number of cases, either alone or before other classical symptoms. Recognising rashes is important in identifying new and earlier COVID-19 cases.

positive: Radiological Society of North America Chest CT Classification System for Reporting COVID-19 Pneumonia: Interobserver Variability and Correlation with RT-PCR PURPOSE: To evaluate the Radiological Society of North America (RSNA) chest CT classification system for reporting COVID-19 pneumonia. MATERIALS AND METHODS: Chest CT scans of consecutive patients with suspected COVID-19 were retrospectively and independently evaluated by two chest radiologists and a fifth-year radiology resident using the RSNA chest CT classification system for reporting COVID-19 pneumonia. Interobserver agreement was evaluated by calculating weighted kappa (ĸ) coefficients. Proportion of patients with real-time reverse transcriptase polymerase chain reaction (RT-PCR) confirmed COVID-19 in each of the four chest CT categories ("typical", "indeterminate", "atypical", and "negative" features for COVID-19) was calculated. RESULTS: Ninety-six patients (61 males, median age 70 years [range 29-94]) were included, of whom 45 had RT-PCR confirmed COVID-19. The number of patients assigned to chest CT categories "typical", "indeterminate", "atypical", and "negative" by the three readers ranged from 18-29, 26-43, 19-31, and 5-8 respectively. □ coefficient between the chest radiologists was 0.663 (95% confidence interval [CI]: 0.565-0.761). □ coefficients between the chest radiologists and the fifth-year radiology resident were 0.570 (95% CI: 0.443-0.696) and 0.564 (95% CI: 0.451-0.678). Proportion of patients with RT-PCR confirmed COVID-19 in the chest CT categories "typical", "indeterminate", "atypical", and "negative" for the three readers ranged from 76.9%-96.6%, 51.2%-64.1%, 2.8%-5.3%, and 20-25%, respectively. CONCLUSION: The RSNA chest CT classification system for reporting COVID-19 pneumonia has moderate to substantial interobserver agreement. However, the proportion of RT-PCR confirmed COVID-19 cases in the categories "atypical appearance" and "negative for pneumonia" is non-negligible.

positive: Diarrhea Is Associated With Prolonged Symptoms and Viral Carriage in Corona Virus Disease 2019 BACKGROUND & AIMS: We compared clinical, laboratory, radiological, and outcome features of patients with SARS-CoV-2 infection (COVID-19) with pneumonia, with vs without diarrhea. METHODS: We performed a retrospective, single-center analysis of 84 patients with SARS-CoV-2 pneumonia in Wuhan Union Hospital, China, from January 19 through February 7, 2020. Cases were confirmed by real-time reverse-transcriptase PCR of nasal and pharyngeal swab specimens for SARS-CoV-2 RNA. Blood samples were analyzed for white blood cell count, lymphocyte count, alanine aminotransferase, creatine kinase, lactate dehydrogenase, D-dimer, C-reactive protein, and in some cases, immunoglobulins, complement, lymphocyte subsets, and cytokines. Virus RNA was detected in stool samples by real-time PCR. RESULTS: Of the 84 patients with SARS-CoV-2 pneumonia, 26 (31%) had diarrhea. The duration of fever and dyspnea in patients with diarrhea was significantly longer than those without diarrhea (all P < .05). Stool samples from a higher proportion of patients with diarrhea tested positive for virus RNA (69%) than from patients without diarrhea (17%) (P < .001). As of February 19, a lower proportion of patients with diarrhea had a negative result from the latest throat swab for SARS-CoV-2 (77%) than patients without diarrhea (97%) (P = .010), during these patients' hospitalization. Of 76 patients with a negative result from their latest throat swab test during hospitalization, a significantly higher proportion of patients with diarrhea had a positive result from the retest for SARS-CoV-2 in stool (45%) than patients without diarrhea (20%) (P = .039). CONCLUSIONS: At a single center in Wuhan, China, 31% of patients with SARS-CoV-2 pneumonia had diarrhea. A significantly higher proportion of patients with diarrhea have virus RNA in stool than patients without diarrhea. Elimination of SARS-CoV-2 from stool takes longer than elimination from the nose and throat.

positive: A simple laboratory parameter facilitates early identification of COVID-19 patients The total number of COVID-19 patients since the outbreak of this infection in Wuhan, China has reached 40000 and are still growing. To facilitate triage or identification of the large number of COVID-19 patients from other patients with similar symptoms in designated fever clinics, we set to identify a practical marker that could be conveniently utilized by first-line health-care workers in clinics. To do so, we performed a case-control study by analyzing clinical and laboratory findings between PCR-confirmed SARS-CoV-2 positive patients (n=52) and SARS-CoV-2 negative patients (n=53). The patients in two cohorts all had similar symptoms, mainly fever and respiratory symptoms. The rates of patients with leukocyte counts (normal or decreased number) or lymphopenia (two parameters suggested by current National and WHO COVID-19 guidelines) had no differences between these two cohorts, while the rate of eosinopenia (decreased number of eosinophils) in SARS-CoV-2 positive patients (79%) was much higher than that in SARS-CoV-2 negative patients (36%). When the symptoms were combined with eosinopenia, this combination led to a diagnosis sensitivity and specificity of 79% and 64%, respectively, much higher than 48% and 53% when symptoms were combined with leukocyte counts (normal or decreased number) and/ or lymphopenia. Thus, our analysis reveals that eosinopenia may be a potentially more reliable laboratory predictor for SARS-CoV-2 infection than leukocyte counts and lymphopenia recommended by the current guidelines.

positive: Effectiveness of Computed Tomography in the Diagnosis of Novel Coronavirus-2019 Coronaviruses (CoV) belong to the coronavirus genus of the coronaviridae family. All CoVs are pleomorphic RNA viruses containing crown-like peplomers of 80-160 nm in size. This virus is a zoonotic pathogen seen with a wide range of clinical features from asymptomatic state to intensive care in humans. So far, seven human coronaviruses have been identified with the last one being Coronavirus-2019 (COVID-19). These pathogens typically lead to mild disease, but SARS and MERS type coronaviruses have caused severe respiratory disease and even mortality within the last 20 years. COVID-19 virus has rapidly spread worldwide after China and is continuing to cause huge economical and social impacts. Given the scarcity of resources including healthcare staff, hospital capacities, test kits, etc., timely diagnosis and treatment of this virus are of paramount importance. However, there is no vaccination or drug developed for the treatment of this disease up to today. Because the spreading rate of the virus is very high worldwide and there is no definitive treatment, diagnosis becomes even more important. The objective of this review is to evaluate the use of chest computed tomography, one of the commonly used radiologic imaging modalities, in the diagnosis of COVID-19 in light with the current literatüre.

positive: Epidemiological, Clinical Characteristics and Outcome of Medical Staff Infected with COVID-19 in Wuhan, China: A Retrospective Case Series Analysis Backgrounds Since December 2019, a novel coronavirus epidemic has emerged in Wuhan city, China and then rapidly spread to other areas. As of 20 Feb 2020, a total of 2,055 medical staff confirmed with coronavirus disease 2019 (COVID-19) caused by SARS-Cov-2 in China had been reported. We sought to explore the epidemiological, clinical characteristics and prognosis of novel coronavirus-infected medical staff. Methods In this retrospective study, 64 confirmed cases of novel coronavirus-infected medical staff admitted to Union Hospital, Wuhan between 16 Jan, 2020 to 15 Feb, 2020 were included. Two groups concerned were extracted from the subjects based on duration of symptoms: group 1 (<= 10 days) and group 2 (>10 days). Epidemiological and clinical data were analyzed and compared across groups. The Kaplan-Meier plot was used to inspect the change in hospital discharge rate. The Cox regression model was utilized to identify factors associated with hospital discharge. Findings The median age of medical staff included was 35 years old. 64% were female and 67% were nurses. None had an exposure to Huanan seafood wholesale market or wildlife. A small proportion of the cohort had contact with specimens (5%) as well as patients in fever clinics (8%) and isolation wards (5%). Fever (67%) was the most common symptom, followed by cough (47%) and fatigue (34%). The median time interval between symptoms onset and admission was 8.5 days. On admission, 80% of medical staff showed abnormal IL-6 levels and 34% had lymphocytopenia. Chest CT mainly manifested as bilateral (61%), subpleural (80%) and ground-glass (52%) opacities. During the study period, no patients was transferred to intensive care unit or died, and 34 (53%) had been discharged. Higher body mass index (BMI) (HR 0.14; 95% CI 0.03-0.73), fever (HR 0.24; 95% CI 0.09-0.60) and higher levels of IL-6 on admission (HR 0.31; 95% CI 0.11-0.87) were unfavorable factors for discharge. Interpretation In this study, medical staff infected with COVID-19 have relatively milder symptoms and favorable clinical course, which may be partly due to their medical expertise, younger age and less underlying diseases. Smaller BMI, absence of fever symptoms and normal IL-6 levels on admission are favorable for discharge for medical staff. Further studies should be devoted to identifying the exact patterns of SARS-CoV-2 infection among medical staff.

positive: Epidemiology and Transmission of COVID-19 in Shenzhen China: Analysis of 391 cases and 1,286 of their close contacts Background Rapid spread of SARS-CoV-2 in Wuhan prompted heightened surveillance in Shenzhen and elsewhere in China. The resulting data provide a rare opportunity to measure key metrics of disease course, transmission, and the impact of control. Methods The Shenzhen CDC identified 391 SARS-CoV-2 cases from January 14 to February 12, 2020 and 1286 close contacts. We compare cases identified through symptomatic surveillance and contact tracing, and estimate the time from symptom onset to confirmation, isolation, and hospitalization. We estimate metrics of disease transmission and analyze factors influencing transmission risk. Findings Cases were older than the general population (mean age 45) and balanced between males (187) and females (204). Ninety-one percent had mild or moderate clinical severity at initial assessment. Three have died, 225 have recovered (median time to recovery is 21 days). Cases were isolated on average 4.6 days after developing symptoms; contact tracing reduced this by 1.9 days. Household contacts and those travelling with a case where at higher risk of infection (ORs 6 and 7) than other close contacts. The household secondary attack rate was 15%, and children were as likely to be infected as adults. The observed reproductive number was 0.4, with a mean serial interval of 6.3 days. Interpretation Our data on cases as well as their infected and uninfected close contacts provide key insights into SARS-CoV-2 epidemiology. This work shows that heightened surveillance and isolation, particularly contact tracing, reduces the time cases are infectious in the community, thereby reducing R. Its overall impact, however, is uncertain and highly dependent on the number of asymptomatic cases. We further show that children are at similar risk of infection as the general population, though less likely to have severe symptoms; hence should be considered in analyses of transmission and control.

positive: A diagnostic model for coronavirus disease 2019 (COVID-19) based on radiological semantic and clinical features: a multi-center study OBJECTIVES: Rapid and accurate diagnosis of coronavirus disease 2019 (COVID-19) is critical during the epidemic. We aim to identify differences in CT imaging and clinical manifestations between pneumonia patients with and without COVID-19, and to develop and validate a diagnostic model for COVID-19 based on radiological semantic and clinical features alone. METHODS: A consecutive cohort of 70 COVID-19 and 66 non-COVID-19 pneumonia patients were retrospectively recruited from five institutions. Patients were divided into primary (n = 98) and validation (n = 38) cohorts. The chi-square test, Student’s t test, and Kruskal-Wallis H test were performed, comparing 1745 lesions and 67 features in the two groups. Three models were constructed using radiological semantic and clinical features through multivariate logistic regression. Diagnostic efficacies of developed models were quantified by receiver operating characteristic curve. Clinical usage was evaluated by decision curve analysis and nomogram. RESULTS: Eighteen radiological semantic features and seventeen clinical features were identified to be significantly different. Besides ground-glass opacities (p = 0.032) and consolidation (p = 0.001) in the lung periphery, the lesion size (1–3 cm) is also significant for the diagnosis of COVID-19 (p = 0.027). Lung score presents no significant difference (p = 0.417). Three diagnostic models achieved an area under the curve value as high as 0.986 (95% CI 0.966~1.000). The clinical and radiological semantic models provided a better diagnostic performance and more considerable net benefits. CONCLUSIONS: Based on CT imaging and clinical manifestations alone, the pneumonia patients with and without COVID-19 can be distinguished. A model composed of radiological semantic and clinical features has an excellent performance for the diagnosis of COVID-19. KEY POINTS: • Based on CT imaging and clinical manifestations alone, the pneumonia patients with and without COVID-19 can be distinguished. • A diagnostic model for COVID-19 was developed and validated using radiological semantic and clinical features, which had an area under the curve value of 0.986 (95% CI 0.966~1.000) and 0.936 (95% CI 0.866~1.000) in the primary and validation cohorts, respectively. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00330-020-06829-2) contains supplementary material, which is available to authorized users.

positive: COVID-19 in Post-Operative Patients: Imaging Findings Background: Coronavirus 2019 (COVID-19) in the post-operative period is challenging. Its clinical manifestations may have similarities to other septic, thoracic, or gastrointestinal post-surgical complications. Additionally, the post-operative period may be a time of increased risk for severe manifestations of COVID-19. We sought to evaluate the frequency of COVID-19 in a cohort of patients who had recently had operations who were undergoing imaging for acute symptoms and the role of chest computed tomography (CT) in this setting. Patients and Methods: We included all patients who had chest CT for acute symptoms in the 15 days after a surgical procedure between March 1 and 31, 2020. Results: Of 46 patients with acute post-operative symptoms requiring chest imaging, eight (17%) were ultimately diagnosed with COVID-19. Among them, five (62%) required mechanical ventilation and two (25%) died. All had abnormal chest CT with typical findings of COVID-19 in 87%. Computed tomography provided an alternate diagnosis in 53% of patients who did not have COVID-19. The average time between a COVID-19-positive chest CT and the polymerase chain reaction (PCR) confirmation was 1.2 days (range, 0-4 days). Conclusion: COVID-19 is a serious post-operative condition associated with significant morbidity and mortality. Chest CT provides prompt diagnosis of COVID-19. In centers with a high prevalence of COVID-19, chest acquisition should be included in CT scans done for acute post-operative symptoms.

positive: Clinical characteristics of 3,062 COVID‐19 patients: a meta‐analysis OBJECTIVE: We aim to systematically review the clinical characteristics of Coronavirus disease 2019 (COVID‐19). METHODS: Seven datebases were searched to collect studies about the clinical characteristics of COVID‐19 from 1 January 2020 to 28 February 2020. Then, meta‐analysis was performed by using Stata12.0 software. RESULTS: A total of 38 studies involving 3 062 COVID‐19 patients were included. Meta‐analysis showed that a higher proportion of infected patients were male (56.9%). The incidence rate of respiratory failure or ARDS was 19.5% and the fatality rate was 5.5%. Fever (80.4%), fatigue (46%), cough (63.1%) and expectoration (41.8%) were the most common clinical manifestations. Other common symptoms included muscle soreness (33%), anorexia (38.8%), chest tightness (35.7%), shortness of breath (35%), dyspnea (33.9%). Minor symptoms included nausea and vomiting (10.2%), diarrhea (12.9%), headache (15.4%), pharyngalgia(13.1%), shivering (10.9%) and abdominal pain (4.4%). Patients with asymptomatic was 11.9%. Normal leukocytes counts (69.7%), lymphopenia (56.5%), elevated C‐reactive protein levels (73.6%), elevated ESR (65.6%) and oxygenation index decreased (63.6%) were observed in most patients. About 37.2% of patients with elevated D‐dimer, 25.9% of patients with leukopenia, along with abnormal levels of liver function (29%) and renal function (25.5%). Other findings included leukocytosis (12.6%) and elevated procalcitonin (17.5%). Only 25.8% of patients had lesions involving single lung and 75.7% of patients had lesions involving bilateral lungs. CONCLUSIONS: The most commonly experienced symptoms of COVID‐19 patients were fever, fatigue, cough and expectoration. A relatively small percentage of patients were asymptomatic. Most patients showed normal leucocytes counts, lymphopenia, elevated levels of C‐reactive protein and ESR. Bilateral lungs involvement was common. This article is protected by copyright. All rights reserved.

positive: High resolution CT findings and clinical features of novel coronavirus pneumonia in Guangzhou/ 中华放射学杂志 Objective@#To investigate the initial HRCT manifestations and clinical features of imported novel coronavirus pneumonia (NCP) in Guangzhou.@*Methods@#A retrospective analysis of 91 NCP patients admitted to the Guangzhou Eighth People’s Hospital from January 22 to 30, 2020 was performed including 39 males and 52 females, with a median age of 50 (33-62) years, then their clinical features and HRCT characteristics were analyzed.@*Results@#The main clinical presentations included fever in 70 cases and cough in 57 cases(mainly dry coughin39 cases). The first time HRCT showed that 24 cases with NCP were normal, however other 67 cases were abnormal. The ground glass opacity in the lung on HRCT was found in 65 cases, including 64 cases with dilated blood vessel crossing the lesion, 50 cases with thickened adjacent pleura, and 47 cases with thickening of interstitial septum. The patchy opacity was seen in 42 cases, and no enlarged lymph nodes were observed in all patients. As for the lesion distribution, there were two cases with bilateral diffuse changes, 57 cases with multiple lesions, 8 cases with the lesion in only one lobe. The lesions were mainly located under the pleura area in 46 cases, including 39 cases in the lower lobe and other 7 cases in the upper lobe. And there were 13 cases without characteristic distribution in the lung.@*Conclusions@#The initial images of NCP in Guangzhou mainly showed multiple ground glass opacity, which were mostly seen in the subpleural and lower lung fields, most of them with thickened pulmonary interstitium. Guangzhou has a higher proportion of NCP patients with mild and general patients, and some confirmed patients show negative HRCT for the first time. Patients without HRCT changes should be reviewed in a timely manner.

positive: (18)F-FDG PET/CT and Serial Chest CT Findings in a COVID-19 Patient With Dynamic Clinical Characteristics in Different Period Neurological symptoms and gastrointestinal symptoms were rare at onset in COVID-19. Here we report a 37-year-old man with vertigo, fever, and diarrhea symptoms as the first manifestation. (18)F-FDG PET/CT spotted multiple ground glass opacity (GGO) lesions in the lungs, with increased tracer uptake in both lung GGOs and the whole colon. Serial CT examinations showed the emersion and dissipation of lung GGOs. We illustrate the symptoms initiation, the laboratory test results, the imaging examination, and the treatment strategy in the duration of COVID-19 with a timeline chart.

positive: Clinical Characteristics and Outcomes of 421 Patients With COVID-19 Treated in a Mobile Cabin Hospital BACKGROUND: In December 2019, a novel coronavirus-associated pneumonia, now known as coronavirus disease 2019 (COVID-19), was first detected in Wuhan, China. To prevent the rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and treat patients with mild symptoms, sports stadiums and convention centers were reconstructed into mobile hospitals. RESEARCH QUESTION: It is unknown whether a mobile cabin hospital can provide a safe treatment site for patients with mild COVID-19 symptoms. STUDY DESIGN AND METHODS: This study retrospectively reviewed the medical records of 421 patients with COVID-19 admitted to a mobile cabin hospital in Wuhan from February 9, 2020, to March 5, 2020. Clinical data comprised patient age, sex, clinical presentation, chest imaging, nucleic acid testing, length of hospitalization, and outcomes. RESULTS: Of the patients who were discharged from the cabin hospital, 362 (86.0%) were categorized as recovered; 14.0% developed severe symptoms and were transferred to a designated hospital. The most common presenting symptoms were fever (60.6%) and cough (52.0%); 5.2% exhibited no obvious symptoms. High fever (> 39.0°C) was more common in severe cases than in recovered cases (18.6% vs 6.6%). The distribution of lung lesions was peripheral in 85.0% of patients, multifocal in 69.4%, and bilateral in 68.2%. The most common pattern was ground-glass opacity (67.7%), followed by patchy shadowing (49.2%). The incidence of patchy shadowing was higher in patients with severe disease (66.1%) than in those who recovered (31.8%, P < .0001). The median length of hospitalization was 17 days (interquartile range, 14-19 days), and the median time taken for positive real-time reverse transcriptase polymerase chain reaction results to become negative in recovered patients was 8 days (interquartile range, 6-10 days). INTERPRETATION: Mobile cabin hospitals provide a safe treatment site for patients with mild COVID-19 symptoms and offer an effective isolation area to prevent the spread of severe acute respiratory syndrome coronavirus 2.

positive: Lack of coordination and medical disinformation in Canadian self-assessment tools for COVID-19 As SARS-CoV-2 threatens to overwhelm health systems in Canada, it is imperative that provinces are able to plan and manage an effective and reduced risk response. For this response to be most effective, it must reflect an evidence-based, pan-Canadian response. We designed four different prototypical patients with a combination of common COVID-19 symptoms and opportunities for exposure who were made to self-assess using the 10 provincial COVID-19 self-assessment tools on 1 April. These tools were developed to allow individuals to self-triage, allowing health systems direct capacity to testing and care. We assessed the consistency of the self-assessment tools and of the guidance provided to the patients. While the tools generally screen in three areas, the scope of included COVID-19 associated symptoms as well as the opportunities for exposure, and therefore transmission, vary between provinces such that no two provinces screened in the same way. This was, in turn, reflected in the inconsistency in guidance found. A patient with cough who had travelled abroad or had close contact with a confirmed case within 14 days received the most consistent guidance, with remaining patients receiving guidance ranging from mandatory quarantine or self-isolation to being told they did not have COVID-19 symptoms, guidance at odds with medical evidence. Thus, there is not a single, evidence-based Canadian standard of care simply for self-assessment. Without consistency in public health guidance, Canadians cannot appropriately self-isolate to mitigate community transmission, nor can the necessary valid and reliable data be collected to inform critical epidemiological models that help guide pandemic response. If federal and provincial governments are unable to coordinate a response, Parliament must use its available jurisdiction to legislate a duty on both to follow national standards, so as to improve coordination on COVID-19 in coming months.

positive: Clinical features of patients with coronavirus disease 2019 from a designated hospital in Beijing, China Clinical and laboratory data on patients with coronavirus disease 2019 (COVID-19) in Beijing, China, remain extremely limited. In this study, we summarized the clinical characteristics of patients with COVID-19 from a designated hospital in Beijing. In total, 55 patients with laboratory-confirmed SARS-CoV-2 infection in Beijing 302 Hospital were enrolled in this study. Demographic data, symptoms, comorbidities, laboratory values, treatments, and clinical outcomes were all collected and retrospectively analyzed. A total of 15 (27.3%) patients had severe symptoms, the mean age was 44.0 years (interquartile range [IQR], 34.0-56.0), and the median incubation period was 7.5 days (IQR, 5.0-11.8). A total of 26 (47.3%) patients had exposure history in Wuhan of less than 2 weeks, whereas 20 (36.4%) patients were associated with familial clusters. Also, eighteen (32.7%) patients had underlying comorbidities including hypertension. The most common symptom of illness was fever (45; 81.8%); 51 (92.7%) patients had abnormal findings on chest computed tomography. Laboratory findings showed that neutrophil count, percentage of lymphocyte, percentage of eosinophil, eosinophil count, erythrocyte sedimentation rate, albumin, and serum ferritin are potential risk factors for patients with a poor prognosis. A total of 26 patients (47.3%) were still hospitalized, whereas 29 (52.7%) patients had been discharged. Compared with patients in Wuhan, China, the symptoms of patients in Beijing are relatively mild. Older age, more comorbidities, and more abnormal prominent laboratory markers were associated with a severe condition. On the basis of antiviral drugs, it is observed that antibiotics treatment, appropriate dosage of corticosteroid, and gamma globulin therapy significantly improve patients' outcomes. Early identification and timely medical treatment are important to reduce the severity of patients with COVID-19.

positive: Identification of Symptoms Prognostic of COVID-19 Severity: Multivariate Data Analysis of a Case Series in Henan Province BACKGROUND: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease (COVID-19), has been declared a global pandemic. Identifying individuals whose infection can potentially become severe is critical to control the case fatality rate of COVID-19. However, knowledge of symptoms that are prognostic of COVID-19 severity is lacking. OBJECTIVE: The objective of our study was to identify symptoms prognostic of COVID-19 infection severity. METHODS: We analyzed documented symptoms, including fever, cough, fatigue, expectoration, sore throat, chest distress, headache, diarrhea, rhinorrhea, stuffed nose, nausea, vomiting, muscle or joint ache, shortness of breath, and their associations with disease severity using a case series, including 655 confirmed cases from January 23 to February 5, 2020 in Henan Province, China. We also analyzed the influence of individual characteristics, including age, gender, and comorbidities, on symptoms with prognostic value. RESULTS: Fatigue (95% CI 0.141 to 0.334, P<.001), expectoration (95% CI 0.107 to 0.305, P<.001) and stuffed nose (95% CI -0.499 to -0.082, P=.006) were identified as the prognostic symptoms of COVID-19 patients from the multivariate analysis. Fever occurred in 603/655 (92.1%) of the patients but was not associated with disease severity. Fatigue accounted for 184/655 (28.1%) of the patients and was linearly associated with infection severity with statistical significance. Expectoration occurred in 169/655 (25.8%) patients in the cohort and was the sole prognostic factor for patients with cardiovascular complications, including hypertension. Shortness of breath, chest distress, muscle or joint ache, and dry cough, which occurred in 33 (5%), 83 (12.7%), 78 (11.9%), and 276 (42.1%) of the 655 patients, respectively, were significantly enriched among patients classified as severe. Stuffed nose and nausea were associated with favorable disease severity, especially among male patients. More female than male patients were documented as having muscle or joint ache. Headache was most enriched in patents aged 15 to 39 years, followed by those aged 40 to 64 years, with statistical significance. CONCLUSIONS: Fatigue and expectoration are signs of severe COVID-19 infection. Shortness of breath, chest distress, muscle or joint ache, and dry cough are prevalent in severe patients. Expectoration is commonly present in older individuals and patients with cardiovascular disorders, including hypertension. Shortness of breath is prognostic of severe infection in male patients. Stuffed nose and nausea are favorable prognostic factors of severe infection, especially among male patients.

positive: Clinical features, laboratory characteristics, and outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19): Early report from the United States. Background Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV2), is an ongoing pandemic that has already affected millions of patients worldwide, and is associated with significant morbidity and mortality burden. Although the clinical and laboratory characteristics of this illness have been reported in patients from China and Europe, data are scant in the United States. Methods We extracted data regarding all patients hospitalized at our hospital with COVID-19 infection between March 1 and April 4, 2020. Presenting signs and symptoms, laboratory and imaging findings, treatment, and complications were recorded from electronic medical records (EMRs). The primary composite endpoint was admission to intensive care unit (ICU), shock, or death. Results We had a total of 43 patients tested for COVID-19 at the emergency room (ER) or during hospitalization, 16 (37%) of whom were admitted with COVID-19 infection. The mean age was 65.5 years and 75% were males. The most common presenting symptoms were fever (94%), cough (88%), and dyspnea (81%). A loss of smell and taste sensations were reported by three (19%) patients. Low oxygen saturation was present in 38% of patients, whilst 31% were hypotensive on admission. Hyponatremia (50%), elevated C-reactive protein (CRP; 100%), and lactate dehydrogenase (LDH; 80%) were common. Acute renal failure, myocardial injury, and elevation in aminotransferases occurred in 69%, 19%, and 38% patients, respectively. The primary composite endpoint occurred in 50% of patients. A total of three patients died; all were aged 70 years or older. Conclusions Laboratory abnormalities and acute renal failure were common in hospitalized patients with SARS-CoV2 infection in our center. Admission to ICU and mechanical ventilation were common.

positive: Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China Previous studies have showed clinical characteristics of patients with the 2019 novel coronavirus disease (COVID-19) and the evidence of person-to-person transmission. Limited data are available for asymptomatic infections. This study aims to present the clinical characteristics of 24 cases with asymptomatic infection screened from close contacts and to show the transmission potential of asymptomatic COVID-19 virus carriers. Epidemiological investigations were conducted among all close contacts of COVID-19 patients (or suspected patients) in Nanjing, Jiangsu Province, China, from Jan 28 to Feb 9, 2020, both in clinic and in community. Asymptomatic carriers were laboratory-confirmed positive for the COVID-19 virus by testing the nucleic acid of the pharyngeal swab samples. Their clinical records, laboratory assessments, and chest CT scans were reviewed. As a result, none of the 24 asymptomatic cases presented any obvious symptoms while nucleic acid screening. Five cases (20.8%) developed symptoms (fever, cough, fatigue, etc.) during hospitalization. Twelve (50.0%) cases showed typical CT images of ground-glass chest and 5 (20.8%) presented stripe shadowing in the lungs. The remaining 7 (29.2%) cases showed normal CT image and had no symptoms during hospitalization. These 7 cases were younger (median age: 14.0 years; P=0.012) than the rest. None of the 24 cases developed severe COVID-19 pneumonia or died. The median communicable period, defined as the interval from the first day of positive nucleic acid tests to the first day of continuous negative tests, was 9.5 days (up to 21 days among the 24 asymptomatic cases). Through epidemiological investigation, we observed a typical asymptomatic transmission to the cohabiting family members, which even caused severe COVID-19 pneumonia. Overall, the asymptomatic carriers identified from close contacts were prone to be mildly ill during hospitalization. However, the communicable period could be up to three weeks and the communicated patients could develop severe illness. These results highlighted the importance of close contact tracing and longitudinally surveillance via virus nucleic acid tests. Further isolation recommendation and continuous nucleic acid tests may also be recommended to the patients discharged. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s11427-020-1661-4 and is accessible for authorized users.

positive: Need for Caution in the Diagnosis of Radiation Pneumonitis in the COVID-19 Pandemic Abstract: Introduction Patients with cancer are at high-risk for mortality from coronavirus-disease 2019 (COVID-19). Radiation pneumonitis (RP) is a common toxicity of thoracic radiotherapy with overlapping clinical and imaging features with COVID-19, however, RP is treated with high-dose corticosteroids, which may exacerbate COVID-19-associated lung injury. We reviewed patients who presented with symptoms of RP during the intensification of a regional COVID-19 epidemic to report on their clinical course and COVID-19 testing results. Methods The clinical course and chest computed tomography (CT) imaging findings of consecutive patients who presented with symptoms of RP in March 2020 were reviewed. The first regional COVID-19 case was diagnosed on 3/1/2020. All patients underwent COVID-19 qualitative RNA testing. Results Four patients with clinical suspicion for RP were assessed. Three out of four patients tested positive for COVID-19. All patients presented with symptoms of cough and dyspnea. Two patients had a fever, of whom only one tested positive for COVID-19. Two patients started on an empiric high-dose corticosteroid taper for presumed RP, but both had clinical deterioration, and ultimately tested positive for COVID-19 and required hospitalization. Chest CT findings in patients suspected of RP, but ultimately diagnosed with COVID-19 showed ground-glass opacities mostly pronounced outside the radiation field. Conclusions As this pandemic continues, patients with symptoms of RP require diagnostic attention. We recommend that patients suspected of RP be tested for COVID-19 before starting empiric corticosteroids and for careful attention be paid to chest CT imaging in order to prevent potential exacerbation of COVID-19 in these high-risk patients.

positive: Time Kinetics of Viral Clearance and Resolution of Symptoms in Novel Coronavirus Infection

positive: Anosmia as a prominent symptom of COVID-19 infection According to WHO recommendations, everyone must protect themselves against Coronavirus disease 2019 (COVID-19), which will also protect others. Due to the lack of current effective treatment and vaccine for COVID-19, screening, rapid diagnosis and isolation of the patients are essential (1, 2). Therefore, identifying the early symptoms of COVID-19 is of particular importance and is a health system priority. Early studies from COVID-19 outbreak in China have illustrated several non-specific signs and symptoms in infected patients, including fever, dry cough, dyspnea, myalgia, fatigue, lymphopenia, and radiographic evidence of pneumonia (3, 4). Recently, a probability of association between COVID-19 and altered olfactory function has been reported in South Korea, Iran, Italy, France, UK and the United States (5-8). However, to our knowledge, the definite association between COVID-19 and anosmia has not been published.

positive: Prevalence and Duration of Acute Loss of Smell or Taste in COVID-19 Patients Initially, acute loss of smell (anosmia) and taste (ageusia) was not considered important symptoms for coronavirus disease 2019 (COVID-19). To determine the prevalence of these symptoms and to evaluate their diagnostic significance, we (approximately 150 physicians of the Daegu Medical Association) prospectively collected data of cases of anosmia and ageusia from March 8, 2020, via telephone interview among 3,191 patients in Daegu, Korea. Acute anosmia or ageusia was observed in 15.3% (488/3,191) patients in the early stage of COVID-19 and in 15.7% (367/2,342) patients with asymptomatic-to-mild disease severity. Their prevalence was significantly more common among females and younger individuals (P = 0.01 and P < 0.001, respectively). Most patients with anosmia or ageusia recovered within 3 weeks. The median time to recovery was 7 days for both symptoms. Anosmia and ageusia seem to be part of important symptoms and clues for the diagnosis of COVID-19, particularly in the early stage of the disease.

positive: A case of COVID-19 and pneumonia returning from Macau in Taiwan: Clinical course and anti-SARS-CoV-2 IgG dynamic A 46-year-old woman presented to the emergency department with 2-day fever and cough at seven days after returning from Macau. COVID-19 and pneumonia was diagnosed based on the positive real-time RT-PCR tests for oropharyngeal swab samples and the presence of anti-SARS-COV-2 IgG starting from the illness day 11 and post-exposure 18–21 days.

positive: [Novel coronavirus pneumonia (COVID-19) CT distribution and sign features]. Objective: To investigate the imaging findings of 2019 novel coronavirus pneumonia (COVID-19). Methods: From January 20 to February 5, 2020, a total of 130 patients diagnosed with COVID-19 from seven hospitals in China were collected. The imaging data were reviewed and analyzed in detail. Results: (1) Distribution: the lesion detected in the lung unilaterally in 14 cases (10.7%) and bilaterally in 116 cases (89.3%). According to the distribution in the lobes of the lung, all cases could be classified into subpleural distribution (102 cases, 78.4%), centrilobular distribution (99 cases, 76.1%) and diffused distribution (8 cases, 6.1%). (2) Number of lesions: single lesion 9 cases (6.9%); multiple lesions 113 cases (86.9%), diffuse lesions 8 cases (6.1%). (3) Imaging density: 70 cases (53.8%) of ground-glass opacity (GGO), 60 cases (46.2%) of GGO + consolidation. (4) Accompanying signs: 100 cases (76.9%) with vascular thickening, 98 cases (75.3%) with "pleural parallel sign" ; "intralobular septal thickening" in 100 cases (76.9%); "halo sign" in 13 cases (10%); "reversed-halo sign" in 6 cases (4.6%); pleural effusion in 3 cases (2.3 %), and pneumatocele in 2 cases (1.5%); no case with pulmonary cavity. Among 35 patients that underwent follow-up CT, 21 patients (60%) improved while 14 (40%) exacerbated. Conclusions: COVID-19 imaging characteristic mainly has subpleural, centrilobular and diffused distribution. The first two distributions can overlap or progress to diffused distribution. In the later period, it was mainly manifested as organizing pneumonia and fibrosis. The most valuable characteristic is the pleural parallel sign.

positive: Diarrhea during COVID-19 infection: pathogenesis, epidemiology, prevention and management Abstract Background and aims The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 / COVID-19) pandemic is a worldwide emergency. An increasing number of diarrhea cases is reported. Here we investigate the epidemiology, clinical presentation, molecular mechanisms, management, and prevention of SARS-CoV-2 associated diarrhea. Methods We searched on PubMed, EMBASE, and Web of Science up to March 2020 to identify studies documenting diarrhea and mechansism of intestinal inflammation in patients with confirmed diagnosis of SARS-CoV-2 infection. Results Clinical studies show an incidence rate of diarrhea ranging from 2% to 50% of cases. It may precede or trail respiratory symptoms. A pooled analysis revealed an overall percentage of diarrhea onset of 10.4%. SARS-CoV uses the the angiotensin-converting enzyme 2 (ACE2) and the serine protease TMPRSS2 for S protein priming. ACE2 and TMPRSS2 are not only expressed in lung, but also in the small intestinal epithelia. ACE2 is expressed furthermore in the upper esophagus, liver, and colon. SARS-CoV-2 binding affinity to ACE2 is significantly higher (10-20 times) compared with SARS-CoV. Several reports indicate viral RNA shedding in stool detectable longer time period than in nasopharyngeal swabs. Current treatment is supportive, but several options appear promising and are the subject of investigation. Conclusion Diarrhea is a frequent presenting symptom in patients infected with SARS-CoV-2. Increasing evidence indicates possible fecal oral transmission, indicating the need for a rapid and effective modification of the screening and diagnostic algorithms. The optimal methods to prevent, manage, and treat diarrhea in COVID-19 infected patients are subjects of intensive research.

positive: Identifying and Ranking Common COVID-19 Symptoms from Arabic Twitter Objective: The aim of this study is to identify the most common symptoms reported by covid-19 patients in the Arabic language and order the symptoms appearance based on the collected data. Methods: We search the Arabic content of Twitter for personal reports of covid-19 symptoms from March 1st to May 27th, 2020. We identify 463 Arabic users who tweeted testing positive for covid-19 and extract the symptoms they publicly associate with covid-19. Furthermore, we ask them directly through personal messages to opt in and rank the appearance of the first three symptoms they experienced right before (or after) diagnosed with covid-19. Finally, we track their Twitter timeline to identify additional symptoms that were mentioned within +-5 days from the day of tweeting having covid-19. In summary, a list of 270 covid-19 reports were collected and symptoms were (at least partially) ranked from early to late. Results: The collected reports contained roughly 900 symptoms originated from 74% (n=201) male and 26% (n=69) female Twitter users. The majority (82%) of the tracked users were living in Saudi Arabia (46%) and Kuwait (36%). Furthermore, 13% (n=36) of the collected reports were asymptomatic. Out of the users with symptoms (n=234), 66% (n=180) provided a chronological order of appearance for at least three symptoms. Fever 59% (n=139), Headache 43% (n=101), and Anosmia 39% (n=91) were found to be the top three symptoms mentioned by the reports. They count also for the top-3 common first symptoms in a way that 28% (n=65) said their covid journey started with a Fever, 15% (n=34) with a Headache and 12% (n=28) with Anosmia. Out of the Saudi symptomatic reported cases (n=110), the most common three symptoms were Fever 59% (n=65), Anosmia 42% (n=46), and Headache 38% (n=42).

positive: Coronavirus Disease 2019 (COVID-19) in Neonates and Children From China: A Review At the end of 2019, a novel coronavirus began to spread in Wuhan, Hubei Province, China. The confirmed cases increased nationwide rapidly, in part due to the increased population mobility during the Chinese Lunar New Year festival. The World Health Organization (WHO) subsequently named the novel coronavirus pneumonia Coronavirus Disease 2019 (COVID-19) and named the virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Soon, transmission from person to person was confirmed and the virus spread to many other countries. To date, many cases have been reported in the pediatric age group, most of which were from China. The management and treatment strategies have also been improved, which we believe would be helpful to pediatric series in other countries as well. However, the characteristics of neonatal and childhood infection still have not been evaluated in detail. This review summarizes the current understanding of SARS-CoV-2 infection in neonates and children from January 24 to May 1, as an experience from China.

positive: Early Guillain-Barré syndrome in coronavirus disease 2019 (COVID-19): a case report from an Italian COVID-hospital Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy associated with dysimmune processes, often related to a previous infectious exposure. During Italian severe acute respiratory syndrome coronavirus-2 outbreak, a woman presented with a rapidly progressive flaccid paralysis with unilateral facial neuropathy after a few days of mild respiratory symptoms. Coronavirus was detected by nasopharyngeal swab, but there was no evidence of its presence in her cerebrospinal fluid, which confirmed the typical albumin-cytological dissociation of GBS, along with consistent neurophysiological data. Despite immunoglobulin infusions and intensive supportive care, her clinical picture worsened simultaneously both from the respiratory and neurological point of view, as if reflecting different aspects of the same systemic inflammatory response. Similar early complications have already been observed in patients with para-infectious GBS related to Zika virus, but pathological mechanisms have yet to be established.

positive: 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.

positive: Human Saliva: Non-Invasive Fluid for Detecting Novel Coronavirus (2019-nCoV) The breakthrough of novel coronavirus (2019-nCoV) in Wuhan, a city of China, has damaged the status of health and quality of life. In the sequel of this epidemic or contagious disease, the patient experiences fever, chest paint, chills, a rapid heartbeat, breathing difficulties, pneumonia, and kidney failure. It has been suggested that this disease can spread through human-to-human transmission or by super spreading. By the help of the non-invasive fluid “saliva”, it is easy to detect the virus. This can help with the comfort of the patient as well as healthcare personnel. Under this perspective, we discuss the epidemic situation of 2019-nCOV and its relationship with human saliva.

positive: Neurological manifestations in COVID‐19 caused by SARS‐CoV‐2

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: Addressing multiple gastroenterological aspects of coronavirus disease 2019 The outbreak of the coronavirus disease 2019 (COVID19) pandemic has become the biggest challenge for the whole human community since many years. It seems that the proper identification of all people infected with severe acute respiratory syndrome coronavirus 2 (SARSCoV2) is the best strategy to limit the transmission. However, in a significant proportion of patients, there are no clinical manifestations of the disease, and symptoms may be very mild or atypical. There is a growing body of evidence that digestive manifestations of COVID19 are frequently reported and may precede typical respiratory symptoms. Moreover, SARSCoV2 particles were found in the gastrointestinal epithelial cells, and viral RNA was detected in the feces of patients with COVID19. These data suggest that gastrointestinal symptoms in COVID19 are not accidental findings and they may result from direct digestive involvement. Patients with newonset diarrhea, abdominal pain, nausea, and vomiting without any other evident etiological factors should be tested for SARSCoV2 infection. Gastroenterologists and members of other medical specialties should also remember that the current epidemiological situation has changed diagnostic and therapeutic algorithms in the management of several gastrointestinal and liver disorders. This review article summarizes the currently available data on multiple gastroenterological aspects of COVID19 and provides information on practical recommendations and position statements of the most prominent associations in the field of gastroenterology, which appeared in response to the emergence of the pandemic.

positive: Early Prediction of Disease Progression in 2019 Novel Coronavirus Pneumonia Patients Outside Wuhan with CT and Clinical Characteristics Objective: To determine the predictive value of CT and clinical characteristics for short-term disease progression in patients with 2019 novel coronavirus pneumonia (NCP). Materials and Methods: 224 patients with confirmed 2019 novel coronavirus (COVID-19) infection outside Wuhan who had chest CT examinations were retrospectively screened. Clinical data were obtained from electronic medical records. CT images were reviewed and scored for lesion distribution, lobe and segment involvement, ground-glass opacities, consolidation, and interstitial thickening. All included patients with moderate NCP were observed for at least 14 days from admission to determine whether they exacerbated to severe NCP (progressive group) or not (stable group). CT and clinical characteristics between the two groups were compared, and multivariate logistic regression and sensitivity analyses were performed to identify the risk factors for developing severe NCP. Results: A total of 141 patients with moderate NCP were included, of which 15 (10.6%) patients developed severe NCP during hospitalization and assigned to the progressive group. Multivariate logistic regression analysis showed that higher neutrophil-to-lymphocyte ratio (NLR) (odds ratio [OR] and 95% confidence interval [CI], 1.26 [1.04-1.53]; P = 0.018) and CT severity score (OR and 95% CI, 1.25 [1.08-1.46]; P = 0.004) on admission were independent predictors for progression to severe NCP, and sensitivity analysis confirmed the consistent results in nonimported patients but not in imported patients. However, no significant difference in lung involvement was found on CT between imported and nonimported patients (all P > 0.05). Patients who were admitted more than 4 days from symptom onset tended to have more severe lung involvement. Spearman correlation analysis showed the close association between CT severity score and inflammatory indexes (r = 0.17~0.47, all P < 0.05). Conclusion: CT severity score was associated with inflammatory levels and higher NLR and CT severity score on admission were independent risk factors for short-term progression in patients with NCP outside Wuhan. Furthermore, early admission and surveillance by CT should be recommended to improve clinical outcomes.

positive: Ear nose throat-related symptoms with a focus on loss of smell and/or taste in COVID-19 patients PURPOSE: To determine the frequency and severity of general and ear nose throat (ENT)- related symptoms, especially smell and/or loss of sense of taste (STL) in COVID-19 disease, as well as to investigate the recovery process of STL. MATERIALS AND METHODS: Patients with a positive COVID-19 diagnosis were given a questionnaire consisting of general questions (age, sex, date of symptoms, smoking history, concomitant diseases), questions about the most obvious symptom at presentation (one option only), the severity and frequency of symptoms (general and ENT), and STL (recovery time and degree of recovery). RESULTS: The study population consisted of 172 patients, 18–65 years old (mean age, 37.8 ± 12.5 years; 51.2% female; 76.2% nonsmokers). Cough (n = 30, 17.4%) and loss of sense of smell (n = 18, 10.4%) were the most obvious general and ENT symptoms, respectively. Eighty-eight patients (51.2%) reported loss of sense of smell, and 81 patients (47.1%) reported loss of sense of taste. The mean recovery times for loss of sense of smell and loss of sense of taste were 8.02 ± 6.41 and 8.20 ± 7.07 days, respectively. The loss of sense of smell and loss of sense of taste were the unique symptoms in four (4.54%) and one (1.23%) patients, respectively. CONCLUSION: STL is a common symptom in COVID-19 and may be the first and/or only symptom of this disease. In patients presenting with STL complaints, surveillance for possible COVID-19 disease and screening tests will facilitate the struggle against the disease.

positive: [Comparison of the clinical characteristics between RNA positive and negative patients clinically diagnosed with 2019 novel coronavirus pneumonia]. Objective: To raise awareness about 2019 novel coronavirus pneumonia (NCP) and reduce missed diagnosis rate and misdiagnosis rate by comparing the clinical characteristics between RNA positive and negative patients clinically diagnosed with NCP. Methods: From January 2020 to February 2020, 54 patients who were newly diagnosed with NCP in Wuhan Fourth Hospital were included in this study. RT-PCR method was used to measure the level of 2019-nCov RNA in pharyngeal swab samples of these patients. The patients were divided into RNA positive and negative group, and the differences of clinical, laboratory, and radiological characteristics were compared. Results: There were 31 RNA of 2019-nCov positive cases, and 23 negative cases. Common clinical symptoms of two groups were fever (80.64% vs. 86.96%) , chills (61.29% vs.52.17%) , cough (80.64% vs.95.65%) , fatigue (61.30% vs.56.52%) , chest distress (77.42% vs.73.91%) . Some other symptoms were headache, myalgia, dyspnea, diarrhea, nausea and vomiting. The laboratory and radiological characteristics of two groups mainly were lymphopenia, increased erythrocyte sedimentation rate, increased C-reactive protein, increased lactate dehydrogenase, decreased oxygenation index, normal white blood cell count and bilateral chest CT involvement. There was no statistically significant difference in other clinical characteristics except for dyspnea between two groups. Conclusions: RNA positive and negative NCP patients shared similar clinical symptoms, while RNA positive NCP patients tended to have dyspnea. Therefore, we should improve the understanding of NCP to prevent missed diagnosis and misdiagnosis; In addition, more rapid and accurate NCP diagnostic approaches should be further developed.

positive: A comparative multi-centre study on the clinical and imaging features of comfirmed and uncomfirmed patients with COVID-19 Background Previous studies had described the differences in clinical characteristics between ICU and non-ICU patients. However, seldom study focused on confirmed and unconfirmed groups. Our aim was to compare clinical and imaging characteristics of COVID-19 patients outside Hubei province between confirmed and unconfirmed group. Methods We retrospectively enrolled 163 consecutive adult patients with suspected COVID-19 from three tertiary hospitals in two provinces outside Hubei province from January 12, 2020 to February 13, 2020 and the differences in epidemiological, clinical, laboratory and imaging characteristics between the two groups were compared. Results This study enrolled 163 patients with 62 confirmed cases and 101 unconfirmed cases. Most confirmed patients were clustered (31, 50.0%) and with definite epidemiological exposure. Symptoms of COVID-19 were nonspecific, largely fever and dry cough. Laboratory findings in confirmed group were characterized by normal or reduced white blood cell count, reduced the absolute value of lymphocytes, and elevated levels of C-reactive protein (CRP) and accelerated Erythrocyte sedimentation rate (ESR). The typical chest CT imaging features of patients with confirmed COVID-19 were peripherally distributed multifocal GGO with predominance in the lower lung lobe. Compared with unconfirmed patients, confirmed patients had significantly higher proportion of dry cough, leucopenia, lymphopenia and accelerated ESR (P<0.05); but not with alanine aminotransferase, aspartate aminotransferase, D-dimer, lactic dehydrogenase, and myoglobin (P>0.05). Proportion of peripheral, bilateral or lower lung distribution and multi-lobe involvement, GGO, crazy-paving pattern, air bronchogram and pleural thickening in the confirmed group were also higher (P<0.05). Conclusions Symptoms of COVID-19 were nonspecific. Leukopenia, lymphopenia and ESR, as well as chest CT could be used as a clue for clinical diagnosis of COVID-19.

positive: Clinical Profile of Cases of COVID-19 in Far Western Province of Nepal. The novel coronavirus (COVID-19) cause various symptoms such as pneumonia, fever, breathing difficult and lung infection. Till now, total 9 cases are reported in Nepal and 4 cases from this province. This case series is to describe the initial clinical features of COVID-19 among the patients admitted in isolation ward of Seti Provincial Hospital. Oropharyngeal swab was taken from all four patients and sample was transfer to national reference laboratory. Three patients were coming from infected country and one is local transmission. Age of patients was range from 20 to 40 years of age with male preponderance. The patient coming from United Arab Emirate was presented with mild symptoms and others were asymptomatic. More tests, contact tracing and keeping them in quarantine are the necessitated action need to be taken by government of Nepal. Keywords: COVID-19; local transmission; oropharyngeal swab.

positive: COVID-19 pathophysiology: A review Abstract In December 2019, a novel coronavirus, now named as SARS-CoV-2, caused a series of acute atypical respiratory diseases in Wuhan, Hubei Province, China. The disease caused by this virus was termed COVID-19. The virus is transmittable between humans and has caused pandemic worldwide. The number of death tolls continues to rise and a large number of countries have been forced to do social distancing and lockdown. Lack of targeted therapy continues to be a problem. Epidemiological studies showed that elder patients were more susceptible to severe diseases, while children tend to have milder symptoms. Here we reviewed the current knowledge about this disease and considered the potential explanation of the different symptomatology between children and adults.

positive: The characteristics and clinical value of chest CT images of novel coronavirus pneumonia AIM To investigate the characteristics and clinical value of chest computed tomography (CT) images of novel coronavirus pneumonia (NCP). MATERIALS AND METHODS Clinical data and CT images of 80 cases of NCP were collected. The clinical manifestations and laboratory test results of the patients were analysed. The lesions in each lung segment of the patient's chest CT images were characterised. Lesions were scored according to length and diffusivity. RESULTS The main clinical manifestations were fever, dry cough, fatigue, a little white sputum, or diarrhoea. A total of 1,702 scored lesions were found in the first chest CT images of 80 patients. The lesions were located mainly in the subpleural area of the lungs (92.4%). Most of the lesions were ground-glass opacity, and subsequent fusions could increase in range and spread mainly in the subpleural area. Pulmonary consolidation accounted for 44.1% of all of the lesions. Of the 80 cases, 76 patients (95%) had bilateral lung disease, four (5%) patients had unilateral lung disease, and eight (10%) patients had cord shadow. CONCLUSION The chest CT of NCP patients is characterised by the onset of bilateral ground-glass lesions located in the subpleural area of the lung, and progressive lesions that result in consolidation with no migratory lesions. Pleural effusions and mediastinal lymphadenopathy are rare. As patients can have inflammatory changes in the lungs alongside a negative early nucleic acid test, chest CT, in combination with epidemiological and laboratory tests, is a useful examination to evaluate the disease and curative effect.

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: Beware: Gastrointestinal symptoms can be a manifestation of COVID-19 BACKGROUND There is an increasing number of reports on the presentation of gastrointestinal symptoms in cases of COVID-19. AIM To review the studies reporting gastrointestinal symptoms in COVID-19. RESULTS Fifteen articles (2,800 patients) were identified. Gastrointestinal symptom frequency varied from 3.0% to 40.7% and included diarrhea (7.5%), náusea (4.5%), anorexia (4.4%), vomiting (1.3%), abdominal pain (0.5%), and belching/reflux (0.3%). Those symptoms can be the first manifestation of COVID-19, but whether they reflect a better or worse prognosis, is controversial. The potential relation of the angiotensin converting enzyme 2 receptor in the digestive tract as an entry route for the virus is discussed. CONCLUSION Gastrointestinal symptoms may be common in COVID-19, in some cases appearing as the first manifestation, even before fever and respiratory symptoms. Therefore, clinicians and gastroenterologists must be aware of those atypical cases during the current pandemic, as well as of the fecal-oral route and corresponding preventive measures.

positive: A Unique Presentation of Delirium in a Patient with Otherwise Asymptomatic COVID-19 OBJECTIVE: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), manifests with a wide spectrum of presentations. Most reports of COVID-19 highlight fever and upper respiratory symptoms as the dominant initial presentations, consistent with the World Health Organization guidelines regarding suspected SARS-CoV-2 infection. However, atypical presentations of this disease have been evolving since the initial outbreak of the pandemic in December 2019. We report a case of an older male patient who presented at our hospital with an unusual manifestation of COVID-19. DESIGN: Brief report. SETTING: A university hospital in Saudi Arabia. PARTICIPANT: A 73-year-old man who presented with confusion in the absence of any respiratory symptoms or fever. INTERVENTION: The patient was initially admitted with delirium and underwent a further work-up. MEASUREMENTS: Given his recent history of domestic travel and the declaration of a global COVID-19 pandemic status, the patient was administered a swab test for SARS-CoV-2. RESULTS: The patient's positive test led to a diagnosis of COVID-19. Although he began to experience a spiking fever and mild upper respiratory symptoms, he recovered rapidly with no residual sequela. CONCLUSION: The recognition of atypical presentations of COVID-19 infection, such as delirium, is critical to the timely diagnosis, provision of appropriate care, and avoidance of outbreaks within healthcare facilities during this pandemic. J Am Geriatr Soc 68:1382-1384, 2020.

positive: Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia Background: The newly identified 2019-nCoV, which appears to have originated in Wuhan, the capital city of Hubei province in central China, is spreading rapidly nationwide. A number of cases of neonates born to mothers with 2019-nCoV pneumonia have been recorded. However, the clinical features of these cases have not been reported, and there is no sufficient evidence for the proper prevention and control of 2019- nCoV infections in neonates. Methods: The clinical features and outcomes of 10 neonates (including 2 twins) born to 9 mothers with confirmed 2019-nCoV infection in 5 hospitals from January 20 to February 5, 2020 were retrospectively analyzed. Results: Among these 9 pregnant women with confirmed 2019-nCoV infection, onset of clinical symptoms occurred before delivery in 4 cases, on the day of delivery in 2 cases, and after delivery in 3 cases. In most cases, fever and a cough were the first symptoms experienced, and 1 patient also had diarrhea. Of the newborns born to these mothers, 8 were male and 2 were female; 4 were full-term infants and 6 were born premature; 2 were small-for-gestational-age (SGA) infants and 1 was a large-for-gestational-age (LGA) infant; there were 8 singletons and 2 twins. Of the neonates, 6 had a Pediatric Critical Illness Score (PCIS) score of less than 90. Clinically, the first symptom in the neonates was shortness of breath (n=6), but other initial symptoms such as fever (n=2), thrombocytopenia accompanied by abnormal liver function (n=2), rapid heart rate (n=1), vomiting (n=1), and pneumothorax (n=1) were observed. Up to now, 5 neonates have been cured and discharged, 1 has died, and 4 neonates remain in hospital in a stable condition. Pharyngeal swab specimens were collected from 9 of the 10 neonates 1 to 9 days after birth for nucleic acid amplification tests for 2019-nCoV, all of which showed negative results. Conclusions: Perinatal 2019-nCoV infection may have adverse effects on newborns, causing problems such as fetal distress, premature labor, respiratory distress, thrombocytopenia accompanied by abnormal liver function, and even death. However, vertical transmission of 2019-nCoV is yet to be confirmed.

positive: Acute urticaria with pyrexia as the first manifestations of a COVID-19 infection

positive: Coronavirus Disease 2019 in Critically Ill Children: A Narrative Review of the Literature Coronavirus disease 2019 has spread around the world. In the 3 months since its emergence, we have learned a great deal about its clinical management and its relevance to the pediatric critical care provider. In this article, we review the available literature and provide valuable insight into the clinical management of this disease, as well as information on preparedness activities that every PICU should perform.

positive: Olfactory and gustatory dysfunctions due to the coronavirus disease (COVID-19): a review of current evidence INTRODUCTION: It is reported that coronavirus disease (COVID-19) can affect the sense of smell and taste of infected people. The pathobiology of this virus is still incompletely known, and it is therefore important to explore the impact of COVID-19 infections on olfactory and gustatory functions. We aimed to review current evidence on olfactory and gustatory dysfunctions caused by COVID-19. METHODS: This study was a narrative review performed in 2020 to investigate the olfactory and gustatory dysfunctions of the COVID-19. We searched eight keywords in six databases to determine the related documents on the main objective of the study. To discover studies meeting the inclusion criteria, the authors screened the titles and abstracts of the identified articles. The appropriate studies were included and their results were discussed to make the final selection. RESULTS: We have studied 24 current articles on the olfactory and gustatory dysfunctions due to COVID-19. A review of current studies has shown that we have a surge in the spread of olfactory and gustatory dysfunctions that happened during the epidemic of COVID-19 infection. Most studies (95.8%) have confirmed the symptoms of anosmia in patients with SARS-CoV-2 infection. A review of current studies showed that, in addition to anosmia, evidence of ageusia and dysgeusia (parageusia) was also seen in patients with COVID-19. CONCLUSION: The results of our study support recent reports that SARS-CoV-2 may infect oral and nasal tissues and cause olfactory and gustatory dysfunctions. These findings may aid future research on the diagnosis, prevention, and treatment of COVID-19 consequences.

positive: Clinical and radiological features of novel coronavirus pneumonia. Recently, COVID-19 has spread in more than 100 countries and regions around the world, raising grave global concerns. COVID-19 transmits mainly through respiratory droplets and close contacts, causing cluster infections. The symptoms are dominantly fever, fatigue, and dry cough, and can be complicated with tiredness, sore throat, and headache. A few of patients have symptoms such as stuffy nose, runny nose, and diarrhea. The severe disease can progress rapidly into the acute respiratory distress syndrome (ARDS). Reverse transcription polymerase chain reaction (RT-PCR) and Next-generation sequencing (NGS) are the gold standard for diagnosing COVID-19. Chest imaging is used for cross validation. Chest CT is highly recommended as the preferred imaging diagnosis method for COVID-19 due to its high density and high spatial resolution. The common CT manifestation of COVID-19 includes multiple segmental ground glass opacities (GGOs) distributed dominantly in extrapulmonary/subpleural zones and along bronchovascular bundles with crazy paving sign and interlobular septal thickening and consolidation. Pleural effusion or mediastinal lymphadenopathy is rarely seen. In CT imaging, COVID-19 manifests differently in its various stages including the early stage, the progression (consolidation), and the absorption. In its early stage, it manifests as scattered flaky GGOs in various sizes, dominated by peripheral pulmonary zone/subpleural distributions. In the progression state, GGOs increase in number and/or size, and lung consolidations may become visible. The main manifestation in the absorption stage is interstitial change of both lungs, such as fibrous cords and reticular opacities. Differentiation between COVID-19 pneumonia and other viral pneumonias are also analyzed. Thus, CT examination can help reduce false negatives of nucleic acid tests.

positive: Clinical Characteristics of Children with COVID-19: A Rapid Review and Meta-Analysis Abstract Background: Most guidelines on COVID-19 published so far include recommendations for patients regardless of age. Clinicians need a more accurate understanding of the clinical characteristics of children with COVID-19. Methods: We searched studies reporting clinical characteristics in children with COVID-19 published until March 31, 2020. We screened the literature, extracted the data and evaluated the risk of bias and quality of evidence of the included studies. We combined some of the outcomes (symptoms) in a single-arm meta-analysis using a random-effects model. Results: Our search retrieved 49 studies, including 25 case reports, 23 case series and one cohort study, with a total of 1667 patients. Our meta-analysis showed that most children with COVID-19 have mild symptoms. Eighty-three percent of the children were within family clusters of cases, and 19% had no symptoms. At least 7% with digestive symptoms. The main symptoms of children were fever (48%, 95% confidence interval [CI]: 39%, 56%) and cough (39%, 95% CI: 30%, 48%). The lymphocyte count was below normal level in only 15% [95% CI: 8%, 22%] of children which is different from adult patients. 66% [95% CI: 55%, 77%] of children had abnormal findings in CT imaging. Conclusions: Most children with COVID-19 have only mild symptoms, and many children are asymptomatic. Fever and cough are the most common symptoms in children. Vomiting and diarrhea were not common in children. The lymphocyte count is usually within the normal range in children.

positive: 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.

positive: A case series describing the epidemiology and clinical characteristics of COVID-19 infection in Jilin Province Since its outbreak in Wuhan, Hubei Province China, 2019-coronavirus infected disease (COVID-19) had been widely spread all over the world, the control of which calls for a better understanding of its epidemiology and clinical characteristics. We included 12 confirmed cases of COVID-19 in First Affiliated Hospital of Jilin University from 23 January 2020 to 11 February 2020, which were retrospectively analyzed for epidemiological, demographic, clinical, laboratory, and radiological features. All the patients were confirmed by nucleic acid detection, the average age of whom was 45.25 years (range, 23–79 years). Most patients had a history of Wuhan traveling or had contact with Wuhan travelers or infected cases. Obvious family cluster was observed. Clinical manifestations included fever (12/12), fatigue (10/12), cough (6/12), sore throat (4/12), headache (3/12), and diarrhea (2/12). Only three out of eight patients had pneumonia manifestation on radiography. Most patients had a normal white blood cell (WBC) count and normal or reduced lymphocyte (LY) count. Pneumonia changes were observed in all the four patients who underwent a chest CT scan. Only one elderly patient developed severe pneumonia, while all the rest were mild disease and had a self-limiting course.

positive: Insight into 2019 novel coronavirus — an updated intrim review and lessons from SARS-CoV and MERS-CoV Abstract Background The rapid spread of the coronavirus disease 2019 (COVID-19), caused by a zoonotic beta-coronavirus entitled 2019 novel coronavirus (2019-nCoV), has become a global threat. Awareness of the biological features of 2019-nCoV should be updated in time and needs to be comprehensively summarized to help optimize control measures and make therapeutic decisions. Methods Based on recently published literatures, official documents and selected up-to-date preprint studies, we reviewed the virology and origin, epidemiology, clinical manifestations, pathology and treatment of 2019-nCoV infection, in comparison with severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV) infection. Results The genome of 2019-nCoV partially resembled SARS-CoV and MERS-CoV, and indicating a bat origin. The COVID-19 generally had a high reproductive number, a long incubation period, a short serial interval and a low case fatality rate (much higher in patients with comorbidities) than SARS and MERS. Clinical presentation and pathology of COVID-19 greatly resembled SARS and MERS, with less upper respiratory and gastrointestinal symptoms, and more exudative lesions in post-mortems. Potential treatments included remdesivir, chloroquine, tocilizumab, convalescent plasma and vaccine immunization (when possible). Conclusion The initial experience from the current pandemic and lessons from the previous two pandemics can help improve future preparedness plans and combat disease progression.

positive: Novel Coronavirus Infection (COVID-19) in Humans: A Scoping Review and Meta-Analysis A growing body of literature on the 2019 novel coronavirus (SARS-CoV-2) is becoming available, but a synthesis of available data has not been conducted. We performed a scoping review of currently available clinical, epidemiological, laboratory, and chest imaging data related to the SARS-CoV-2 infection. We searched MEDLINE, Cochrane CENTRAL, EMBASE, Scopus and LILACS from 01 January 2019 to 24 February 2020. Study selection, data extraction and risk of bias assessment were performed by two independent reviewers. Qualitative synthesis and meta-analysis were conducted using the clinical and laboratory data, and random-effects models were applied to estimate pooled results. A total of 61 studies were included (59,254 patients). The most common disease-related symptoms were fever (82%, 95% confidence interval (CI) 56%–99%; n = 4410), cough (61%, 95% CI 39%–81%; n = 3985), muscle aches and/or fatigue (36%, 95% CI 18%–55%; n = 3778), dyspnea (26%, 95% CI 12%–41%; n = 3700), headache in 12% (95% CI 4%–23%, n = 3598 patients), sore throat in 10% (95% CI 5%–17%, n = 1387) and gastrointestinal symptoms in 9% (95% CI 3%–17%, n = 1744). Laboratory findings were described in a lower number of patients and revealed lymphopenia (0.93 × 10(9)/L, 95% CI 0.83–1.03 × 10(9)/L, n = 464) and abnormal C-reactive protein (33.72 mg/dL, 95% CI 21.54–45.91 mg/dL; n = 1637). Radiological findings varied, but mostly described ground-glass opacities and consolidation. Data on treatment options were limited. All-cause mortality was 0.3% (95% CI 0.0%–1.0%; n = 53,631). Epidemiological studies showed that mortality was higher in males and elderly patients. The majority of reported clinical symptoms and laboratory findings related to SARS-CoV-2 infection are non-specific. Clinical suspicion, accompanied by a relevant epidemiological history, should be followed by early imaging and virological assay.

positive: Varicella‐like exanthem associated with COVID‐19 in an 8‐year‐old girl: A diagnostic clue? It has been reported that the novel coronavirus disease (COVID‐19) may be associated with a papulovesicular skin eruption predominantly involving the trunk. We hereby present a case of COVID‐19–associated varicella‐like exanthem in an 8‐year‐old girl with mild systemic symptoms.

positive: The impact of early scientific literature in response to COVID-19: a scientometric perspective Background. In the early phases of a new pandemic, identifying the most relevant evidence and quantifying which studies are shared the most can help researchers and policy makers. The aim of this study is to describe and quantify the impact of early scientific production in response to COVID-19 pandemic. Methods. The study consisted of: 1) review of the scientific literature produced in the first 30 days since the first COVID-19 paper was published; 2) analysis of papers' metrics with the construction of a Computed-Impact-Score (CIS) that represents a unifying score over heterogeneous bibliometric indicators. In this study we use metrics and alternative metrics collected into five separate categories. On top of those categories we compute the CIS. Highest CIS papers are further analyzed. Results. 239 papers have been included in the study. The mean of citations, mentions and social media interactions resulted in 1.63, 10 and 1250, respectively. The paper with highest CIS resulted "Clinical features of patients[...]" by Chaolin Huang et al., which rated first also in citations and mentions. This is the first paper describing patients affected by the new disease and reporting data that are clearly of great interest to both the scientific community and the general population. Conclusions. The early response of scientific literature during an epidemic does not follow a pre- established pattern. Being able to monitor how communications spread from the scientific world toward the general population using both traditional and alternative metric measures is essential, especially in the early stages of a pandemic.

positive: 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.

positive: Epidemiologic and Clinical Characteristics of 91 Hospitalized Patients with COVID-19 in Zhejiang, China: A retrospective, multi-centre case series Background Recent studies have focused initial clinical and Epidemiologic characteristics on the COVID-19, mainly revealing situation in Wuhan, Hubei. Aim To reveal more data on the epidemiologic and clinical characteristics of COVID-19 patients outside of Wuhan, in Zhejiang, China. Design Retrospective case series. Methods 88 cases of laboratory-confirmed and 3 cases of clinical-confirmed COVID-19 were admitted to five hospitals in Zhejiang province, China. Data were collected from 20 January 2020 to 11 February 2020. Results Of all 91 patients, 88 (96.70%) were laboratory-confirmed COVID-19 with throat swab samples that tested positive for SARS-Cov-2 while 3 (3.30%) were clinical-diagnosed COVID-19 cases. The median age of the patients was 50 (36.5-57) years, and female accounted for 59.34%. In this sample 40 (43.96%) patients had contracted the diseases from local cases, 31 (34.07%) patients had been to Wuhan/Hubei, 8 (8.79%) cases had contacted with people from Wuhan, 11 (12.09%) cases were confirmed aircraft transmission. In particular within the city of Ningbo, 60.52% cases can be traced back to an event held in a temple. The most common symptoms were fever (71.43%), cough (60.44%) and fatigue (43.96%). The median of incubation period was 6 (IQR, 3-8) days and the median time from first visit to a doctor to confirmed diagnosis was 1 (1-2) days. According to the Chest computed tomography scans, 67.03% cases had bilateral pneumonia. Conclusions Social activity cluster, family cluster and travel by airplane were how COVID-19 patients get transmitted and could be rapidly diagnosed COVID-19 in Zhejiang.

positive: Anosmia as a prominent symptom of COVID-19 infection. According to WHO recommendations, everyone must protect themselves against Coronavirus disease 2019 (COVID-19), which will also protect others. Due to the lack of current effective treatment and vaccine for COVID-19, screening, rapid diagnosis and isolation of the patients are essential (1, 2). Therefore, identifying the early symptoms of COVID-19 is of particular importance and is a health system priority. Early studies from COVID-19 outbreak in China have illustrated several non-specific signs and symptoms in infected patients, including fever, dry cough, dyspnea, myalgia, fatigue, lymphopenia, and radiographic evidence of pneumonia (3, 4). Recently, a probability of association between COVID-19 and altered olfactory function has been reported in South Korea, Iran, Italy, France, UK and the United States (5-8). However, to our knowledge, the definite association between COVID-19 and anosmia has not been published.

positive: Coronavirus disease 2019 (COVID-19): A literature review Abstract In early December 2019, an outbreak of coronavirus disease 2019 (COVID-19), caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), occurred in Wuhan City, Hubei Province, China. On January 30, 2020 the World Health Organization declared the outbreak as a Public Health Emergency of International Concern. As of February 14, 2020, 49,053 laboratory-confirmed and 1,381 deaths have been reported globally. Perceived risk of acquiring disease has led many governments to institute a variety of control measures. We conducted a literature review of publicly available information to summarize knowledge about the pathogen and the current epidemic. In this literature review, the causative agent, pathogenesis and immune responses, epidemiology, diagnosis, treatment and management of the disease, control and preventions strategies are all reviewed.

positive: Novel Coronavirus disease (COVID-19) in newborns and infants: what we know so far Recently, an outbreak of viral pneumonitis in Wuhan, Hubei, China successively spread as a global pandemia, led to the identification of a novel betacoronavirus species, the 2019 novel coronavirus, successively designated 2019-nCoV then SARS-CoV-2). The SARS-CoV-2 causes a clinical syndrome designated coronavirus disease 2019 (COVID19) with a spectrum of manifestations ranging from mild upper respiratory tract infection to severe pneumonitis, acute respiratory distress syndrome (ARDS) and death. Few cases have been observed in children and adolescents who seem to have a more favorable clinical course than other age groups, and even fewer in newborn babies. This review provides an overview of the knowledge on SARS-CoV-2 epidemiology, transmission, the associated clinical presentation and outcomes in newborns and infants up to 6 months of life.

positive: Characteristics of COVID-19 infection in Beijing Abstract Background Since the first case of a novel coronavirus (COVID-19) infection pneumonia was detected in Wuhan, China, a series of confirmed cases of the COVID-19 were found in Beijing. We analyzed the data of 262 confirmed cases to determine the clinical and epidemiological characteristics of COVID-19 in Beijing. Methods We collected patients who were transferred by Beijing Emergency Medical Service to the designated hospitals. The information on demographic, epidemiological, clinical, laboratory test for the COVID-19 virus, diagnostic classification, cluster case and outcome were obtained. Furthermore we compared the characteristics between severe and common confirmed cases which including mild cases, no-pneumonia cases and asymptomatic cases, and we also compared the features between COVID-19 and 2003 SARS. Findings By Feb 10, 2020, 262 patients were transferred from the hospitals across Beijing to the designated hospitals for special treatment of the COVID-19 infected by Beijing emergency medical service. Among of 262 patients, 46 (17.6%) were severe cases, 216 (82.4%) were common cases, which including 192 (73.3%) mild cases, 11(4.2%) non-pneumonia cases and 13 (5.0%) asymptomatic cases respectively. The median age of patients was 47.5 years old and 48.5% were male. 192 (73.3%) patients were residents of Beijing, 50 (26.0%) of which had been to Wuhan, 116 (60.4%) had close contact with confirmed cases, 21 (10.9%) had no contact history. The most common symptoms at the onset of illness were fever (82.1%), cough (45.8%), fatigue (26.3%), dyspnea (6.9%) and headache (6.5%). The median incubation period was 6.7 days, the interval time from between illness onset and seeing a doctor was 4.5 days. As of Feb 10, 17.2% patients have discharged and 81.7% patients remain in hospital in our study, the fatality of COVID-19 infection in Beijing was 0.9%. Interpretation On the basis of this study, we provided the ratio of the COVID-19 infection on the severe cases to the mild, asymptomatic and non-pneumonia cases in Beijing. Population was generally susceptible, and with a relatively low fatality rate. The measures to prevent transmission was very successful at early stage, the next steps on the COVID-19 infection should be focused on early isolation of patients and quarantine for close contacts in families and communities in Beijing. Funding Beijing Municipal Science and Technology Commission and Ministry of Science and Technology.

positive: Symptom Cluster of ICU nurses treating COVID-19 pneumonia patients in Wuhan, China Abstract Objective In treating highly infectious COVID-19 pneumonia, ICU nurses face a high risk of developing somatic symptom disorder (SSD). The present study aims to investigate the symptoms and causes of SSD of ICU nurses treating COVID-19 pneumonia. The research results are expected to provide evidence for the establishment of a better management strategy. Methods This study enrolled a total of 140 ICU nurses who were selected by Jiangsu Province Hospital to work in Wuhan (the epicenter of the COVID-19 epidemic in China) on 3rd February 2020. A questionnaire “Somatic Symptom Disorders for ICU Nurses in Wuhan No.1 Hospital” was designed based on the “International Classification of Functioning, Disability and Health” (ICF). Exploratory factor analysis was performed to cluster the symptoms, and logistic regression analysis to find the risk factors of the symptoms. Results Five major symptoms were chest-discomfort-and-palpitation (31.4%), dyspnea (30.7%), nausea (21.4%), headache (19.3%), and dizziness (17.9%). In exploratory factor analysis, the symptoms were classified into three clusters: Cluster A of breathing and sleep disturbances (dizziness, sleepiness, dyspnea); Cluster B of gastrointestinal complaints and pain (nausea, headache), and Cluster C of general symptoms (xerostomia, fatigue, chest-discomfort-and-palpitation). In Cluster A, urine/feces splash, sex, and sputum splash were independent predictive factors. In Cluster B, fall of protective glasses and urine/feces splash were independent predictive factors. In Cluster C, urine/feces splash and urine/feces clearance were independent predictive factors. Conclusion The ICU nurses in Wuhan showed varying and overlapping SSDs. These SSDs could be classified into three symptom clusters. Based on the characteristics of their SSDs, specific interventions could be implemented to safeguard the health of ICU nurses.

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: Strong associations and moderate predictive value of early symptoms for SARS-CoV-2 test positivity among healthcare workers, the Netherlands, March 2020 Healthcare workers (n = 803) with mild symptoms were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n = 90 positive) and asked to complete a symptom questionnaire. Anosmia, muscle ache, ocular pain, general malaise, headache, extreme tiredness and fever were associated with positivity. A predictive model based on these symptoms showed moderate discriminative value (sensitivity: 91.2%; specificity: 55.6%). While our models would not justify presumptive SARS-CoV-2 diagnosis without molecular confirmation, it can contribute to targeted screening strategies.

positive: Epidemiologic and Clinical Characteristics of 26 Cases of COVID-19 Arising from Patient-to-Patient Transmission in Liaocheng, China INTRODUCTION: Over 40,000 cases of coronavirus (CoV) disease 2019 (COVID-19) have been confirmed in China. The causative agent, 2019 novel CoV (2019-nCoV), has spread rapidly to more than 25 countries worldwide. Human-to-human transmission has accounted for most of the infections outside Wuhan. Most studies to date on COVID-19 have focused on disease etiology and the genomics of 2019-nCoV, with few reports on the epidemiologic and clinical characteristics of infected patients. METHODS: We report early clinical features of 26 patients with confirmed COVID-19 who were admitted to Liaocheng Infectious Disease Hospital in Shandong Province. RESULTS: The median age of the 26 patients with COVID-19 in this study was 42 years. The most common occupation was retail staff (16 patients, 61.54%), with 11 patients or their family members working at the same supermarket. Only 2 patients had visited Wuhan since December 2019; the other cases of 2019-nCoV infection arose from patient-to-patient transmission. Twelve patients had more than one sign or symptom; however, seven patients had no sign or symptom. The average time from symptom onset to admission was 4.5 days. CT revealed signs of bronchitis in 2 patients and unilateral and bilateral pneumonia in 9 and 15 patients, respectively. The patients received the following treatments: antiviral therapy (100%), Chinese medicine (76.92%), antibiotics (50%), gastric mucosal protection (19.23%), immunotherapy (7.69%), and glucocorticoids (3.85%). Most patients (25/26) required ≥1 treatment. DISCUSSION: In contrast to previous reports, most patients (24/26) had not been in close contact with individuals from Wuhan. Additionally, 11 patients or their family members worked at the same supermarket, suggesting active viral transmission in a location frequented by a large number of people. Close monitoring is essential for preventing the large-scale spread of the virus in such places.

positive: Skin manifestations of COVID-19. Cutaneous manifestations, a well-known effect of viral infections, are beginning to be reported in patients with COVID-19 disease. These manifestations most often are morbilliform rash, urticaria, vesicular eruptions, acral lesions, and livedoid eruptions. Some of these cutaneous manifestations arise before the signs and symptoms more commonly associated with COVID-19, suggesting that they could be presenting signs of COVID-19. utaneous manifestations are well known to occur in the setting of viral illnesses, and occasionally these manifestations have diagnostic or prognostic value. With COVID-19, although we are at a relatively early point in the pandemic, cutaneous manifestations in infected patients are beginning to emerge from around the world. In this article, we describe some of the current cutaneous abnormalities observed in patients with COVID-19.

positive: The international EAN survey on neurological symptoms in patients with COVID‐19 infection BACKGROUND AND PURPOSE: Although the main clinical features of COVID‐19 infection are pulmonary, several associated neurological signs, symptoms and diseases are emerging. Incidence and characteristics of neurological complications are unclear. For this reason, the European Academy of Neurology (EAN) core COVID‐19 Task Force initiated a survey on neurological symptoms observed in patients with COVID‐19 infection. METHODS: A 17‐question on‐line survey was made available on the EAN website and distributed to EAN members and other worldwide physicians starting on April 9(th), 2020. RESULTS: By April 27(th,) 2020, proper data were collected from 2,343 responders (out of 4,199), of whom 82.0% were neurologists, mostly from Europe. Most responders (74.7%) consulted patients with COVID‐19 mainly in emergency rooms and in COVID‐19 units. The majority (67.0%) had evaluated fewer than 10 patients with neurological manifestations of COVID‐19 (neuro COVID‐19). The most frequently reported neurological findings were headache (61.9%), myalgia (50.4%), anosmia (49.2%), ageusia (39.8%), impaired consciousness (29.3%), and psychomotor agitation (26.7%). Encephalopathy and acute cerebrovascular disorders were reported at 21.0%. Neurological manifestations were generally interpreted as being possibly related to COVID‐19, they were most commonly recognized in patients with multiple general symptoms, and occurred at any time during infection. CONCLUSION: Neurologists are currently and actively involved in the management of neurological issues related to the COVID‐19 pandemic. This survey justifies setting up a prospective registry to better capture the prevalence of patients with neuro COVID‐19, neurological disease characteristics and the contribution of neurological manifestations to outcome.

positive: Updates on What ACS Reported: Emerging Evidences of COVID-19 with Nervous System Involvement [Image: see text] With the ongoing pandemic of coronavirus disease (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), our knowledge of the pathogenesis of COVID-19 is still in its infancy. Almost every aspect of the pathogen remains largely unknown, ranging from mechanisms involved in infection transmission, interplay with the human immune system, and covert mechanisms of end-organ damage. COVID-19 has manifested itself worldwide with a syndromic appearance that is dominated by respiratory dysregulations. While clinicians are focused on correcting respiratory homeostasis, echoing the original SARS, SARS-CoV-2 is also invading other end-organs, which may not exhibit overt clinical features. Nervous system involvement was not initially considered to play a significant role in patients with COVID-19. However, since this viewpoint was initially published, multiple studies have been released regarding the possible neurovirulence of SARS-CoV-2. In our previous viewpoint, we implored our colleagues to recognize the covert tactics of SARS-CoV-2 and emphasized that symptoms like anosmia, dysgeusia, ataxia, and altered mental status could be early signs of the neurotropic potential of this virus. The past few weeks, after the viewpoint surfaced, it was noticed that it has enabled clinicians and healthcare professionals to compute the neurovirulence associated with SARS-CoV-2 in COVID-19 patients, as evidenced by very recently reported studies.

positive: Cutaneous manifestations in COVID‐19: Family cluster of Urticarial Rash Coronavirus disease (COVID‐19) is rapidly spread across the world. Many clinical manifestations of the virus are described, and new symptoms are emerging, only few cases of patients with skin manifestation were described since the pandemic was announced by the WHO on March. Common clinical features of COVID‐19 reported include fever, cough, myalgia, fatigue, headache, shortness of breath and diarrhea.

positive: Epidemiological and clinical characteristics analysis of COVID-19 in the surrounding areas of Wuhan, Hubei Province in 2020 AIM: Since December 2019, new COVID-19 outbreaks have occurred and spread around the world. However, the clinical characteristics of patients in other areas around Wuhan, Hubei Province are still unclear. In this study, we performed epidemiological and clinical characteristics analysis on these regional cases. METHODS: We retrospectively investigated COVID-19 patients positively confirmed by nucleic acid Q-PCR at Taihe Hospital from January 16 to February 4, 2020. Their epidemiological, clinical manifestations, and imaging characteristics were analysed. RESULTS: Among the 73 patients studied, 12.3 % developed symptoms after returning to Shiyan from Wuhan, and 71.2 % had a history of close contact with Wuhan personnel or confirmed cases. Among these patients, 9 cases were associated with family clustering. The first main symptoms presented by these patients were fever (84.9 %) and cough (21.9 %). The longest incubation period was 26 days, and the median interval from the first symptoms to admission was 5 days. Of the patients, 67.1 % were originally healthy people with no underlying diseases, others mostly had common comorbidities including hypertension (12.3 %) and diabetes (5.5 %), 10.9 % were current smokers, 30.1 % had low white blood cell counts and 45.2 % showed decreased lymphocytes at the first time of diagnosis. CT scans showed that multiple patchy ground glass shadows outside of the patient lungs were commonly observed, and a single sub-pleural sheet of ground glass shadow with enhanced vascular bundles was also found located under the pleura. Patient follow-up to February 14 presented 38.4 % severe cases and 2.7 % critical cases. After follow-up, the parameter of lymphocyte counts below 0.8 × 109/L cannot be used to predict severe and critical groups from the ordinary group, and a lower proportion of smokers and higher proportion of diabetes patients occur in the poor outcome group. Other co-morbidities are observed but did not lead to poor outcomes. CONCLUSION: The epidemiological characteristics of patients in the area around Wuhan, such as Shiyan, at first diagnosis are described as follows: Patients had histories of Wuhan residences in the early stage and family clustering in the later period. The incubation period was relatively long, and the incidence was relatively hidden, but the virulence was relatively low. The initial diagnosis of the patients was mostly ordinary, and the percentage of critical patients who evolved into the ICU during follow-up is 2.7 %, which is lower than the 26.1 % reported by Wuhan city. According to the Shiyan experience, early diagnosis with multiple swaps of the Q-PCR test and timely treatment can reduce the death rate. Diabetes could be one of the risk factors for progression to severe/critical outcomes. No evidence exists that smoking protects COVID-19 patients from developing to severe/critical cases, and the absolute number of lymphocytes at initial diagnosis could not predict the progression risk from severe to critical condition. Multivariate regression analysis should be used to further guide the allocation of clinical resources.

positive: 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.

positive: Clinical Characteristics of Coronavirus Pneumonia 2019 (COVID-19): An Updated Systematic Review OBJECTIVE Clinical characteristics of novel coronavirus pneumonia (COVID-19) have been described in numerous studies but yielded varying results. We aimed to conduct a systematic review on scientific literatures and to synthesize critical data on clinical traits of COVID-19 from its initial outbreak to pandemic. METHODS Systematic searches were conducted to identify retrospective observational study that contained clinical characteristics on COVID-19 through multiple databases. Two reviewers independently evaluated eligible publications. Data on clinical characteristics of COVID-19 were extracted and analyzed. RESULTS Seventy-two retrospective studies demonstrating the clinical characteristics of COVID-19 were included. A total of 3470 COVID-19 patients were synthesized to the final analysis in an unbiased manner. The most common symptom was fever (2878 [83.0%]), and 63.4% of the patients presented fever as onset symptom. There were 2528 [88.2%] of 2866 cases had abnormal lung findings on chest CT scan. Laboratory findings showed that 1498 [62.8%] of 2387 cases had lymphopenia, and 1354 [64.8%] of 2091 cases had an increased level of C-reactive protein (CRP). A total of 185 [11.5%] patients were admitted to intensive care unit (ICU) while the overall case fatality rate (CFR) was 3.7%. Compared to patients admitted outside of Hubei, China, those from Hubei had a significant higher ICU admission rate (21.9% vs. 2.5%, p<0.001). Also, CFR attributed to COVID-19 was significantly higher in Hubei than that of non-Hubei admissions (10.4% vs. 0.6%, p<0.001). INTERPRETATION This large patient-based systematic review presents a more precise profiling of the COVID-19 from its outbreak to current pandemic. Dynamic evolvements of COVID-19 are needed to be characterized in future studies.

positive: Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study OBJECTIVE: To investigate the occurrence of olfactory and gustatory dysfunctions in patients with laboratory-confirmed COVID-19 infection. METHODS: Patients with laboratory-confirmed COVID-19 infection were recruited from 12 European hospitals. The following epidemiological and clinical outcomes have been studied: age, sex, ethnicity, comorbidities, and general and otolaryngological symptoms. Patients completed olfactory and gustatory questionnaires based on the smell and taste component of the National Health and Nutrition Examination Survey, and the short version of the Questionnaire of Olfactory Disorders-Negative Statements (sQOD-NS). RESULTS: A total of 417 mild-to-moderate COVID-19 patients completed the study (263 females). The most prevalent general symptoms consisted of cough, myalgia, and loss of appetite. Face pain and nasal obstruction were the most disease-related otolaryngological symptoms. 85.6% and 88.0% of patients reported olfactory and gustatory dysfunctions, respectively. There was a significant association between both disorders (p < 0.001). Olfactory dysfunction (OD) appeared before the other symptoms in 11.8% of cases. The sQO-NS scores were significantly lower in patients with anosmia compared with normosmic or hyposmic individuals (p = 0.001). Among the 18.2% of patients without nasal obstruction or rhinorrhea, 79.7% were hyposmic or anosmic. The early olfactory recovery rate was 44.0%. Females were significantly more affected by olfactory and gustatory dysfunctions than males (p = 0.001). CONCLUSION: Olfactory and gustatory disorders are prevalent symptoms in European COVID-19 patients, who may not have nasal symptoms. The sudden anosmia or ageusia need to be recognized by the international scientific community as important symptoms of the COVID-19 infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00405-020-05965-1) contains supplementary material, which is available to authorized users.

positive: Early epidemiological and clinical manifestations of COVID-19 in Japan Background: Severe acute respiratory syndrome coronaviruses -2 (SARS-COV2) named as COVID-19 had spread worldwide and leading to 1,210,956 confirmed cases and 67,594 deaths Methods: A data of 1192 confirmed cases and 43 deaths due to COVID-19 in Japan collected from the Ministry of Health, Labour and Welfare of Japan and analysed for different epidemiological parameters and their clinical manifestations. We used Clauset-Newman-Moore (CNM) clustering algorithm to develop web-network of confirmed cases to identified clusters of community transmission. Results: Out of 1192 confirmed cases, 90.60% were symptomatic and 9.39% were asymptomatic. The prevalence of COVID19 in males was 56.29% and 43.20 % in females. The mean interval (SD) from symptom onset to diagnosis was 6-22.6 days while mean interval (SD) from contact to onset of symptoms was 5-19.5 days. People of age range 40-79 were more infected and deaths median age was 80. The main symptoms were fever, dry cough, fatigue and pneumonia. The main infected cities were Tokyo (195/1192, 16.35%), Hokkaido (160/1192 13.42%), Aichi (150/1192, 12.58%) and Osaka (145/1192, 12.16%). Only 2.34% cases had travel history from Wuhan China and Osaka music concert was identify as main cluster for community transmission. While 556 (46.64%) cases were clinically diagnosed and 557 (46.72%) were confirmed by using RT-PCR. Conclusions: Other than, declare emergency Japan need to change their approach of diagnosing COVID-19, as asymptomatic cases prevalence is high and maybe it is reason for current sudden increase of cases. Screening centre should be establish away from hospitals, which are treating positive cases.

positive: Pregnancy and Perinatal Outcomes of Women With Coronavirus Disease (COVID-19) Pneumonia: A Preliminary Analysis. OBJECTIVE. The purpose of this study was to describe the clinical manifestations and CT features of coronavirus disease (COVID-19) pneumonia in 15 pregnant women and to provide some initial evidence that can be used for guiding treatment of pregnant women with COVID-19 pneumonia. MATERIALS AND METHODS. We reviewed the clinical data and CT examinations of 15 consecutive pregnant women with COVID-19 pneumonia in our hospital from January 20, 2020, to February 10, 2020. A semiquantitative CT scoring system was used to estimate pulmonary involvement and the time course of changes on chest CT. Symptoms and laboratory results were analyzed, treatment experiences were summarized, and clinical outcomes were tracked. RESULTS. Eleven patients had successful delivery (10 cesarean deliveries and one vaginal delivery) during the study period, and four patients were still pregnant (three in the second trimester and one in the third trimester) at the end of the study period. No cases of neonatal asphyxia, neonatal death, stillbirth, or abortion were reported. The most common early finding on chest CT was ground-glass opacity (GGO). With disease progression, crazy paving pattern and consolidations were seen on CT. The abnormalities showed absorptive changes at the end of the study period for all patients. The most common onset symptoms of COVID-19 pneumonia in pregnant women were fever (13/15 patients) and cough (9/15 patients). The most common abnormal laboratory finding was lymphocytopenia (12/15 patients). CT images obtained before and after delivery showed no signs of pneumonia aggravation after delivery. The four patients who were still pregnant at the end of the study period were not treated with antiviral drugs but had achieved good recovery. CONCLUSION. Pregnancy and childbirth did not aggravate the course of symptoms or CT features of COVID-19 pneumonia. All the cases of COVID-19 pneumonia in the pregnant women in our study were the mild type. All the women in this study-some of whom did not receive antiviral drugs-achieved good recovery from COVID-19 pneumonia.

positive: Comment on 'Two cases of COVID-19 presenting with a clinical picture resembling chilblains: first report from the Middle East': pernio unrelated to COVID-19

positive: Coronaviruses and SARS-CoV-2: A Brief Overview In late December 2019, several cases of pneumonia of unknown origin were reported from China, which in early January 2020 were announced to be caused by a novel coronavirus. The virus was later denominated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and defined as the causal agent of Coronavirus Disease 2019 (COVID-19). Despite massive attempts to contain the disease in China, the virus has spread globally, and COVID-19 was declared a pandemic by the World Health Organization (WHO) in March 2020. Here we provide a short background on coronaviruses, and describe in more detail the novel SARS-CoV-2 and attempts to identify effective therapies against COVID-19.

positive: Clinical characteristics of IgG4-RD patients infected with COVID-19 in Hubei, China OBJECTIVE: IgG4-related disease (IgG4-RD) is an immune-mediated multi-organ, chronic and progressive disease. Therefore, we conducted a study to investigate the susceptibility of COVID-19 in IgG4-RD patients in Hubei province, and to characterize the clinical manifestation of COVID-19 in IgG4-RD patients. METHODS: A follow-up system that includes over 200 IgG4-RD patients across the country during the past ten years. A total of ninety-one patients with IgG4-RD who live in Hubei, China were identified and responded to our survey. Medical history, clinical symptoms, laboratory tests, CT imaging, and treatment were obtained through a standardized data collection form, and then independently reviewed by two investigators. RESULTS: 2 of 91 cases were infected with COVID-19. Both of them were classified as moderate type. The symptoms such as fever and cough and radiologic features were similar to other COVID-19 patients. Neither of them episode recurrent of IgG4-RD nor progressed to severe or critical condition of COVID-19 under the condition of continuous oral low-dose of glucocorticoids. Besides, patient 2 took a long time for SARS-CoV-2 nucleic acid to turn negative. CONCLUSION: IgG4-RD patients may belongs to the susceptible population of COVID-19 infection, and thus need more careful personal protection. Early identification and properly treatment are very important to prevent IgG4-RD patients with COVID-19 from progression to severe condition.

positive: Featuring COVID-19 cases via screening symptomatic patients with epidemiologic link during flu season in a medical center of central Taiwan Abstract Background Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CO-V-2), was first reported in Wuhan, Hubei province, China has now rapidly spread over 50 countries. For the prevention and control of infection, Taiwan Centers for Disease Control initiated testing of SARS-CoV-2 on January 24th 2020 for persons suspected with this disease. Until February 28th, 43 flu-like symptomatic patients were screened in China Medical University Hospital. Methods Two patients were confirmed positive for SARS-CoV-2 infection by rRT-PCR as COVID-19 patients A and B. Causative pathogens for included patients were detected using FilmArray™ Respiratory Panel. We retrospectively analyzed the clinical presentations, laboratory data, radiologic findings, and travel and exposure contact histories, of the COVID-19 patients in comparison to those with other respiratory infections. Results Through contact with Taiwan No. 19 case patient on 27th January, COVID-19 patients A and B were infected. Both patients had no identified comorbidities and developed mild illness with temporal fever, persistent cough, and lung interstitial infiltrates. Owing to the persistence of positive SARS-CoV-2 in respiratory specimen, the two COVID-19 patients are still in the isolation rooms despite recovery until 10th of March. The results of FilmArrayTM Respiratory Panel revealed 22 of the 41 non-COVID-19 patients were infected by particular pathogens. In general, seasonal respiratory pathogens are more prevalent than SARS-CoV-2 in symptomatic patients in non- COVID-19 endemic area during the flu season. Since all patients shared similar clinical and laboratory findings, expanded surveillance of detailed exposure history for suspected patients and application of rapid detection tools are highly recommended.

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: Gastrointestinal Infection Could Be New Focus for Coronavirus Diagnosis It's not news to tell you that the coronavirus, known as COVID-19, is a worldwide pandemic. The initial outbreak of this novel virus in Wuhan in the Hubei province of China, first described in December 2019, has since moved on to being declared a pandemic by the World Health Organization. The classic description of COVID-19 is a respiratory illness that manifests with fever, dry cough, and dyspnea on exertion. However, gastrointestinal (GI) complication of COVID-19 is emerging as well. This was observed with similar viral respiratory illnesses, such as severe acute respiratory syndrome (SARS), which emerged in 2003, and the Middle East respiratory syndrome (MERS), which emerged in 2012. In a recently published, single-center case series of 138 consecutive hospitalized patients with confirmed COVID-19, investigators reported that approximately 10% of patients initially presented with GI symptoms, prior to the subsequent development of respiratory symptoms. Common and often very subtle symptoms included diarrhea, nausea, and abdominal pain, with a less common symptom being nonspecific GI illness. New studies are expanding our understanding of the possible fecal transmission of COVID-19. Assessment by polymerase chain reaction (PCR) has provided evidence of the virus in the stool and the oropharynx outside the nasopharynx and respiratory tract. Virus in the stool may be evident on presentation and last throughout the course of illness resolution for up to 12 days after the respiratory virus evidence is gone. In fact, in one of the most recent studies looking at 73 patients, approximately 24% remained positive in their stool for evidence of the virus, though not necessarily infection, after showing negative in respiratory samples. The Centers for Disease Control and Prevention (CDC) recommends that after two negative respiratory tests separated by ≥ 24 hours, patients can be dismissed from having transmissibility infection risk for COVID-19. The potential for fecal-oral transmission of COVID-19 needs to be strongly considered. Considering these cases and the lessons from SARS, many authors recommend that real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from feces should be performed routinely in SARS-CoV-2 patients.

positive: Olfactory and Gustatory Dysfunction in Coronavirus Disease 19 (COVID-19) Coronavirus-disease-2019 (COVID-19) caused by the severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) shows a rapid spread over-the-world. Given scarce resources, non-laboratory diagnostics is crucial. In this cross-sectional study, two-thirds of European patients with polymerase chain reaction confirmed COVID-19 reported olfactory and gustatory dysfunction, indicating the significance of this history in the early diagnostics.

positive: Objective olfactory testing in patients presenting with sudden onset olfactory dysfunction as the first manifestation of confirmed COVID-19 infection Abstract Background: The aims of this study are to investigate the COVID-19 status of patients with initial sudden olfactory anosmia (ISOA) using nasopharyngeal swabs for RT-PCR analysis and to explore their olfactory dysfunctions with psychophysical olfactory evaluation. Methodology: This prospective study included 78 ISOA patients who fulfilled a patient-reported outcome questionnaire and underwent a nasopharyngeal swabs. Among these, 46 patients performed psychophysical olfactory evaluation using sniffing tests. Based on the duration of the ISOA, two groups of patients were compared: patients with anosmia duration [≤]12 days (group 1) and those with duration >12 days (group 2). Results: Among group 1, 42 patients (87.5%) had a positive viral load regarding RT-PCR while 6 patients (12.5%) were negative. In group 2, 7 patients (23%) had a positive viral load and 23 patients (77%) were negative. Among the 46 patients having performed a psychophysical olfactory evaluation, we observed anosmia in 52% (N=24), hyposmia in 24% (N=11) and normosmia in 24% (N=11) of patients. The viral load significantly decreased throughout the 14-days following the onset of the olfactory disorder. Conclusions: Our results support that a high proportion of ISOA patients are Covid+. Our study supports the need to add anosmia to the list of symptoms used in screening tools for possible COVID-19 infection.

positive: Diagnosis and treatment of coronavirus disease 2019 (COVID-19): Laboratory, PCR, and chest CT imaging findings Since December 2019, more than 3 million cases of coronavirus disease 2019 (COVID-19) and about 200,000 deaths have been reported worldwide. The outbreak of this novel disease has become a global health emergency and continues to rapidly spread around the world. Based on the clinical data, approved cases are divided into four classes including mild, moderate, severe, and critical. About 5% of cases were considered critically ill and 14% were considered to have the severe classification of the disease. In China, the fatality rate of this infection was about 4%. This review focuses on currently available information on the etiology, clinical symptoms, diagnosis, and mechanism of action of COVID-19. Furthermore, we present an overview of diagnostic approaches and treatment of this disease according to available findings. This review paper will help the physician to diagnose and successfully treat COVID-19.

positive: High-resolution Chest CT Features and Clinical Characteristics of Patients Infected with COVID-19 in Jiangsu, China Abstract Background A pneumonia associated with the coronavirus disease 2019 (COVID-19) recently emerged in China. It was recognized as a global health hazard. Methods 234 inpatients with COVID-19 were included. Detailed clinical data, chest HRCT basic performances and certain signs were recorded, and ground-glass opacity (GGO), consolidation, fibrosis and air trapping were quantified. Both clinical types and CT stages were evaluated. Results Most patients (approximately 90%) were classified as common type and with epidemiologic history. Fever and cough were main symptoms. Chest CT showed abnormal attenuation in bilateral multiple lung lobes, distributed in the lower and/or periphery of the lungs (94.98%), with multiple shapes. GGO and vascular enhancement sign were most frequent seen, followed by interlobular septal thickening and air bronchus sign as well as consolidation, fibrosis and air trapping. There were significant differences in most of CT signs between different stage groups. The SpO2 and OI were decreased in stage IV, and the CT score of consolidation, fibrosis and air trapping was significantly lower in stage I (P <0.05). A weak relevance was between the fibrosis score and the value of PaO2 and SpO2 (P <0.05). Conclusions Clinical performances of patients with COVID-19, mostly with epidemiologic history and typical symptoms, were critical valuable in the diagnosis of the COVID-19. While chest HRCT provided the distribution, shape, attenuation and extent of lung lesions, as well as some typical CT signs of COVID-19 pneumonia.

positive: Non-epileptic seizures in autonomic dysfunction as the initial symptom of COVID-19

positive: Clinical course of COVID-19 in a liver transplant recipient on hemodialysis and response to tocilizumab therapy: A case report The novel coronavirus disease 2019 (COVID-19) is a highly infectious and rapidly spreading disease. There are limited published data on the epidemiology and outcomes of COVID-19 infection among organ transplant recipients. After initial flulike symptoms, progression to an inflammatory phase may occur, characterized by cytokine release rapidly leading to respiratory and multiorgan failure. We report the clinical course and management of a liver transplant recipient on hemodialysis, who presented with COVID-19 pneumonia, and despite completing a 5-day course of hydroxychloroquine, later developed marked inflammatory manifestations with rapid improvement after administration of off-label, single-dose tocilizumab. We also highlight the role of lung ultrasonography in early diagnosis of the inflammatory phase of COVID-19. Future investigation of the effects of immunomodulators among transplant recipients with COVID-19 infection will be important.

positive: Consensus for prevention and management of coronavirus disease 2019 (COVID-19) for neurologists Coronavirus disease 2019 (COVID‐19) has become a pandemic disease globally. Although COVID-19 directly invades lungs, it also involves the nervous system. Therefore, patients with nervous system involvement as the presenting symptoms in the early stage of infection may easily be misdiagnosed and their treatment delayed. They become silent contagious sources or ‘virus spreaders’. In order to help neurologists to better understand the occurrence, development and prognosis, we have developed this consensus of prevention and management of COVID‐19. It can also assist other healthcare providers to be familiar with and recognise COVID-19 in their evaluation of patients in the clinic and hospital environment.

positive: Computed Tomography Manifestations of 5 Cases of the Novel Coronavirus Disease 2019 (COVID-19) Pneumonia From Patients Outside Wuhan Clinical, laboratory, and computed tomography (CT) findings of 5 cases of the novel Coronavirus Disease 2019 (COVID-19) pneumonia from patients outside of Wuhan were reviewed. The human-to-human transmission of the virus may explain the infection of the disease outside of Wuhan. CT examination is important in the early detection and follow-up of the disease. With a history of exposure or travelling, symptoms of fever and cough, and the typical CT manifestation such as ground-glass opacity with a peripheral distribution, we should also think of the possibility of the COVID-19 pneumonia in patients outside of Wuhan.

positive: Review of the Clinical Characteristics of Coronavirus Disease 2019 (COVID-19) In late December 2019, a cluster of cases with 2019 Novel Coronavirus pneumonia (SARS-CoV-2) in Wuhan, China, aroused worldwide concern. Previous studies have reported epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19). The purpose of this brief review is to summarize those published studies as of late February 2020 on the clinical features, symptoms, complications, and treatments of COVID-19 and help provide guidance for frontline medical staff in the clinical management of this outbreak.

positive: Chest computed tomography images of early coronavirus disease (COVID-19)

positive: A framework for identifying regional outbreak and spread of COVID-19 from one-minute population-wide surveys Coronavirus infection spreads in clusters and therefore early identification of these clusters is critical for slowing down the spread of the virus. Here, we propose that daily population-wide surveys that assess the development of symptoms caused by the virus could serve as a strategic and valuable tool for identifying such clusters to inform epidemiologists, public health officials, and policy makers. We show preliminary results from a survey of over 38,000 Israelis and call for an international consortium to extend this concept in order to develop predictive models. We expect such data to allow: Faster detection of spreading zones and patients; Obtaining a current snapshot of the number of people in each area who have developed symptoms; Predicting future spreading zones several days before an outbreak occurs; Evaluating the effectiveness of the various social distancing measures taken, and their contribution to reduce the number of symptomatic people. Such information can provide a valuable tool for decision makers to decide which areas need strengthening of social distancing measures and which areas can be relieved. Researchers from the U.S, Spain, and Italy have adopted our approach and we are collaborating to further improve it. We call with urgency for other countries to join this international consortium, and to share methods and data collected from these daily, simple, one-minute surveys.

positive: Neurological Consequences of 2019-nCoV Infection: A Comprehensive Literature Review First identified in November 2019 in Hubei Province, the coronavirus disease of 2019 (COVID-19) caused by SARS-CoV-2 soon spread worldwide to become a global health pandemic. The COVID-19 preferentially damages the respiratory system that produces symptoms such as fever, cough, and shortness of breath. However, the infection often tends to disseminate to involve various organ systems. Recent evidence indicates that SARS-CoV-2 can cause significant neurological damage and resultant neurological symptoms and complications. Here, we provide a comprehensive and thorough review of original articles, case reports, and case series to delineate the possible mechanisms of nervous system invasion and damage by SARS-CoV-2 and subsequent consequences. We divided the neurological manifestations into three categories: (1) Central Nervous System involvement, (2) Peripheral Nervous System manifestations, and (3) Skeletal Muscle Injury. Headache and dizziness were found to be the most prevalent symptoms followed by impaired consciousness. Among the symptoms indicating peripheral nervous system invasion, anosmia and dysgeusia were commonly reported. Skeletal muscle injury predominantly presents as myalgia. In addition, encephalitis, myelitis, cerebrovascular disease, Guillain-Barre syndrome, and Miller Fischer syndrome were among the commonly noted complications. We also emphasized the association of pre-existing comorbidities with neurological manifestations. The aim of this review is to provide a deeper understanding of the potential neurological implications to help neurologists have a high index of clinical suspicion allowing them to manage the patient appropriately.

positive: Smell and taste alterations in Covid‐19: a cross‐sectional analysis of different cohorts BACKGROUND: : Olfactory (OD) and gustatory (GD) dysfunction have been proven to be a typical symptom of SARS‐CoV‐2 infection. However, their prevalence in different patient populations still needs to be clarified. METHODS: : A cross‐sectional study was performed from March 27 to April 1 2020 in Northern Italy. Physicians administered a survey‐based questionnaire to SARS‐CoV‐2 positive patients with the aim of assessing symptoms, focusing on OD and GD. Two groups were studied: patients hospitalized at ASST Spedali Civili University Hospital of Brescia (A); home‐quarantined subjects (B). RESULTS: : A total of 508 patients were enrolled: 295 in Group A and 213 in Group B. Mean age (±SD) was 55±15 years; 56% were men. Overall, OD and GD were present in 56% (95% CI 51‐60%) and 63% (59‐67%) of cases, respectively. In Group A, the prevalence of OD and GD was 44% (38‐50%) and 52% (46‐58%). In Group B, the prevalence of OD and GD was 72% (65‐79%) and 79% (73‐84%). In the entire cohort, total loss of olfaction and taste was reported in 64% and 60% of cases, respectively. OD and GD occurred as the first symptom in 10% and 11% of cases; in the remaining cases, they occurred after a mean of 4±3 days following the first symptom. At the time of the questionnaire, complete resolution of OD and GD was reported in 52% and 55% of cases (mean duration: 9±5 in both). CONCLUSIONS: : OD and GD are more prevalent in home‐quarantined subjects, and they are independently associated with younger age and female gender. This article is protected by copyright. All rights reserved

positive: 2019-novel coronavirus outbreak: A new challenge OBJECTIVES: Following the public health emergency declared by the World Health Organization and the recent outbreak by 2019-nCoV in China and through other 29 countries, we aimed to summarize the clinical aspects of novel beta-coronavirus infection and its possible clinical presentations together with suggested therapeutic algorithms for patients who may require antibiotic treatment. METHODS: We reviewed the currently available literature of microbiologically confirmed infections by 2019-ConV (or COVID-19) occurred at the time of writing (13 February 2020). A literature search was performed using the PubMed database and the Cochrane library. Search terms included "novel coronavirus" or "2019-nCoV" or “COVID-19”. RESULTS: Published cases occurred mostly in males (age ranged from 8 to 92). Cardiovascular, digestive and endocrine system diseases were commonly reported, except previous chronic pulmonary diseases (e.g., COPD, asthma, bronchiectasis) that were surprisingly underreported. Fever was presented in all the case series available, flanked by cough, dyspnea, myalgias and fatigue. Multiple bilateral lobular and subsegmental areas of consolidation or bilateral ground-glass opacities were the main reported radiological features of 2019-nCoV, at least in the early phases of disease. CONCLUSIONS: The new 2019-nCoV epidemics is mainly associated with respiratory disease and few extrapulmonary signs. However, there is a low rate of associated pre-existing respiratory comorbidities.

positive: A case of SARS-CoV-2 carrier for 32 days with several times false negative nucleic acid tests In 2019, a novel coronavirus (SARS-CoV-2) was first discovered in Wuhan, Hubei, China, causing severe respiratory disease in humans, and has been identified as a public health emergency of international concern. With the spread of the virus, there are more and more false negative cases of RT-PCR nucleic acid detection in the early stage of potential infection. In this paper, we collected the epidemiological history, clinical manifestations, outcomes, laboratory results and images of a SARS-CoV-2 carrier with no significant past medical history. The patient was quarantined because of her colleague had been diagnosed. After the onset of clinical symptoms, chest CT results showed patchy ground-glass opacity (GGO) in her lungs, but it took a total of nine nucleic acid tests to confirm the diagnosis, among which the first eight RT-PCR results were negative or single-target positive. In addition to coughing up phlegm during her stay in the hospital, she did not develop chills, fever, abdominal pain, diarrhea and other clinical symptoms. Since initial antiviral treatment, the lung lesions were absorbed. But the sputum nucleic acid test was still positive. In combination with antiviral and immune therapy, the patient tested negative for the virus. Notably, SARS-CoV-2 was detected only in the lower respiratory tract samples (sputum) throughout the diagnosis and treatment period. This is a confirmed case of SARS-CoV-2 infection with common symptoms, and her diagnosis has undergone multiple false negatives ,suggesting that it is difficult to identify certain carriers of the virus and that such patients may also increase the spread of the SARS-CoV-2.

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: Detection of severe acute respiratory syndrome Coronavirus-2 in the tears of patients with Coronavirus disease 2019 OBJECTIVES: Since there are few reports on the ocular involvement of coronavirus disease 2019 (COVID-19) patients, this study aimed to assess the presence of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) in the tears of patients with COVID-19. METHODS: In this prospective case series, nasopharyngeal and tear sampling of 43 patients with severe COVID-19 were performed. The quantitative reverse transcription polymerase chain reaction (RT-PCR) was conducted to detect SARS-CoV-2. Ocular and systemic signs and symptoms were recorded from their medical history. RESULTS: The mean age of patients was 56 ± 13 years. The average disease time from initiation of symptoms was 3.27 days, range: 1–7 days. Forty-one patients (95.3%) had fever at the time of sampling. Only one patient had conjunctivitis. Thirty (69.8%) nasopharyngeal and three (7%) tear samples were positive for SARS-CoV-2. The result of tear sample was positive in the patient with conjunctivitis. All patients with positive tear RT-PCR results had positive nasopharyngeal RT-PCR results. CONCLUSIONS: Ocular manifestation was rare in this series of severe COVID-19 patients, however, 7% of the patients had viral RNA in their conjunctival secretions. Therefore, possibility of ocular transmission should be considered even in the absence of ocular manifestations.

positive: Lung Base Findings of Coronavirus Disease (COVID-19) on Abdominal CT in Patients With Predominant Gastrointestinal Symptoms. OBJECTIVE. This series of patients presented to the emergency department (ED) with abdominal pain, without the respiratory symptoms typical of coronavirus disease (COVID-19), and the abdominal radiologist was the first to suggest COVID-19 infection because of findings in the lung bases on CT of the abdomen. CONCLUSION. COVID-19 infection can present primarily with abdominal symptoms, and the abdominal radiologist must suggest the diagnosis when evaluating the lung bases for typical findings.

positive: The different clinical characteristics of corona virus disease cases between children and their families in China – the character of children with COVID-19 This study aims to analyze the different clinical characteristics between children and their families infected with severe acute respiratory syndrome coronavirus 2. Clinical data from nine children and their 14 families were collected, including general status, clinical, laboratory test, and imaging characteristics. All the children were detected positive result after their families onset. Three children had fever (22.2%) or cough (11.2%) symptoms and six (66.7%) children had no symptom. Among the 14 adult patients, the major symptoms included fever (57.1%), cough (35.7%), chest tightness/pain (21.4%), fatigue (21.4%) and sore throat (7.1%). Nearly 70% of the patients had normal (71.4%) or decreased (28.6%) white blood cell counts, and 50% (7/14) had lymphocytopenia. There were 10 adults (71.4%) showed abnormal imaging. The main manifestations were pulmonary consolidation (70%), nodular shadow (50%), and ground glass opacity (50%). Five discharged children were admitted again because their stool showed positive result in SARS-CoV-2 PCR. COVID-19 in children is mainly caused by family transmission, and their symptoms are mild and prognosis is better than adult. However, their PCR result in stool showed longer time than their families. Because of the mild or asymptomatic clinical process, it is difficult to recognize early for pediatrician and public health staff.

positive: Clinical Features, Diagnosis, and Treatment of COVID-19 in Hospitalized Patients: A Systematic Review of Case Reports and Case Series Introduction: The 2019 novel coronavirus (COVID-19) has been declared a public health emergency worldwide. The objective of this systematic review was to characterize the clinical, diagnostic, and treatment characteristics of hospitalized patients presenting with COVID-19. Methods: We conducted a structured search using PubMed/Medline, Embase, and Web of Science to collect both case reports and case series on COVID-19 published up to April 24, 2020. There were no restrictions regarding publication language. Results: Eighty articles were included analyzing a total of 417 patients with a mean age of 48 years. The most common presenting symptom in patients who tested positive for COVID-19 was fever, reported in up to 62% of patients from 82% of the analyzed studies. Other symptoms including rhinorrhea, dizziness, and chills were less frequently reported. Additionally, in studies that reported C-reactive protein (CRP) measurements, a large majority of patients displayed an elevated CRP (60%). Progression to acute respiratory distress syndrome (ARDS) was the most common complication of patients testing positive for COVID-19 (21%). CT images displayed ground-glass opacification (GGO) patterns (80%) as well as bilateral lung involvement (69%). The most commonly used antiviral treatment modalities included, lopinavir (HIV protease inhibitor), arbidiol hydrochloride (influenza fusion inhibitor), and oseltamivir (neuraminidase inhibitor). Conclusions: Development of ARDS may play a role in estimating disease progression and mortality risk. Early detection of elevations in serum CRP, combined with a clinical COVID-19 symptom presentation may be used as a surrogate marker for the presence and severity of the disease. There is a paucity of data surrounding the efficacy of treatments. There is currently not a well-established gold standard therapy for the treatment of diagnosed COVID-19. Further prospective investigations are necessary.

positive: Clinical Features of Patients with Coronavirus Disease 2019 (COVID‐19) from a Designated Hospital in Beijing, China Clinical and laboratory data available on patients with coronavirus disease 2019 (COVID‐19) in Beijing, China remain extremely limited. Here, we summarized the clinical characteristics of patients with COVID‐19 in a designated hospital in Beijing, China. 55 patients with laboratory‐confirmed SARS‐CoV‐2 infection were admitted to Beijing 302 Hospital and enrolled in this study. Demographic data, symptoms, comorbidities, laboratory values, treatments, and clinical outcomes were all collected and retrospectively analyzed. 15 (27.3%) of the patients had non‐severe symptom, the mean age was 44.0 years (interquartile range 34.0‐56.0), and median incubation period was 7.5 days (interquartile range 5.0‐11.8). 26 (47.3%) patients had exposure history in Wuhan while 20 (36.4%) were associated with familial clusters. 18 (32.7%) had underlying comorbidities including hypertension. The most common symptoms of illness were fever (45, 81.8%), 51 (92.7%) patients had abnormal findings on chest CT. Laboratory findings showed that neutrophil count, percentage of lymphocyte, percentage of eosinophil, eosinophil count, erythrocyte sedimentation rate, albumin, and serum ferritin are potential risk factors for patients with poor prognosis. 26 patients (47.3%) were still hospitalized while 29 (52.7%) had been discharged at this point. Compared with patients in Wuhan, the symptoms of patients in Beijing are relatively mild. Older age, more comorbidities, and more abnormal prominent laboratory markers were associated with severe condition. On the basis of antiviral drugs, antibiotics treatment, appropriate dosage of corticosteroid and gamma globulin therapy significantly improve patients’ outcomes. Early identification and timely medical treatment are important to reduce the severity of patients with COVID‐19. This article is protected by copyright. All rights reserved.

positive: SARS Clinical Features, United States, 2003 We compared the clinical features of 8 U.S. case-patients with laboratory-confirmed severe acute respiratory syndrome (SARS) to 65 controls who tested negative for SARS coronavirus (SARS-CoV) infection. Shortness of breath, vomiting, diarrhea, progressive bilateral infiltrates on chest radiograph, and need for supplemental oxygen were significantly associated with confirmed SARS-CoV infection.

positive: COVID‐19 patients' clinical characteristics, discharge rate, and fatality rate of meta‐analysis The aim of this study was to analyze the clinical data, discharge rate, and fatality rate of COVID‐19 patients for clinical help. The clinical data of COVID‐19 patients from December 2019 to February 2020 were retrieved from four databases. We statistically analyzed the clinical symptoms and laboratory results of COVID‐19 patients and explained the discharge rate and fatality rate with a single‐arm meta‐analysis. The available data of 1994 patients in 10 literatures were included in our study. The main clinical symptoms of COVID‐19 patients were fever (88.5%), cough (68.6%), myalgia or fatigue (35.8%), expectoration (28.2%), and dyspnea (21.9%). Minor symptoms include headache or dizziness (12.1%), diarrhea (4.8%), nausea and vomiting (3.9%). The results of the laboratory showed that the lymphocytopenia (64.5%), increase of C‐reactive protein (44.3%), increase of lactic dehydrogenase (28.3%), and leukocytopenia (29.4%) were more common. The results of single‐arm meta‐analysis showed that the male took a larger percentage in the gender distribution of COVID‐19 patients 60% (95% CI [0.54, 0.65]), the discharge rate of COVID‐19 patients was 52% (95% CI [0.34,0.70]), and the fatality rate was 5% (95% CI [0.01,0.11]).

positive: Clinical progression of patients with COVID-19 in Shanghai, China BACKGROUND: Studies on the 2019 novel coronavirus disease (COVID-19) have generally been limited to the description of the epidemiology and initial clinical characteristics. We investigated the temporal progression in patients with COVID-19. METHODS: In this retrospective, single-center study, we included confirmed cases of COVID-19 from Jan 20 to Feb 6, 2020 in Shanghai. Final date of follow-up was February 25, 2020. RESULTS: Of the 249 patients enrolled, the median age was 51 years old, and 126 (50.6%) were male. The duration from onset of symptoms to hospitalization was 4(2-7) days in symptomatic patients. Fever was occurred in 235(94.3%) patients. A total of 215 (86.3%) patients had been discharged after 16(12-20) days hospitalization. The estimated median duration of fever in all the patients with fever was 10 days (95 confidential intervals [CIs]: 8-11 days) after onset of symptoms. Patients who were transferred to intensive care units (ICU) had significantly longer duration of fever as compared to those not in ICU (31 days v.s. 9 days after onset of symptoms, respectively, P <0.0001). Radiological aggravation of initial image was observed in 163 (65.7%) patients on day 7 after onset of symptoms. 154(94.5%) of these patients showed radiological improvement on day 14. The median duration to negative reverse-transcriptase PCR tests of upper respiratory tract samples was 11 days (95 CIs: 10-12 days). Viral clearance was more likely to be delayed in patients in ICU than those not in ICU (P <0.0001). In multivariate logistical analysis, age (Odds ratio [OR]â¯=â¯1.06) and CD4 T cell count (ORâ¯=â¯0.55 per 100 cells/ul increase) were independently associated with ICU admission. CONCLUSIONS: The majority of COVID-19 cases are mild. The clinical progression pattern suggests that early control of viral replication and application of host-directed therapy in later stage is essential to improve the prognosis of CVOID-19.

positive: A COVID-19 case report from asymptomatic contact: implication for contact isolation and incubation management BACKGROUND: As of 2 March, 2020, at least 80 151 coronavirus disease 2019 (COVID-19) cases were reported in China. Most of the patients had a history of visiting Hubei Province or contacting with people who had ever stayed in or passed by Hubei Province or were exposed to symptoms. Some patients got infected through only asymptomatic contact. This study aimed to report the epidemic features and lab identification of a patient confirmed with COVID-19 infection through only asymptomatic contact. CASE PRESENTATION: A 44-year-old man, who lived in Nanchang, Jiangxi Province, China until 6 March 2020, suffered from cough on 27 January 2020. Fever symptoms appeared on 28 January, with a maximum temperature of 38.8 °C, accompanied by cough, sore throat, headache, fatigue, muscle ache, joint ache, and other symptoms. The symptoms continued until he was hospitalized on 30 January. Coronavirus conventional polymerase chain reaction assay was positive for the throat swab sample. The patient, along with his wife and son, drove from Nanchang to back to Honghu City, Hubei Province, on 23 January 2020. After staying with his parents and brother’s family for 3 days, the patient drove back to Nanchang and arrived on 25 January. On the way back home, they stopped by Tongshan service area, Hubei Province, without any close contact with other people. After arriving home in Nanchang City, Jiangxi Province, none of them left their residence. In addition, his parents stayed at home for 20 days with his younger brother’s family before they got back. His younger brother and one of his brother’s children visited Wuhan on 5 January and came home on 6 January 2020. CONCLUSIONS: This report suggested that, in the early phase of COVID-19 pneumonia, routine screening could miss patients who were virus carriers. Highlighting travel history is of paramount importance for the early detection and isolation of severe acute respiratory syndrome coronavirus 2 cases.

positive: The effect of a national lockdown in response to COVID-19 pandemic on the prevalence of clinical symptoms in the population SARS-CoV-2, a novel coronavirus and the cause of COVID-19, was isolated in December 2019 and has since been declared a pandemic by the World Health Organization (WHO). The vast and rapid spread of COVID-19 calls for immediate action from policy-makers and in many countries, various lockdown measures were implemented. Here, we utilized nationwide surveys that assess COVID-19 associated symptoms to analyse the effect of the lockdown policy in Israel on the prevalence of clinical symptoms in the population. Daily symptom surveys were distributed online and included fever, respiratory symptoms, gastrointestinal symptoms, anosmia and Ageusia. A total of 1,003,298 surveys were filled out to date. We used a single measure of symptoms, Symptoms Ratio (SR), defined as a weighted mean of symptoms found to be prevalent in COVID-19 patients. Notably, following severe lockdown measures, we found that between March 15 and April 22, the mean SR sharply declined by 78.9%, as did every individual symptom, including our most common symptoms of cough and rhinorrhea or nasal congestion, which decreased from 14.5% and 13.8% of the survey responders, respectively, to 2.4% and 2.5%. We also observed reduction in symptoms separately in the vast majority of cities in Israel. Overall, these results demonstrate a profound decrease in a variety of clinical symptoms following the implementation of a lockdown in Israel. As our survey symptoms are not specific to COVID-19 infection, this effect likely represents an overall nationwide reduction in the prevalence of infectious diseases, including COVID-19. This quantification may be of major interest for COVID-19 pandemic, as many countries consider implementation of lockdown strategies.

positive: Gastrointestinal and Liver Manifestations of COVID-19 The worldwide pandemic of COVID-19, caused by the virus SARS-CoV,-2 has continued to progress, and increasing information is becoming available about the incidence of digestive symptoms as well as abnormal liver-associated enzymes in patients who are infected. These are postulated to be related to the virus's use of ACE-2 receptors located on certain intestinal cells, cholangiocytes, and hepatocytes. This brief review summarizes the available limited data on digestive manifestations of COVID-19. A significant proportion of COVID-19 patients can present initially with only digestive complaints. The most common digestive symptoms are anorexia, nausea, vomiting, and diarrhea. Liver-related transaminases are elevated in a substantial proportion of patients, although generally only mildly elevated. Currently there is no firm evidence to suggest that severity of digestive symptoms corresponds to severity of COVID-19 clinical course, however, more severe alterations in liver enzymes may correlate with worse clinical course. Given use of antiviral and antibacterial agents in sicker patients, drug-induced liver injury cannot be ruled out either in these cases. Although viral RNA can be detected in stool, it is unclear whether fecal-oral transmission can be achieved by the virus. As further data becomes available, our understanding of the digestive manifestations of COVID-19 will continue to evolve.

positive: A Middle East respiratory syndrome screening clinic for health care personnel during the 2015 Middle East respiratory syndrome outbreak in South Korea: A single-center experience BACKGROUND: Transmission of Middle East respiratory syndrome (MERS) to health care personnel (HCP) is a major concern. This study aimed to review cases of MERS-related events, such as development of MERS-like symptoms or exposure to patients. METHODS: A MERS screening clinic (MSC) for HCP was setup in the National Medical Center during the MERS outbreak in 2015. Clinical and laboratory data from HCP who visited the MSC were retrospectively reviewed. Additionally, these data were compared with the results of postoutbreak questionnaire surveys and interviews about MERS-related symptoms and risk-related events. RESULTS: Of the 333 HCP who participated in MERS patient care, 35 HCP (10.5%) visited the MSC for MERS-like symptoms. No one was infected with MERS, and the most common symptom was fever (68.6%) followed by cough (34.3%). However, 106 of 285 postoutbreak survey participants experienced at least 1 MERS-related symptom and 26 reported exposure to patients without appropriate personal protective equipment, whereas only 4 HCP visited the MSC to report exposure events. CONCLUSIONS: Although a considerable number of HCP experienced MERS-related symptoms or unprotected exposure during MERS patient care, some did not take appropriate action. These findings imply that for infection control strategy to be properly performed, education should be strengthened so that HCP can accurately recognize the risk situation and properly notify the infection control officer.

positive: Clinical characteristics and drug therapies in patients with the common-type coronavirus disease 2019 in Hunan, China Background Clinical characteristics of patients with the coronavirus disease 2019 (COVID-19) may present differently within and outside the epicenter of Wuhan, China. More clinical investigations are needed. Objective The study was aimed to describe the clinical characteristics, laboratory parameters, and therapeutic methods of COVID-19 patients in Hunan, China. Setting The First Hospital of Changsha, First People’s Hospital of Huaihua, and the Central Hospital of Loudi, Hunan province, China. Methods This was a retrospective multi-center case-series analysis. Patients with confirmed COVID-19 diagnosis hospitalized at the study centers from January 17 to February 10, 2020, were included. The following data were obtained from electronic medical records: demographics, medical history, exposure history, underlying comorbidities, symptoms, signs, laboratory findings, computer tomography scans, and treatment measures. Main outcome measure Epidemiological, clinical, laboratory, and radiological characteristics and treatments. Results A total of 54 patients were included (51 had the common-type COVID-19, three had the severe-type), the median age was 41, and 52% of them were men. The median time from the first symptoms to hospital admission was seven days. Among patients with the common-type COVID-19, the median length of stay was nine days, and 21 days among patients with severe COVID-19. The most common symptoms at the onset of illness were fever (74.5%), cough (56.9%), and fatigue (43.1%) among patients in the common-type group. Fourteen patients (37.8%) had a reduced WBC count, 23 (62.2%) had reduced eosinophil ratio, and 21 (56.76%) had decreased eosinophil count. The most common patterns on chest-computed tomography were ground-glass opacity (52.2%) and patchy bilateral shadowing (73.9%). Pharmacotherapy included recombinant human interferon α2b, lopinavir/ritonavir, novaferon, antibiotics, systematic corticosteroids and traditional Chinese medicine prescription. The outcome of treatment indicated that in patients with the common-type COVID-19, interferon-α2b, but not novaferon, had some benefits, antibiotics treatment was not needed, and corticosteroids should be used cautiously. Conclusion As of February 10, 2020, the symptoms of COVID-19 patients in Hunan province were relatively mild comparing to patients in Wuhan, the epicenter. We observed some treatment benefits with interferon-α2b and corticosteroid therapies but not with novaferon and antibiotic treatment in our study population. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11096-020-01031-2) contains supplementary material, which is available to authorized users.

positive: Urinary Frequency as a Possibly Overlooked Symptom in COVID-19 Patients: Does SARS-CoV-2 Cause Viral Cystitis? The current coronavirus disease 2019 (COVID-19) pandemic is a challenge for physicians in triaging patients in emergency rooms. We found a potentially dangerous overlap of classical urinary symptoms and the as yet not fully described symptoms of COVID-19. After a patient was primarily triaged as a urosepsis case and then subsequently diagnosed with COVID-19, we focused on an increase in urinary frequency as a symptom of COVID-19 and identified this in seven males out of 57 patients currently being treated in our COVID-19 wards. In the absence of any other causes, urinary frequency may be secondary to viral cystitis due to underlying COVID-19 disease. We propose consideration of urinary frequency as an anamnestic tool in patients with infective symptoms to increase awareness among urologists during the current COVID-19 pandemic to prevent fatal implications of misinterpreting urological symptoms.

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: Evaluation of ocular symptoms and tropism of SARS‐CoV‐2 in patients confirmed with COVID‐19 PURPOSE: The SARS‐CoV‐2 RNA has been detected in tears and conjunctival samples from infected individuals. Conjunctivitis is also reported in a small number of cases. We evaluated ocular symptoms and ocular tropism of SARS‐CoV‐2 in a group of patients with COVID‐19. METHOD: Fifty‐six patients infected with SARS‐CoV‐2 were recruited as subjects. Relevant medical histories were obtained from the electronic medical record system. Ocular history and ocular symptoms data were obtained by communicating directly with the subjects. The Ocular Surface Disease Index (OSDI) and Salisbury Eye Evaluation Questionnaire (SEEQ) were used to assess the anterior ocular surface condition before and after the onset of disease. RESULTS: Patients classified as severe COVID‐19 cases were more likely to have hypertension compared to mild cases (p = 0.035). Of the 56 subjects, thirteen patients (23%) were infected in Wuhan, 32 patients (57%) were community‐infected, 10 patients (18%) were unknown origin, 1 (2%) was a physician likely infected by a confirmed patient. Three patients wore face mask with precaution when contacting the confirmed patients. Fifteen (27%) had aggravated ocular symptoms, of which 6 (11%) had prodromal ocular symptoms before disease onset. The differences in mean scores of OSDI questionnaire and SEEQ between before and after onset of COVID‐19 were all significant (p < 0.05 for both). CONCLUSIONS: Ocular symptoms are relatively common in COVID‐19 disease and may appear just before the onset of respiratory symptoms. Our data provided the anecdotal evidences of transmission of SARS‐CoV‐2 via ocular surface.

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: Gastrointestinal and liver manifestations in patients with COVID-19 As the outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread over the world, the World Health Organization has declared the outbreak of COVID-19 an international public health emergency. Besides typical respiratory symptoms and signs of COVID-19, digestive symptoms and liver injury have been frequently reported during the course of the disease. In this review, we summarized the recent studies reporting of gastrointestinal and liver manifestations during the course of COVID-19. Digestive symptoms, including anorexia, nausea, vomiting, and diarrhea, are not uncommon in patients with COVID-19, and in some cases digestive symptoms may occur in the absence of any respiratory symptoms. Furthermore, SARS-CoV-2 could be detected in the stool of infected patients, implicating the possibility of fecal–oral transmission. Attention should also be paid to monitor liver function during the course of COVID-19, especially in patients with higher disease severity.

positive: What We Know So Far (As of March 26, 2020) About COVID-19 – An MRT Point of View

positive: Clinical characteristics and radiological features of children infected with the 2019 novel coronavirus AIM: To identify and summarise the common findings from 2019 novel coronavirus (2019-nCoV) infections in children. MATERIALS AND METHODS: The clinical characteristics and radiological findings (chest radiography and chest computed tomography [CT]) of nine children infected with the 2019-nCoV were reviewed in this retrospective case series. RESULTS: Among the children, six had fever (including two children with cough), one had only cough, one had a stuffy nose when initially diagnosed, and one was an asymptomatic carrier. Chest radiographs seemed mostly normal in six cases whereas increased and/or disordered bilateral bronchovascular shadows and dense hilar shadows were seen in three cases. Chest CT exhibited no obvious abnormal signs in four cases. Typical CT findings included patchy, peripheral ground-grass opacities, subpleural lamellar dense shadows, and parenchymal bands. Pleural effusions, mediastinal lymphadenopathy, cavitation, and pleural thickening were absent. CONCLUSION: The clinical manifestations and radiological findings of the 2019-nCoV-infected children were mild and lacked a typical pattern.

positive: Asymptomatic and Presymptomatic SARS-CoV-2 Infections in Residents of a Long-Term Care Skilled Nursing Facility — King County, Washington, March 2020 Older adults are susceptible to severe coronavirus disease 2019 (COVID-19) outcomes as a consequence of their age and, in some cases, underlying health conditions (1). A COVID-19 outbreak in a long-term care skilled nursing facility (SNF) in King County, Washington that was first identified on February 28, 2020, highlighted the potential for rapid spread among residents of these types of facilities (2). On March 1, a health care provider at a second long-term care skilled nursing facility (facility A) in King County, Washington, had a positive test result for SARS-CoV-2, the novel coronavirus that causes COVID-19, after working while symptomatic on February 26 and 28. By March 6, seven residents of this second facility were symptomatic and had positive test results for SARS-CoV-2. On March 13, CDC performed symptom assessments and SARS-CoV-2 testing for 76 (93%) of the 82 facility A residents to evaluate the utility of symptom screening for identification of COVID-19 in SNF residents. Residents were categorized as asymptomatic or symptomatic at the time of testing, based on the absence or presence of fever, cough, shortness of breath, or other symptoms on the day of testing or during the preceding 14 days. Among 23 (30%) residents with positive test results, 10 (43%) had symptoms on the date of testing, and 13 (57%) were asymptomatic. Seven days after testing, 10 of these 13 previously asymptomatic residents had developed symptoms and were recategorized as presymptomatic at the time of testing. The reverse transcription-polymerase chain reaction (RT-PCR) testing cycle threshold (Ct) values indicated large quantities of viral RNA in asymptomatic, presymptomatic, and symptomatic residents, suggesting the potential for transmission regardless of symptoms. Symptom-based screening in SNFs could fail to identify approximately half of residents with COVID-19. Long-term care facilities should take proactive steps to prevent introduction of SARS-CoV-2 (3). Once a confirmed case is identified in an SNF, all residents should be placed on isolation precautions if possible (3), with considerations for extended use or reuse of personal protective equipment (PPE) as needed (4).

positive: 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.

positive: Augmented Curation of Unstructured Clinical Notes from a Massive EHR System Reveals Specific Phenotypic Signature of Impending COVID-19 Diagnosis Understanding the temporal dynamics of COVID-19 patient phenotypes is necessary to derive fine-grained resolution of pathophysiology. Here we use state-of-the-art deep neural networks over an institution-wide machine intelligence platform for the augmented curation of 15.8 million clinical notes from 30,494 patients subjected to COVID-19 PCR diagnostic testing. By contrasting the Electronic Health Record (EHR)-derived clinical phenotypes of COVID-19-positive (COVIDpos, n=635) versus COVID-19-negative (COVIDneg, n=29,859) patients over each day of the week preceding the PCR testing date, we identify anosmia/dysgeusia (37.4-fold), myalgia/arthralgia (2.6-fold), diarrhea (2.2-fold), fever/chills (2.1-fold), respiratory difficulty (1.9-fold), and cough (1.8-fold) as significantly amplified in COVIDpos over COVIDneg patients. The specific combination of cough and diarrhea has a 3.2-fold amplification in COVIDpos patients during the week prior to PCR testing, and along with anosmia/dysgeusia, constitutes the earliest EHR-derived signature of COVID-19 (4-7 days prior to typical PCR testing date). This study introduces an Augmented Intelligence platform for the real-time synthesis of institutional knowledge captured in EHRs. The platform holds tremendous potential for scaling up curation throughput, with minimal need for retraining underlying neural networks, thus promising EHR-powered early diagnosis for a broad spectrum of diseases.

positive: The Clinical and Radiological Manifestations in Coronavirus Disease (COVID-19) with Negative Nucleic Acid Results BACKGROUND: COVID-19 was a new emerging disease with high infectiousness. Its diagnosis primarily depended on real time-polymerase chain reaction (RT-PCR) results. This study investigated epidemiological, clinical and radiological characteristics of COVID-19 with negative RT-PCR results before confirmation. METHODS: COVID-19 patients were enrolled and divided into two groups, negative group with negative RT-PCR results before confirmation and positive group with positive results at the first detection. Epidemiological and clinical features were compared. Dynamic chest CT images of negative group were evaluated. RESULT: Nighty-nine laboratory-confirmed COVID-19 including eight patients (8%) with negative RT-PCR results were included. Patients from negative group had similar epidemiological features as the average age (50.25±13.27 y in the negative group and 53.70±16.64 y in the positive group) and gender distribution (males made up 50% of the negative group and 62.6% of the positive group) were comparable. No significant difference of clinical symptoms were observed between the two groups. It was found that fever was the most common symptom for both groups, followed by cough, expectoration, chest distress, fatigue and gastroenterological symptoms. Moreover, ground-glass opacities and consolidations were main manifestations in chest CT of COVID-19 patients with or without confirmed RT-PCR results. CONCLUSIONS: Regardless of initial RT-PCR results, COVID-19 patients had similar epidemiological, clinical and chest CT features. Our study suggested values of early chest CT scan in COVID-19 screening and dynamic significance of radiology in disease monitoring to guide clinical decision.

positive: SARS-CoV-2 (COVID-19) and Chronic Myeloid Leukemia (CML): a Case Report and Review of ABL Kinase Involvement in Viral Infection

positive: Infants Born to Mothers With a New Coronavirus (COVID-19) A novel viral respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for an epidemic of the coronavirus disease 2019 (COVID-19) in cases in China and worldwide. Four full-term, singleton infants were born to pregnant women who tested positive for COVID-19 in the city of Wuhan, the capital of Hubei province, China, where the disease was first identified. Of the three infants, for who consent to be diagnostically tested was provided, none tested positive for the virus. None of the infants developed serious clinical symptoms such as fever, cough, diarrhea, or abnormal radiologic or hematologic evidence, and all four infants were alive at the time of hospital discharge. Two infants had rashes of unknown etiology at birth, and one had facial ulcerations. One infant had tachypnea and was supported by non-invasive mechanical ventilation for 3 days. One had rashes at birth but was discharged without parental consent for a diagnostic test. This case report describes the clinical course of four live born infants, born to pregnant women with the COVID-19 infection.

positive: COVID-19 in a Designated Infectious Diseases HospitalOutside Hubei Province,China Background A new type of novel coronavirus infection (COVID-19) occurred in Wuhan, Hubei Province. Previous investigations reported patients in Wuhan city often progressed into severe or critical and had a high mortality rate.The clinical characteristics of affected patients outside the epicenter of Hubei province are less well understood. Methods All confirmed COVID-19 case treated in the Third People's Hospital of Shenzhen,from January 11, 2020 to February 6, 2020, were included in this study. We analyzed the epidemiological and clinical features of these cases to better inform patient management in normal hospital settings. Results Among the 298 confirmed cases, 233(81.5%) had been to Hubei while 42(14%) had not clear epidemiological history. Only 192(64%) cases presented with fever as initial symptom. The lymphocyte count decreased in 38% patients after admission. The number (percent) of cases classified as non-severe and severe was 240(80.6%) and 58(19.4%) respectively. Thirty-two patients (10.7%) needed ICU care. Compared to the non-severe cases, severe cases were associated with older age, underlying diseases, as well as higher levels of CRP, IL-6 and ESR. The median (IRQ) duration of positive viral test were 14(10-19). Slower clearance of virus was associated with higher risk of progression to severe clinical condition. As of February 14, 2020, 66(22.1%) patients were discharged and the overall mortality rate remains 0. Conclusions In a designated hospital outside the Hubei Province, COVID-19 patients were mainly characterized by mild symptoms and could be effectively manage by properly using the existing hospital system.

positive: Clinical characteristics of a case series of children with coronavirus disease 2019 We reported the clinical characteristics of a case series of 10 patients with coronavirus disease 2019 (COVID-19) aged from 1 year to 18 years. Seven patients had contact with confirmed COVID-19 family members before onset. Fever (4 [40.0%]) and cough (3 [30.0%]) were the most common symptoms. No patient showed leucopenia and lymphopenia on admission. Pneumonia was observed in chest CT images in 5 (50.0%) patients. Five (50.0%) patients received antiviral treatment. No patient had severe complications or developed a severe illness in our study. Our study indicated that COVID-19 children present less severe symptoms and have better outcomes.

positive: Novel coronavirus infection in children outside of Wuhan, China BACKGROUND: Since December 8, 2019, an epidemic of coronavirus disease 2019 (COVID-19) has spread rapidly, but information about children with COVID-19 is limited. METHODS: This retrospective and the single-center study were done at the Public Health Clinic Center of Changsha, Hunan, China. We identified all hospitalized children diagnosed with COVID-19 between January 8, 2019 and February 19, 2020, in Changsha. Epidemiological and clinical data of these children were collected and analyzed. Outcomes were followed until February 26th, 2020. RESULTS: By February 19, 2020, nine pediatric patients were identified as having 2019-nCoV infection in Changsha. Six children had a family exposure and could provide the exact dates of close contact with someone who was confirmed to have 2019-nCoV infection, among whom the median incubation period was 7.5 days. The initial symptoms of the nine children were mild, including fever (3/9), diarrhea (2/9), cough (1/9), and sore throat (1/9), two had no symptoms. Two of the enrolled patients showed small ground-glass opacity of chest computed tomography scan. As of February 26, six patients had a negative RT-PCR for 2019-nCoV and were discharged. The median time from exposure to a negative RT-PCR was 14 days. CONCLUSIONS: The clinical symptoms of the new coronavirus infection in children were not typical and showed a less aggressive clinical course than teenage and adult patients. Children who have a familial clustering or have a family member with a definite diagnosis should be reported to ensure a timely diagnosis.

positive: SARS-CoV-2 Infection Leads to Neurological Dysfunction A number of neurological disease complications have been seen following infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While most person with COVID-19 respiratory disease demonstrate headache, nausea and vomiting, up to 40% present also experience dizziness, confusion, cerebrovascular disease, muscle pain, ataxia and seizures. Loss of taste and smell, defects in visual acuity and pain occur in parallel. Such central nervous system (CNS) signs and symptoms linked to laboratory-confirmed SARS-CoV-2 infection is often life threatening. Health care providers currently evaluating patients with neurologic symptoms need consider COVID-19 in any differential diagnosis. These considerations will facilitate prompt testing, isolation and prevention of viral transmission speeding best clinical outcomes. [Figure: see text]

positive: COVID-19 in otolaryngologist practice: a review of current knowledge PURPOSE: Otorhinolaryngological manifestations are common symptoms of COVID-19. This study provides a brief and precise review of the current knowledge regarding COVID-19, including disease transmission, clinical characteristics, diagnosis, and potential treatment. The article focused on COVID-19-related information useful in otolaryngologist practice. METHODS: The Medline and Web of Science databases were searched without a time limit using terms “COVID-19”, “SARS-CoV-2” in conjunction with “otorhinolaryngological manifestation”, “ENT”, and “olfaction”. RESULTS: The most common otolaryngological dysfunctions of COVID-19 were cough, sore throat, and dyspnea. Rhinorrhea, nasal congestion and dizziness were also present. COVID-19 could manifest as an isolated sudden hyposmia/anosmia. Upper respiratory tract (URT) symptoms were commonly observed in younger patients and usually appeared initially. They could be present even before the molecular confirmation of SARS-CoV-2. Otolaryngologists are of great risk of becoming infected with SARS-CoV-2 as they cope with URT. ENT surgeons could be easily infected by SARS-CoV-2 during performing surgery in COVID-19 patients. CONCLUSION: Ear, nose and throat (ENT) symptoms may precede the development of severe COVID-19. During COVID-19 pandemic, patients with cough, sore throat, dyspnea, hyposmia/anosmia and a history of travel to the region with confirmed COVID-19 patients, should be considered as potential COVID-19 cases. An otolaryngologist should wear FFP3/N95 mask, glasses, disposable and fluid resistant gloves and gown while examining such individuals. Not urgent ENT surgeries should be postponed. Additional studies analyzing why some patients develop ENT symptoms during COVID-19 and others do not are needed. Further research is needed to determine the mechanism leading to anosmia.

positive: Consensus study of risk factors and symptoms of SARS-CoV-2 (COVID-19) using biomedical literature and social media data Background In December 2019, Coronavirus disease 2019 (COVID-19) outbreak started in China and rapidly spread around the world. Lack of any vaccine or optimized intervention raised the importance of characterizing risk factors and symptoms for the early identification and successful treatment of COVID-19 patients. Methods We systematically integrated and analyzed published biomedical literature and public social media data to expand our landscape of clinical and demographic variables of COVID-19. Through semantic analysis, 45 retrospective cohort studies, which evaluated 303 clinical and demographic variables across 13 different outcomes of COVID-19, and 84,140 tweet posts from 1,036 COVID-19 positive users were collected. In total, 59 symptoms were identified across both datasets. Findings Approximately 90% of clinical and demographic variables showed inconsistency across outcomes of COVID-19. From the consensus analysis, we identified clinical and demographic variables that were specific for individual outcomes of COVID-19. Also, 25 novel symptoms that have been not previously well characterized, but were mentioned in social media. Furthermore, we observed that there were certain combinations of symptoms that were frequently mentioned together among COVID-19 patients. Interpretation Identified outcome-specific clinical and demographic variables, symptoms, and combinations of symptoms may serve as surrogate indicators to identify COVID-19 patients and predict their clinical outcomes providing appropriate treatments.

positive: Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: a retrospective case series study OBJECTIVE: To study the neurological manifestations of patients with coronavirus disease 2019 (COVID-19). DESIGN: Retrospective case series SETTING: Three designated COVID-19 care hospitals of the Union Hospital of Huazhong University of Science and Technology in Wuhan, China. PARTICIPANTS: Two hundred fourteen hospitalized patients with laboratory confirmed diagnosis of severe acute respiratory syndrome from coronavirus 2 (SARS-CoV-2) infection. Data were collected from 16 January 2020 to 19 February 2020. MAIN OUTCOME MEASURES: Clinical data were extracted from electronic medical records and reviewed by a trained team of physicians. Neurological symptoms fall into three categories: central nervous system (CNS) symptoms or diseases (headache, dizziness, impaired consciousness, ataxia, acute cerebrovascular disease, and epilepsy), peripheral nervous system (PNS) symptoms (hypogeusia, hyposmia, hypopsia, and neuralgia), and skeletal muscular symptoms. Data of all neurological symptoms were checked by two trained neurologists. RESULTS: Of 214 patients studied, 88 (41.1%) were severe and 126 (58.9%) were non-severe patients. Compared with non-severe patients, severe patients were older (58.7 ± 15.0 years vs 48.9 ± 14.7 years), had more underlying disorders (42 [47.7%] vs 41 [32.5%]), especially hypertension (32 [36.4%] vs 19 [15.1%]), and showed less typical symptoms such as fever (40 [45.5%] vs 92 [73%]) and cough (30 [34.1%] vs 77 [61.1%]). Seventy-eight (36.4%) patients had neurologic manifestations. More severe patients were likely to have neurologic symptoms (40 [45.5%] vs 38 [30.2%]), such as acute cerebrovascular diseases (5 [5.7%] vs 1 [0.8%]), impaired consciousness (13 [14.8%] vs 3 [2.4%]) and skeletal muscle injury (17 [19.3%] vs 6 [4.8%]). CONCLUSION: Compared with non-severe patients with COVID-19, severe patients commonly had neurologic symptoms manifested as acute cerebrovascular diseases, consciousness impairment and skeletal muscle symptoms.

positive: Classification of the cutaneous manifestations of COVID‐19: a rapid prospective nationwide consensus study in Spain with 375 cases BACKGROUND: Cutaneous manifestations of COVID‐19 disease are poorly characterized. OBJECTIVES: To describe the cutaneous manifestations of COVID‐19 disease and to relate them to other clinical findings METHODS: Nationwide case collection survey of images and clinical data. Using a consensus, we described 5 clinical patterns. We later described the association of these patterns with patient demographics, timing in relation to symptoms of the disease, severity, and prognosis. RESULTS: Lesions may be classified as acral areas of erythema with vesicles or pustules (Pseudo‐chilblain) (19%), other vesicular eruptions (9%), urticarial lesions (19%), maculopapular eruptions (47%) and livedo or necrosis (6%). Vesicular eruptions appear early in the course of the disease (15% before other symptoms). The pseudo‐chilblain pattern frequently appears late in the evolution of the COVID‐19 disease (59% after other symptoms), while the rest tend to appear with other symptoms of COVID‐19. Severity of COVID‐19 shows a gradient from less severe disease in acral lesions to most severe in the latter groups. Results are similar for confirmed and suspected cases, both in terms of clinical and epidemiological findings. Alternative diagnoses are discussed but seem unlikely for the most specific patterns (pseudo‐chilblain and vesicular). CONCLUSIONS: We provide a description of the cutaneous manifestations associated with COVID‐19 infection. These may help clinicians approach patients with the disease and recognize paucisymptomatic cases.

positive: A Unique Presentation of Delirium in a Patient with Otherwise Asymptomatic COVID‐19 OBJECTIVE: Infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), which causes coronavirus disease 2019 (COVID‐19), manifests with a wide spectrum of presentations. Most reports of COVID‐19 highlight fever and upper respiratory symptoms as the dominant initial presentations, consistent with the World Health Organization guidelines regarding suspected SARS‐CoV‐2 infection. However, atypical presentations of this disease have been evolving since the initial outbreak of the pandemic in December 2019. We report a case of an older male patient who presented at our hospital with an unusual manifestation of COVID‐19. DESIGN: Brief report. SETTING: A university hospital in Saudi Arabia. PARTICIPANT: A 73‐year‐old man who presented with confusion in the absence of any respiratory symptoms or fever. INTERVENTION: The patient was initially admitted with delirium and underwent a further work‐up. MEASUREMENTS: Given his recent history of domestic travel and the declaration of a global COVID‐19 pandemic status, the patient was administered a swab test for SARS‐CoV‐2. RESULTS: The patient's positive test led to a diagnosis of COVID‐19. Although he began to experience a spiking fever and mild upper respiratory symptoms, he recovered rapidly with no residual sequela. CONCLUSION: The recognition of atypical presentations of COVID‐19 infection, such as delirium, is critical to the timely diagnosis, provision of appropriate care, and avoidance of outbreaks within healthcare facilities during this pandemic.

positive: Optimizing diagnostic strategy for novel coronavirus pneumonia, a multi-center study in Eastern China COVID-19 caused by a novel coronavirus SARS-CoV-2 emerged in Wuhan, Hubei province since December 2019, and caused a rapid outbreak throughout China and globally. Cities outside Hubei are also facing great challenge and require implementing of effective and feasible strategy in precision diagnosing novel coronavirus pneumonia (NCP). We described a multicenter prospective study on diagnostic strategy of suspected NCP patients from January 22nd to February 9th, 2020 in Eastern China cities. Nasopharyngeal swabs were collected from the patients. The epidemiological characteristics, clinical symptoms, laboratory assessments, and computed tomographic (CT) scans were obtained. Pathogen screen were performed including RT-PCR, multiplex PCR, rapid flu antigen tests and mNGS. We enrolled 53 suspected NCP patients, among whom 20 were laboratory-confirmed. Fourteen (70%) and 3 (15%) patients were positive for the first and second SARS-CoV-2 RT-PCR test, respectively. All NCP patients were positive for mNGS. Chest CT images and the symptoms of early stage NCP patients were similar to other viral pneumonia patients. We identified 11 of 20 co-infections in NCP cases, including regular respiratory virus, fungi and bacteria synchronously. Genomic analysis showed that 8 of 10 cases had no mutation in virus genome, while 2 cases had only one single mutation in N gene. Our study discovered that a combination of chest CT, SARS-CoV-2 RT-PCR and multi-plex PCR is recommended in regions outside Hubei province. Co-infection of other pathogens with SARS-CoV-2 exists and should be acknowledged. Repeated sampling, change of specimen type or metagenomics sequencing could further facilitate during critical clinical cases.

positive: COVID-19 versus non-COVID-19 pneumonia: A retrospective cohort study Background and Objective: Since the outbreak of coronavirus disease 2019 (COVID-19) in December 2019 in Wuhan, Hubei Province, China, it has spread around the world and become a global public health emergency. It is important to distinguish COVID-19 from other viral pneumonias in order to properly screen and diagnose patients, reduce nosocomial infections, and complement the inadequacy of nucleic acid testing. In this study, we retrospectively analysed the clinical data of COVID-19 versus non-COVID-19 patients treated at our hospital between January 17 and February 27, 2020 in order to summarize our clinical experience in the differential diagnosis of COVID-19. Methods: In this retrospective cohort study, 23 confirmed COVID-19 patients were consecutively enrolled from January 17 to February 27, 2020, while 29 confirmed non-COVID-19 patients were enrolled in West China Hospital of Sichuan University. We collected baseline data, epidemiological data, clinical characteristics, imaging findings, viral nucleic acid test results, and survival data. SPSS v22.0 was used for statistical analysis. Outcomes were followed up until March 25. Results: A total of 52 patients were included in this study, including 23 COVID-19 patients and 29 non-COVID-19 patients. No significant between-group difference was observed in age, sex, primary signs or symptoms, cellular immunity, or platelet count. Significant between-group differences were observed in clinical characteristics such as dry cough, contact with individuals from Wuhan, some underlying diseases, nucleated cell count, chest imaging findings, viral nucleic acid test result,28-day mortality, and 28-day survival. Conclusion: Epidemiological data, clinical symptoms, nucleic acid test results for COVID-19 and chest CT manifestation may help distinguish COVID-19 from non-COVID-19 cases, prevent imported cases and nosocomial infections.

positive: 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.

positive: Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China Previous studies have showed clinical characteristics of patients with the 2019 novel coronavirus disease (COVID-19) and the evidence of person-to-person transmission. Limited data are available for asymptomatic infections. This study aims to present the clinical characteristics of 24 cases with asymptomatic infection screened from close contacts and to show the transmission potential of asymptomatic COVID-19 virus carriers. Epidemiological investigations were conducted among all close contacts of COVID-19 patients (or suspected patients) in Nanjing, Jiangsu Province, China, from Jan 28 to Feb 9, 2020, both in clinic and in community. Asymptomatic carriers were laboratory-confirmed positive for the COVID-19 virus by testing the nucleic acid of the pharyngeal swab samples. Their clinical records, laboratory assessments, and chest CT scans were reviewed. As a result, none of the 24 asymptomatic cases presented any obvious symptoms while nucleic acid screening. Five cases (20.8%) developed symptoms (fever, cough, fatigue, etc.) during hospitalization. Twelve (50.0%) cases showed typical CT images of ground-glass chest and 5 (20.8%) presented stripe shadowing in the lungs. The remaining 7 (29.2%) cases showed normal CT image and had no symptoms during hospitalization. These 7 cases were younger (median age: 14.0 years; P=0.012) than the rest. None of the 24 cases developed severe COVID-19 pneumonia or died. The median communicable period, defined as the interval from the first day of positive nucleic acid tests to the first day of continuous negative tests, was 9.5 days (up to 21 days among the 24 asymptomatic cases). Through epidemiological investigation, we observed a typical asymptomatic transmission to the cohabiting family members, which even caused severe COVID-19 pneumonia. Overall, the asymptomatic carriers identified from close contacts were prone to be mildly ill during hospitalization. However, the communicable period could be up to three weeks and the communicated patients could develop severe illness. These results highlighted the importance of close contact tracing and longitudinally surveillance via virus nucleic acid tests. Further isolation recommendation and continuous nucleic acid tests may also be recommended to the patients discharged.

positive: Self-reported COVID-19 symptoms on Twitter: An analysis and a research resource Objective To mine Twitter to quantitatively analyze COVID-19 symptoms self-reported by users, compare symptom distributions against clinical studies, and create a symptom lexicon for the research community. Materials and methods We retrieved tweets using COVID-19-related keywords, and performed several layers of semi-automatic filtering to curate self-reports of positive-tested users. We extracted COVID-19-related symptoms mentioned by the users, mapped them to standard IDs, and compared the distributions with multiple studies conducted in clinical settings. Results We identified 203 positive-tested users who reported 932 symptoms using 598 unique expressions. The most frequently-reported symptoms were fever/pyrexia (65%), cough (56%), body aches/pain (40%), headache (35%), fatigue (35%), and dyspnea (34%) amongst users who reported at least 1 symptom. Mild symptoms, such as anosmia (26%) and ageusia (24%) were frequently reported on Twitter, but not in clinical studies. Conclusion The spectrum of COVID-19 symptoms identified from Twitter may complement those identified in clinical settings.

positive: Digestive Manifestations in Patients Hospitalized with COVID-19 Background: The prevalence and significance of digestive manifestations in COVID-19 remain uncertain. Methods: Consecutive patients hospitalized with COVID-19 were identified across a geographically diverse alliance of medical centers in North America. Data pertaining to baseline characteristics, symptomatology, laboratory assessment, imaging, and endoscopic findings from the time of symptom onset until discharge or death were manually abstracted from electronic health records to characterize the prevalence, spectrum, and severity of digestive manifestations. Regression analyses were performed to evaluate the association between digestive manifestations and severe outcomes related to COVID-19. Results: A total of 1992 patients across 36 centers met eligibility criteria and were included. Overall, 53% of patients experienced at least one gastrointestinal symptom at any time during their illness, most commonly diarrhea (34%), nausea (27%), vomiting (16%), and abdominal pain (11%). In 74% of cases, gastrointestinal symptoms were judged to be mild. In total, 35% of patients developed an abnormal alanine aminotransferase or total bilirubin level; these were elevated to less than 5 times the upper limit of normal in 77% of cases. After adjusting for potential confounders, the presence of gastrointestinal symptoms at any time (odds ratio 0.93, 95% confidence interval 0.76-1.15) or liver test abnormalities on admission (odds ratio 1.31, 95% confidence interval 0.80-2.12) were not independently associated with mechanical ventilation or death. Conclusions: Among patients hospitalized with COVID-19, gastrointestinal symptoms and liver test abnormalities were common but the majority were mild and their presence was not associated with a more severe clinical course.

positive: Screening and managing of suspected or confirmed novel coronavirus (COVID-19) patients: experiences from a tertiary hospital outside Hubei province Objectives: To report our experiences screening and managing patients with suspected or confirmed novel coronavirus (COVID-19) disease using a hospital-specific protocol. Design: Longitudinal cohort study. Setting: A 1,200 bed tertiary care teaching hospital in Chengdu, Sichuan, China. Participants: 802 adults presenting to hospital with concerns of having COVID-19, 1,246 inpatients and 2,531 hospital visitors. Interventions: Screening and management of patients using a hospital-specific protocol, which included fever triage, monitoring visitors and patients, emergency response, personnel training for healthcare team members, health education for patients and family, medical materials management, disinfection and wastes disposal protocols. Results: Between 23 January and 28 February 2020, 73 people were identified as having fever plus respiratory signs with/without a history of exposure and were tested for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by our hospital lab using RT PCR. Forty-five of these 73 people were subsequently excluded based on one negative RT PCR result plus positive results to quick screening tests for flu or other respiratory viruses. The remaining 28 people received a second RT PCR test 24 h later. Three people were confirmed positive for COVID-19 based on two consecutive positive RT PCR tests whilst 25 people were excluded based on two consecutive negative tests. The three COVID-19 confirmed cases received non-critical care. There were no new infections of medical staff or new infections of other hospital inpatients. Conclusions: All three cases were detected as a result of vigilant monitoring of hospital visitors. Whilst screening out-patients presenting to a fever clinic remains important, monitoring visitors must not be overlooked.

positive: Clinical Characteristics and Differential Clinical Diagnosis of Novel Coronavirus Disease 2019 (COVID-19) Novel Coronavirus Disease (COVID-19) has become a rapidly growing pandemic involving several nations. It is of serious concern and extreme challenge not only to the health personnel but also to the countries for containment. The causative organism is SARS-CoV-2, RNA virus of subgenus Sarbecovirus, similar to the SARS virus, and seventh member of the human coronavirus family responsible for this zoonotic infection. It binds to the human angiotensin converting enzyme (hACE-2) receptor and causes constitutional and respiratory symptoms. The major mode of transmission is human to human and the median incubation period is 4 days. The most common symptom as studied from various cohorts of COVID-19 patients are fever (83–98%) followed by fatigue (70%) and dry cough (59%); gastrointestinal symptoms are relatively uncommon differentiating it from SARS and MERS. Most of the SAR-CoV-2 infection are mild (80%) with a usual recovery period of 2 weeks. COVID-19 commonly affects males in the middle age and elderly age group, with highest case fatality (8–15%) among those aged >80 years. The disease begins with fever, dry cough, fatigue and myalgia progressing to dyspnoea and ARDS over 6 and 8 days post exposure, respectively. Underlying co-morbidities increase mortality in COVID-19. Poor prognostic factors are elderly, co-morbidities, severe lymphopaenia, high CRP and D-dimer >1 μg/L. The overall mortality rate ranges from 1.5 to 3.6%. COVID-19 has to be differentiated from other viral and bacterial pneumonias as they are more common among healthy adults. Despite constant and vigorous efforts by researchers and health agencies, we are far from containment, cure or prevention by vaccine; hence right information and stringent prevention and control measures are the only weapon in the armoury to combat the ongoing infection.

positive: Clinical characteristics of 225 patients with COVID-19 in a tertiary Hospital near Wuhan, China Abstract Background The 2019 coronavirus disease (COVID-19) was first identified in Wuhan, Hubei, China in December 2019, caused by a novel coronavirus (SARS-CoV-2). There is a need to study the clinical features of patients in a hospital near Wuhan. Objective To identify clinical features of patients with COVID-19 in a tertiary hospital near Wuhan. Study design General information, clinical manifestations, laboratory data, and computed tomography (CT) data were collected for 225 patients diagnosed of COVID-19 admitted between January 20 and February 14, 2020, to the Hanchuan City People’s Hospital. Results The patients included 120 male and 105 females who had no connection to the Wuhan Huanan Seafood Market. Their average age was 50 ± 14 years. The major clinical symptoms were fever (84.44% of patients), cough (56.44% of patients), and dyspnea (4.00% of patients); 3.56%–22.67% of subjects suffered from expectoration, fatigue, chills, headache, chest pain, and pharyngalgia. Hypertension was present in 20.89% of patients. The counts of white blood cells (WBCs) and lymphocytes were normal or decreased in 86.67% and 99.11% of patients. CRP was increased in 86.22% of patients, PCT in 10.67%, and ESR in 90.22%. CT showed that 86.22% of patients had multiple patchy glassy shadows in both lungs, particularly in the peripheral area. Thirty-seven (16.44%) patients were diagnosed with severe COVID-19. Methylprednisolone was administered in 44.44% of cases. The mortality among the patients was 0.89%. Conclusions Clinical characteristics of COVID-19 patients in the tertiary hospital near Wuhan are very similar to those found in Wuhan, but the lower mortality.

positive: Rhabdomyolysis as a Presentation of 2019 Novel Coronavirus Disease An emerging viral infection is a global public health challenge. The development of modern, fast, and extensive transportation makes the outbreak hard to contain. Everyone is at risk, and the outbreak can rapidly turn into a pandemic crisis, like what we are currently facing for the 2019 novel coronavirus disease (COVID-19). Prompt diagnosis of the case is required to improve patients’ prognosis and control of the outbreak. The common manifestations of COVID-19 include fever, cough, dyspnea, and malaise. However, patients may present with atypical symptoms that pose a diagnostic challenge. We report the first case of an elderly male who presented with rhabdomyolysis and later was diagnosed with COVID-19. Clinicians should be aware that rhabdomyolysis can be an initial presentation of COVID-19 or can occur at any time during the disease course. Patients with rhabdomyolysis should receive aggressive fluid administration to prevent acute kidney injury (AKI). However, COVID-19 patients are at risk of worsening oxygenation and acute hypoxemic respiratory failure from fluid overload. Therefore, cautious fluid administration is needed in COVID-19 patients with rhabdomyolysis.

positive: A Diabetic Patient With 2019-nCoV (COVID-19) Infection Who Recovered and Was Discharged From Hospital Novel coronavirus has become a global health hazard and its high infectivity is alarming. The imaging findings of the 2019-nCoV infection in our young diabetic patient featured ground-glass opacities and consolidations in both lungs. The lung lesions may involute rapidly during the course. The patient showed improvement both clinically and on computed tomography imaging at discharged after 2 weeks’ treatment. Computed tomography scans of patients helped monitor the changes continuously, which could timely provide the information of the evolution of the disease or therapeutic effect to clinicians.

positive: COVID-19 and the Digestive System. The outbreak of novel coronavirus pneumonia in 2019 (Coronavirus disease 2019 [COVID-19]) is now threatening global public health. Although COVID-19 is principally defined by its respiratory symptoms, it is now clear that the virus can also affect the digestive system. In this review, we elaborate on the close relationship between COVID-19 and the digestive system, focusing on both the clinical findings and potential underlying mechanisms of COVID-19 gastrointestinal pathogenesis.

positive: The Ocular Manifestations and Transmission of COVID-19: Recommendations for Prevention BACKGROUND: Coronavirus disease-2019 (COVID-19), caused by a novel coronavirus termed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has been linked to ocular signs and symptoms in several case reports. Research has demonstrated that SARS-CoV-2 is spread primarily through close contact via respiratory droplets, but there is the possibility for ocular transmission, with the conjunctiva as a conduit as well as a source of infection. DISCUSSION: Ocular manifestations of SARS-CoV-2 include follicular conjunctivitis, and have been repeatedly noted as an initial or subsequent symptom of COVID-19-positive patients. Particularly in patients with ocular manifestations, there is evidence that the virus may present in tears, based on the detection of SARS-CoV-2 in conjunctival swab samples via reverse transcription polymerase chain reaction. The virus may therefore be transmittable from the ocular surface to a new host via contact with the ocular mucosa, tears, or subsequent fomites. CONCLUSIONS: All health care professionals should ask patients about ocular symptoms consistent with SARS-CoV-2, and use eye protection such as goggles or face shields as part of the standard personal protective equipment for high-risk patients in addition to wearing of masks by both the patient and provider, and should consider tears to be potentially infectious.

positive: Comparison of clinical characteristics of coronavirus disease (COVID-19) and severe acute respiratory syndrome (SARS) as experienced in Taiwan • From our data, we know 2019-nCoV invades more common in male, not likely the SARS that is female predominant. • The 2019-nCoV patients are around 20 years older than the population of SARS. Young adults are susceptible to SARS than the children and elderly. • Hypoalbuminemia are noted in SARS patients, it needs a longer time to study whether the 2019-nCoV possesses the same presentation.

positive: Don't Overlook Digestive Symptoms in Patients With 2019 Novel Coronavirus Disease (COVID-19)

positive: Eleven faces of coronavirus disease 2019 BACKGROUND AND AIMS: The outbreak of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has recently spread worldwide and been declared a pandemic. We aim to describe here the various clinical presentations of this disease by examining eleven cases. METHODS: Electronic medical records of 11 patients with COVID‐19 were collected, and demographics, clinical manifestations, outcomes, key laboratory results, and radiological images are discussed. RESULTS: The clinical course of the eleven cases demonstrated the complexity of the COVID‐19 profile with different clinical presentations. Clinical manifestations range from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Laboratory detection of the viral nucleic acid can yield false‐negative results, and serological testing of virus‐specific IgG and IgM antibodies should be used as an alternative for diagnosis. Patients with common allergic diseases did not develop distinct symptoms and severe courses. Cases with a pre‐existing condition of chronic obstructive pulmonary disease or complicated with a secondary bacterial pneumonia were more severe. CONCLUSION: All different clinical characteristics of COVID‐19 should be taken into consideration to identify patients that need to be in strict quarantine for the efficient containment of the pandemic.

positive: Ophthalmologists’ strategy for the prevention and control of coronavirus pneumonia with conjunctivitis or with conjunctivitis as the first symptom/ 伴发或首发病毒性结膜炎的新型冠状病毒感染下眼科医师的防控策略 China is currently in a critical stage of controlling the outbreak of novel coronavirus pneumonia (COVID-19). As ophthalmologists working in the center of Wuhan city, the virus’s front line, we recently found conjunctivitis in five COVID-19 patients of a total of 92 COVID-19 patients.One of these five patients had conjunctivitis as the first symptom and was then diagnosed with COVID-19.These observations suggest: the mechanism and pathway of transmission of the novel coronavirus need to be further clarified; the symptoms of conjunctivitis accompanying novel coronavirus infection and conjunctiva as an important entrance point of the virus need to be further verified; early diagnosis, implementation of medical isolation, and giving appropriate treatment to patients with asymptomatic and mild-symptom conjunctivitis are essential to prevent the spread of the epidemic; those with conjunctivitis symptoms should be distinguished from other types of viral conjunctivitis; strict personal protection measures should be taken; and more sensitive techniques should be developed as soon as possible for virus detection in tear and conjunctiva swabs.

positive: Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series OBJECTIVE: To study the clinical characteristics of patients in Zhejiang province, China, infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) responsible for coronavirus disease 2019 (covid-2019) , DESIGN: Retrospective case series , SETTING: Seven hospitals in Zhejiang province, China , PARTICIPANTS: 62 patients admitted to hospital with laboratory confirmed SARS-Cov-2 infection Data were collected from 10 January 2020 to 26 January 2020 , MAIN OUTCOME MEASURES: Clinical data, collected using a standardised case report form, such as temperature, history of exposure, incubation period If information was not clear, the working group in Hangzhou contacted the doctor responsible for treating the patient for clarification , RESULTS: Of the 62 patients studied (median age 41 years), only one was admitted to an intensive care unit, and no patients died during the study According to research, none of the infected patients in Zhejiang province were ever exposed to the Huanan seafood market, the original source of the virus;all studied cases were infected by human to human transmission The most common symptoms at onset of illness were fever in 48 (77%) patients, cough in 50 (81%), expectoration in 35 (56%), headache in 21 (34%), myalgia or fatigue in 32 (52%), diarrhoea in 3 (8%), and haemoptysis in 2 (3%) Only two patients (3%) developed shortness of breath on admission The median time from exposure to onset of illness was 4 days (interquartile range 3-5 days), and from onset of symptoms to first hospital admission was 2 (1-4) days , CONCLUSION: As of early February 2020, compared with patients initially infected with SARS-Cov-2 in Wuhan, the symptoms of patients in Zhejiang province are relatively mild , (C) 2020 BMJ Publishing Group Ltd

positive: Estimated effectiveness of symptom and risk screening to prevent the spread of COVID-19 Traveller screening is being used to limit further spread of COVID-19 following its recent emergence, and symptom screening has become a ubiquitous tool in the global response. Previously, we developed a mathematical model to understand factors governing the effectiveness of traveller screening to prevent spread of emerging pathogens (Gostic et al., 2015). Here, we estimate the impact of different screening programs given current knowledge of key COVID-19 life history and epidemiological parameters. Even under best-case assumptions, we estimate that screening will miss more than half of infected people. Breaking down the factors leading to screening successes and failures, we find that most cases missed by screening are fundamentally undetectable, because they have not yet developed symptoms and are unaware they were exposed. Our work underscores the need for measures to limit transmission by individuals who become ill after being missed by a screening program. These findings can support evidence-based policy to combat the spread of COVID-19, and prospective planning to mitigate future emerging pathogens.

positive: Chest CT findings and clinical features of coronavirus disease 2019 in children. OBJECTIVES To describe the CT features and clinical characteristics of pediatric patients with coronavirus disease 2019 (COVID-19). METHODS A total of 9 COVID-19 infected pediatric patients were included in this study. Clinical history, laboratory examination, and detailed CT imaging features were analyzed. All patients underwent the first CT scanning on the same day of being diagnosed by real-time reverse-transcription polymerase chain reaction (rRT-PCR). A low-dose CT scan was performed during follow-up. RESULTS All the child patients had positive results. Four patients had cough and one patient had fever. One patient presented both cough and fever. Two children presented other symptoms like sore throat and stuffy nose. One child showed no clinical symptom. Five patients had positive initial CT findings with subtle lesions like ground-glass opacity (GGO) or spot-like mixed consolidation. Three patients were reported with negative results in the initial and follow-up CT examination. One patient was reported with initial negative CT findings but turning positive during the first follow-up. All patients had absorbed lesions on follow-up CT images after treatment. CONCLUSIONS Pediatric COVID-19 patients have certain imaging and clinical features as well as disease prognosis. Children with COVID-19 tend to have normal or subtle CT findings and relatively better outcome.

positive: Clinical Characteristics of 24 Asymptomatic Infections with COVID-19 Screened among Close Contacts in Nanjing, China Background: Previous studies have showed clinical characteristics of patients with the 2019 novel coronavirus disease (COVID-19) and the evidence of person-to-person transmission. Limited data are available for asymptomatic infections. This study aims to present the clinical characteristics of 24 cases with asymptomatic infection screened from close contacts and to show the transmission potential of asymptomatic COVID-19 virus carriers. Methods: Epidemiological investigations were conducted among all close contacts of COVID-19 patients (or suspected patients) in Nanjing, Jiangsu Province, China, from Jan 28 to Feb 9, 2020, both in clinic and in community. Asymptomatic carriers were laboratory-confirmed positive for the COVID-19 virus by testing the nucleic acid of the pharyngeal swab samples. Their clinical records, laboratory assessments, and chest CT scans were reviewed. Findings: None of the 24 asymptomatic cases presented any obvious symptoms before nucleic acid screening. Five cases (20.8%) developed symptoms (fever, cough, fatigue and etc.) during hospitalization. Twelve (50.0%) cases showed typical CT images of ground-glass chest and five (20.8%) presented stripe shadowing in the lungs. The remaining seven (29.2%) cases showed normal CT image and had no symptoms during hospitalization. These seven cases were younger (median age: 14.0 years; P = 0.012) than the rest. None of the 24 cases developed severe COVID-19 pneumonia or died. The median communicable period, defined as the interval from the first day of positive nucleic acid tests to the first day of continuous negative tests, was 9.5 days (up to 21 days among the 24 asymptomatic cases). Through epidemiological investigation, we observed a typical asymptomatic transmission to the cohabiting family members, which even caused severe COVID-19 pneumonia. Interpretation: The asymptomatic carriers identified from close contacts were prone to be mildly ill during hospitalization. However, the communicable period could be up to three weeks and the communicated patients could develop severe illness. These results highlighted the importance of close contact tracing and longitudinally surveillance via virus nucleic acid tests. Further isolation recommendation and continuous nucleic acid tests may also be recommended to the patients discharged.

positive: Manifestations of Digestive system in hospitalized patients with novel coronavirus pneumonia in Wuhan, China: a single-center, descriptive study/ 中华消化杂志 Objective@#To study the manifestations of digestive system of hospitalized patients with novel coronavirus pneumonia (NCP) in Wuhan, China, and to provide reference for disease control and treatment.@*Methods@#The data of hospitalized patients with NCP in the Sino-French Branch of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology was retrospectively analyzed, which included general information, nucleic acid test, severity degree of disease, incubation period, initial symptoms and manifestations of digestive system. The general information, positive rate of nucleic acid detection, and manifestations of digestive system were compared between critical patients who required non-invasive or invasive assisted ventilation (critical group) and non-critical patients without assisted ventilation (non-critical group). Continuous corrected chi-square test and independent sample median test were performed for statistical analysis.@*Results@#Among the 305 patients there were 146 males (47.9%) and 159 females (52.1%), median age 57 years old. Nucleic acid assay of nasopharynx swab or pharynx swab of 84.1% (228/271) patients were positive. Forty-six patients (15.1%) were in critical group and 259 patients (84.9%) were in non-critical group. The incubation period was one to fifteen days, and the median period was six days. The initial symptoms mainly were fever (81.1%, 163/201), cough (39.3%, 79/201), fatigue (54.7%, 110/201), and loss of appetite (50.2%, 101/201). In one to ten days after the disease onset, 79.1% (159/201) of patients developed gastrointestinal symptoms including nausea (29.4%, 59/201), vomiting (15.9%, 32/201), or abdominal pain (6.0%, 12/201). 49.5% (146/295) of patients had diarrhea, median time was 3.3 days, (3.3±1.6) times per day, and a duration of (4.1±2.5) days. Excluding possible drug-related diarrhea, the incidence of diarrhea still was 22.2%. Only 6.9% (4/58) of patients were found leukocytes or fecal occult blood positive in regular stool test. ALT, AST, or bilirubin increased in 39.1% (119/304) of patients at admission. Patients with ALT or AST ≥ 80 U/L only accounted for 7.9% (24/304) and 6.3% (19/304), respectively. About 2.0% (6/304) of patients also had increased bilirubin level, average level was (37.4 ± 21.1) μmol/L. The median age of critical group was older than that of non-critical group (65.5 years vs. 56 years), at admission the rates of abnormal liver function test abnormal and slightly increased AST (40~80 U/L) of critical group were both higher than those of non-critical group (67.4% (31/46) vs. 34.1% (88/258) and 47.8% (22/46) vs. 21.7% (56/228)), and the differences were statistically significant (x2=5.885, 18.154 and 15.723;all P <0.05). There were no statistically significant differences in the proportion of male (58.7% (27/46) vs. 45.9% (119/259)), the positive rate of nucleic acid detection (94.6% (35/37) vs. 82.5% (193/234)), the percentage of patients with gastrointestinal symptoms (85.0% (17/20) vs. 78.5% (142/181)), the rate of diarrhea (44.7% (17/38)vs. 50.2% (129/257)) and ratio of patients with abnormal bilirubin level (6.5% (3/46) vs. 1.2% (3/258)) (all P>0.05).@*Conclusions@#The manifestation of digestive system of hospitalized NCP patients in Wuhan is significant, the ratio of patients with diarrhea and abnormal aminotransferase level is high. And at admission the rate of patients with abnormal liver function rate of critical group is higher than that of non-critical group, which will provide reference for the prevention and treatment of NCP.

positive: Characteristics of and Public Health Responses to the Coronavirus Disease 2019 Outbreak in China In December 2019, cases of unidentified pneumonia with a history of exposure in the Huanan Seafood Market were reported in Wuhan, Hubei Province. A novel coronavirus, SARS-CoV-2, was identified to be accountable for this disease. Human-to-human transmission is confirmed, and this disease (named COVID-19 by World Health Organization (WHO)) spread rapidly around the country and the world. As of 18 February 2020, the number of confirmed cases had reached 75,199 with 2009 fatalities. The COVID-19 resulted in a much lower case-fatality rate (about 2.67%) among the confirmed cases, compared with Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). Among the symptom composition of the 45 fatality cases collected from the released official reports, the top four are fever, cough, short of breath, and chest tightness/pain. The major comorbidities of the fatality cases include hypertension, diabetes, coronary heart disease, cerebral infarction, and chronic bronchitis. The source of the virus and the pathogenesis of this disease are still unconfirmed. No specific therapeutic drug has been found. The Chinese Government has initiated a level-1 public health response to prevent the spread of the disease. Meanwhile, it is also crucial to speed up the development of vaccines and drugs for treatment, which will enable us to defeat COVID-19 as soon as possible.

positive: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2): An Update Coronaviruses (CoVs) belong to the family of Coronaviridae, the order Nidovirales, and the genus Coronavirus. They are the largest group of viruses causing respiratory and gastrointestinal infections. Morphologically, CoVs are enveloped viruses containing a non-segmented positive-sense, single-stranded ribonucleic acid (RNA) viruses. CoVs are categorized into four important genera that include Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus. A novel member of human CoV that has recently emerged in Wuhan, China, is now formally named as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). This is a unique strain of RNA viruses that have not been previously observed in humans. The virus has wide host adaptability and is capable of causing severe diseases in humans, masked palm civets, mice, dogs, cats, camels, pigs, chickens, and bats. The SARS-CoV-2 typically causes respiratory and gastrointestinal sickness in both humans and animals. It can be transmitted through aerosols and direct/indirect contact, as well as during medical cases and laboratory sample handling. Specific structural proteins, which might be found on the surface of the virus, play an important role in the pathogenesis and development of the complications. The disease is characterized by distinct medical signs and symptoms that include high fever, chills, cough, and shortness of breath or difficulty in breathing. The infected people may also present with other symptoms such as diarrhea, myalgia, fatigue, expectoration, and hemoptysis. It is important from the public health and economic point of view as it affects the growth of the country, which is majorly attributed to the restriction in the movement of the people and the cost associated with the control and prevention of the disease. Since there is no specific therapeutic intervention nor a vaccine available against the virus, supportive management and treatment with non-specific therapeutic agents (repurposed drugs) may provide relief to the patients. Some preventive strategies of the disease include blocking the routes of transmission of the infections, disinfection of instruments used during medical case handling, using personal protective equipment, proper and early diagnosis of the disease, avoiding contact with the sick patients, and quarantine of the infected/exposed people.

positive: Acute Myelitis as a Neurological Complication ofCovid-19:A Case Report and MRI Findings During the recent outbreak of COVID-19 caused by SARS-CoV-2 coronavirus, there is rising concerns about neurological complications of COVID-19. Fever, headache and anosmia may occur early during the disease course. Other neurological sequalae such as encephalitis may occur in later phases. We report a case of acute myelitis in a 32 year old male Covid-19 positive patient who presented with a two-day history of flu-like symptoms then sudden onset paraplegia and urinary retention. The incidence is not known and the pathogenesis of the disease behind this manifestation is still not fully understood. Nevertheless considering the broad differential diagnosis of acute myelitis, prompt clinical and diagnostic work up was crucial to exclude other causes. Patients presenting with neurological symptoms such as loss of consciousness, ataxia, convulsions, status epilepticus, encephalitis, myelitis or neuritis should raise concerns for Covid-19 infection during this pandemic prompting early diagnosis and initiation of proper management.

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: Prevalence and Clinical Presentation of Health Care Workers With Symptoms of Coronavirus Disease 2019 in 2 Dutch Hospitals During an Early Phase of the Pandemic Importance: On February 27, 2020, the first patient with coronavirus disease 2019 (COVID-19) was reported in the Netherlands. During the following weeks, at 2 Dutch teaching hospitals, 9 health care workers (HCWs) received a diagnosis of COVID-19, 8 of whom had no history of travel to China or northern Italy, raising the question of whether undetected community circulation was occurring. Objective: To determine the prevalence and clinical presentation of COVID-19 among HCWs with self-reported fever or respiratory symptoms. Design, Setting, and Participants: This cross-sectional study was performed in 2 teaching hospitals in the southern part of the Netherlands in March 2020, during the early phase of the COVID-19 pandemic. Health care workers employed in the participating hospitals who experienced fever or respiratory symptoms were asked to voluntarily participate in a screening for infection with the severe acute respiratory syndrome coronavirus 2. Data analysis was performed in March 2020. Main Outcomes and Measures: The prevalence of severe acute respiratory syndrome coronavirus 2 infection was determined by semiquantitative real-time reverse transcriptase-polymerase chain reaction on oropharyngeal samples. Structured interviews were conducted to document symptoms for all HCWs with confirmed COVID-19. Results: Of 9705 HCWs employed (1722 male [18%]), 1353 (14%) reported fever or respiratory symptoms and were tested. Of those, 86 HCWs (6%) were infected with severe acute respiratory syndrome coronavirus 2 (median age, 49 years [range, 22-66 years]; 15 [17%] male), representing 1% of all HCWs employed. Most HCWs experienced mild disease, and only 46 (53%) reported fever. Eighty HCWs (93%) met a case definition of fever and/or coughing and/or shortness of breath. Only 3 (3%) of the HCWs identified through the screening had a history of travel to China or northern Italy, and 3 (3%) reported having been exposed to an inpatient with a known diagnosis of COVID-19 before the onset of symptoms. Conclusions and Relevance: Within 2 weeks after the first Dutch case was detected, a substantial proportion of HCWs with self-reported fever or respiratory symptoms were infected with severe acute respiratory syndrome coronavirus 2, likely as a result of acquisition of the virus in the community during the early phase of local spread. The high prevalence of mild clinical presentations, frequently not including fever, suggests that the currently recommended case definition for suspected COVID-19 should be used less stringently.

positive: Novel Coronavirus: Current Understanding of Clinical Features, Diagnosis, Pathogenesis, and Treatment Options Since December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in devastating consequences worldwide and infected more than 350,000 individuals and killed more than 16,000 people. SARS-CoV-2 is the seventh member of the coronavirus family to affect humans. Symptoms of COVID-19 include fever (88%), cough (68%), vomiting (5%) and diarrhoea (3.7%), and transmission of SARS-CoV-2 is thought to occur from human to human via respiratory secretions released by the infected individuals when coughing and sneezing. COVID-19 can be detected through computed tomography scans and confirmed through molecular diagnostics tools such as polymerase chain reaction. Currently, there are no effective treatments against SARS-CoV-2, hence antiviral drugs have been used to reduce the development of respiratory complications by reducing viral load. The purpose of this review is to provide a comprehensive update on the pathogenesis, clinical aspects, diagnosis, challenges and treatment of SARS-CoV-2 infections.

positive: Long-Term Care Facilities and the Coronavirus Epidemic: Practical Guidelines for a Population at Highest Risk

positive: Analysis on the Clinical Characteristics of 36 Cases of Novel Coronavirus Pneumonia in Kunming Objective: To analyze the clinical characteristics of patients with novel coronavirus pneumonia in Kunming City, and to study the correlation between nutritional status and immune function. Methods: Clinical data of 36 patients with novel coronavirus pneumonia in isolation area of Kunming Third People's Hospital from January 31 to February 15, 2020 were collected, and the basic situation, clinical characteristics, laboratory examination and CT imaging characteristics were analyzed. Serum albumin (ALB), prealbumin (PAB), hypersensitive c-reactive protein (hs-crp), CD3T cells, CD4T cells, CD8T cells and normal control group were analyzed. A simple linear regression analysis of the relationship between proalbumin and T cell subpopulation counts in the blood of patients. Results: (1) The patients with new coronavirus pneumonia in Kunming were mainly of common type. (2) 50% of the patients' first symptoms were fever and cough; (3) The total number of white blood cells in peripheral blood was normal or decreased in 23 cases (79%), and the lymphocyte count decreased in 5 cases (13.89%), without anemia. Hypersensitive c-reactive protein increased in 19 (52.78%) cases, and procalcitonin increased in 1 case. Albumin decreased in 5 cases (13.89%), proalbumin decreased in 15 cases (41.67%), alanine transaminase increased slightly in 4 cases (11.11%), alanine transaminase increased slightly in 4 cases (11.11%), total bilirubin increased slightly in 11 cases (30.56%), and renal function and blood coagulation were normal. Absolute value of CD3+T cells is with a decrease in 21 cases (58.3%), CD4+T in 28 cases (77.8%), CD8+T in 17 cases (47.2%), and CD4+/ CD8+ inverse in 6 cases (16.7%). (4) The prealbumin, CD3 T cells, CD4 T cells and CD8 T cells in the new coronavirus pneumonia group were significantly lower than those in the normal control group, and the hypersensitive c-reactive protein was higher than that in the normal control group. (5) The levels of PAB in the serum of the patients were linearly correlated with hs-crp, CD3 T cells, CD4 T cells and CD8 T cells, and the correlation coefficients were -0.474, 0.558, 0.467 and 0.613, respectively, showing statistical differences. Conclusion: The clinical characteristics of the novel coronavirus pneumonia in Kunming are different from those in Wuhan. The changes of serum proalbumin and T cell subsets are relatively obvious. Changes in serum proalbumin may contribute to the early warning of novel coronavirus pneumonia. The nutritional status of patients with common and mild pneumonia should be considered.

positive: AGA Clinical Practice Update on Management of Inflammatory Bowel Disease During the COVID-19 Pandemic: Expert Commentary Description The purpose of this AGA Institute Clinical Practice Update is to rapidly review the emerging evidence and provide timely expert recommendations regarding the management of patients with inflammatory bowel disease during the COVID-19 pandemic. Methods This expert commentary was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely perspective on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology.

positive: Clinical features and outcomes of COVID-19 patients with gastrointestinal symptoms

positive: Five common skin manifestations of COVID‐19 identified COVID‐19, also called coronavirus, is an infectious disease caused by SARS‐CoV‐2. First identified in December 2019, in March 2020 it was announced by the World Health Organisation that COVID‐19 had become a global pandemic. The disease can affect different organ systems, and early reports have suggested skin symptoms. The researchers, working with dermatologists across Spain, reviewed 375 patients with suspected, or confirmed, COVID‐19, with the aim of developing a detailed classification of the different types of skin symptoms associated with COVID‐19 with corresponding images. An initial 120 images were reviewed by four dermatologists, without knowing any other clinical information, and they identified patterns of symptoms associated with COVID‐19. These patterns were then applied to the rest of the images and further refined. Five common skin symptoms were identified this way. These symptoms are chilblain‐like lesions, outbreaks of small blisters, wheals, rashes comprised of small flat and raised red bumps, and livedo and necrosis. Livedo is a skin condition where circulation is impaired within the blood vessels of the skin, necrosis refers to the premature death of skin tissue. These symptoms are associated with different severity of COVID‐19 infection, from less severe disease in the chilblain‐like lesions, to most severe in patients with livedo. The researchers noted that some of the skin symptoms associated with COVID‐19 are common and can have many causes, particularly wheals and rashes. As such, they may not be particularly helpful as an aide to diagnosis.

positive: What do surgeons need to know about the digestive disorders and paraclinical abnormalities induced by COVID-19? The symptoms associated with COVID-19 are mainly characterized by a triad composed of fever, dry cough and dyspnea. However, digestive symptoms have also been reported. At first considered as infrequent, they in fact seem to affect more than half of patients. The symptoms mainly include anorexia, diarrhea, nausea and/or vomiting and abdominal pain. Even though prognosis is associated with lung injury, digestive symptoms seem significantly more frequent in patients presenting with severe COVID-19 infection. Digestive presentations, which may be isolated or which can precede pulmonary symptoms, have indeed been reported, with diarrhea as a leading clinical sign. The main biological abnormalities that can suggest COVID-19 infection at an early stage are lymphopenia, elevated CRP and heightened ASAT transaminases. Thoraco-abdominal scan seems useful as a means of on the one hand ruling out digestive pathology not connected with coronavirus and on the other hand searching for pulmonary images consistent with COVID-19 infection. No data exist on the value of digestive endoscopy in cases of persistent digestive symptoms. Moreover, the endoscopists may themselves be at significant risk of contamination. Fecal-oral transmission of the infection is possible, especially insofar as viral shedding in stools seems frequent and of longer duration than at the ENT level, including in patients with negative throat swab and without digestive symptoms. In some doubtful cases, virologic assessment of stool samples can yield definitive diagnosis. In the event of prolonged viral shedding in stools, a patient's persistent contagiousness is conceivable but not conclusively established. Upcoming serology should enable identification of the patients having been infected by the COVID-19 epidemic, particularly among previously undetected pauci-symptomatic members of a health care staff. Resumption of medico-surgical activity should be the object of a dedicated strategy preceding deconfinement.

positive: Pregnancy and Perinatal Outcomes of Women With Coronavirus Disease (COVID-19) Pneumonia: A Preliminary Analysis OBJECTIVE. The purpose of this study was to describe the clinical manifestations and CT features of coronavirus disease (COVID-19) pneumonia in 15 pregnant women and to provide some initial evidence that can be used for guiding treatment of pregnant women with COVID-19 pneumonia. MATERIALS AND METHODS. We reviewed the clinical data and CT examinations of 15 consecutive pregnant women with COVID-19 pneumonia in our hospital from January 20, 2020, to February 10, 2020. A semiquantitative CT scoring system was used to estimate pulmonary involvement and the time course of changes on chest CT. Symptoms and laboratory results were analyzed, treatment experiences were summarized, and clinical outcomes were tracked. RESULTS. Eleven patients had successful delivery (10 cesarean deliveries and one vaginal delivery) during the study period, and four patients were still pregnant (three in the second trimester and one in the third trimester) at the end of the study period. No cases of neonatal asphyxia, neonatal death, stillbirth, or abortion were reported. The most common early finding on chest CT was ground-glass opacity (GGO). With disease progression, crazy paving pattern and consolidations were seen on CT. The abnormalities showed absorptive changes at the end of the study period for all patients. The most common onset symptoms of COVID-19 pneumonia in pregnant women were fever (13/15 patients) and cough (9/15 patients). The most common abnormal laboratory finding was lymphocytopenia (12/15 patients). CT images obtained before and after delivery showed no signs of pneumonia aggravation after delivery. The four patients who were still pregnant at the end of the study period were not treated with antiviral drugs but had achieved good recovery. CONCLUSION. Pregnancy and childbirth did not aggravate the course of symptoms or CT features of COVID-19 pneumonia. All the cases of COVID-19 pneumonia in the pregnant women in our study were the mild type. All the women in this study-some of whom did not receive antiviral drugs-achieved good recovery from COVID-19 pneumonia.

positive: 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.

positive: In-flight Transmission Cluster of COVID-19: A Retrospective Case Series Objectives: No data were available about in-flight transmission of SARS-CoV-2. Here, we report an in-flight transmission cluster of COVID-19 and describe the clinical characteristics of these patients. Methods: After a flight, laboratory-confirmed COVID-19 was reported in 12 patients. Ten patients were admitted to the designated hospital. Data were collected from 25th January to 28th February 2020. Clinical information was retrospectively collected. Results: All patients are passengers without flight attendants. The median age was 33 years, and 70% were females. None was admitted to intensive care unit, and no patients succumbed through 28th February. The median incubation period was 3.0 days and from illness onset to hospital admission was 2 days. The most common symptom was fever. Two patients were asymptomatic and negative for chest CT scan throughout the disease course. On admission, initial RT-PCR were positive in 9 patients, however initial chest CT were positive in only half patients. The median lung total severity score of chest CT was 6. Notably, Crazy-Paving pattern, pleural effusion, and ground-glass nodules were also seen. Conclusion: It is potential for COVID-19 transmission by airplane, but the symptoms are mild. Passengers and attendants must be protected during the flight.

positive: Initial Clinical Impressions of the Critical Care of COVID-19 Patients in Seattle, New York City, and Chicago Since the first recognition of a cluster of novel respiratory viral infections in China in late December 2019, intensivists in the United States have watched with growing concern as infections with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus―now named Coronavirus Disease of 2019 (COVID-19)―have spread to hospitals in the United States. Because COVID-19 is extremely transmissible and can progress to a severe form of respiratory failure, the potential to overwhelm available critical care resources is high and critical care management of COVID-19 patients has been thrust into the spotlight. COVID-19 arrived in the United States in January and, as anticipated, has dramatically increased the usage of critical care resources. Three of the hardest-hit cities have been Seattle, New York City, and Chicago with a combined total of over 14,000 cases as of March 23, 2020. In this special article, we describe initial clinical impressions of critical care of COVID-19 in these areas, with attention to clinical presentation, laboratory values, organ system effects, treatment strategies, and resource management. We highlight clinical observations that align with or differ from already published reports. These impressions represent only the early empiric experience of the authors and are not intended to serve as recommendations or guidelines for practice, but rather as a starting point for intensivists preparing to address COVID-19 when it arrives in their community.

positive: Neurological Impact of Coronavirus Disease (COVID-19): Practical Considerations for the Neuroscience Community Abstract Background The coronavirus disease of 2019 (COVID-19) that is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently been designated a pandemic by the World Health Organization, affecting 2.7 million individuals globally as of April 25, 2020 with over 187,000 deaths. A growing body of evidence supports central nervous system (CNS) involvement. Methods We conducted a review of the literature for articles concerning COVID-19 pathophysiology, neurological manifestations, and neuroscience provider recommendations and guidelines. Results CNS manifestations range from vague non-focal complaints to severe neurologic impairment associated with encephalitis. It is unclear whether neurological dysfunction is due to direct viral injury or systemic disease. The virus may affect brainstem pathways that lead to indirect respiratory dysfunction in addition to direct pulmonary injury. Necessary adaptations in patient management, triage, and diagnosis are evolving in light of ongoing scientific and clinical findings. Conclusions This review consolidates the current body of literature regarding the neurological impact of coronaviruses, discusses the reported neurologic manifestations of COVID-19, and highlights recommendations for patient management. Specific recommendations pertaining to clinical practice for neurologists and neurosurgeons are provided.

positive: Prevalence and Characteristics of Gastrointestinal Symptoms in Patients with SARS-CoV-2 Infection in the United States: A Multicenter Cohort Study

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

positive: Persistent hiccups as an atypical presenting complaint of COVID-19 Hiccups (singultus) are reflex inspiratory movements that involve the swallowing reflex arc and can be classified as acute (<48 h) or persistent (>48 h). A 62-year-old man with no history of malignancy or pulmonary disease presented to the Emergency Department with a four-day history of persistent hiccups. Other than episodic hiccupping, his physical examination was otherwise unremarkable. An abnormal chest X-ray led to a CT scan of the chest with IV contrast, which demonstrated regional, peripheral groundglass opacities of the upper lobes with small focal groundglass opacities scattered throughout the lungs. He was tested for COVID-19 per admission protocol, started on hydroxychloroquine, his hiccups improved, and he was discharged to home after 3 days. An emergency medicine physician should keep COVID-19 on the differential and be vigilant of exposure in atypical presentations.

positive: Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths Abstract Since the emergence of coronavirus disease 2019 (COVID-19) (formerly known as the 2019 novel coronavirus [2019-nCoV]) in Wuhan, China in December 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more than 75,000 cases have been reported in 32 countries/regions, resulting in more than 2000 deaths worldwide. Despite the fact that most COVID-19 cases and mortalities were reported in China, the WHO has declared this outbreak as the sixth public health emergency of international concern. The COVID-19 can present as an asymptomatic carrier state, acute respiratory disease, and pneumonia. Adults represent the population with the highest infection rate; however, neonates, children, and elderly patients can also be infected by SARS-CoV-2. In addition, nosocomial infection of hospitalized patients and healthcare workers, and viral transmission from asymptomatic carriers are possible. The most common finding on chest imaging among patients with pneumonia was ground-glass opacity with bilateral involvement. Severe cases are more likely to be older patients with underlying comorbidities compared to mild cases. Indeed, age and disease severity may be correlated with the outcomes of COVID-19. To date, effective treatment is lacking; however, clinical trials investigating the efficacy of several agents, including remdesivir and chloroquine, are underway in China. Currently, effective infection control intervention is the only way to prevent the spread of SARS-CoV-2.

positive: Clinical Insights into the Gastrointestinal Manifestations of COVID-19 The month of December 2019 became a critical part of the time of humanity when the first case of coronavirus disease 2019 (COVID-19) was reported in the Wuhan, Hubei Province in China. As of April 13th, 2020, there have been approximately 1.9 million cases and 199,000 deaths across the world, which were associated with COVID-19. The COVID-19 is the seventh coronavirus to be identified to infect humans. In the past, Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome were the two coronaviruses that infected humans with a high fatality, particularly among the elderly. Fatalities due to COVID-19 are higher in patients older than 50 years of age or those with multimorbid conditions. The COVID-19 is mainly transmitted through respiratory droplets, with the most common symptoms being high fever, cough, myalgia, atypical symptoms included sputum production, headache, hemoptysis and diarrhea. However, the incubation period can range from 2 to 14 days without any symptoms. It is particularly true with gastrointestinal (GI) symptoms in which patients can still shed the virus even after pulmonary symptoms have resolved. Given the high percentage of COVID-19 patients that present with GI symptoms (e.g., nausea and diarrhea), screening patients for GI symptoms remain essential. Recently, cases of fecal–oral transmission of COVID-19 have been confirmed in the USA and China, indicating that the virus can replicate in both the respiratory and digestive tract. Moreover, the epidemiology, clinical characteristics, diagnostic procedures, treatments and prevention of the gastrointestinal manifestations of COVID-19 remain to be elucidated.

positive: Meta-analysis of outcomes of patients with COVID-19 infection with versus without gastrointestinal symptoms This systematic review analyzed whether the presence or absence of gastrointestinal symptoms in patients with SARS-COV-2 infection is associated with adverse outcomes. Searching the Cochrane Center Register of Controlled Trials, we included any studies looking at patients with COVID-19 with gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal pain) compared to those with COVID-19 but without gastrointestinal manifestations as a control group. The final search yielded 186 articles, all of which were individually screened. Seven studies were identified but three were excluded: one due to lack of a control group without gastrointestinal symptoms, one reported as viral RNA in the stool, and one with only non-critically ill patients. Results of the meta-analysis showed a pooled odds ratio for mortality among those with COVID-19 and gastrointestinal symptoms of 0.91 (confidence interval 0.49–1.68) with heterogeneity of 0% and a pooled odds ratio for acute respiratory distress syndrome of 2.94 (confidence interval 1.17–7.40) with heterogeneity of 0%. In conclusion, gastrointestinal symptoms with COVID-19 are associated with a higher risk of acute respiratory distress syndrome, but do not increase the risk for mortality.

positive: Have the symptoms of patients with COVID-19 changed over time during hospitalization?

positive: Q&A: The novel coronavirus outbreak causing COVID-19

positive: Neurological Manifestations of COVID‐19: A systematic review and current update The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), was first identified in December of 2019 in the city of Wuhan, China. Since the outbreak, various reports detail its symptoms and outcomes, primarily focusing on respiratory complications. However, reports are emerging of the virus’ effects systemically, including that of the nervous system. A review of all current published literature was conducted, and we report that headache and anosmia were common neurological manifestations of SARS‐CoV‐2. Less common symptoms include seizure, stroke and isolated cases of Guillain‐Barre syndrome. Further research is now warranted to precisely determine the relationship between those patients developing neurological sequelae, their clinical state and any subsequent morbidity and mortality.

positive: Episcleritis as an ocular manifestation in a patient with COVID‐19

positive: COVID‐19 is a Real Headache! After the emergence of a novel coronavirus named SARS‐CoV‐2, coronavirus disease 2019 (COVID‐19) was initially characterized by fever, sore throat, cough, and dyspnea, mainly manifestations of respiratory system. However, other manifestations such as headache, abdominal pain, diarrhea, loss of taste and smell were added to the clinical spectrum, during the course of the COVID‐19 pandemic. The reports on the neurological findings are increasing rapidly and headache seems to be the leader on the symptom list. Headache was reported in 11%‐34% of the hospitalized COVID‐19 patients, but clinical features of these headaches were totally missing in available publications. According to our initial experience, significant features of headache presentation in the symptomatic COVID‐19 patients were new‐onset, moderate‐severe, bilateral headache with pulsating or pressing quality in the temporoparietal, forehead or periorbital region. The most striking features of the headache were sudden to gradual onset and poor response to common analgesics, or high relapse rate, that was limited to the active phase of the COVID‐19. Symptomatic COVID‐19 patients, around 6%‐10%, also reported headache as a presenting symptom. The possible pathophysiological mechanisms of headache include activation of peripheral trigeminal nerve endings by the SARS‐CoV‐2 directly or through the vasculopathy and/or increased circulating pro‐inflammatory cytokines and hypoxia. We concluded that as a common non‐respiratory symptom of COVID‐19, headache should not be overlooked, and its characteristics should be recorded with scrutiny.

positive: Early Predictors of Clinical Deterioration in a Cohort of 239 Patients Hospitalized for Covid-19 Infection in Lombardy, Italy We described features of hospitalized Covid-19 patients and identified predictors of clinical deterioration. We included patients consecutively admitted at Humanitas Research Hospital (Rozzano, Milan, Italy); retrospectively extracted demographic; clinical; laboratory and imaging findings at admission; used survival methods to identify factors associated with clinical deterioration (defined as intensive care unit (ICU) transfer or death), and developed a prognostic index. Overall; we analyzed 239 patients (29.3% females) with a mean age of 63.9 (standard deviation [SD]; 14.0) years. Clinical deterioration occurred in 70 patients (29.3%), including 41 (17.2%) ICU transfers and 36 (15.1%) deaths. The most common symptoms and signs at admission were cough (77.8%) and elevated respiratory rate (34.1%), while 66.5% of patients had at least one coexisting medical condition. Imaging frequently revealed ground-glass opacity (68.9%) and consolidation (23.8%). Age; increased respiratory rate; abnormal blood gas parameters and imaging findings; coexisting coronary heart disease; leukocytosis; lymphocytopenia; and several laboratory parameters (elevated procalcitonin; interleukin-6; serum ferritin; C-reactive protein; aspartate aminotransferase; lactate dehydrogenase; creatinine; fibrinogen; troponin-I; and D-dimer) were significant predictors of clinical deterioration. We suggested a prognostic index to assist risk-stratification (C-statistic; 0.845; 95% CI; 0.802–0.887). These results could aid early identification and management of patients at risk, who should therefore receive additional monitoring and aggressive supportive care.

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

positive: Corona Virus Disease-19 (COVID-19) Presenting as Conjunctivitis: Atypically High-risk During a Pandemic

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: Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. Importance The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, is serious and has the potential to become an epidemic worldwide. Several studies have described typical clinical manifestations including fever, cough, diarrhea, and fatigue. However, to our knowledge, it has not been reported that patients with COVID-19 had any neurologic manifestations. Objective To study the neurologic manifestations of patients with COVID-19. Design, Setting, and Participants This is a retrospective, observational case series. Data were collected from January 16, 2020, to February 19, 2020, at 3 designated special care centers for COVID-19 (Main District, West Branch, and Tumor Center) of the Union Hospital of Huazhong University of Science and Technology in Wuhan, China. The study included 214 consecutive hospitalized patients with laboratory-confirmed diagnosis of severe acute respiratory syndrome coronavirus 2 infection. Main Outcomes and Measures Clinical data were extracted from electronic medical records, and data of all neurologic symptoms were checked by 2 trained neurologists. Neurologic manifestations fell into 3 categories: central nervous system manifestations (dizziness, headache, impaired consciousness, acute cerebrovascular disease, ataxia, and seizure), peripheral nervous system manifestations (taste impairment, smell impairment, vision impairment, and nerve pain), and skeletal muscular injury manifestations. Results Of 214 patients (mean [SD] age, 52.7 [15.5] years; 87 men [40.7%]) with COVID-19, 126 patients (58.9%) had nonsevere infection and 88 patients (41.1%) had severe infection according to their respiratory status. Overall, 78 patients (36.4%) had neurologic manifestations. Compared with patients with nonsevere infection, patients with severe infection were older, had more underlying disorders, especially hypertension, and showed fewer typical symptoms of COVID-19, such as fever and cough. Patients with more severe infection had neurologic manifestations, such as acute cerebrovascular diseases (5 [5.7%] vs 1 [0.8%]), impaired consciousness (13 [14.8%] vs 3 [2.4%]), and skeletal muscle injury (17 [19.3%] vs 6 [4.8%]). Conclusions and Relevance Patients with COVID-19 commonly have neurologic manifestations. During the epidemic period of COVID-19, when seeing patients with neurologic manifestations, clinicians should suspect severe acute respiratory syndrome coronavirus 2 infection as a differential diagnosis to avoid delayed diagnosis or misdiagnosis and lose the chance to treat and prevent further transmission.

positive: Clinical characteristics of 3062 COVID-19 patients: A meta-analysis We aimed to systematically review the clinical characteristics of coronavirus disease 2019 (COVID-19). Seven databases were searched to collect studies about the clinical characteristics of COVID-19 from January 1, 2020 to February 28, 2020. Then, meta-analysis was performed by using Stata12.0 software. A total of 38 studies involving 3062 COVID-19 patients were included. Meta-analysis showed that a higher proportion of infected patients was male (56.9%). The incidence rate of respiratory failure or acute respiratory distress syndrome was 19.5% and the fatality rate was 5.5%. Fever (80.4%), fatigue (46%), cough (63.1%), and expectoration (41.8%) were the most common clinical manifestations. Other common symptoms included muscle soreness (33%), anorexia (38.8%), chest tightness (35.7%), shortness of breath (35%), dyspnea (33.9%). Minor symptoms included nausea and vomiting (10.2%), diarrhea (12.9%), headache (15.4%), pharyngalgia (13.1%), shivering (10.9%), and abdominal pain (4.4%). The proportion of patients that was asymptomatic was 11.9%. Normal leukocyte counts (69.7%), lymphopenia (56.5%), elevated C-reactive protein levels (73.6%), elevated ESR (65.6%), and oxygenation index decreased (63.6%) were observed in most patients. About 37.2% of patients were found with elevated D-dimer, 25.9% of patients with leukopenia, along with abnormal levels of liver function (29%), and renal function (25.5%). Other findings included leukocytosis (12.6%) and elevated procalcitonin (17.5%). Only 25.8% of patients had lesions involving a single lung and 75.7% of patients had lesions involving bilateral lungs. The most commonly experienced symptoms of COVID-19 patients were fever, fatigue, cough, and expectoration. A relatively small percentage of patients were asymptomatic. Most patients showed normal leucocytes counts, lymphopenia, elevated levels of C-reactive protein and ESR. Bilateral lung involvement was common.

positive: Self-reported symptoms of covid-19 including symptoms most predictive of SARS-CoV-2 infection, are heritable Susceptibility to infection such as SARS-CoV-2 may be influenced by host genotype. TwinsUK volunteers (n=2633) completing the C-19 Covid symptom tracker app allowed classical twin studies of covid-19 symptoms including predicted covid-19, a symptom-based algorithm predicting true infection derived in app users tested for SARS-CoV-2. We found heritability for fever = 41 (95% confidence intervals 12-70)%; anosmia 47 (27-67)%; delirium 49 (24-75)%; and predicted covid-19 gave heritability = 50 (29-70)%.

positive: CT Scans Obtained for Nonpulmonary Indications: Associated Respiratory Findings of COVID-19 Background Atypical manifestations of COVID-19 are being encountered as the pandemic unfolds, leading to non-chest CT scans that may uncover unsuspected pulmonary disease. Purpose To investigate patients with primary non-respiratory symptoms who underwent abdomen/pelvis or cervical spine/neck CT with unsuspected findings highly suspicious for pulmonary COVID-19. Materials and Methods This retrospective study from March 10, 2020 to April 6, 2020 involved three institutions, two in a region considered a hotspot (area of high prevalence) for COVID-19. Patients without known COVID-19 were included who presented to the emergency room (ER) with primary non-respiratory [gastrointestinal (GI) or neurological] symptoms, had lung parenchymal findings suspicious for COVID-19 on a non-chest CT but no concurrent chest CT and had COVID-19 testing in the ER. Group 1 patients had RT PCR obtained pre-CT read (COVID-19 suspected on presentation); Group 2 had RT PCR obtained post-CT read (COVID-19 not suspected). Presentation and imaging findings were compared and outcomes were evaluated. Descriptive statistics and Fisher exact tests were used for analysis. Results Group 1 comprised 62 patients [31 men, 31 women, mean age 67(SD ±17) years] and group 2 comprised 57 patients [28 men, 29 women, mean age 63(SD ± 16) years). Cough and fever were more common in group 1 (37/62, 60%, 29/62, 47%) than group 2 (9/57, 16%, 12/57, 21%) respectively, with no significant difference in the remaining symptoms. There were 101 abdomen/pelvis and 18 cervical spine/neck CTs. In Group 1, non-chest CT findings provided the initial evidence of COVID-19 related pneumonia in 32/62 (52%); for Group 2, it was 44/57 (77%). Overall, the most common CT findings were ground glass opacity (114/119, 96%) and consolidation (47/119,40%). 29/119 (24%) patients required major interventions (vasopressor medication or intubation) and 27/119 (23%) died. Patients who underwent cervical spine/neck CT had worse outcomes than those with abdominal/pelvic CT (p =0.01). Conclusion In a substantial percentage of patients with primary non-respiratory symptoms who underwent non-chest CT, the CT provided the first evidence of COVID-19 related pneumonia.

positive: Are COVID-19 infected children with gastrointestinal symptoms different from those without symptoms? A comparative study of the clinical characteristics and epidemiological trend of 244 pediatric cases from Wuhan Objective: COVID-19 patients presenting with gastrointestinal (GI) symptoms occur in both adults and children. To date, however, no large sample size study focusing on gastrointestinal symptoms in pediatric cases has been published. We analyzed COVID-19 infected children in Wuhan who presented with initial GI symptoms to determine the GI characteristics and epidemiological trend of the disease. Design: We retrospectively analyzed 244 children patients confirmed with COVID-19 at Wuhan Children's Hospital from 21 Jan to 20 Mar 2020. Symptomatic cases were divided into two groups according to whether the patients presented with or without GI symptoms on admission. Demographic, epidemiological, symptoms, and laboratory data were compared. We also analyzed the respective trends of case number changes of GI cases and asymptomatic cases. Results: 34 out of 193 symptomatic children had GI symptoms. They had lower median age and weight, a higher rate of fever, a longer length of stay and more hematological and biochemical abnormalities than patients without GI symptoms. There was no significant difference in chest CT findings or stool SARS-CoV-2 test positive percentages between the two groups. The number of patients admitted with GI symptoms showed an overall downward trend with time. At the time of writing, 242 patients were discharged, one died, and one critically ill patient was still in the intensive care unit. Conclusion: COVID-19 infected children with GI symptoms are prone to presenting with more clinical and laboratory abnormalities than patients without GI symptoms. More attention and timely hospital admission are needed for these patients.

positive: Coronavirus Disease: A Review of a New Threat to Public Health In December 2019, several patients from Wuhan, China were admitted to hospitals with symptoms of pneumonia. As the number of patients presenting with similar symptoms started to rise, the causative agent was eventually isolated from samples. It was initially called the 2019 novel coronavirus (2019-nCoV) and has been recently relabelled as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); the disease it causes has been named coronavirus disease 2019 (COVID-19). Over the next few weeks, the virus spread from Wuhan to affect different provinces in China and, after a few months, it is now present in 109 countries. As of March 10, 2020, there have been 113,702 confirmed cases globally, and 4,012 deaths have been registered. The World Health Organization (WHO) called COVID-19 a pandemic on March 11, 2020. There are multiple drug trials going on with some positive results. However, since no vaccine is available, the best way to combat the virus is by preventive methods.

positive: Chest Imaging in Patients Hospitalized With COVID-19 Infection - A Case Series Abstract COVID-19 (Corona Virus Disease-19) is a zoonotic illness first reported in the city of Wuhan, China in December 2019, and is now officially a global pandemic as declared by the World Health Organization. The infection is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 infected patients can be asymptomatic carriers or present with mild-to-severe respiratory symptoms. Imaging, including computed tomography is not recommended to screen/diagnose COVID-19 infections, but plays an important role in management of these patients, and to rule out alternative diagnoses or coexistent diseases. In our multicenter case series, we outline the clinical presentations and illustrate the most common imaging manifestations in patients hospitalized with COVID-19.

positive: Initial stage of the COVID-19 infection process in human population The simplest approximation for the first stages of the infection spread is considered. The specific feature of the COVID-19 characterized by its long latent period is taken into account. Exponential increase of numbers of infected people is determined by the half period of the maximal latent time for the COVID-19. The averaging over latent period leads to additional increase of the infected numbers.

positive: Erythematous Papular Rash: A Dermatological Feature of COVID-19 COVID-19 is the clinical expression of the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection. Most patients have mild symptoms, but a significant proportion have severe or critical disease, which can include cardiac injury, sepsis, acute kidney failure and respiratory failure. It is also worth highlighting the increasing number of reported COVID-19 cases with dermatological disease/manifestations. The cutaneous clinical spectrum is wide and includes maculopapular, urticarial, varicelliform and petechial rashes, pseudo perniosis, livedo reticularis, and pityriasis rosea-like, violaceous and pustular lesions. Until the physiological mechanism is fully understood, it is important to describe these manifestations, which could help identify a typical pattern. This report describes a cutaneous manifestation in a COVID-19 patient. LEARNING POINTS: SARS-CoV-2 presents with multiple symptoms with the dermatological manifestations currently under-recognized. Clinicians should be aware of patients presenting only with cutaneous symptoms, which in some cases are the initial clinical feature of COVID-19.

positive: Clinical Course of COVID‐19 in a Liver Transplant Recipient on Hemodialysis and Response to Tocilizumab Therapy: A Case Report The novel coronavirus disease 2019 (COVID‐19) is a highly infectious and rapidly spreading disease. There are limited published data on the epidemiology and outcomes of COVID‐19 infection among organ transplant recipients. After initial flulike symptoms, progression to an inflammatory phase may occur, characterized by cytokine release rapidly leading to respiratory and multiorgan failure. We report the clinical course and management of a liver transplant recipient on hemodialysis, who presented with COVID‐19 pneumonia, and despite completing a 5‐day course of hydroxychloroquine, later developed marked inflammatory manifestations with rapid improvement after administration of off‐label, single‐dose tocilizumab. We also highlight the role of lung ultrasonography in early diagnosis of the inflammatory phase of COVID‐19. Future investigation of the effects of immunomodulators among transplant recipients with COVID‐19 infection will be important.

positive: Dysregulation of immune response in patients with COVID-19 in Wuhan, China ;Clinical Infectious Diseases ;Oxford Academic Abstract 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

positive: The international EAN survey on neurological symptoms in patients with COVID-19 infection BACKGROUND AND PURPOSE: Although the main clinical features of COVID-19 infection are pulmonary, several associated neurological signs, symptoms and diseases are emerging. Incidence and characteristics of neurological complications are unclear. For this reason, the European Academy of Neurology (EAN) core COVID-19 Task Force initiated a survey on neurological symptoms observed in patients with COVID-19 infection. METHODS: A 17-question on-line survey was made available on the EAN website and distributed to EAN members and other worldwide physicians starting on April 9th , 2020. RESULTS: By April 27th, 2020, proper data were collected from 2,343 responders (out of 4,199), of whom 82.0% were neurologists, mostly from Europe. Most responders (74.7%) consulted patients with COVID-19 mainly in emergency rooms and in COVID-19 units. The majority (67.0%) had evaluated fewer than 10 patients with neurological manifestations of COVID-19 (neuro COVID-19). The most frequently reported neurological findings were headache (61.9%), myalgia (50.4%), anosmia (49.2%), ageusia (39.8%), impaired consciousness (29.3%), and psychomotor agitation (26.7%). Encephalopathy and acute cerebrovascular disorders were reported at 21.0%. Neurological manifestations were generally interpreted as being possibly related to COVID-19, they were most commonly recognized in patients with multiple general symptoms, and occurred at any time during infection. CONCLUSION: Neurologists are currently and actively involved in the management of neurological issues related to the COVID-19 pandemic. This survey justifies setting up a prospective registry to better capture the prevalence of patients with neuro COVID-19, neurological disease characteristics and the contribution of neurological manifestations to outcome.

positive: COVID19: A Systematic Approach to Early Identification and Healthcare Worker Protection The COVID-19 outbreak spread rapidly throughout the globe, with worldwide infections and deaths continuing to increase dramatically. To control disease spread and protect healthcare workers, accurate information is necessary. We searched PubMed and Google Scholar for studies published from December 2019 to March 31, 2020 with the terms “COVID-19,” “2019-nCoV,” “SARS-CoV-2,” or “Novel Coronavirus Pneumonia.” The main symptoms of COVID-19 are fever (83–98.6%), cough (59.4–82%), and fatigue (38.1–69.6%). However, only 43.8% of patients have fever early in the disease course, despite still being infectious. These patients may present to clinics lacking proper precautions, leading to nosocomial transmission, and infection of workers. Potential COVID-19 cases must be identified early to initiate proper triage and distinguish them quickly from similar infections. Early identification, accurate triage, and standardized personal protection protocols can reduce the risk of cross infection. Containing disease spread will require protecting healthcare workers.

positive: Using the internet search data to investigate symptom characteristics of COVID-19: a big data study OBJECTIVE: Analyzing the symptom characteristics of Coronavirus Disease 2019(COVID-19) to improve control and prevention. METHODS: Using the Baidu Index Platform (http://index.baidu.com) and the website of Chinese Center for Disease Control and Prevention as data resources to obtain the search volume (SV) of keywords for symptoms associated with COVID-19 from January 1 to February 20 in each year from 2017 to 2020 and the epidemic data in Hubei province and the other top 9 impacted provinces in China. Data of 2020 were compared with those of the previous three years. Data of Hubei province were compared with those of the other 9 provinces. The differences and characteristics of the SV of COVID-19-related symptoms, and the correlations between the SV of COVID-19 and the number of newly confirmed/suspected cases were analyzed. The lag effects were discussed. RESULTS: Comparing the SV from January 1, 2020 to February 20, 2020 with those for the same period of the previous three years, Hubei's SV for cough, fever, diarrhea, chest tightness, dyspnea, and other symptoms were significantly increased. The total SV of lower respiratory symptoms was significantly higher than that of upper respiratory symptoms (P<0.001). The SV of COVID-19 in Hubei province was significantly correlated with the number of newly confirmed/suspected cases (r(confirmed) = 0.723, r(suspected) = 0.863, both P< 0.001). The results of the distributed lag model suggested that the patients who searched relevant symptoms on the Internet may begin to see doctors in 2-3 days later and be confirmed in 3-4 days later. CONCLUSION: The total SV of lower respiratory symptoms was higher than that of upper respiratory symptoms, and the SV of diarrhea also increased significantly. It warned us to pay attention to not only the symptoms of the lower respiratory tract but also the gastrointestinal symptoms, especially diarrhea in patients with COVID-19. Internet search behavior had a positive correlation with the number of newly confirmed/suspected cases, suggesting that big data has an important role in the early warning of infectious diseases.

positive: COVID-19 symptoms predictive of healthcare workers' SARS-CoV-2 PCR results BACKGROUND: Coronavirus 2019 disease (COVID-19) is caused by the virus SARS-CoV-2, transmissible both person-to-person and from contaminated surfaces. Early COVID-19 detection among healthcare workers (HCWs) is crucial for protecting patients and the healthcare workforce. Because of limited testing capacity, symptom-based screening may prioritize testing and increase diagnostic accuracy. METHODS AND FINDINGS: We performed a retrospective study of HCWs undergoing both COVID-19 telephonic symptom screening and nasopharyngeal SARS-CoV-2 assays during the period, March 9-April 15, 2020. HCWs with negative assays but progressive symptoms were re-tested for SARS-CoV-2. Among 592 HCWs tested, 83 (14%) had an initial positive SARS-CoV-2 assay. Fifty-nine of 61 HCWs (97%) who were asymptomatic or reported only sore throat/nasal congestion had negative SARS-CoV-2 assays (P = 0.006). HCWs reporting three or more symptoms had an increased multivariate-adjusted odds of having positive assays, 1.95 (95% CI: 1.10-3.64), which increased to 2.61 (95% CI: 1.50-4.45) for six or more symptoms. The multivariate-adjusted odds of a positive assay were also increased for HCWs reporting fever and a measured temperature ≥ 37.5°C (3.49 (95% CI: 1.95-6.21)), and those with myalgias (1.83 (95% CI: 1.04-3.23)). Anosmia/ageusia (i.e. loss of smell/loss of taste) was reported less frequently (16%) than other symptoms by HCWs with positive assays, but was associated with more than a seven-fold multivariate-adjusted odds of a positive test: OR = 7.21 (95% CI: 2.95-17.67). Of 509 HCWs with initial negative SARS-CoV-2 assays, nine had symptom progression and positive re-tests, yielding an estimated negative predictive value of 98.2% (95% CI: 96.8-99.0%) for the exclusion of clinically relevant COVID-19. CONCLUSIONS: Symptom and temperature reports are useful screening tools for predicting SARS-CoV-2 assay results in HCWs. Anosmia/ageusia, fever, and myalgia were the strongest independent predictors of positive assays. The absence of symptoms or symptoms limited to nasal congestion/sore throat were associated with negative assays.

positive: [Clinical analysis of 23 patients with coronavirus disease 2019 in Xinyang City of Henan Province]. OBJECTIVE To analyze the epidemiological characteristics and clinical features of the patients with coronavirus disease 2019 (COVID-19), so as to provide basis for clinical diagnosis. METHODS The epidemiology, clinical symptoms, laboratory and radiologic data of 23 patients with COVID-19 admitted to the Fifth People's Hospital of Xinyang City from January 22nd to January 29th, 2020 were retrospectively analyzed. RESULTS There was 23 patients with COVID-19, with 15 men and 8 women, and the median age was 46.0 (40.5, 52.0) years old (ranged from 27 years old to 80 years old). Nine patients had basic disease (39.1%), including hypertension (17.4%), cardiovascular diseases (17.4%), diabetes (8.7%), hypothyroidism (4.3%) and past history of tuberculosis (4.3%). All the 23 patients had contact history in Wuhan area or with confirmed cases. Clinical symptoms included fever (100%), cough (69.6%), expectoration (43.5%), myalgia (26.1%), headache (17.4%) and dyspnea (17.4%), and the less common symptom was diarrhea (4.3%). Blood routine tests showed leukocytopenia in 11 patients (47.8%), normal leukocyte counts in 10 patients (43.5%), and leukocytosis in 2 patients (8.7%); lymphopenia was found in 13 patients (56.5%). All 23 patients had different degrees of infective lesions in chest CT, with 7 patients (30.4%) on one side and 16 patients (69.6%) on both sides. There were 19 mild patients, 4 severe patients, and no critical or death case. Complications included acute respiratory distress syndrome (17.4%). No patient was reported with liver, kidney or heart dysfunction or secondary infection. CONCLUSIONS Epidemic history of contact, fever, pneumonia signs of chest CT, normal or decreased count of leukocyte and lymphopenia are the clinical basis for diagnosis of COVID-19. However, at present, the treatment of patients has not been completed, and the effective treatment strategy and final prognosis are unclear.

positive: [Clinical features and chest CT findings of coronavirus disease 2019 in infants and young children]. OBJECTIVE To study the clinical features and chest CT findings of coronavirus disease 2019 (COVID-19) in infants and young children. METHODS A retrospective analysis was performed for the clinical data and chest CT images of 9 children, aged 0 to 3 years, who were diagnosed with COVID-19 by nucleic acid detection between January 20 and February 10, 2020. RESULTS All 9 children had an epidemiological history, and family clustering was observed for all infected children. Among the 9 children with COVID-19, 5 had no symptoms, 4 had fever, 2 had cough, and 1 had rhinorrhea. There were only symptoms of the respiratory system. Laboratory examination showed no reductions in leukocyte or lymphocyte count. Among the 9 children, 6 had an increase in lymphocyte count and 2 had an increase in leukocyte count. CT examination showed that among the 9 children, 8 had pulmonary inflammation located below the pleura or near the interlobar fissure and 3 had lesions distributed along the bronchovascular bundles. As for the morphology of the lesions, 6 had nodular lesions and 7 had patchy lesions; ground glass opacity with consolidation was observed in 6 children, among whom 3 had halo sign, and there was no typical paving stone sign. CONCLUSIONS Infants and young children with COVID-19 tend to have mild clinical symptoms and imaging findings not as typical as those of adults, and therefore, the diagnosis of COVID-19 should be made based on imaging findings along with epidemiological history and nucleic acid detection. Chest CT has guiding significance for the early diagnosis of asymptomatic children.

positive: Chilblain‐like lesions in pediatrics dermatological outpatients during the COVID‐19 outbreak

positive: Clinical Manifestations of Children with COVID-19: a Systematic Review Context: The coronavirus disease 2019 (COVID-19) outbreak is an unprecedented global public health challenge, leading to thousands of deaths every day worldwide. Despite the epidemiological importance, clinical patterns of children with COVID-19 remain unclear. Objective: To describe the clinical, laboratorial and radiological characteristics of children with COVID-19. Data Sources: The Medline database was searched between December 1st 2019 and March 30th 2020. Study Selection: Inclusion criteria were: (1) studied patients younger than 18 years old; (2) presented original data from cases of COVID-19 confirmed by reverse-transcription polymerase chain reaction; and (3) contained descriptions of clinical manifestations, laboratory tests or radiological examinations. Data Extraction: Number of cases, gender, age, clinical manifestations, laboratory tests, radiological examinations and outcomes. Results: A total of 34 studies (1,118 cases) were included. From all the cases, 1,111 had their severity classified: 14.3% were asymptomatic, 36.4% were mild, 46.0% were moderate, 2.2% were severe and 1.2% were critical. The most prevalent symptom was fever (16.3%), followed by cough (14.4%), nasal symptoms (3.6%), diarrhea (2.7%) and nausea/vomiting (2.5%). One hundred forty-five (12.9%) children were diagnosed with pneumonia and 43 (3.8%) upper airway infections were reported. Reduced lymphocyte count were reported in 13.1% of cases. Abnormalities on computed tomography was reported in 62.7% of cases. The most prevalent abnormalities reported were ground glass opacities, patchy shadows and consolidations. Only one death was reported. Conclusions: Clinical manifestations of children with COVID-19 differ widely from adults cases. Fever and respiratory symptoms should not be considered a hallmark of COVID-19 in children.

positive: Trends in clinical features of novel coronavirus disease (COVID-19): A systematic review and meta-analysis of studies published from December 2019 to February 2020 BACKGROUND: Since novel coronavirus disease (COVID-19) emerged, various clinical features of COVID-19 have been reported. METHODS: We conducted a systematic review of published studies reporting the clinical features of COVID-19. Two investigators independently searched PubMed (December 2019–February 2020) for eligible articles. A meta-analysis was performed to measure the frequencies of clinical outcomes and symptoms of COVID-19. A stratified analysis was conducted according to the timeline of outbreak and exposure histories: Group I, most patients were exposed to the Hunan seafood wholesale market and lived in Wuhan, Hubei province; Group II, patients lived in Hubei province but were not directly exposed to the market; and Group III, patients lived outside Hubei. RESULTS: Thirteen studies, all from China, were eligible. The estimated mortality rate among all studies was 2.12%, but that in Group I was 8.66%. The incidence of acute respiratory distress syndrome in Group I was 20.00%. Both fever and cough were major symptoms, and their frequencies were higher in Group I than in Groups II and III, while the frequency of diarrhea in Group I was lower than that in Group III. The estimated frequency of dyspnea in Group I was 37.18%, while those in Groups II and III were 16.95% and 7.03%, respectively. CONCLUSIONS: The trends in the clinical features of COVID-19 changed from December 2019 to February 2020. During this observation period, as the infection continued to spread, the clinical conditions for majority of patients became less severe with the changes in the route of transmission.

positive: Clinical and Demographic Characteristics of Cluster Cases and Sporadic Cases of Coronavirus Disease 2019 (COVID-19) in 141 Patients in the Main District of Chongqing, China, Between January and February 2020. BACKGROUND In December 2019, an outbreak of coronavirus disease 2019 (COVID-19), due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), occurred in Wuhan, China. Patients with COVID-19 were also identified in Chongqing. This study aimed to investigate the clinical and demographic characteristics of cluster cases and sporadic cases of COVID-19 in 141 patients in the main district of Chongqing during one month, between January and February 2020. MATERIAL AND METHODS A retrospective study included 141 patients with a diagnosis of COVID-19. The diagnosis was confirmed using real-time reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2. The patients were divided into cluster cases (n=90) and sporadic cases (n=51). Demographic and clinical characteristics were compared between the two study groups and included the presence of comorbidities, the presenting symptoms, chest computed tomography (CT) imaging findings, and laboratory findings. RESULTS The mean age of the 141 patients diagnosed with COVID-19 was 47.3 years, and the most common presenting symptom was a persistent cough (48.9%). The 90 cluster cases (63.8%) were older than the sporadic cases, and cross-infection from family gathering occurred in 82.2%, and cough was more common than fever, and there was an increased prevalence of asymptomatic, mild, and moderate cases. Cluster cases showed fewer typical manifestations of COVID-19 on chest CT. However, the laboratory findings between the cluster and sporadic cases showed no significant differences. CONCLUSIONS There were demographic and clinical differences between cluster cases and sporadic cases of COVID-19 in the main district of Chongqing during the month between January to February 2020.

positive: [Clinical analysis of 150 cases of 2019 novel coronavirus infection in Nanyang City, Henan Province] Objective: To analyze the epidemiological characteristics and clinical features of the patients with 2019-nCoV infection in Nanyang City, so as to provide evidence for clinical diagnosis and treatment. Methods: The epidemiology, clinical symptoms, atory and radiologic data of 150 patients with 2019-nCoV infection admitted to the designated hospitals in Nanyang City from January 24,2020 to February 16, 2020 were retrospectively analyzed. Results: The 150 patients with 2019 nCov infection consisted of 67 men and 83 women, and the median age was (45±16) years; 69 of them were the first generation case,60 of them were the second generation case, 6 of them were the third generation case,the median incubation period of the first generation case was (5.4±2.2) days, and the second generation case was (6.7±3.1) days, and the first-generation cases are the majority in severe patients (69%) . The most common basic disease was hypertension (13 cases, 9%), diabetes (9 cases, 6%), and the most common symptom is fever(142 cases, 95%, 63% showed moderate fever) , cough and sputum(108 cases,72%), fatigue(23 cases,15%), anorexia(20 cases, 13%), headache, diarrhea, muscle soreness, sore throat as the first symptoms. The average time from onset of symptoms to consultation was (4.2±2.2) days for all patients. The changes in peripheral blood cells were mainly lymphonpenia (83 cases, 55%) and eosinophilia (95 cases, 63%), The lymphocyte count of the severe and critically ill patients was more significantly reduced, and some patients had increased myocardial enzymes, mainly LDH (47 cases, 31%), and a few patients had liver function damage, mainly manifested in ALT and AST. High, very few patients have renal impairment. Among the inflammation-related indicators, the main manifestations are increased CRP (66 cases, 43%) and ESR (86 cases, 57%), elevated D-Dimer in 29% of patients. 144 cases have different degrees of infective lesions in chest CT examination, with 30 cases (21%) on one side and 144 cases (79%) on both sides. Morphologically, most of the lesions were patchy ground glass lesions, which could be accompanied by air bronchus signs and some consolidation and paving stone signs. Of the cases showing "white lung", 87% were sever ill or critically ill. After active treatment, 45% of patients were discharged according to discharge standards. 33% of sever and critically ill patients were discharged, 49% of them were degraded hospitalization.The average length of hospitalization was (12±4) days. Conclusion: A history of epidemiological exposure, fever, chest CT with signs of pneumonia, normal or decreased WBC, and lymphocytopenia, eosinophilia are the clinical basis for the diagnosis of this disease, and most of the sever patients were the first generation cases. The degree of lymphocytopenia is related to the severity of the disease.

positive: Observations about Symptomatic and Asymptomatic infections of 494 patients with COVID-19 in Shanghai,China BACKGROUND: Humans are generally susceptible to SARS-CoV-2, which has caused a global pandemic of COVID-19. The screening of infected people in the population still mainly depends on clinical symptoms. However, there is limited research on the characteristics of clinical symptoms in different populations, especially in imported cases. METHODS: To retrospectively analyze the clinical data of 494 confirmed COVID-19 patients admitted to a designated hospital in Shanghai from January 20, 2020, to March 31, 2020, we compared the clinical manifestations in different populations and their influencing factors in COVID-19 patients. RESULTS: (1) Of the 494 patients, 453 (91.7%) had different symptoms at admission, and 39 (7.89%) patients were asymptomatic. (2) We compared the symptoms of patients according to different stratifications and found the following results: a. The proportion of dyspnea was significantly higher in male patients than in female patients (P < 0.05). b. The proportions of a stuffy nose, sore throat, and olfactory and gustatory dysfunction were significantly higher in children than in adult patients (P < 0.05). c. The proportions of fever, chest tightness, shortness of breath, and fatigue were significantly higher in local cases than in imported cases. In comparison, the proportions of nasal congestion, stuffy nose, sore throat, headache, and olfactory and gustatory dysfunction were significantly lower in imported cases than in imported cases (P < 0.05). d. The proportions of chest tightness, shortness of breath, and dyspnea were significantly higher in severely ill patients than in those with mild symptoms (P < 0.05). (3) Thirty-one asymptomatic patients were significantly younger than symptomatic patients, and they had a higher proportion of imported cases, white blood cell (WBC) and lymphocyte (LYM) count levels, and fewer abnormal CT cases than the group of symptomatic patients (P < 0.05). (4) The number of days since the onset of the disease needed for the symptoms to disappear was associated with the epidemiological history (imported cases), the number of days until the pharyngeal swab nucleic acid test turned negative, the days of hospitalization, the days of onset, and the WBC and LYM count levels (P < 0.05). CONCLUSION: The majority of COVID-19 patients (91.7%) had early symptoms. whereas 7.89% of COVID-19 patients were asymptomatic. Younger patients had fewer symptoms, mainly the upper respiratory symptoms, and the illness condition was milder, which was more common in imported cases. Elderly male patients had severe symptoms when admitted. The number of days needed for the patient's symptoms to disappear was closely related to the number of days necessary for the pharyngeal swab nucleic acid test to turn negative.

positive: Covid-19 in South Korea — Challenges of Subclinical Manifestations

positive: Follow-up of skin lesions during the evolution of COVID-19: a case report The disease caused by the new coronavirus (COVID-19) has many systemic manifestations affecting the upper airways, lungs, gastrointestinal tract and inducing hematological repercussions. With the evolution of the pandemic, skin lesions were observed. However, there is little information about the evolution of the lesions at this moment. The authors report a case of a patient who had more than one exposure to the coronavirus during the evolution of the disease and manifested different types of edematous lesions. The lesions started in the prodromal period and changed their presentation and localization during the evolution of COVID-19. The lesions regressed quickly with the use of corticoid cream and antihistamine. Viral skin lesions are frequent causes of exanthema. However, viral etiology is not always investigated in acute urticarial and atypical erythematous-edematous conditions. The immunological basis of acute urticaria has points in common with COVID-19, justifying the appearance of lesions. Investigation of viral etiology should always be remembered in acute urticarial and edematous conditions.

positive: Cutaneous manifestations of COVID-19: Report of three cases and a review of literature ABSTRACT Background Various cutaneous manifestations have been observed in patients with COVID-19 infection. However, overall similarities in the clinical presentation of these dermatological manifestations have not yet been summarized. Objective This review aims to provide an overview of various cutaneous manifestations in patients with COVID-19 through three case reports and a literature review. Methods A literature search was conducted using PubMed, OVID, and Google search engines for original and review articles. Studies written in the English language that mentioned cutaneous symptoms and COVID-19 were included. Results Eighteen articles and three additional cases reported in this paper were included in this review. Of these studies, 6 are case series and 12 are case report studies. The most common cutaneous manifestation of COVID-19 was found to be maculopapular exanthem (morbilliform), presenting in 36.1% (26/72) patients. The other cutaneous manifestations included: a papulovesicular rash (34.7%, 25/72), urticaria (9.7%, 7/72), painful acral red purple papules (15.3%, 11/72) of patients, livedo reticularis lesions (2.8%, 2/72) and petechiae (1.4%, 1/72). Majority of lesions were localized on the trunk (66.7%, 50/72), however, 19.4% (14/72) of patients experienced cutaneous manifestations in the hands and feet. Skin lesion development occurred after the onset of respiratory symptoms or before COVID-19 diagnosis in 12.5% (9/72) of the patients, and lesions spontaneously healed in all patients within 10 days. Majority of the studies reported no correlation between COVID-19 severity and skin lesions. Conclusion Infection with COVID-19 may result in dermatological manifestations with various clinical presentations, which may aid in the timely diagnosis of this infection.

positive: Epidemiology and clinical features of COVID-19: A review of current literature Abstract Coronavirus disease 2019 is a pandemic influencing the first half of the year 2020. The virus has rapidly spread to many countries. Studies are rapidly published to share information regarding epidemiology, clinical and diagnostic patterns, and prognosis. The following review condenses the surge of information into an organized format.

positive: Clinical Manifestation and Laboratory Characteristics of SARS-CoV-2 Infection in Pregnant Women The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic has become a major challenge to public health in China and other countries, considering its pathogenicity across all age groups. Pregnancy is a unique physiological condition, and is characterized by altered immunity and elevated hormone levels to actively tolerate the semi-allogeneic fetus, which undergoes a sudden and substantial fluctuation during the immediate postpartum period. Changes in clinical features, laboratory characteristics, and imaging features of pregnant women during the pre-partum and post-partum periods require further elucidation. Here, we retrospectively analyzed the clinical features, laboratory characteristics, and imaging features of eight pregnant cases of SARS-CoV-2 infection during the pre-partum and post-partum periods. Our results showed that four of the eight pregnant women were asymptomatic before delivery but became symptomatic post-partum. Correspondingly, white blood cell (WBC) counts increased and lymphocyte (LYMPH) counts decreased. C-reactive protein (CRP) levels in the serum also increased to a higher level than those in general pregnancy. Therefore, it is imperative to closely monitor laboratory parameters including the WBC count, LYMPH count, and CRP, along with other imaging features in chest CT scans, to promptly prevent, diagnose, and treat a SARS-CoV-2 infection during pregnancy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-020-00227-0) contains supplementary material, which is available to authorized users.

positive: Clinical and pathological characteristics of 2019 novel coronavirus disease (COVID-19): a systematic review Importance: In 2002-2003, a severe pulmonary infectious disease occurred in Guangdong, China. The disease was caused by SARS-CoV, 17 years apart, also happen in China, and SARS-CoV-2, this epidemic has posed a significant hazard to people health both China and the whole world. Objective: Summarized the latest epidemiological changes, clinical manifestations, auxiliary examination and pathological characteristics of COVID-19. Evidence Review: PubMed database were searched from 2019 to 2020 using the index terms novel coronavirus or COVID-19 or 2019-nCoV or SARS-CoV-2 and synonyms. Articles that reported clinical characteristics, laboratory results, imageological diagnosis and pathologic condition were included and were retrospectively reviewed for these cases. This paper adopts the method of descriptive statistics. Results: 34 COVID-19-related articles were eligible for this systematic review;Four of the articles were related to pathology. We found that Fever (86.0%), cough (63.9%) and Malaise/Fatigue (34.7%) were the most common symptoms in COVID-19. But in general, the clinical symptoms and signs of COVID-19 were not obvious. Compared with SARS, COVID-19 was transmitted in a more diverse way. The mortality rates of COVID-19 were 2.5%, and the overall infection rate of healthcare worker of COVID-19 was 3.9%. We also found that the pathological features of COVID-19 have greatly similar with SARS, which manifested as ARDS. But the latest pathological examination of COVID-19 revealed the obvious mucinous secretions in the lungs. Interpretation: The clinical and pathological characteristics of SARS and COVID-19 in China are very similar, but also difference. The latest finds of pathological examination on COVID-19 may upend existing treatment schemes, so the early recognition of disease by healthcare worker is very important.

positive: Clinical features of coronavirus disease 2019 (COVID-19) in a cohort of patients with disability due to spinal cord injury Study design: Cohort study of patients with spinal cord injury (SCI) Objectives: To describe the clinical and analytical features of a Covid-19 infected cohort with SCI to contribute new knowledge for a more accurate diagnosis and to outline prevention measures. Setting: This study was conducted at the National Hospital for Paraplegics (Toledo, Spain). Methods: A cohort analysis of seven patients with SCI infected by Covid-19 was carried out. Diagnosis was confirmed with reverse transcriptase polymerase chain reaction (RT-PCR) of nasal exudate or sputum samples. Clinical, analytical and radiographic findings were registered. Results: RT-PCR detected COVID-19 infection in all patients, affecting males and people with a cervical level of injury more often (5 out 7). The average delay for diagnostic confirmation was 4 days (interquartile range, 1-10). Fever was the most frequent symptom (6 out of 7). The second most common symptom was asthenia (4 out of 7), followed by dyspnea, cough and expectoration (3 out of 7 for each symptom). The MEWS score for Covid-19 severity rating was classified as severe in 5 out of 7. All but one patient showed radiological alterations evident in chest X-Rays at the time of diagnosis. All patients recovered gradually. Conclusion: Our patients with SCI and Covid-19 infection exhibited fewer symptoms than the general population. Furthermore, they presented similar or greater clinical severity. The clinical evolution was not as pronounced as had been expected. This study recommends close supervision of the SCI population to detect early compatible signs and symptoms of Covid-19 infection.

positive: Olfactory Dysfunction: A Highly Prevalent Symptom of COVID-19 With Public Health Significance. OBJECTIVE Coronavirus disease 2019 (COVID-19) is a global pandemic affecting millions of individuals, killing hundreds of thousands. Although typically described with characteristic symptoms of fever, cough, and shortness of breath, greater understanding of COVID-19 has revealed myriad clinical manifestations. Olfactory dysfunction (OD)-hyposmia and anosmia-has recently been recognized as an important symptom of COVID-19 and increasingly gained traction as a public health tool for identifying COVID-19 patients, in particular otherwise asymptomatic carriers who, unawares, may be major drivers of disease spread. The objective of this study is to review the scientific evidence about anosmia in COVID-19. DATA SOURCES PubMed, Google Scholar, and Web of Science. REVIEW METHODS Comprehensive literature search of primary studies pertinent to the objectives of this review using the chosen data sources. CONCLUSIONS Current evidence shows that OD is highly prevalent in COVID-19, with up to 80% of patients reporting subjective OD and objective olfactory testing potentially showing even higher prevalence. OD is frequently accompanied by taste dysfunction. Up to 25% of COVID-19 patients may experience sudden-onset OD as the first symptom. A large proportion of COVID-19 OD cases may resolve over the period of a few weeks. IMPLICATIONS FOR PRACTICE Sudden anosmia should be considered a symptom of COVID-19. Assessing for sudden-onset anosmia may increase sensitivity of COVID-19 screening strategies, in particular for identifying patients at the earliest stages of disease. Since many cases of OD due to COVID-19 may resolve in the short term, conservative management, including observation, is reasonable, while advanced imaging is unnecessary.

positive: Ocular Manifestations of COVID-19 (SARS-CoV-2): A Critical Review of Current Literature The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China in the city of Wuhan in December of 2019 and since then more than 5,000,000 people have been infected, with approximately 338,000 deaths worldwide. The virus causes the coronavirus disease 2019 (COVID-19), which is characterized by fever, myalgia and cough, with severe acute respiratory syndrome being the most fearsome complication. Nevertheless, the vast majority of cases present mild symptoms or none. Central nervous system and cardiovascular manifestations have been reported. The range of ocular manifestations, either as a result of the infection or as a result of the treatment, has not yet been discussed. In this study, a systematic review of current literature relevant to COVID-19 was performed with focus on modes of transmission, ocular manifestations related to infection and medications, as well as the control of infection in ophthalmic practice.

positive: A national prospective cohort study of SARS/COV2 pandemic outcomes in the U.S.: The CHASING COVID Cohort Introduction: The Chasing COVID Cohort (C3) study is a US-based, geographically and socio-demographically diverse sample of adults (18 and older) enrolled into a prospective cohort study during the upswing of the U.S. COVID-19 pandemic. Methods: We used internet-based strategies to enroll C3 participants beginning March 28th, 2020. Following baseline questionnaire completion, study participants will be contacted monthly (for 6 months) to complete assessments of engagement in non-pharmaceutical interventions (e.g., use of cloth masks, avoiding large gatherings); COVID-19 symptoms; SARS/COV2 testing and diagnosis; hospitalizations; healthcare access; and uptake of health messaging. Dried blood spot (DBS) specimens will be collected at the first follow-up assessment (last week of April 2020) and at month 3 (last week of June 2020) and stored until a validated serologic test is available. Results: As of April 20, 2020, the number of people that completed the baseline survey and provided contact information for follow-up was 7,070. Participants resided in all 50 US states, the District of Columbia, Puerto Rico, and Guam. At least 24% of participants were frontline workers (healthcare and other essential workers). Twenty-three percent (23%) were 60+ years, 24% were Black or Hispanic, 52% were men, and 52% were currently employed. Nearly 20% reported recent COVID-like symptoms (cough, fever or shortness of breath) and a high proportion reported engaging in non-pharmaceutical interventions that reduce SARS/COV2 spread (93% avoided groups >20, 58% wore masks; 73% quarantined). More than half (54%) had higher risk for severe COVID-19 illness should they become infected with SARS/COV2 based on age, underlying health conditions (e.g., chronic lung disease), or daily smoking. Discussion: A geographically and socio-demographically diverse group of participants was rapidly enrolled in the C3 during the upswing of the SARS/COV2 pandemic. Strengths of the C3 include the potential for direct observation of, and risk factors for, seroconversion and incident COVID disease (among those with or without antibodies to SARS/COV2) in areas of active transmission.

positive: Neurological manifestations of COVID-19: a review of what we know so far Coronavirus disease 2019 (COVID-19) has become a pandemic disease globally. While it mostly presents with respiratory symptoms, it has already been found that it could manifest with a series of neurological symptoms as well, either at presentation or during the course of the disease. Symptoms vary from non-specific such as headache or dizziness to more specific such as convulsions and cerebrovascular disease (CVD). This study aims to give an overview of the neurological manifestations of COVID-19 and discuss the potential pathogenetic mechanisms of central nervous system (CNS) involvement. Clinicians and especially internists, neurologists, and infectious disease specialists should be aware of these symptoms and able to recognize them early. Prompt diagnosis and immediate management of the neurological manifestations of the novel coronavirus will not only improve the prognosis of COVID-19 patients but will also prevent the dissemination of the disease due to misdiagnosed cases.

positive: Improved Early Recognition of Coronavirus Disease-2019 (COVID-19): Single-Center Data from a Shanghai Screening Hospital BACKGROUND: In December 2019, an outbreak of a novel coronavirus disease (COVID-19; previously known as 2019-nCoV) was reported in Wuhan, Hubei province, China, which has subsequently affected more than 200 countries worldwide including Europe, North America, Oceania, Africa and other places. The number of infected people is rapidly increasing, while the diagnostic method of COVID-19 is only by nucleic acid testing. OBJECTIVE: To explain the epidemiological characteristics, clinical features, imaging manifestations and to judge diagnostic value of COVID-19 by analyzing the clinical data of COVID-19 suspected and confirmed patients in a non-outbreak, Shanghai, China. To clarify the early epidemiology and clinical characteristics about COVID-19. METHODS: Cross-sectional, single-center case reports of the 86 patients screened at Zhoupu Hospital in Pudong New District, Shanghai, China, from January 23 to February 16, 2020. Epidemiology, demography, clinical, laboratory and chest CTs were collected and analyzed. The screened patients were divided into COVID-19 and non-COVID-19 based on nucleic acid test results. RESULTS: Of the 86 screened patients, 11 were confirmed (12.8%) by nucleic acid testing (mean age 40.73 ± 11.32, 5 males). No significant differences were found in clinical symptoms including fever, cough, dyspnea, sore throat, and fatigue (P > 0.05). No statistical difference was observed in plasma C-reactive protein (CRP) between the two groups (COVID-19 and non-COVID-19 ) of patients (P = 0.402), while the white blood cell count and lymphocyte count of the confirmed patients were slightly lower than those of the suspected patients (P < 0.05). Some non-COVID-19 chest CTs also showed subpleural lesions, such as ground-glass opacities (GGO) combined with bronchiectasis; or halo nodules distributed under the pleura with focal GGO; consolidation of subpleural distribution or combined with air bronchi sign and vascular bundle sign, etc. CONCLUSION: The early clinical manifestations and imaging findings of COVID-19 are not characteristic in non-outbreak areas. Etiological testing should be performed as early as possible for clinically suspected patients.

positive: [Early detection and disease assessment of patients with novel coronavirus pneumonia]. In December 2019, the outbreak of novel coronavirus (2019- nCoV) in wuhan, China, attracting attention worldwidely. The novel coronavirus has the characteristics of rapid transmission, atypical clinical symptoms, and easy to affect both lungs, leading to missed diagnosis and misdiagnosis, as well as difficult to detection and assessment at early stage. Fever, cough, myalgia, weakness, dyspnea and imagings may be helpful for the early detection of novel coronavirus pneumonia. At the same time, the rate of disease progression, fever, CT manifestations, hypoxia degree, age, basic diseases, and laboratory indicators can also be used to evaluate the severity of the novel coronavirus pneumonia.

positive: Tackling Corona Virus Disease 2019 (COVID 19) in Workplaces Coronaviruses are zoonotic viruses and six species of Coronaviruses are known to cause human disease such as cause common cold, severe acute respiratory syndrome and the Middle East Respiratory Syndrome. In January 2020, scientists in Wuhan, China isolated a novel coronavirus (SARS-CoV-2), responsible for an outbreak of unknown pneumonia that had not been previously reported among humans. This virus spreads from person to person, through respiratory droplets, close contact, and by touching surfaces or objects contaminated by the virus. The incubation period varies between 2 days and 14 days. Symptoms usually include fever, cough, difficulty in breathing, pneumonia, severe acute respiratory syndrome. Older age and co-morbid conditions increase the fatality. Any person with a history of travel to and from COVID-19 affected countries in the past 14 days or any person who has had close contact with a laboratory confirmed COVID-19 are suspect cases and needs evaluation. Currently no vaccine is available and treatment is mainly supportive. Measures at workplace should include- avoiding non-essential travel, identifying and isolating sick employees at the earliest, hand hygiene, respiratory hygiene, environmental hygiene and social distancing.

positive: Obstetric Anesthesia During the Coronavirus Disease 2019 Pandemic With increasing numbers of Coronavirus Disease 2019 (COVID19) cases due to efficient human-to-human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the United States, preparation for the unpredictable setting of labor and delivery is paramount. The priorities are 2-fold in the management of obstetric patients with COVID-19 infection or persons under investigation (PUI): (1) caring for the range of asymptomatic to critically ill pregnant and postpartum women; (2) protecting health care workers and beyond from exposure during the delivery hospitalization (health care providers, personnel, family members). The goal of this review is to provide evidence-based recommendations or, when evidence is limited, expert opinion for anesthesiologists caring for pregnant women during the COVID19 pandemic with a focus on preparedness and best clinical obstetric anesthesia practice.

positive: First case of severe childhood novel coronavirus pneumonia in China/ 中华儿科杂志

positive: Neurologic manifestations in hospitalized patients with COVID-19: The ALBACOVID registry OBJECTIVE: The coronavirus disease 2019 (COVID-19) has spread worldwide since December 2019. Neurological symptoms have been reported as part of the clinical spectrum of the disease. We aim to determine whether neurological manifestations are common in hospitalized COVID-19 patients and to describe their main characteristics. METHODS: We systematically review all patients diagnosed with COVID-19 admitted to hospital in a Spanish population during March 2020. Demographic characteristics, systemic and neurological clinical manifestations, and complementary tests were analyzed. RESULTS: Of 841 patients hospitalized with COVID-19 (mean age 66.4 years, 56.2% men) 57.4% developed some form of neurological symptom. Nonspecific symptoms such as myalgias (17.2%), headache (14.1%), and dizziness (6.1%) were present mostly in the early stages of infection. Anosmia (4.9%) and dysgeusia (6.2%) tended to occur early (60% as the first clinical manifestation) and were more frequent in less severe cases. Disorders of consciousness occurred commonly (19.6%), mostly in older patients and in severe and advanced COVID-19 stages. Myopathy (3.1%), dysautonomia (2.5%), cerebrovascular diseases (1.7%), seizures (0.7%), movement disorders (0.7%), encephalitis (n=1), Guillain-Barré syndrome (n=1), and optic neuritis (n=1) were also reported, but less frequent. Neurological complications were the main cause of death in 4.1% of all deceased study subjects. CONCLUSIONS: Neurological manifestations are common in hospitalized COVID-19 patients. In our series, more than half of patients presented some form of neurological symptom. Clinicians need to maintain close neurological surveillance for prompt recognition of these complications. The investigation of the mechanisms and emerging consequences of SARS-CoV-2 neurological involvement require further studies.

positive: COVID-19: Specific and non-specific clinical manifestations and symptoms: The current state of knowledge Coronavirus disease 2019 (COVID-19), due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become an epidemiological threat and a worldwide concern. SARS-CoV-2 has spread to 210 countries worldwide and more than 6,500,000 confirmed cases and 384,643 deaths have been reported, while the number of both confirmed and fatal cases is continually increasing. COVID-19 is a viral disease that can affect every age group—from infants to the elderly—resulting in a wide spectrum of various clinical manifestations. COVID-19 might present different degrees of severity—from mild or even asymptomatic carriers, even to fatal cases. The most common complications include pneumonia and acute respiratory distress syndrome. Fever, dry cough, muscle weakness, and chest pain are the most prevalent and typical symptoms of COVID-19. However, patients might also present atypical symptoms that can occur alone, which might indicate the possible SARS-CoV-2 infection. The aim of this paper is to review and summarize all of the findings regarding clinical manifestations of COVID-19 patients, which include respiratory, neurological, olfactory and gustatory, gastrointestinal, ophthalmic, dermatological, cardiac, and rheumatologic manifestations, as well as specific symptoms in pediatric patients.

positive: Ophthalmic Manifestations Of Coronavirus (COVID-19) Since December 2019, coronavirus disease 2019 (COVID-19) has become a global pandemic caused by the highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1] There have been several reports of eye redness and irritation in COVID-19 patients, both anecdotal and published, suggesting that conjunctivitis may be an ocular manifestation of SARS-CoV-2 infection A study conducted during the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak detected SARS-CoV in tear samples in SARS patients in Singapore [2] Lack of eye protection was a primary risk factor of SARS-CoV transmission from SARS patients to healthcare workers in Toronto, prompting a concern that respiratory illness could be transmitted through ocular secretions [3][[4] Similar concerns have been raised with SARS-CoV-2, especially among eye care providers and those on the front lines triaging what could be initial symptoms of COVID-19 As conjunctivitis is a common eye condition, ophthalmologists may be the first medical professionals to evaluate a patient with COVID-19 Indeed, one of the first providers to voice concerns regarding the spread of Coronavirus in Chinese patients was Li Wenliang, MD, an ophthalmologist He later died from COVID-19 and was believed to have contracted the virus from an asymptomatic glaucoma patient in his clinic The authors of this article have attempted to collect the most up-to-date information on ophthalmic manifestations of COVID-19 as a resource for identifying symptoms, providing diagnostic pearls, and mitigating transmission

positive: COVID-19 and Anosmia in Tehran, Iran Patients with acute olfactory disorders typically present to the otolaryngologist with both acute hyposmia and less often with anosmia. With the onset of COVID-19 we have noticed an increase in the number of patients who have presented with new onset of complete smell loss to the senior author’s practice in Tehran, Iran. This anosmia and the frequency with which patients present is highly unusual. Coronaviruses have been known to cause common cold symptoms. COVID-19 infections have been described as causing more severe respiratory infections and the symptoms reported by authors from Wuhan, China have not specifically included anosmia. We describe patients who have presented during a two-week period of the COVID-19 pandemic with complete loss of sense of smell. Most had either no symptoms or mild respiratory symptoms. Many had a normal otolaryngologic exam. A relationship between COVID-19 and anosmia should be considered during the pandemic. We hypothesize that the mechanism of injury is similar to that of other coronavirus infections that cause central and peripheral neurologic deficits.

positive: First documentation of persistent SARS-CoV-2 infection presenting with late acute severe myocarditis. A 64 year-old man presented with severe myocarditis 6 weeks after an initial almost asymptomatic SARS-CoV2 infection. He was found to have a persistent positive swab. Mechanisms explaining myocardial injury in patients with COVID-19 remains unclear, but this case suggests that severe acute myocarditis can develop in the late phase of COVID-19 infection, even after a symptom-free interval.

positive: Nosocomial outbreak of COVID-19 pneumonia in Wuhan, China BACKGROUND: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infected over 3300 healthcare workers in early 2020 in China. Little information is known about nosocomial infections of healthcare workers in the initial period. We analysed data from healthcare workers with nosocomial infections in Wuhan Union Hospital (Wuhan, China) and their family members. METHODS: We collected and analysed data on exposure history, illness timelines and epidemiological characteristics from 25 healthcare workers with laboratory-confirmed coronavirus disease 2019 (COVID-19) and two healthcare workers in whom COVID-19 was highly suspected, as well as 10 of their family members with COVID-19, between 5 January and 12 February 2020. The demographics and clinical features of the 35 laboratory-confirmed cases were investigated and viral RNA of 12 cases was sequenced and analysed. RESULTS: Nine clusters were found among the patients. All patients showed mild to moderate clinical manifestation and recovered without deterioration. The mean period of incubation was 4.5 days, the mean±sd clinical onset serial interval (COSI) was 5.2±3.2 days, and the median virus shedding time was 18.5 days. Complete genomic sequences of 12 different coronavirus strains demonstrated that the viral structure, with small irrelevant mutations, was stable in the transmission chains and showed remarkable traits of infectious traceability. CONCLUSIONS: SARS-CoV-2 can be rapidly transmitted from person to person, regardless of whether they have symptoms, in both hospital settings and social activities, based on the short period of incubation and COSI. The public health service should take practical measures to curb the spread, including isolation of cases, tracing close contacts, and containment of severe epidemic areas. Besides this, healthcare workers should be alert during the epidemic and self-quarantine if self-suspected of infection.

positive: Asymptomatic SARS-CoV-2 infected patients with persistent negative CT findings

positive: Clinical characteristics of severe acute respiratory syndrome coronavirus 2 reactivation Summary Objectives Previous studies on the pneumonia outbreak caused by the 2019 novel coronavirus disease (COVID-19) were based on information from the general population. However, limited data was available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reactivation. This study aimed to evaluate the clinical characteristics of the SARS-CoV-2 reactivation. Methods Clinical records, laboratory results, and chest CT scans were retrospectively reviewed for 55 patients with laboratory-confirmed COVID-19 pneumonia (i.e., with throat swab samples that were positive for SARS-CoV-2) who were admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, from Jan. 8 to Feb. 10, 2020. Results All 55 patients had a history of epidemiological exposure to COVID-19, and 5 (9%) patients who discharged from hospital presented with SARS-CoV-2 reactivation. Among the 5 reactivated patients, other symptoms were also observed, including fever, cough, sore throat, and fatigue. One of the 5 patients had progressive lymphopenia (from 1.3 to 0.56 × 109 cells per L) and progressive neutrophilia (from 4.5 to 18.28 × 109 cells per L). All 5 reactivated patients presented normal aminotransferase levels. Throat swab samples from the 5 reactivated patients were tested for SARS-CoV-2, indicating all positive for the virus. Conclusions Findings from this small group of cases suggested that there was currently evidence for reactivation of SARS-CoV-2 and there might be no specific clinical characteristics to distinguish them.

positive: 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.

positive: Severe acute respiratory syndrome coronavirus 2 is penetrating to dementia research. 1. Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus infectious disease 2019 (COVID-19), which was first reported in Wuhan, China, in late December, 2019. Despite the tremendous efforts to control the disease, SARS-CoV-2 has infected 1,5 million people and caused the death of more than a hundred thousand people across the globe as of writing. Recently, Mao et al. [1] investigated the penetration potential of SARS-CoV-2 into the central nervous system in 214 patients. They reported that 36.4% of the patients had some neurologic findings which are ranged from nonspecific manifestations, e.g., dizziness, headache, and seizure, to specific manifestations, e.g., loss of sense of smell or taste, and stroke. Whether these common symptoms in their patients are related to SARS-CoV-2 infection is not known. However, it is important to mention here that dramatic neurologic symptoms, i.e., depressed level of consciousness, seizure, and stroke, are common in the patients at the late stage of the disease, accounting for increased mortality rate in severely affected patients. Nevertheless, to objectively delve into the direct relation between the neurologic symptoms and COVID-19, medical comorbidities of patients should also be considered [2]. Further studies are needed because we are in the midst of an ongoing pandemic of COVID-19, and neurologists may be confronted with new-onset neurologic symptoms owing to COVID-19. SARS-CoV-2 penetrates via human angiotensin-converting enzyme-2 receptor (ACE-2) that was also utilized by severe acute respiratory syndrome coronavirus (SARS CoV) [3]. Glial cells and neurons have been reported to express ACE-2 receptors, which make them a potential target of COVID-19. It was indicated that SARS CoV causes neuronal death by invading the brain via olfactory epithelium [4]. The electron microscopy, immunohistochemistry, and real-time reverse transcription- PCR findings have corroborated the presence of SARS-CoV in the brain tissue [4] and cerebrospinal fluid [5]. Together, it can be speculated that SARS-CoV-2 can affect the brain by penetrating the brain via the cribriform plate, which can account for the early findings of the COVID-19 like altered sense of smell or hyposmia. Because SARS-CoV-2 causes severe respiratory symptoms in people aged 60 years and older, it has important implications for patients with Alzheimer's disease (AD) [6]. Therefore, in the countries that have taken action to the virus, clinic studies of AD have been stopped to protect the patients. However, rigorous quarantine of elders has aborted clinic trials and experimental studies conducted with transgenic animals. Transgenic models are quite expensive; the loss of these animals has costly consequences. There is no doubt that this storm will stop, but its catastrophic effects on dementia research will continue for a time. Thus, dementia researchers and pharmaceutical companies should determine an emergency action plan to exit the chaos of this pandemic. Here, we listed some challenges in dementia research during the COVID-19 outbreak and table some suggestions. All countries try to control SARS-CoV-2 by social distancing. Therefore, neurology clinics were closed, and routine examination of Alzheimer's patients was stopped. However, the lockdown of patients with AD caused clinical studies to stop. which has severely affected dementia research. Additionally, the arrest of experimental studies due to the closing of universities in two hundred countries also deprives experimental achievements. The closing of universities may lead to data loss, death of expensive transgenic animals, international researchers to be faced with visa problems, and be lost the laboratory staff whose contract has expired [7]. It is impossible that forecasting when this COVID-19 pandemic will end is impossible and thus, it is essential that a solution be developed to continue dementia studies on Alzheimer's patients. Remote monitoring of the patients with the use of technology is in the lead of possible solutions. Clinicians can continue to follow their patients by telemedicine [8], but extended lockdown of patients may cause depression in both patients and their caregivers [9]. It is also known that movement restriction exacerbates AD symptoms [10]. The monitorization of the patient in this condition with telemedicine would not provide objective data. In addition, when patients living in rural areas are considered, it will not be a surprise that reaching equally all patients is impossible. Therefore, a collective action plan protecting dementia research during the COVID-19 outbreak should be prepared by a consortium of pharmaceutical companies, researchers, clinicians, and patients. Data loss is in the lead of expected problems during the COVID-19 outbreak. For example, the planned ending dates of phase 2/3 trials of gantenerumab (Roche) and solanezumab (Lilly) were missed [11]. It is highly essential that patients be monitored from their homes with telemedicine to protect them. Nonetheless, it is not sufficient for the continuation of clinical trials and experimental studies. We suggest that patients of phase trails should be isolated in fully-equipped nursing homes managed by qualified personnel. In this way, the patients can be more effectively protected from SARS-CoV-2 and the depression caused by the lockdown.Young family members going out for basic needs could infect older family members. Also, patients with AD pay less attention to hand hygiene, which makes them more susceptible to SARS-CoV-2. Moreover, cats have recently been shown to be infected by SARS-CoV-2 [12]. Patients with AD may not follow directions of neurologists on telemedicine and thus, the interaction of Alzheimer's patients with pets can cause a dangerous scenario. Consequently, the lockdown of patients with dementia in their homes might not be an appropriate exit strategy for the future of dementia research. On the other hand, it is important to mention here that the nursing home capacity of the United States may not be sufficient for 5,8 million Alzheimer's patients aged 65 years and older [13]. Thus, we highlight that only the patients involved in the clinic trails should be followed in the nursing homes. The other patients can be monitored with telemedicine from their homes. The data will hardly be lost in patients isolated in nursing homes. In this strategy, secondary risk factors affecting the clinic trails like depression are also removed. The motivations of clinicians and researchers is as important as the patients in the catastrophic atmosphere of the outbreak. Governments, media, and funders can support the motivations of clinicians and researchers. For example, research funders and pharmaceutical companies can extend project deadlines and provide an additional promotion to the researchers who have completed their clinic trails. Consequently, a global action plan should be prepared to block SARS-CoV-2 penetration to dementia research. At first glance, it may be thought that the most appropriate strategy for patients with dementia is social isolation in their homes during the outbreak as in healthy young people and elders. However, we suggest that isolating patients with dementia in fully-equipped nursing homes can be a more appropriate exit strategy for the protection of dementia patients and research.

positive: Covid-19 Has Come Home to Roost in Gastroenterology

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

positive: Imaging dynamic observation of COVID-19 patients cured by imported coronavirus pneumonia/ 中华放射学杂志 Objective@#To explore the imaging changes of lung lesions in patients with imported COVID-19 patients when reaching the discharge standard.@*Method@#The clinical and CT imaging data of 60 patients with imported COVID-19 cured and discharged from January to February 2020 in Anhui Province were retrospectively collected. The clinical characteristics of the patients and the characteristics of chest CT images at discharge were analyzed.@*Results@#Fever (57 cases) and cough (55 cases) were the main symptoms in 60 patients. At the initial diagnosis, 5 cases were mild, 53 were ordinary, and 2 were severe. In 5 light patients, 3 cases were negative in the whole course of CT examination, 2 cases were negative in the first time and abnormal in the second time. . The first CT imaging features of 55 patients (53 common type and 2 severe type)were mainly bilateral lung involvement (51 cases), multiple lesions (33 cases), more common under the pleura (40 cases), and ground glass opacities were the most common. (55 cases). The clinical features of chest CT in clinical outcomes are that the ground glass shadow in the lung gradually fades and was completely absorbed (19 cases); the scope of ground glass shadow in the lung expanded and progressed to crazy-paving, consolidation shadow, and the lesion gradually absorbs again followed by Fibrous cord shadows (27 cases); ground-glass opacities in the lungs quickly progressed to a consolidation and then slowly absorbed . Most of the lesions were accompanied by more residual fibrous cord shadows (4 cases). In 2 severe patients, the lesions in the lungs were larger ground glass, and a big amount of fibrous foci remained after slowly absorption.@*Conclusion@#Chest CT plays an important role in the diagnosis and treatment of imported COVID-19, and the degree of lung involvement seen on CT images is in good agreement with clinical outcome.

positive: A primer on viral‐associated olfactory loss in the era of COVID‐19 Early reports have suggested that smell loss may be an early symptom associated with the pandemic known as COVID‐19. The possibility that severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) might cause olfactory dysfunction is certainly plausible. Patients presenting to specialized smell clinics are commonly diagnosed with upper respiratory infection (URI)‐associated olfactory loss and most are presumed to be viral related. In acute phases of infection, it is common to experience some smell loss as a result of nasal inflammation, mucosal edema, and obstruction of airflow into the olfactory cleft. In most cases, these episodes of smell loss are self‐limiting and coincide with resolution of URI symptoms. However, in some cases the smell loss persists for months to years and this is presumed to occur through a more direct olfactory insult by the virus. It remains too early to know whether infection with SARS‐CoV‐2 causes persistent olfactory dysfunction. However, given the scale of this pandemic, if SARS‐CoV‐2 does cause chronic olfactory loss in even a small portion of those infected, then the overall population prevalence could be quite large. This review provides a brief, practical overview of viral‐associated olfactory loss, realizing that evidence related to COVID‐19 will likely not be clear for some time. Our goal is to highlight the existence and importance of this condition and provide information geared for both providers and patients. Practical suggestions regarding evaluation and treatment will be provided, realizing that there may be constraints on medical resources and the nature of this pandemic remains dynamic. This article is protected by copyright. All rights reserved

positive: Shedding Light on Dysphagia Associated With COVID-19: The What and Why The most common symptom of COVID-19 in critically ill patients is ARDS (acute respiratory distress syndrome), with many patients requiring invasive or noninvasive respiratory support in the intensive care unit. Oropharyngeal dysphagia may be a consequence of the respiratory-swallowing incoordination common in ARDS or may occur following the respiratory support interventions. In this commentary, we highlight the risk and complications of oropharyngeal dysphagia in patients with COVID-19 and urge medical and rehabilitation professionals to consider dysphagia a prognostic complication, provide appropriate referrals, and initiate early interventions as appropriate.

positive: Severe acute respiratory syndrome coronavirus 2 is penetrating to dementia research 1. Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus infectious disease 2019 (COVID-19), which was first reported in Wuhan, China, in late December, 2019. Despite the tremendous efforts to control the disease, SARS-CoV-2 has infected 1,5 million people and caused the death of more than a hundred thousand people across the globe as of writing. Recently, Mao et al. [1] investigated the penetration potential of SARS-CoV-2 into the central nervous system in 214 patients. They reported that 36.4% of the patients had some neurologic findings which are ranged from nonspecific manifestations, e.g., dizziness, headache, and seizure, to specific manifestations, e.g., loss of sense of smell or taste, and stroke. Whether these common symptoms in their patients are related to SARS-CoV-2 infection is not known. However, it is important to mention here that dramatic neurologic symptoms, i.e., depressed level of consciousness, seizure, and stroke, are common in the patients at the late stage of the disease, accounting for increased mortality rate in severely affected patients. Nevertheless, to objectively delve into the direct relation between the neurologic symptoms and COVID-19, medical comorbidities of patients should also be considered [2]. Further studies are needed because we are in the midst of an ongoing pandemic of COVID-19, and neurologists may be confronted with new-onset neurologic symptoms owing to COVID-19. SARS-CoV-2 penetrates via human angiotensin-converting enzyme-2 receptor (ACE-2) that was also utilized by severe acute respiratory syndrome coronavirus (SARS CoV) [3]. Glial cells and neurons have been reported to express ACE-2 receptors, which make them a potential target of COVID-19. It was indicated that SARS CoV causes neuronal death by invading the brain via olfactory epithelium [4]. The electron microscopy, immunohistochemistry, and real-time reverse transcription- PCR findings have corroborated the presence of SARS-CoV in the brain tissue [4] and cerebrospinal fluid [5]. Together, it can be speculated that SARS-CoV-2 can affect the brain by penetrating the brain via the cribriform plate, which can account for the early findings of the COVID-19 like altered sense of smell or hyposmia. Because SARS-CoV-2 causes severe respiratory symptoms in people aged 60 years and older, it has important implications for patients with Alzheimer's disease (AD) [6]. Therefore, in the countries that have taken action to the virus, clinic studies of AD have been stopped to protect the patients. However, rigorous quarantine of elders has aborted clinic trials and experimental studies conducted with transgenic animals. Transgenic models are quite expensive; the loss of these animals has costly consequences. There is no doubt that this storm will stop, but its catastrophic effects on dementia research will continue for a time. Thus, dementia researchers and pharmaceutical companies should determine an emergency action plan to exit the chaos of this pandemic. Here, we listed some challenges in dementia research during the COVID-19 outbreak and table some suggestions. All countries try to control SARS-CoV-2 by social distancing. Therefore, neurology clinics were closed, and routine examination of Alzheimer's patients was stopped. However, the lockdown of patients with AD caused clinical studies to stop. which has severely affected dementia research. Additionally, the arrest of experimental studies due to the closing of universities in two hundred countries also deprives experimental achievements. The closing of universities may lead to data loss, death of expensive transgenic animals, international researchers to be faced with visa problems, and be lost the laboratory staff whose contract has expired [7]. It is impossible that forecasting when this COVID-19 pandemic will end is impossible and thus, it is essential that a solution be developed to continue dementia studies on Alzheimer's patients. Remote monitoring of the patients with the use of technology is in the lead of possible solutions. Clinicians can continue to follow their patients by telemedicine [8], but extended lockdown of patients may cause depression in both patients and their caregivers [9]. It is also known that movement restriction exacerbates AD symptoms [10]. The monitorization of the patient in this condition with telemedicine would not provide objective data. In addition, when patients living in rural areas are considered, it will not be a surprise that reaching equally all patients is impossible. Therefore, a collective action plan protecting dementia research during the COVID-19 outbreak should be prepared by a consortium of pharmaceutical companies, researchers, clinicians, and patients. Data loss is in the lead of expected problems during the COVID-19 outbreak. For example, the planned ending dates of phase 2/3 trials of gantenerumab (Roche) and solanezumab (Lilly) were missed [11]. It is highly essential that patients be monitored from their homes with telemedicine to protect them. Nonetheless, it is not sufficient for the continuation of clinical trials and experimental studies. We suggest that patients of phase trails should be isolated in fully-equipped nursing homes managed by qualified personnel. In this way, the patients can be more effectively protected from SARS-CoV-2 and the depression caused by the lockdown.Young family members going out for basic needs could infect older family members. Also, patients with AD pay less attention to hand hygiene, which makes them more susceptible to SARS-CoV-2. Moreover, cats have recently been shown to be infected by SARS-CoV-2 [12]. Patients with AD may not follow directions of neurologists on telemedicine and thus, the interaction of Alzheimer's patients with pets can cause a dangerous scenario. Consequently, the lockdown of patients with dementia in their homes might not be an appropriate exit strategy for the future of dementia research. On the other hand, it is important to mention here that the nursing home capacity of the United States may not be sufficient for 5,8 million Alzheimer's patients aged 65 years and older [13]. Thus, we highlight that only the patients involved in the clinic trails should be followed in the nursing homes. The other patients can be monitored with telemedicine from their homes. The data will hardly be lost in patients isolated in nursing homes. In this strategy, secondary risk factors affecting the clinic trails like depression are also removed. The motivations of clinicians and researchers is as important as the patients in the catastrophic atmosphere of the outbreak. Governments, media, and funders can support the motivations of clinicians and researchers. For example, research funders and pharmaceutical companies can extend project deadlines and provide an additional promotion to the researchers who have completed their clinic trails. Consequently, a global action plan should be prepared to block SARS-CoV-2 penetration to dementia research. At first glance, it may be thought that the most appropriate strategy for patients with dementia is social isolation in their homes during the outbreak as in healthy young people and elders. However, we suggest that isolating patients with dementia in fully-equipped nursing homes can be a more appropriate exit strategy for the protection of dementia patients and research.

positive: Diarrhea is associated with prolonged symptoms and viral carriage in COVID-19 Abstract Background & Aims We compared clinical, laboratory, radiological, and outcome features of patients with SARS-CoV-2 infection (COVID-19) with pneumonia, with vs without diarrhea. Methods We performed a retrospective, single-center analysis of 84 patients with SARS-CoV-2 pneumonia in Wuhan Union Hospital, China, from January 19 through February 7, 2020. Cases were confirmed by real-time reverse-transcriptase PCR of nasal and pharyngeal swab specimens for SARS-CoV-2 RNA. Blood samples were analyzed for white blood cell count, lymphocyte count, alanine aminotransferase, creatine kinase, lactate dehydrogenase, D-dimer, C-reactive protein, and in some cases, immunoglobulins, complement, lymphocyte subsets, and cytokines. Virus RNA was detected in stool samples by real-time PCR. Results Of the 84 patients with SARS-CoV-2 pneumonia, 26 (31%) had diarrhea. The duration of fever and dyspnea in patients with diarrhea was significantly longer than those without diarrhea (all P<.05). Stool samples from a higher proportion of patients with diarrhea tested positive for virus RNA (69%) than from patients without diarrhea (17%) (P<.001). As of February 19, a lower proportion of patients with diarrhea had a negative result from the latest throat swab for SARS-CoV-2 (77%) than patients without diarrhea (97%) (P=.010), during these patients’ hospitalization. Of 76 patients with a negative result from their latest throat swab test during hospitalization, a significantly higher proportion of patients with diarrhea had a positive result from the retest for SARS-CoV-2 in stool (45%) than patients without diarrhea (20%) (P=.039). Conclusions At a single center in Wuhan, China, 31% of patients with SARS-CoV-2 pneumonia had diarrhea. A significantly higher proportion of patients with diarrhea have virus RNA in stool than patients without diarrhea. Elimination of SARS-CoV-2 from stool takes longer than elimination from the nose and throat.

positive: Clinical and Epidemiological Characteristics of 1,420 European Patients with mild‐to‐moderate Coronavirus Disease 2019 BACKGROUND: The clinical presentation of European patients with mild‐to‐moderate Covid‐19 infection is still unknown. OBJECTIVE: To study the clinical presentation of Covid‐19 in Europe. METHODS: Patients with positive diagnosis of Covid‐19 were recruited from 18 European hospitals. Epidemiological and clinical data were obtained through a standardized questionnaire. Bayesian analysis was used for analyzing the relationship between outcomes. RESULTS: 1,420 patients completed the study (962 females, 30.7% of health care workers). The mean age of patients was 39.17±12.09 years. The most common symptoms were headache (70.3%), loss of smell (70.2%), nasal obstruction (67.8%), cough (63.2%), asthenia (63.3%), myalgia (62.5%), rhinorrhea (60.1%), gustatory dysfunction (54.2%) and sore throat (52.9%). Fever was reported by on 45.4%. The mean duration of Covid‐19 symptoms of mild‐to‐moderate cured patients was 11.5±5.7 days. The prevalence of symptoms significantly varied according to age and sex. Young patients more frequently had ear, nose, and throat complaints, whereas elderly individuals often presented fever, fatigue and loss of appetite. Loss of smell, headache, nasal obstruction and fatigue were more prevalent in female patients. The loss of smell was a key symptom of mild‐to‐moderate Covid19 patients and was not associated with nasal obstruction and rhinorrhea. Loss of smell persisted at least 7 days after the disease in 37.5% of cured patients. CONCLUSION: The clinical presentation of mild‐to‐moderate Covid‐19 substantially varies according to the age and the sex characteristics of patients. Olfactory dysfunction seems to be an important underestimated symptom of mild‐to‐moderate Covid‐19 that needs to be recognized as such by the WHO.

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: Case of the Index Patient Who Caused Tertiary Transmission of Coronavirus Disease 2019 in Korea: the Application of Lopinavir/Ritonavir for the Treatment of COVID-19 Pneumonia Monitored by Quantitative RT-PCR Since mid-December of 2019, coronavirus disease 2019 (COVID-19) has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, β-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.

positive: [Clinical and epidemiological characteristics of 34 children with 2019 novel coronavirus infection in Shenzhen]. Objective: To describe the characteristics of clinical manifestations and epidemiology of children with 2019 novel coronavirus (2019-nCoV) infection. Methods: All 34 children with laboratory-confirmed 2019-nCoV infection by quantitative real-time reverse transcription-PCR through nasopharyngeal swab specimens were admitted to the Third People's Hospital of Shenzhen from January 19 to Febuary 7, 2020. Clinical data and epidemiological history of these patients were retrospectively collected and analyzed. Results: Among the 34 cases, 14 were males, and 20 were females. The median age was 8 years and 11 months. No patients had underlying diseases. There were 28 children (82%) related with a family cluster outbreak. There were 26 children (76%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 22 (65%) common cases, 9 (26%) mild cases and 3 (8.8%) asymptomatic cases. No severe or critical cases were identified. The most common symptoms were fever (17 cases, 50%) and cough (13 cases, 38% ). In the 34 cases, the white blood cell counts of 28 cases (82%) were normal. Five cases had white blood cell counts more than 10×10(9)/L. One case had white blood cell counts less than 4×10(9)/L. Neutropenia and lymphopenia was found in one case, respectively. C-reactive protein levels and erythrocyte sedimentation rates were elevated in 1 and 5 case, respectively. Elevated procalcitonin was found in 1 case and D-Dimer in 3 cases. The levels of lactic dehydrogenase (LDH) were more than 400 U/L in 10 cases. The CT images of these patients showed bilateral multiple patchy or nodular ground-glass opacities and/or infiltrating shadows in middle and outer zone of the lung or under the pleura. Twenty patients were treated with lopinavir and ritonavir. Glucocorticoids and immunoglobulin were not used in any cases. All the cases improved and were discharged from hospital. Further following up was need. Conclusions: The clinical manifestations in children with 2019-nCoV infection are non-specific and are milder than that in adults. Chest CT scanning is heplful for early diagnosis. Children's infection is mainly caused by family cluster outbreak and imported cases. Family daily prevention is the main way to prevent 2019-nCoV infection.

positive: Gastrointestinal, and hepatic involvement in Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infection: A review Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infection has caused a pandemic Coronavirus Disease-19 (COVID-19) that began in Wuhan city, China, in December 2019. Till 14(th) April 19,39,801 people have been affected by this virus 1,20,897 of whom died. Though respiratory symptoms are the typical manifestation of this disease, gastrointestinal (GI) symptoms such as anorexia, nausea, vomiting, loss of taste sensation, diarrhea, abdominal pain, and discomfort have been reported. The pooled prevalence of GI symptom is 17.6% (95% confidence interval [CI], 12.3%–24.5%), as indicated in a meta-analysis. A few studies suggested that the presence of GI symptoms is associated with poorer prognosis. The virus is excreted in feces during the acute disease, and even after the nasopharyngeal swab has become negative for viral ribonucleic acid (RNA). Fecal viral excretion may have clinical significance due to possible feco-oral transmission of the infection. 10.5% to 53% of patients with COVID-19, particularly those with severe disease, have been shown to have an elevation of hepatic enzymes through biochemical and clinical jaundice, are uncommon. Knowledge about this disease in general and GI involvement, in particular, is currently evolving.

positive: Concomitant neurological symptoms observed in a patient diagnosed with coronavirus disease 2019

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: Does this patient have COVID-19? A practical guide for the internist Coronavirus disease 2019 (COVID-19) is currently causing a pandemic and will likely persist in endemic form in the foreseeable future. Physicians need to correctly approach this new disease, often representing a challenge in terms of differential diagnosis. Although COVID-19 lacks specific signs and symptoms, we believe internists should develop specific skills to recognize the disease, learning its ‘semeiotic’. In this review article, we summarize the key clinical features that may guide in differentiating a COVID-19 case, requiring specific testing, from upper respiratory and/or influenza-like illnesses of other aetiology. We consider two different clinical settings, where availability of the different diagnostic strategies differs widely: outpatient and inpatient. Our reasoning highlights how challenging a balanced approach to a patient with fever and flu-like symptoms can be. At present, clinical workup of COVID-19 remains a hard task to accomplish. However, knowledge of the natural history of the disease may aid the internist in putting common and unspecific symptoms into the correct clinical context.

positive: [Clinical analysis of 31 cases of 2019 novel coronavirus infection in children from six provinces (autonomous region) of northern China]. Objective: To analyze the epidemiological history, clinical manifestations, treatment and the short-term prognosis of 31 cases of 2019 novel coronavirus(2019-nCoV) infection in children from six provinces (autonomous region) in northern China. Methods: A retrospective analysis of the epidemiological history, clinical symptoms, signs, laboratory examinations, chest imaging, treatment and the short-term prognosis of 31 cases of 2019-nCoV was conducted. The patients were diagnosed between January 25th, 2020 and February 21st, 2020 in 21 hospitals in 17 cities of six provinces(autonomous region) of Shaanxi, Gansu, Ningxia, Hebei, Henan and Shandong. Results: The age of the 31 children with 2019-nCoV infection was 7 years and 1 month (6 months -17 years). Nine cases (29%) were imported cases. Other 21 cases (68%) had contact with confirmed infected adults. One case (3%) had contact with asymptomatic returnees from Wuhan. Among the 31 children, 28 patients (90%) were family cluster cases. The clinical types were asymptomatic type in 4 cases (13%), mild type in 13 cases (42%), and common type in 14 cases (45%). No severe or critical type existed. The most common symptom was fever (n=20, 65%), including 1 case of high fever, 9 cases of moderate fever, 10 cases of low fever. Fever lasted from 1 day to 9 days. The fever of fifteen cases lasted for ≤3 d, while in other 5 cases lasted > 3 d. Other symptoms included cough (n=14, 45%), fatigue (n=3, 10%) and diarrhea (n=3, 9%). Pharyngalgia, runny nose, dizziness, headache and vomiting were rare. In the early stage, the total leukocytes count in peripheral blood decreased in 2 cases (6%), the lymphocytes count decreased in 2 cases (6%), and the platelet count increased in 2 cases (6%).Elevation of C-reactive protein (10%, 3/30), erythrocyte sedimentation rate(19%,4/21), procalcitonin(4%,1/28), liver enzyme(22%, 6/27) and muscle enzyme (15%, 4/27) occurred in different proportions. Renal function and blood glucose were normal. There were abnormal chest CT changes in 14 cases, including 9 cases with patchy ground glass opacities and nodules, mostly located in the lower lobe of both lungs near the pleural area. After receiving supportive treatment, the viral nucleic acid turned negative in 25 cases within 7-23 days. Among them, 24 children (77%) recovered and were discharged from hospital. No death occurred. Conclusions: In this case series, 2019-nCoV infections in children from six provinces (autonomous region) in northern China are mainly caused by close family contact. Clinical types are asymptomatic, mild and common types. Clinical manifestations and laboratory examination results are nonspecific. Close contact history of epidemiology, nucleic acid detection and chest imaging are important bases for diagnosis. After general treatment, the short-term prognosis is good.

positive: The clinical characteristics of pneumonia patients coinfected with 2019 novel coronavirus and influenza virus in Wuhan, China The outbreak of 2019 novel coronavirus (COVID-19) infection emerged in Wuhan, China, in December 2019. Since then the novel coronavirus pneumonia disease has been spreading quickly and many countries and territories have been affected, with major outbreaks in China, South Korea, Italy, and Iran. Influenza virus has been known as a common pathogen in winter and it can cause pneumonia. It was found clinically that very few patients were diagnosed with both COVID-19 and influenza virus. A total of 5 of the 115 patients confirmed with COVID-19 were also diagnosed with influenza virus infection, with three cases being influenza A and two cases being influenza B. In this study, we describe the clinical characteristics of those patients who got infected with COVID-19 as well as influenza virus. Common symptoms at onset of illness included fever (five [100%] patients), cough (five [100%] patients), shortness of breath (five [100%] patients), nasal tampon (three [60%] patients), pharyngalgia (three [60%] patients), myalgia (two [40%] patients), fatigue (two [40%] patients), headache (two [40%] patients), and expectoration (two [40%] patients). The laboratory results showed that compared to the normal values, the patients' lymphocytes were reduced (four [80%] patients), and liver functions alanine aminotransferase and aspartate aminotransferase (two [40%] patients and two [40%] patients) and C-reactive protein (four [80%] patients) were increased when admitted to hospital. They stayed in the hospital for 14, 30, 17, 12, and 19 days (28.4 ± 7.02), respectively. The main complications for the patients were acute respiratory distress syndrome (one [20%] patients), acute liver injury (three [60%] patients), and diarrhea (two [40%] patients). All patients were given antiviral therapy (including oseltamivir), oxygen inhalation, and antibiotics. Three patients were treated with glucocorticoids including two treated with oral glucocorticoids. One of the five patients had transient hemostatic medication for hemoptysis. Fortunately, all patients did not need intensive care unit and were discharged from the hospital without death. In conclusion, those patients with both COVID-19 and influenza virus infection did not appear to show a more severe condition because based on the laboratory findings, imaging studies, and patient prognosis, they showed similar clinical characteristics as those patients with COVID-19 infection only. However, it is worth noting that the symptoms of nasal tampon and pharyngalgia may be more prone to appear for those coinfection patients.

positive: Neurologic Characteristics in Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-Analysis Importance: Coronavirus disease 2019 (COVID-19) is a newly emerging infectious disease that has caused a global pandemic. The presenting symptoms are mainly respiratory symptom, yet studies have reported nervous system involvement in the disease. A systematic review and meta-analysis of these studies are required to understanding the neurologic characteristic of the disease and help physicians with early diagnosis and management. Objective: To conduct a systematic review and meta-analysis on the neurologic characteristics in patients with COVID-19. Evidence Review: Authors conducted a literature search through PubMed from January 1st, 2020 to April 8th, 2020. Furthermore, the authors added additional sources by reviewing related references. Studies presenting the neurologic features of COVID-19 patients in their data were included. Case reports and case series were also included in this review. The quality of the studies was assessed based on the Oxford Center for Evidence-Based Medicine guidelines. Selected studies were included in the meta-analysis of proportion and the heterogeneity test. Finding: From 280 identified studies, 33 were eligible, with 7,559 participants included. Most of the included studies were from China (29 [88%]). Muscle injury or myalgia was the most common (19.2%, 95%CI 15.4–23.2%) neurologic symptom of COVID-19, followed by headache (10.9%, 95%CI 8.62–13.51%); dizziness (8.7%, 95%CI 5.02–13.43%); nausea with or without vomiting (4.6%, 95%CI 3.17–6.27%); concurrent cerebrovascular disease (4.4%, 95%CI 1.92–7.91%); and impaired consciousness (3.8%, 95%CI 0.16–12.04%). Underlying cerebrovascular disease was found in 8.5% (95%CI 4.5–13.5%) of the studies. Conclusion: Neurologic findings vary from non-specific to specific symptoms in COVID-19 patients. Some severe symptoms or diseases can present in the later stage of the disease. Physicians should be aware of the presence of neurologic signs and symptoms as a chief complaint of COVID-19, in order to improve management and prevent a worsening outcome of the patients.

positive: 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.

positive: Coronavirus Disease (COVID-19): Spectrum of CT Findings and Temporal Progression of the Disease Coronavirus disease is an emerging infection caused by a novel coronavirus that is moving rapidly. High resolution computed tomography (CT) allows objective evaluation of the lung lesions, thus enabling us to better understand the pathogenesis of the disease. With serial CT examinations, the occurrence, development, and prognosis of the disease can be better understood. The imaging can be sorted into four phases: early phase, progressive phase, severe phase, and dissipative phase. The CT appearance of each phase and temporal progression of the imaging findings are demonstrated.

positive: COVID-19 in 2 Persons with Mild Upper Respiratory Tract Symptoms on a Cruise Ship, Japan We describe 2 cases of coronavirus disease in patients with mild upper respiratory symptoms. Both patients worked on a cruise ship quarantined off the coast of Japan. One patient had persistent, low-grade upper respiratory tract symptoms without fever. The other patient had rapid symptom cessation but persistent viral RNA detection.

positive: A benchmark of online COVID-19 symptom checkers Background A large number of online COVID-19 symptom checkers and chatbots have been developed but anecdotal evidence suggests that their conclusions are highly variable. To our knowledge, no study has evaluated the accuracy of COVID-19 symptom checkers in a statistically rigorous manner. Methods In this paper, we evaluate 10 different COVID-19 symptom checkers screening 50 COVID-19 case reports alongside 410 non-COVID-19 control cases. Results We find that the number of correctly assessed cases varies considerably between different symptom checkers, with Symptoma (F1=0.92, MCC=0.85) showing the overall best performance followed by Infermedica (F1=0.80, MCC=0.61).

positive: 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.

positive: A retrospective study of the initial 25 COVID-19 patients in Luoyang, China PURPOSE: To summarize the chest CT imaging and clinical features of the initial COVID-19 patients and provide a clinical diagnostic method that is more effective and can be performed earlier. METHODS: This retrospective study investigated the clinical, laboratory and imaging information of 25 patients in the Luoyang area. There were 15 (60%) male and 10 (40%) female patients ranging from 24 to 88 years old (52 ± 19.30). Data were analyzed by Microsoft Excel and are expressed as the mean ± standard deviation or percentage. RESULTS: Thirteen (52%) patients had been in Wuhan or were in contact with people who had been in Wuhan, and ten (40%) patients were infected by their families or colleagues. The median time from initial symptoms to diagnosis was 7 days. Ninety-two percent of patients had respiratory symptoms, and 8% of them had digestive symptoms. Fever (92%), cough (60%) and fatigue (56%) were the most common symptoms. Most patients had a normal or reduced WBC (96%), reduced lymphocyte count (60%), increased CRP (48%) and increased ESR (44%). Ground glass opacity (GGO) was the typical radiological finding on chest CT. CONCLUSION: Characteristic chest CT imaging features could appear earlier than the viral nucleic acid assay results.

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: Early chest CT features of patients with 2019 novel coronavirus (COVID-19) pneumonia: relationship to diagnosis and prognosis OBJECTIVE: To determine the consistency between CT findings and real-time reverse transcription–polymerase chain reaction (RT-PCR) and to investigate the relationship between CT features and clinical prognosis in COVID-19. METHODS: The clinical manifestations, laboratory parameters, and CT imaging findings were analyzed in 34 COVID-19 patients, confirmed by RT-PCR from January 20 to February 4 in Hainan Province. CT scores were compared between the discharged patients and the ICU patients. RESULTS: Fever (85%) and cough (79%) were most commonly seen. Ten (29%) patients demonstrated negative results on their first RT-PCR. Of the 34 (65%) patients, 22 showed pure ground-glass opacity. Of the 34 (50%) patients, 17 had five lobes of lung involvement, while the 23 (68%) patients had lower lobe involvement. The lesions of 24 (71%) patients were distributed mainly in the subpleural area. The initial CT lesions of ICU patients were distributed in both the subpleural area and centro-parenchyma (80%), and the lesions were scattered. Sixty percent of ICU patients had five lobes involved, while this was seen in only 25% of the discharged patients. The lesions of discharged patients were mainly in the subpleural area (75%). Of the discharged patients, 62.5% showed pure ground-glass opacities; 80% of the ICU patients were in the progressive stage, and 75% of the discharged patients were at an early stage. CT scores of the ICU patients were significantly higher than those of the discharged patients. CONCLUSION: Chest CT plays a crucial role in the early diagnosis of COVID-19, particularly for those patients with a negative RT-PCR. The initial features in CT may be associated with prognosis. KEY POINTS: • Chest CT is valuable for the early diagnosis of COVID-19, particularly for those patients with a negative RT-PCR. • The early CT findings of COVID-19 in ICU patients differed from those of discharged patients.

positive: Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center’s observational study BACKGROUND: An outbreak of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was first detected in Wuhan, Hubei, China. People of all ages are susceptible to SARS-CoV-2 infection. No information on severe pediatric patients with COVID-19 has been reported. We aimed to describe the clinical features of severe pediatric patients with COVID-19. METHODS: We included eight severe or critically ill patients with COVID-19 who were treated at the Intensive Care Unit (ICU), Wuhan Children’s Hospital from January 24 to February 24. We collected information including demographic data, symptoms, imaging data, laboratory findings, treatments and clinical outcomes of the patients with severe COVID-19. RESULTS: The onset age of the eight patients ranged from 2 months to 15 years; six were boys. The most common symptoms were polypnea (8/8), followed by fever (6/8) and cough (6/8). Chest imaging showed multiple patch-like shadows in seven patients and ground-glass opacity in six. Laboratory findings revealed normal or increased whole blood counts (7/8), increased C-reactive protein, procalcitonin and lactate dehydrogenase (6/8), and abnormal liver function (4/8). Other findings included decreased CD16 + CD56 (4/8) and Th/Ts*(1/8), increased CD3 (2/8), CD4 (4/8) and CD8 (1/8), IL-6 (2/8), IL-10 (5/8) and IFN-γ (2/8). Treatment modalities were focused on symptomatic and respiratory support. Two critically ill patients underwent invasive mechanical ventilation. Up to February 24, 2020, three patients remained under treatment in ICU, the other five recovered and were discharged home. CONCLUSIONS: In this series of severe pediatric patients in Wuhan, polypnea was the most common symptom, followed by fever and cough. Common imaging changes included multiple patch-like shadows and ground-glass opacity; and a cytokine storm was found in these patients, which appeared more serious in critically ill patients.

positive: Urticarial eruption in COVID‐19 infection Coronavirus disease (COVID‐19) is spreading quickly across the world, until a pandemic condition was announced by the WHO on March. Many clinical manifestations of this virus are described and new symptoms are emerging particularly outside respiratory sphere, such as anosmia and ageusia which are recent ORL published symptoms. About skin manifestation, few cases of rashes on patients with laboratory‐confirmed Covid‐19 were described in two Chineses cohorts.

positive: New understanding of the damage of SARS-CoV-2 infection outside the respiratory system Abstract Since early December 2019, a number of pneumonia cases associated with unknown coronavirus infection were identified in Wuhan, China, and many additional cases were identified in other regions of China and in other countries within 3 months. Currently, more than 80,000 cases have been diagnosed in China, including more than 3,000 deaths. The epidemic is spreading to the rest of the world, posing a grave challenge to prevention and control. On February 12, 2020, the International Committee on Taxonomy of Viruses and the World Health Organization officially named the novel coronavirus and associated pneumonia as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19), respectively. According to the recent research on SARS-CoV-2, the virus mainly infects the respiratory system but may cause damage to other systems. In this paper, we will systematically review the pathogenic features, transmission routes, and infection mechanisms of SARS-CoV-2, as well as any adverse effects on the digestive system, urogenital system, central nervous system, and circulatory system, in order to provide a theoretical and clinical basis for the diagnosis, classification, treatment, and prognosis assessment of SARS-CoV-2 infection.

positive: Novel coronavirus infection in children outside of Wuhan, China BACKGROUND: Since December 8, 2019, an epidemic of coronavirus disease 2019 (COVID‐19) has spread rapidly, but information about children with COVID‐19 is limited. METHODS: This retrospective and the single‐center study were done at the Public Health Clinic Center of Changsha, Hunan, China. We identified all hospitalized children diagnosed with COVID‐19 between January 8, 2019 and February 19, 2020, in Changsha. Epidemiological and clinical data of these children were collected and analyzed. Outcomes were followed until February 26th, 2020. RESULTS: By February 19, 2020, nine pediatric patients were identified as having 2019‐nCoV infection in Changsha. Six children had a family exposure and could provide the exact dates of close contact with someone who was confirmed to have 2019‐nCoV infection, among whom the median incubation period was 7.5 days. The initial symptoms of the nine children were mild, including fever (3/9), diarrhea (2/9), cough (1/9), and sore throat (1/9), two had no symptoms. Two of the enrolled patients showed small ground‐glass opacity of chest computed tomography scan. As of February 26, six patients had a negative RT‐PCR for 2019‐nCoV and were discharged. The median time from exposure to a negative RT‐PCR was 14 days. CONCLUSIONS: The clinical symptoms of the new coronavirus infection in children were not typical and showed a less aggressive clinical course than teenage and adult patients. Children who have a familial clustering or have a family member with a definite diagnosis should be reported to ensure a timely diagnosis.

positive: A retrospective study of the clinical characteristics of COVID-19 infection in 26 children Background: The outbreak of novel coronavirus pneumonia in China began in December 2019. Studies on novel coronavirus disease (COVID-19) were less based on pediatric patients. This study aimed to reveal the clinical characteristics of COVID-19 in children. Method: This study retrospectively analyzed the clinical symptoms, laboratory results, chest CT, and treatment of children with laboratory-confirmed COVID-19(ie, with samples that were positive for 2019 novel coronavirus[2019-nCoV]) who were admitted to Shenzhen Center of National Infectious Disease Clinical Medical Research from January 16 to February 8, 2020. Result: Nine patients had no obvious clinical symptom. 11 patients developed fever. Other symptoms, including cough(in eleven of seventeen patients), rhinorrhea(in two), diarrhea(in two), vomiting(in two), were also observed. A small minority of patients had lymphocytopenia. Alanine transaminase or transaminase increased in three cases. According to chest CT scan, 11 patients showed unilateral pneumonia, 8 patients had no pulmonary infiltration. No serious complications such as acute respiratory syndrome and acute lung injury occurred in all patients. Conclusion: The clinical characteristics of 2019-nCoV infection in children were different from adult. The overall condition of children were mild and have a good prognosis.

positive: Clinical analysis of ten pregnant women with COVID-19 in Wuhan, China: A retrospective study Abstract Background COVID-19 is spreading globally. This study aims to evaluate the clinical characteristics and outcomes of pregnant women confirmed with COVID-19 to provide reference for clinical work. Methods The clinical features and outcomes of 10 pregnant women confirmed with COVID-19 at Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, a tertiary- care teaching hospital in Hubei province, Wuhan, China from January 23 to February 23, 2020 were retrospectively analyzed. Results All the 10 observed pregnant women including 9 singletons and 1 twin were native people in Wuhan. All of them were diagnosed mild COVID-19, and none one of the patients developed severe COVID-19 or died. Among the 10 patients, two patients underwent vaginal delivery, two patients underwent intrapartum cesarean section, and the remaining six patients underwent elective cesarean section. All of 10 patients showed lung abnormalities by pulmonary CT images after delivery. Their eleven newborns were recorded and no neonatal asphyxia was observed. Conclusions Pulmonary CT screening on admission may be necessary to reduce the risk of nosocomial transmission of COVID-19 during the outbreak period. And COVID-19 is not an indication of cesarean section.

positive: Anosmia and Dysgeusia in the Absence of Other Respiratory Diseases: Should COVID-19 Infection Be Considered? We describe two elderly patients evaluated at emergency departments for anosmia/dysgeusia in the absence of any other respiratory symptoms prior to or upon admission. In the current epidemiological context, clinical and biological work-up led to a diagnosis of COVID-19 infection. Unfortunately, one of the patients died during hospitalization, but the other recovered and was discharged. LEARNING POINTS: In the current epidemiological situation, anosmia and dysgeusia in the absence of other respiratory conditions should be carefully evaluated. Special attention should be given to patients with non-classic COVID-19 symptoms in order to reduce transmission and protect health providers.

positive: Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis BACKGROUND: The prevalence and prognosis of digestive system involvement, including gastrointestinal symptoms and liver injury, in patients with COVID-19 remains largely unknown. We aimed to quantify the effects of COVID-19 on the digestive system. METHODS: In this systematic review and meta-analysis, we systematically searched PubMed, Embase, and Web of Science for studies published between Jan 1, 2020, and April 4, 2020. The websites of WHO, CDC, and major journals were also searched. We included studies that reported the epidemiological and clinical features of COVID-19 and the prevalence of gastrointestinal findings in infected patients, and excluded preprints, duplicate publications, reviews, editorials, single case reports, studies pertaining to other coronavirus-related illnesses, and small case series (<10 cases). Extracted data included author; date; study design; country; patient demographics; number of participants in severe and non-severe disease groups; prevalence of clinical gastrointestinal symptoms such as vomiting, nausea, diarrhoea, loss of appetite, abdominal pain, and belching; and digestive system comorbidities including liver disease and gastrointestinal diseases. Raw data from studies were pooled to determine effect estimates. FINDINGS: We analysed findings from 35 studies, including 6686 patients with COVID-19, that met inclusion criteria. 29 studies (n=6064) reported gastrointestinal symptoms in patients with COVID-19 at diagnosis, and the pooled prevalence of digestive system comorbidities was 4% (95% CI 2–5; range 0–15; I(2)=74%). The pooled prevalence of digestive symptoms was 15% (10–21; range: 2–57; I(2)=96%) with nausea or vomiting, diarrhoea, and loss of appetite being the three most common symptoms. The pooled prevalence of abnormal liver functions (12 studies, n=1267) was 19% (9–32; range 1–53; I(2)=96%). Subgroup analysis showed patients with severe COVID-19 had higher rates of gastrointestinal symptoms (odds ratio [OR] 1·60 [95% CI 1·09–2·36]; p=0·0020; I(2)=44%) and liver injury (2·20 [1·60–3·02]; p<0·00001; I(2)=36%) compared with those with non-severe disease. Patients in Hubei province, where the initial COVID-19 outbreak occurred, were more likely to present with abnormal liver functions (p<0·0001) compared with those outside of Hubei. Paediatric patients with COVID-19 had a similar prevalence of gastrointestinal symptoms to those of adult patients. 10% (95% CI 4–19; range 3–23; I(2)=97%) of patients presented with gastrointestinal symptoms alone without respiratory features. Patients who presented with gastrointestinal system involvement had delayed diagnosis (standardised mean difference 2·85 [95% CI 0·22–5·48]; p=0·030; I(2)=73%). Patients with gastrointestinal involvement had a higher prevalence of complication (OR 2·51 [95% CI 1·62–3·89]; p<0·0001; I(2)=0%). INTERPRETATION: Our study showed that digestive symptoms and liver injury are not uncommon in patients with COVID-19. Increased attention should be paid to the care of this unique group of patients. FUNDING: None.

positive: Sore throat in COVID‐19: Comment on “Clinical characteristics of hospitalized patients with SARS‐CoV‐2 infection: A single arm meta‐analysis” We read with interest the recent meta-analysis by Sun et al.1 that included 50466 patients with Coronavirus Disease 2019 (COVID-19). The author found that fever and cough were the most common symptoms, and several subjects had muscle soreness or fatigue. In addition, they reported that "by reading the included literature, we found that diarrhea, hemoptysis, headache, sore throat, shock, and other symptoms are rare".1 This article is protected by copyright. All rights reserved.

positive: Clinical features and outcomes of pregnant women suspected of coronavirus disease 2019 Summary Background 2019 novel coronavirus disease (COVID-19) has become a worldwide pandemic. Under such circumstance pregnant women are also affected significantly. Objective This study aims to observe the clinical features and outcomes of pregnant women who have been confirmed with COVID-19. Methods The research objects were 55 cases of suspected COVID-19 pregnant women who gave a birth from Jan 20th 2020 to Mar 5th 2020 in our hospital-a big birth center delivering about 30,000 babies in the last 3 years. These cases were subjected to pulmonary CT scan and routine blood test, manifested symptoms of fever, cough, chest tightness or gastrointestinal symptoms. They were admitted to an isolated suite, with clinical features and newborn babies being carefully observed. Among the 55 cases, 13 patients were assigned into the confirmed COVID-19 group for being tested positive sever acute respiratory syndrome coronavirus 2(SARS-CoV-2) via maternal throat swab test, and the other 42 patients were assigned into the control group for being ruled out COVID-19 pneumonia based on new coronavirus pneumonia prevention and control program(the 7th edition). Results There were 2 fever patients during the prenatal period and 8 fever patients during the postpartum period in the confirmed COVID-19 group. In contrast, there were 11 prenatal fever patients and 20 postpartum fever patients in the control group (p>0.05). Among 55 cases, only 2 case had cough in the confirmed group. The imaging of pulmonary CT scan showed ground- glass opacity (46.2%, 6/13), patch-like shadows(38.5%, 5/13), fiber shadow(23.1%, 3/13), pleural effusion (38.5%, 5/13)and pleural thickening(7.7%, 1/13), and there was no statistical difference between the confirmed COVID-19 group and the control group (p>0.05). During the prenatal and postpartum period, there was no difference in the count of WBC, Neutrophils and Lymphocyte, the radio of Neutrophils and Lymphocyte and the level of CRP between the confirmed COVID-19 group and the control group(p<0.05). 20 babies (from confirmed mother and from normal mother) were subjected to SARS-CoV-2 examination by throat swab samples in 24 h after birth and no case was tested positive. Conclusion The clinical symptoms and laboratory indicators are not obvious for asymptomatic and mild COVID-19 pregnant women. Pulmonary CT scan plus blood routine examination are more suitable for finding pregnancy women with asymptomatic or mild COVID-19 infection, and can be used screening COVID-19 pregnant women in the outbreak area of COVID-19 infection.

positive: The rationale of fever surveillance to identify patients with severe acute respiratory syndrome in Taiwan. STUDY OBJECTIVE To establish a predictive scoring system and to determine its effectiveness for severe acute respiratory syndrome (SARS) cases confirmed by RT-PCR in patients with fever. METHODS A study was conducted of 484 consecutive patients seen in the emergency department (ED) of our tertiary care center during the SARS outbreak in Taiwan. The scoring system was divided into triage and screening station stages. Data were analysed with multivariable and logistic regression analysis. RESULTS Of 737 patients who presented to our ED for possible SARS from March to June 2003, we enrolled 484 patients with a temperature >38.0 degrees C (>100.3 degrees F) (age >18 years). Dyspnoea, diarrhoea, travel, close contact, hospital exposure, and household history were identified as predictive indicators in the triage stage. The triage score was the total of six items. With a one-point cutoff value, the sensitivity and specificity were 81.8% (18/22) and 73.6% (340/462). Leukocytosis, thrombocytopenia, lymphopenia, and CXR were identified as predictive indicators in the fever screening stage. Screening station scores (the sum of 10 items) consisted of triage scores, white blood cell count, and CXR. With a three-point cutoff value, the sensitivity and specificity were 95.5% (21/22) and 87.2% (403/462). CONCLUSIONS Syndromic and traditional surveillance play a role in early identification of SARS in an endemic area. The SARS scoring system described is easily applicable and highly effective in screening patients during outbreaks.

positive: The diagnostic value of detecting sudden smell loss among asymptomatic COVID-19 patients in early stage: The possible early sign of COVID-19 IMPORTANCE: The newly emerged coronavirus disease 19 (COVID-19), is threatening the world. Olfactory or gustatory dysfunction is reported as one of the symptoms worldwide. As reported so far, different clinical features have been reported according to outbreak sites and gender; most of the patients, who complained of anosmia or hyposmia, were Europeans. We had a fast review for novel articles about COVID-19 infection and olfactory function. OBSERVATIONS: Rapid reviews for COVID-19 or other viral infection and olfactory and/or gustatory dysfunctions were done in this review. Up to date, a lot of reports have shown that olfactory dysfunction is related to viral infections but no exact mechanism, clinical course, and definite treatment have been discovered, which is also same in COVID-19. In general, intranasal steroid (INS) and oral steroid for short time help improve the recovery of the olfactory function in case of olfactory dysfunction after virus infection. Considering severe respiratory complications and immunocompromised state of COVID-19, the use of steroid should be limited and cautious because we do not have enough data to support the usage of steroid to treat olfactory dysfunction in the clinical course of COVID-19. CONCLUSIONS AND RELEVANCE: In the days of pandemic COVID-19, we should keep in mind that olfactory dysfunctions, even without other upper respiratory infection or otolaryngologic symptoms, might be the early signs of COVID-19.

positive: Clinical and epidemiological characteristics of pediatric SARS-CoV-2 infections in China: A multicenter case series BACKGROUND: As of April 18, 2020, over 2,000,000 patients had been diagnosed with coronavirus disease-2019 (COVID-19) globally, and more than 140,000 deaths had been reported. The clinical and epidemiological characteristics of adult patients have been documented recently. However, information on pediatric patients is limited. We describe the clinical and epidemiological characteristics of pediatric patients to provide valuable insight into the early diagnosis and assessment of COVID-19 in children. METHODS AND FINDINGS: This retrospective, observational study involves a case series performed at 4 hospitals in West China. Thirty-four pediatric patients with COVID-19 were included from January 27 to February 23, 2020. The final follow-up visit was completed by March 16, 2020. Clinical and epidemiological characteristics were analyzed on the basis of demographic data, medical history, laboratory tests, radiological findings, and treatment information. Data analysis was performed for 34 pediatrics patients with COVID-19 aged from 1 to 144 months (median 33.00, interquartile range 10.00–94.25), among whom 14 males (41%) were included. All the patients in the current study presented mild (18%) or moderate (82%) forms of COVID-19. A total of 48% of patients were noted to be without a history of exposure to an identified source. Mixed infections of other respiratory pathogens were reported in 16 patients (47%). Comorbidities were reported in 6 patients (18%). The most common initial symptoms were fever (76%) and cough (62%). Expectoration (21%), vomiting (12%), and diarrhea (12%) were also reported in a considerable portion of cases. A substantial increase was detected in serum amyloid A for 17 patients (among 20 patients with available data; 85%) and in high-sensitivity C-reactive protein for 17 patients (among 29 patients with available data; 59%), whereas a decrease in prealbumin was noticed in 25 patients (among 32 patients with available data; 78%). In addition, significant increases in the levels of lactate dehydrogenase and α-hydroxybutyrate dehydrogenase were detected in 28 patients (among 34 patients with available data; 82%) and 25 patients (among 34 patients with available data; 74%), respectively. Patchy lesions in lobules were detected by chest computed tomographic scans in 28 patients (82%). Ground-glass opacities, which were a typical feature in adults, were rare in pediatric patients (3%). Rapid radiologic progression and a late-onset pattern of lesions in the lobules were also noticed. Lesions in lobules still existed in 24 (among 32 patients with lesions; 75%) patients that were discharged, although the main symptoms disappeared a few days after treatment. All patients were discharged, and the median duration of hospitalization was 10.00 (8.00–14.25) days. The current study was limited by the small sample size and a lack of dynamic detection of inflammatory markers. CONCLUSIONS: Our data systemically presented the clinical and epidemiological features, as well as the outcomes, of pediatric patients with COVID-19. Stratified analysis was performed between mild and moderate cases. The findings offer new insight into early identification and intervention in pediatric patients with COVID-19.

positive: Symptom Criteria for COVID‐19 Testing of Heath Care Workers BACKGROUND: Limitations on testing availability has been a challenge during the COVID‐19 pandemic. An evidence based symptom criteria for identifying heath care workers (HCW) for testing, based on the probability of positive COVID‐19 test results, would allow for a more appropriate use of testing resources. METHODS: This was an observational study of outpatient COVID‐19 testing of HCW. Prior to testing, HCW were asked about the presence of 10 symptoms. Their responses were then compared to their subsequent pharyngeal swab COVID‐19 Polymerase Chain Reaction test results. These data were used to derive and evaluate a symptom based testing criteria. RESULTS: 961 HCW were included in the analysis, of which 225 (23%) had positive test results. Loss of taste or smell was the symptom with the largest positive likelihood ratio (3.33). Dry cough, regardless of the presence or absence of other symptoms, was the most sensitive (74%) and the least specific (32%) symptom. The existing testing criteria consisting of any combination of one or more of three symptoms (fever, shortness of breath, dry cough) was 93% sensitive and 9% specific (AUC = 0.63, 95% CI: 0.59 – 0.67). The derived testing criteria consisting of any combination of one or more of two symptoms (fever, loss of taste or smell) was 89% sensitive and 48% specific (AUC = 0.75, 95% CI: 0.71 – 0.78). The hybrid testing criteria consisting of any combination of one or more of four symptoms (fever, shortness of breath, dry cough, loss of taste or smell) was 98% sensitive and 8% specific (AUC = 0.77, 95% CI: 0.73 – 0.80). CONCLUSION: An evidence based approach to COVID‐19 testing which at least includes fever and loss of taste or smell should be utilized when determining which HCW should be tested.

positive: 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.

positive: Cerebral Venous Sinus Thrombosis as a Presentation of COVID-19 Coronavirus disease 19 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We describe the case of a 59-year-old man who presented with headache, hypertension and a single episode of fever with no other symptoms. He subsequently developed unilateral weakness. Computer tomography identified a cerebral venous sinus thrombosis (CVST). A subsequent test for COVID-19 was positive. This is the first report of CVST as a presenting symptom of COVID-19 infection. LEARNING POINTS: Thrombotic events may be the initial presenting symptom of COVID-19. These thrombotic events include stroke, venous thromboembolism, pulmonary embolism and cardiac complications. Clinicians should carefully consider the risk of thrombosis in patients positive for COVID-19, including prophylaxis and treatment beyond discharge.

positive: Gastrointestinal and liver manifestations in patients with COVID-19 As the outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread over the world, the World Health Organization has declared the outbreak of COVID-19 an international public health emergency. Besides typical respiratory symptoms and signs of COVID-19, digestive symptoms and liver injury have been frequently reported during the course of the disease. In this review, we summarized the recent studies reporting of gastrointestinal and liver manifestations during the course of COVID-19. Digestive symptoms, including anorexia, nausea, vomiting, and diarrhea, are not uncommon in patients with COVID-19, and in some cases digestive symptoms may occur in the absence of any respiratory symptoms. Furthermore, SARS-CoV-2 could be detected in the stool of infected patients, implicating the possibility of fecal-oral transmission. Attention should also be paid to monitor liver function during the course of COVID-19, especially in patients with higher disease severity.

positive: Clinical features, Diagnosis, and Treatment of COVID-19: A systematic review of case reports and case series Objectives: The 2019 novel coronavirus (COVID-19) has been declared a public health emergency worldwide. The objective of this systematic review was to characterize the clinical, diagnostic, and treatment characteristics of patients presenting with COVID-19. Methods: We conducted a structured search using PubMed/Medline, Embase, Web of Science and the Cochrane Library to collect both case reports and case series on COVID-19 published up to February 30, 2020. Results: Thirty-four articles were included analyzing a total of 99 patients with a mean age of 46.2 years. The most common presenting symptom in patients who tested positive for COVID-19 was fever, reported in up to 83% of patients from 76.4% of the analyzed studies. Other symptoms including rhinorrhea, dizziness, and chills were less frequently reported. Additionally, in studies which reported C-reactive protein (CRP) measurements (44%), a large majority of patients displayed an elevated CRP (73%). Progression to acute respiratory distress syndrome (ARDS) was the most common complication of patients testing positive for COVID-19 (33%). CT images displayed ground-glass opacification (GGO) patterns (80%) as well as bilateral lung involvement (71.0%). The most commonly used antiviral treatment modalities included, lopinavir (HIV protease inhibitor), arbidiol hydrochloride (influenza fusion inhibitor), and oseltamivir (neuraminidase inhibitor). Conclusions: Development of ARDS may play a role in estimating disease progression and mortality risk. Early detection of elevations in serum CRP, combined with a clinical COVID-19 symptom presentation may be used as a surrogate marker for presence and severity of disease. There is a paucity of data surrounding the efficacy of treatments. There is currently not a well-established gold standard therapy for the treatment of diagnosed COVID-19. Further prospective investigations are necessary.

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

positive: Clinical Characteristics of 20,662 Patients with COVID-19 in mainland China: A Systemic Review and Meta-analysis Coronavirus disease 2019 (COVID-19) is a global pandemic and has been widely reported; however, a comprehensive systemic review and meta-analysis has not been conducted. We systematically investigated the clinical characteristics of COVID-19 in mainland China to guide diagnosis and treatment. We searched the PubMed, Embase, Scopus, Web of Science, Cochrane Library, bioRxiv, medRxiv, and SSRN databases for studies related to COVID-19 published or preprinted in English or Chinese from January 1 to March 15, 2020. Clinical studies on COVID-19 performed in mainland China were included. We collected primary outcomes including signs and symptoms, chest CT imaging, laboratory tests, and treatments. Study selection, data extraction, and risk of bias assessment were performed by two independent reviewers. Qualitative and quantitative synthesis was conducted, and random-effects models were applied to pooled estimates. This study is registered with PROSPERO (number CRD42020171606). Of the 3624 records identified, 147 studies (20,662 patients) were analyzed. The mean age of patients with COVID-19 was 49.40 years, 53.45% were male, and 38.52% had at least one comorbidity. Fever and cough were the most common symptoms, followed by fatigue, expectoration, and shortness of breath. Most patients with COVID-19 had abnormal chest CT findings with ground glass opacity (70.70%) or consolidation (29.91%). Laboratory findings shown lymphopenia, increased lactate dehydrogenase, increased infection-related indicators, and fibrinolytic hyperactivity. Antiviral therapy, antibiotic therapy, and corticosteroids were administered to 89.75%, 79.13%, and 35.64% of patients, respectively. Most clinical characteristics of COVID-19 are non-specific. Patients with suspected should be evaluated by virological assays and clinically treated.

positive: Clinical Presentation of COVID-19: A Systematic Review Focusing on Upper Airway Symptoms. AIM Pharyngodynia, nasal congestion, rhinorrhea, smell, and taste dysfunctions could be the presenting symptoms of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2. The aim was to perform a systematic review of current evidences on clinical presentation of COVID-19, focusing on upper airway symptoms in order to help otolaryngologists identifying suspected cases. METHODS We searched PubMed and Web of Science electronic databases. RESULTS We included 5 retrospective clinical studies for a total of 1556 hospitalized patients with COVID-19, 57.5% were male and mean age was 49.1 years. Pooled data revealed that pharyngodynia was present in 12.4% of patients, nasal congestion in 3.7%, and rhinorrhea was rare. No reports on COVID-19 and olfactory/gustative disorders matched inclusion criteria but preliminary evidences suggested they could be present. Common symptoms were fever (85.6%), cough (68.7%), and fatigue (39.4%). Frequent comorbidities were hypertension (17.4%), diabetes (3.8%), and coronary heart disease (3.8%); 83% of patients had alterations on chest computed tomography that were bilateral in 89.5% of cases. Ground-glass opacity was the most common finding (50%). Lymphopenia (77.2%) and leucopenia (30.1%) were common. Critical cases with complications were 9%, intensive care unit admission was required in 7.3%, invasive ventilation in 3.4%, and mortality was 2.4%. CONCLUSION Otolaryngologists should know that pharyngodynia, nasal congestion, olfactory, and gustative disorders could be the presenting symptoms of COVID-19. Clinical presentation together with radiological and laboratory findings could help to identify suspected cases.

positive: Coronavirus Disease 2019 (COVID-19): A Perspective from China In December 2019, an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection occurred in Wuhan, Hubei Province, China and spread across China and beyond. On February 12, 2020, WHO officially named the disease caused by the novel coronavirus as Coronavirus Disease 2019 (COVID-19). Since most COVID-19 infected patients were diagnosed with pneumonia and characteristic CT imaging patterns, radiological examinations have become vital in early diagnosis and assessment of disease course. To date, CT findings have been recommended as major evidence for clinical diagnosis of COVID-19 in Hubei, China. This review focuses on the etiology, epidemiology, and clinical symptoms of COVID-19, while highlighting the role of chest CT in prevention and disease control. A full translation of this article in Chinese is available in the supplement. - 请见䃼充资料阅读文章中文版∘

positive: Clinical characteristics of Coronavirus Disease (COVID-19) patients with gastrointestinal symptoms: A report of 164 cases Abstract Objective To explore the clinical characteristics of Coronavirus Disease (COVID-19) patients with gastrointestinal symptoms. Methods The clinical data of 164 COVID-19 patients with gastrointestinal symptoms were extracted and analysed retrospectively. Results In total, 505 COVID-19 patients were divided into two groups: those with gastrointestinal symptoms (G group) and those without gastrointestinal symptoms (NG group). Common gastrointestinal symptoms included inappetence, diarrhoea, nausea, abdominal pain, and vomiting. Significantly higher proportions of patients with fever, dizziness, myalgia, and fatigue were noted in group G than in group NG. Compared with patients without fever, there was a significant difference between G group and NG group in moderate fever or above, while there was no significant difference between the two groups in low fever. The laboratory results showed that patients in the G group had significantly higher C-reactive protein, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase levels than those in the NG group. Moreover, the proportion of patients with severe pneumonia was significantly higher in the G group than in the NG group. Conclusion In Wuhan, the proportion of COVID-19 patients who experience gastrointestinal symptoms is relatively high. Patients who experience gastrointestinal symptoms are more likely to suffer from severe pneumonia, which may help clinicians identify patients at high risk of COVID-19 and thus reduce the incidence of this condition.

positive: 2019 novel coronavirus disease (COVID-19) in Taiwan: Reports of two cases from Wuhan, China Abstract We reported two cases with community-acquired pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who returned from Wuhan, China in January, 2020. The reported cases highlight non-specific clinical presentations of 2019 novel coronavirus disease (COVID-19) as well as the importance of rapid laboratory-based diagnosis.

positive: A territory-wide study of early COVID-19 outbreak in Hong Kong community: A clinical, epidemiological and phylogenomic investigation Background: Initial cases of coronavirus disease 2019 (COVID-19) reported in Hong Kong were mostly imported cases from Mainland China. However, most cases reported in February 2020 were local infections with unknown source, indicating local community transmissions. This study aimed to report the clinical, epidemiological and phylogenomic characteristics of the local cases of COVID-19 in our community. Methods: We extracted the demographic, clinical and epidemiological data from 50 COVID-19 patients, who accounted for 53.8% of the cases in Hong Kong by the end of February 2020. We used both Nanopore and Illumina platforms to perform whole-genome sequencing (WGS) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from these patients. Phylogenetic relatedness among these local cases and their placement in the global phylogeny were examined. The evolutionary rate and divergence time of transmission were also determined. Findings: Of these 50 patients, only three (6.0%) had visited Wuhan while 43 (86.0%) did not have recent travel records. The average interval from symptom onset to hospital admission was 8.5 days. The most common signs and symptoms on admission were cough (74.0%) and fever (58.0%). Radiographic abnormality was found in 46 (92.0%) patients. Three (6.0%) patients required ICU admission. Phylogenetic analysis concurred with epidemiological investigation that 42 (84.0%) cases could be grouped into six transmission clusters. Forty-four (88.0%) cases harboured a common mutation Orf3a G251V. Global phylogeny of SARS-CoV-2 revealed that most (88.0%) cases in Hong Kong were clustered in two subclades with the strains from other countries. The estimated time to the most recent common ancestor (tMRCA) of COVID-2019 outbreak in Hong Kong was December 24, 2019 with an evolutionary rate of 3.04x10-3 substitutions per site per year. The reproduction number value was 1.84 as of February 28, 2020 in Hong Kong. Interpretation: We provided a territory-wide overview of COVID-19 in Hong Kong, which has borders connecting to Mainland China. Transmission in closed settings especially during family and religious gatherings is a hallmark of the recently reported cases. The reproduction number value indicated an ongoing outbreak in the community. Social distancing and vigilant epidemiological control are crucial to the containment of COVID-19 transmission

positive: COVID-19 outbreak at a large homeless shelter in Boston: Implications for universal testing The circumstances of homelessness create the potential for rapid transmission of SARS-CoV-2 in this vulnerable population. Upon observing a cluster of COVID-19 cases from a single large homeless shelter in Boston, Boston Health Care for the Homeless Program conducted symptom assessments and polymerase chain reaction (PCR) testing for SARS-CoV-2 among all guests residing at the shelter over a 2-day period. Of 408 participants, 147 (36.0%) were PCR-positive for SARS-CoV-2. COVID-positive individuals were more likely to be male (p<0.001) but did not differ significantly from COVID-negative individuals with respect to other demographic and clinical characteristics. Cough (7.5%), shortness of breath (1.4%), and fever (0.7%) were all uncommon among COVID-positive individuals. Our findings illustrate the rapidity with which COVID-19 can be widely transmitted in a homeless shelter setting and suggest that universal PCR testing, rather than a symptom triggered approach, may be a better strategy for identifying and mitigating COVID-19 among people experiencing homelessness.

positive: Guillain Barre syndrome associated with COVID-19 infection: A case report Abstract Novel outbreak with coronavirus 2019 began since 31 December 2019. Coronaviruses can cause multiple systemic infections that respiratory complications are the most obvious symptoms. In this report, we describe the symptoms of Guillain Barre syndrome (GBS) in one infected patient with COVID-19, for the first time. We reported a 65-years- old male patient with complaints of acute progressive symmetric ascending quadriparesis. Two weeks prior to hospitalization, the patient suffered from cough, fever, and RT-PCR was reported positive for COVID-19 infection. The electrodiagnostic test showed that the patient is an AMSAN variant of GBS. COVID-19 stimulates inflammatory cells and produces various inflammatory cytokines and as a result, it creates immune-mediated processes. GBS is an immune-mediated disorder and molecular mimicry as a mechanism of autoimmune disorder plays an important role in creating it. It is unclear whether COVID-19 induces the production of antibodies against specific gangliosides. Further investigations should be conducted about the mechanism of GBS in patients with COVID-19, in the future.

positive: Critical care response to a hospital outbreak of the 2019-nCoV infection in Shenzhen, China

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

positive: Brief Review on COVID-19: The 2020 Pandemic Caused by SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the coronavirus disease of 2019 (COVID-19). First identified in Wuhan (Hubei, China) in December of 2019, it has since been declared a pandemic by the World Health Organization in March of 2020. In this study, we will provide a brief review of viral origin, identification, symptoms, transmission, diagnosis, and potential treatment strategies for the newly identified SARS-CoV-2 strain.

positive: Sudden hyposmia as a prevalent symptom of COVID-19 infection. Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has recently caused a pandemic that has involved Italy as the second worldwide nation in terms of infected patients and deaths. The clinical manifestation of Covid-19 ranges from asymptomatic carrier status to severe pneumonia. Asymptomatic individuals in Covid-19 are those who are carriers of the virus but do not show clinical symptoms and are able to transmit the disease in the same degree as symptomatic carriers. In order to contain contagions is of supreme importance to identify asymptomatic patients because this subpopulation is one of the main factors contributing to the spread of this disease. We report on six Italian patients with COVID-19 who presented sudden hyposmia as the only or most prominent disease manifestation, without upper or lower respiratory tract involvement or other major features of the disease. A supra-threshold olfaction test confirmed the hyposmia in all patients. The onset of hyposmia during a Covid-19 outbreak should be considered as a warning sign of an infection that requires a diagnostic test for Covid-19

positive: Respiratory Conditions in Coronavirus Disease 2019 (COVID-19): Important Considerations Regarding Novel Treatment Strategies to Reduce Mortality Abstract A novel virus named 2019 novel coronavirus (2019-nCoV/SARS-CoV-2) causes symptoms that are classified as coronavirus disease (COVID-19). Respiratory conditions are extensively described among more serious cases of COVID-19, and the onset of acute respiratory distress syndrome (ARDS) is one of the hallmark features of critical COVID-19 cases. ARDS can be directly life-threatening because it is associated with low blood oxygenation levels and can result in organ failure. There are no generally recognized effective treatments for COVID-19, but treatments are urgently needed. Anti-viral medications and vaccines are in the early developmental stages and may take many months or even years to fully develop. At present, management of COVID-19 with respiratory and ventilator support are standard therapeutic treatments, but unfortunately such treatments are associated with high mortality rates. Therefore, it is imperative to consider novel new therapeutic interventions to treat/ameliorate respiratory conditions associated with COVID-19. Alternate treatment strategies utilizing clinically available treatments such as hyperbaric oxygen therapy (HBOT), packed red blood cell (pRBC) transfusions, or erthropoiesis-stimulating agent (ESA) therapy were hypothesized to increase oxygenation of tissues by alternative means than standard respiratory and ventilator treatments. It was also revealed that alternative treatments currently being considered for COVID-19 such as chloroquine and hydroxychloroquine by increasing hemoglobin production and increasing hemoglobin availability for oxygen binding and acetazolamine (for the treatment of altitude sickness) by causing hyperventilation with associated increasing levels of oxygen and decreasing levels of carbon dioxide in the blood may significantly ameliorate COVID-19 respiratory symptoms. In conclusion, is recommend, given HBOT, pRBC, and ESA therapies are currently available and routinely utilized in the treatment of other conditions, that such therapies be tried among COVID-19 patients with serious respiratory conditions and that future controlled-clinical trials explore the potential usefulness of such treatments among COVID-19 patients with respiratory conditions.

positive: Psychotic symptoms in COVID-19 patients. A retrospective descriptive study Psychotic symptoms have been related to other coronavirus infections. We conducted a single-centre retrospective and observational study to describe new-onset psychotic episodes in COVID-19 patients. Ten patients infected by the novel coronavirus with psychotic symptoms and no previous history of psychosis were identified by the emergency and liaison psychiatry departments. Nine of the cases presented with psychotic symptoms at least two weeks after the first somatic manifestations attributed to COVID-19 and receiving pharmacological treatment. Structured delusions mixed with confusional features were the most frequent clinical presentations. Hence, COVID-19 patients can develop psychotic symptoms as a consequence of multiple concurrent factors.

positive: COVID-19: Gastrointestinal Manifestations and Potential Fecal–Oral Transmission

positive: [Analysis of the first cluster of cases in a family of novel coronavirus pneumonia in Gansu Province]. The epidemiological history and clinical characteristics of 7 cases of COVID-19 and 1 case of close contact in the first family aggregation epidemic of COVID-19 in Gansu Province were analyzed. The first patient A developed on January 22, 2020, with a history of residence in Wuhan, and confirmed severe cases of NCP on January 24, 2020; patient B, on January 23, 2020, diagnosed on January 31, severe cases; patient C, asymptomatic, diagnosed on January 27; patient D, asymptomatic, diagnosed on January 27; patient E, on January 24, diagnosed on January 28; patient F, asymptomatic, diagnosed on January 31; Patient G was asymptomatic and was diagnosed on January 31. In close contact, H was asymptomatic, PCR test was negative and asymptomatic, and he was discharged early. Among the 7 patients, 1 case died of (B) aggravation, and the other patients' condition was effectively controlled after active treatment. Except for the discharged cases, 5 cases were positive for COVID-19 specific IgM antibody and 1 case was negative. In this clustering outbreak, 4 patients remained asymptomatic, but PCR and IgM antibodies were positive, indicating that asymptomatic patients may be the key point to control the epidemic. Specific IgM antibody screening for patients whose pharyngeal swab nucleic acid test is negative but with ground glass-like lung lesions is very important for early detection and early isolation.

positive: COVID-19 infection among asymptomatic and symptomatic pregnant women: Two weeks of confirmed presentations to an affiliated pair of New York City hospitals Abstract The novel coronavirus 2019, or COVID-19, infection has rapidly spread through the New York metropolitan area since the first reported case in the state on March 1, 2020. New York currently represents an epicenter for COVID-19 infection in the United States, with 84,735 cases reported as of April 2, 2020. We previously presented an early experience with seven COVID-positive patients in pregnancy, including two women who were diagnosed with COVID-19 following an asymptomatic initial presentation. We now describe a series of 43 test-confirmed cases of COVID-19 presenting to a pair of affiliated New York City hospitals over two weeks from March 13 to 27, 2020. Fourteen (32.6%) patients presented without any COVID-associated viral symptoms, and were identified either after developing symptoms during admission or following the implementation of universal testing for all obstetrical admissions on March 22. Of these, 10/14 (71.4%) developed symptoms or signs of COVID-19 infection over the course of their delivery admission or early after postpartum discharge. Of the other 29 (67.4%) patients who presented with symptomatic COVID-19 infection, three women ultimately required antenatal admission for viral symptoms, and an additional patient represented six days postpartum after a successful labor induction with worsening respiratory status that required oxygen supplementation. There were no confirmed cases of COVID-19 detected in neonates upon initial testing on the first day of life. Applying COVID-19 disease severity characteristics as described by Wu et al, 37 (86%) women possessed mild disease, four (9.3%) exhibited severe disease, and two (4.7%) developed critical disease; these percentages are similar to those described for non-pregnant adults with COVID-19 infections (about 80% mild, 15% severe, and 5% critical disease).

positive: Musculoskeletal symptoms in SARS-CoV-2 (COVID-19) patients

positive: 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.

positive: A Comprehensive Literature Review on the Clinical Presentation, and Management of the Pandemic Coronavirus Disease 2019 (COVID-19) Coronavirus disease 2019 (COVID-19) is a declared global pandemic. There are multiple parameters of the clinical course and management of the COVID-19 that need optimization. A hindrance to this development is the vast amount of misinformation present due to scarcely sourced manuscript preprints and social media. This literature review aims to presents accredited and the most current studies pertaining to the basic sciences of SARS-CoV-2, clinical presentation and disease course of COVID-19, public health interventions, and current epidemiological developments. The review on basic sciences aims to clarify the jargon in virology, describe the virion structure of SARS-CoV-2 and present pertinent details relevant to clinical practice. Another component discussed is the brief history on the series of experiments used to explore the origins and evolution of the phylogeny of the viral genome of SARS-CoV-2. Additionally, the clinical and epidemiological differences between COVID-19 and other infections causing outbreaks (SARS, MERS, H1N1) are elucidated. Emphasis is placed on evidence-based medicine to evaluate the frequency of presentation of various symptoms to create a stratification system of the most important epidemiological risk factors for COVID-19. These can be used to triage and expedite risk assessment. Furthermore, the limitations and statistical strength of the diagnostic tools currently in clinical practice are evaluated. Criteria on rapid screening, discharge from hospital and discontinuation of self-quarantine are clarified. Epidemiological factors influencing the rapid rate of spread of the SARS-CoV-2 virus are described. Accurate information pertinent to improving prevention strategies is also discussed. The penultimate portion of the review aims to explain the involvement of micronutrients such as vitamin C and vitamin D in COVID19 treatment and prophylaxis. Furthermore, the biochemistry of the major candidates for novel therapies is briefly reviewed and a summary of their current status in the clinical trials is presented. Lastly, the current scientific data and status of governing bodies such as the Center of Disease Control (CDC) and the WHO on the usage of controversial therapies such as angiotensin-converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs) (Ibuprofen), and corticosteroids usage in COVID-19 are discussed. The composite collection of accredited studies on each of these subtopics of COVID-19 within this review will enable clarification and focus on the current status and direction in the planning of the management of this global pandemic.

positive: Cutaneous manifestations of COVID‐19: A review of the published literature COVID‐19 is a highly contagious respiratory tract infection caused by severe acute respiratory syndrome coronavirus 2 (SARS‐Cov‐2). COVID‐19 outbreak, which caused thousands of deaths, has been declared a pandemic by the World Health Organization in March 2020. The infection has been reported to demonstrate different types of cutaneous manifestations including urticarial, maculopapular, papulovesicular, purpuric, livedoid, and thromboticischemic lesions. Given the high mortality rate of the infection, timely and accurate identification of relevant cutaneous manifestations may play a key role in the early diagnosis and management. In this study, we provide a review with a focus on the reported cutaneous manifestations of COVID‐19. This article is protected by copyright. All rights reserved.

positive: Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China Importance: The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, is serious and has the potential to become an epidemic worldwide. Several studies have described typical clinical manifestations including fever, cough, diarrhea, and fatigue. However, to our knowledge, it has not been reported that patients with COVID-19 had any neurologic manifestations. Objective: To study the neurologic manifestations of patients with COVID-19. Design, Setting, and Participants: This is a retrospective, observational case series. Data were collected from January 16, 2020, to February 19, 2020, at 3 designated special care centers for COVID-19 (Main District, West Branch, and Tumor Center) of the Union Hospital of Huazhong University of Science and Technology in Wuhan, China. The study included 214 consecutive hospitalized patients with laboratory-confirmed diagnosis of severe acute respiratory syndrome coronavirus 2 infection. Main Outcomes and Measures: Clinical data were extracted from electronic medical records, and data of all neurologic symptoms were checked by 2 trained neurologists. Neurologic manifestations fell into 3 categories: central nervous system manifestations (dizziness, headache, impaired consciousness, acute cerebrovascular disease, ataxia, and seizure), peripheral nervous system manifestations (taste impairment, smell impairment, vision impairment, and nerve pain), and skeletal muscular injury manifestations. Results: Of 214 patients (mean [SD] age, 52.7 [15.5] years; 87 men [40.7%]) with COVID-19, 126 patients (58.9%) had nonsevere infection and 88 patients (41.1%) had severe infection according to their respiratory status. Overall, 78 patients (36.4%) had neurologic manifestations. Compared with patients with nonsevere infection, patients with severe infection were older, had more underlying disorders, especially hypertension, and showed fewer typical symptoms of COVID-19, such as fever and cough. Patients with more severe infection had neurologic manifestations, such as acute cerebrovascular diseases (5 [5.7%] vs 1 [0.8%]), impaired consciousness (13 [14.8%] vs 3 [2.4%]), and skeletal muscle injury (17 [19.3%] vs 6 [4.8%]). Conclusions and Relevance: Patients with COVID-19 commonly have neurologic manifestations. During the epidemic period of COVID-19, when seeing patients with neurologic manifestations, clinicians should suspect severe acute respiratory syndrome coronavirus 2 infection as a differential diagnosis to avoid delayed diagnosis or misdiagnosis and lose the chance to treat and prevent further transmission.

positive: All eyes on Coronavirus—What do we need to know as ophthalmologists

positive: Tracing New Clinical Manifestations in Patients with COVID-19 in Chile and Its Potential Relationship with the SARS-CoV-2 Divergence PURPOSE OF REVIEW: In this review, we discuss the current implications of the changing genomic epidemiology of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), etiological agent of the Coronavirus Disease 2019 (COVID-19) and its potential relationship with the change of clinical manifestations in patients with confirmed infection. RECENT FINDINGS: Over the course of the current pandemic, the virus has been found more diverse in new countries. Simultaneously, also new clinical manifestations are observed, particularly more prominent gastrointestinal and neurological findings. SUMMARY: SARS-CoV-2/COVID-19 is changing not only its epidemiology, but also its genomic diversity and clinical manifestations, both aspects coupled, needs to be considered in the study of this ongoing pandemic.

positive: Clinical analysis of 23 cases of 2019 novel coronavirus infection in Xinyang City, Henan Province/ 中华危重病急救医学 Objective@#To analyze the epidemiological characteristics and clinical features of the patients with 2019-nCoV infection, so as to provide basis for clinical diagnosis.@*Methods@#The epidemiology, clinical symptoms, laboratory and radiologic data of 23 patients with 2019-nCoV infection admitted to the Fifth People's Hospital of Xinyang City from January 22,2020 to January 29, 2020 were retrospectively analyzed.@*Results@#The 23 patients with 2019 nCov infection consisted of 15 men and 8 women, and the median age was 46.0 (40.5, 52.0) years (27-80 years); 9 of them had basic disease (39%), including hypertension (17%), cardiovascular diseases (17%), diabetes (9%), hypothyroidism (4%) and old tuberculosis (4%). All the 23 patients had contact history in Wuhan area or with confirmed infections. Clinical symptoms included: fever (100%), cough (70%), expectoration (43%), myalgia (26%), headache (17%) and dyspnea (17%), and the less common symptoms were diarrhea (4.3%). Blood routine test: white blood cells (WBC) < 4×109/L in 11 cases (48%), (4-10)×109/L in 10 cases (43%), >10 × 109/L in 2 cases (9%); lymphocytopenia in 13 cases (56%). All 23 patients had different degrees of infective lesions in chest CT examination, with 9 cases (39%) on one side and 14 cases (61%) on both sides. Classification: 19 mild cases, 4 severe cases, no critical or death case. Complications included acute respiratory distress syndrome [4 (17%)]. No case was reported with the damage of liver or kidney function and with secondary infection.@*Conclusions@#Epidemic history of contact, fever, pneumonia signs of chest CT, normal or decreased count of WBC and lymphocytopenia are the clinical basis for diagnosis of the disease. However, at present, the treatment of patients has not been completed, the effective treatment strategy and final prognosis are not clear.

positive: COVID-19 in otolaryngologist practice: a review of current knowledge PURPOSE: Otorhinolaryngological manifestations are common symptoms of COVID-19. This study provides a brief and precise review of the current knowledge regarding COVID-19, including disease transmission, clinical characteristics, diagnosis, and potential treatment. The article focused on COVID-19-related information useful in otolaryngologist practice. METHODS: The Medline and Web of Science databases were searched without a time limit using terms "COVID-19", "SARS-CoV-2" in conjunction with "otorhinolaryngological manifestation", "ENT", and "olfaction". RESULTS: The most common otolaryngological dysfunctions of COVID-19 were cough, sore throat, and dyspnea. Rhinorrhea, nasal congestion and dizziness were also present. COVID-19 could manifest as an isolated sudden hyposmia/anosmia. Upper respiratory tract (URT) symptoms were commonly observed in younger patients and usually appeared initially. They could be present even before the molecular confirmation of SARS-CoV-2. Otolaryngologists are of great risk of becoming infected with SARS-CoV-2 as they cope with URT. ENT surgeons could be easily infected by SARS-CoV-2 during performing surgery in COVID-19 patients. CONCLUSION: Ear, nose and throat (ENT) symptoms may precede the development of severe COVID-19. During COVID-19 pandemic, patients with cough, sore throat, dyspnea, hyposmia/anosmia and a history of travel to the region with confirmed COVID-19 patients, should be considered as potential COVID-19 cases. An otolaryngologist should wear FFP3/N95 mask, glasses, disposable and fluid resistant gloves and gown while examining such individuals. Not urgent ENT surgeries should be postponed. Additional studies analyzing why some patients develop ENT symptoms during COVID-19 and others do not are needed. Further research is needed to determine the mechanism leading to anosmia.

positive: Clinical characteristics of emergency surgery patients-infected COVID-19 pneumonia in Wuhan, China OBJECTIVE: We aimed to investigate clinical symptom and epidemiological features of ESP-infected COVID-19 SUMMARY BACKGROUND DATA: Almost one million of 2019 novel coronavirus disease (COVID-19) patients were diagnosed in the world wide from December 2019 to now. Thousands of emergency operations were carried out in the interim. However no one focused on the clinical symptom of emergency surgery patients (ESP) with COVID-19 pneumonia. METHODS: Retrospective cohort study of 164 ESP with or without COVID-19 pneumonia in Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 20, 2020. The final date of follow-up was February 5, 2020. The associated clinical, laboratory, epidemiological, demographic, radiological and outcome data were collected and analyzed. RESULTS: Of 164 ESP, the median age was 41 years old (interquartile range (IQR), 29-89) and 136 (82.9%) were women. Associated main clinical symptom including fever (93 [56.7%]), dry cough (56 [34.2%]), fatigue (86 [52.4%]), nausea (78 [47.6%]) and dizziness (77 [47%]). Of 54 ESP-infected COVID-19 patients, the median age was 46 (IQR: 25-89) and 45 (83.3%) were women. The pathological clinical symptoms including fever (54 [100%]), fatigue (48 [88.9%]), nausea (52 [96.3%]), dizziness (46 [85.2%]) and dry cough (44 [81.5%]) were investigated; the lymphopenia (0.37×10(9)/L [IQR: 0.23-0.65]) and increased C-reactive protein (24.7×10(9)/L [IQR: 13.57-38]) were observed. The preoperative fever and postoperative fever in ESP with or without COVID-19 pneumonia were analyzed in this study. Of 54 ESP with COVID-19 patients, 15 (27.8%) patients showed preoperative fever, 54 (100%) had the postoperative fever; Of 110 non-COVID-19 of ESP, 5 (4.5%) patients had preoperative fever, 31 (28.2%) patients had the postoperative fever. The fever in ESP with COVID-19 lasted more than 7 days, markedly exceeded the non-COVID-19 patients (lasted about 3 days). Furthermore, 43 health care workers were infected from exposed to ESP with COVID-19 pneumonia. CONCLUSION: In our study, the clinical symptoms of ESP-infected COVID-19 displayed marked differences from those reported common COVID-19 pneumonia cases. Additionally, the health care workers were confirmed to expose great risk in ESP with COVID-19 pneumonia. Management guidelines of ESP were described in our paper.

positive: Review article: gastrointestinal features in COVID‐19 and the possibility of faecal transmission BACKGROUND: There is little published evidence on the gastrointestinal features of COVID‐19. AIMS: To report on the gastrointestinal manifestations and pathological findings of patients with COVID‐19, and to discuss the possibility of faecal transmission. METHODS: We have reviewed gastrointestinal features of, and faecal test results in, COVID‐19 from case reports and retrospective clinical studies relating to the digestive system published since the outbreak. RESULTS: With an incidence of 3% (1/41)‐79% (159/201), gastrointestinal symptoms of COVID‐19 included anorexia 39.9% (55/138)‐50.2% (101/201), diarrhoea 2% (2/99)‐49.5% (146/295), vomiting 3.6% (5/138)‐66.7% (4/6), nausea 1% (1/99)‐29.4% (59/201), abdominal pain 2.2% (3/138)‐6.0% (12/201) and gastrointestinal bleeding 4% (2/52)‐13.7% (10/73). Diarrhoea was the most common gastrointestinal symptom in children and adults, with a mean duration of 4.1 ± 2.5 days, and was observed before and after diagnosis. Vomiting was more prominent in children. About 3.6% (5/138)‐15.9% (32/201) of adult and 6.5% (2/31)‐66.7% (4/6) of children patients presented vomiting. Adult and children patients can present with digestive symptoms in the absence of respiratory symptoms. The incidence of digestive manifestations was higher in the later than in the early stage of the epidemic, but no differences in digestive symptoms among different regions were found. Among the group of patients with a higher proportion of severe cases, the proportion of gastrointestinal symptoms in severe patients was higher than that in nonsevere patients (anorexia 66.7% vs 30.4%; abdominal pain 8.3% vs 0%); while in the group of patients with a lower severe rate, the proportion with gastrointestinal symptoms was similar in severe and nonsevere cases (nausea and vomiting 6.9% vs 4.6%; diarrhoea 5.8% vs 3.5%). Angiotensin converting enzyme 2 and virus nucleocapsid protein were detected in gastrointestinal epithelial cells, and infectious virus particles were isolated from faeces. Faecal PCR testing was as accurate as respiratory specimen PCR detection. In 36% (5/14)‐53% (39/73) faecal PCR became positive, 2‐5 days later than sputum PCR positive. Faecal excretion persisted after sputum excretion in 23% (17/73)‐82% (54/66) patients for 1‐11 days. CONCLUSIONS: Gastrointestinal symptoms are common in patients with COVID‐19, and had an increased prevalence in the later stage of the recent epidemic in China. SARS‐CoV‐2 enters gastrointestinal epithelial cells, and the faeces of COVID‐19 patients are potentially infectious.

positive: Laboratory findings, signs and symptoms, clinical outcomes of Patients with COVID-19 Infection: an updated systematic review and meta-analysis Background and Aim: Coronaviruses disease 2019 (COVID-19), for the first time detected in Wuhan, China, rapidly speared around the world and be a Public Health Emergency of International Concern (PHEIC). The aim of the current survey is collecting laboratory findings, analysis them and reporting a specific pattern for help to COVID-19 diagnosis. Methods: To collect laboratory characteristics, we searched "PubMed" electronic database with the following keywords: "COVID-19" "2019 novel coronavirus" "laboratory findings" "clinical characteristics". Results: Once the initial searches 493 studies were yielded. After removing duplicates studies 480 studies were remained. The 12 studies obtained from the literature, of which 58.3% (7) of studies were case-control, and 41.7% remaining studies were designed as cross-sectional. Conclusion: The result of the current study showed that in the early stage of COVID-19 infection, maybe there are not significant laboratory findings, but with disease progression, the one or more than signs include increasing AST, ALT, LDH, CK, CRP, ESR, WBC, neutrophil, and decreasing Hemoglobin, lymphocyte count, eosinophil count can be seen. Elevating D-dimer and FDP are associated with ARDS development and can be used as prognostic factors. Keywords: COVID-19; laboratory findings; prognostic factors

positive: Clinical and imaging features of COVID-19 Abstract Since December 2019, multiple cases of 2019 coronavirus disease (COVID-19) have been reported in Wuhan in China's Hubei Province, a disease which has subsequently spread rapidly across the entire country. Highly infectious, COVID-19 has numerous transmission channels and humans are highly susceptible to infection. The main clinical symptoms of COVID-19 are fever, fatigue, and a dry cough. Laboratory examination in the early stage of the disease shows a normal or decreased white blood cell count, and a decreased lymphocyte count. While CT examination serves as the screening and diagnostic basis for COVID-19, its accuracy is limited. The nucleic acid testing is the gold standard for the diagnosis of COVID-19, but has a low sensitivity is low. There is clearly a divide between the two means of examination. This paper reviews the published literature, guidelines and consensus, and summarizes the clinical and imaging characteristics of COVID-19, in order to provide a reliable basis for early diagnosis and treatment.

positive: Potential implications of novel coronavirus disease (COVID-19) related gastrointestinal symptoms for abdominal imaging

positive: Olfactory and Gustatory Dysfunction in a COVID-19 Patient with Ankylosing Spondylitis Treated with Etanercept: Case Report The neurologic manifestations concerning coronavirus disease 2019 (COVID-19) are highly penetrated. Anosmia and ageusia are one of the common acute neurologic symptoms, which develop in the early stage of COVID-19. However, it is not reported that how immunosuppressive agents affect these symptoms. We report olfactory and gustatory dysfunctions in a patient with ankylosing spondylitis (AS) treated with etanercept during COVID-19. A 53-year-old female showing AS controlled with tumor necrosis factor-α inhibitor, etanercept, had been diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, presenting cough and rhinorrhea. One month after diagnosis, she complained about hyposmia and hypogeusia two days before the seronegative conversion of SARS-CoV-2, which were confirmed by a neurological examination. We speculate that the etanercept may have delayed the development of olfactory and gustatory dysfunction in the patient.

positive: Hypogeusia as the initial presenting symptom of COVID-19 COVID-19 is the disease caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first arose in Wuhan, China, in December 2019 and has since been declared a pandemic. The clinical sequelae vary from mild, self-limiting upper respiratory infection symptoms to severe respiratory distress, acute cardiopulmonary arrest and death. Otolaryngologists around the globe have reported a significant number of mild or otherwise asymptomatic patients with COVID-19 presenting with olfactory dysfunction. We present a case of COVID-19 resulting in intensive care unit (ICU) admission, presenting with the initial symptom of disrupted taste and flavour perception prior to respiratory involvement. After 4 days in the ICU and 6 days on the general medicine floor, our patient regained a majority of her sense of smell and was discharged with only lingering dysgeusia. In this paper, we review existing literature and the clinical course of SARS-CoV-2 in relation to the reported symptoms of hyposmia, hypogeusia and dysgeusia.

positive: Hepatic and gastrointestinal involvement in coronavirus disease 2019 (COVID-19): What do we know till now? Abstract Since December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of coronavirus disease 2019 (COVID-19), has posed a serious threat to global health and is currently causing a major pandemic. While patients typically present with fever and a respiratory illness, mounting evidence indicates that patients might also report extra-pulmonary manifestations, including those affecting the liver and gastrointestinal tract. This involvement may have important implications to the disease management, transmission, and prognosis, especially in patients with pre-existing hepatic or digestive co-morbidities. In this review, the characteristics and possible explanations of hepatic and gastrointestinal involvement caused by SARS-CoV-2 infection are summarized, adding to our knowledge of the spectrum of COVID-19. In addition, preventive measures implemented in endoscopy departments to prevent further dissemination of SARS-CoV-2 infection are proposed.

positive: Identification of Symptoms Prognostic of COVID-19 Severity: Multivariate Data Analysis of a Case Series in Henan Province BACKGROUND: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease (COVID-19), has been declared a global pandemic. Identifying individuals whose infection can potentially become severe is critical to control the case fatality rate of COVID-19. However, knowledge of symptoms that are prognostic of COVID-19 severity is lacking. OBJECTIVE: The objective of our study was to identify symptoms prognostic of COVID-19 infection severity. METHODS: We analyzed documented symptoms, including fever, cough, fatigue, expectoration, sore throat, chest distress, headache, diarrhea, rhinorrhea, stuffed nose, nausea, vomiting, muscle or joint ache, shortness of breath, and their associations with disease severity using a case series, including 655 confirmed cases from January 23 to February 5, 2020 in Henan Province, China. We also analyzed the influence of individual characteristics, including age, gender, and comorbidities, on symptoms with prognostic value. RESULTS: Fatigue (95% CI 0.141 to 0.334, P<.001), expectoration (95% CI 0.107 to 0.305, P<.001) and stuffed nose (95% CI –0.499 to –0.082, P=.006) were identified as the prognostic symptoms of COVID-19 patients from the multivariate analysis. Fever occurred in 603/655 (92.1%) of the patients but was not associated with disease severity. Fatigue accounted for 184/655 (28.1%) of the patients and was linearly associated with infection severity with statistical significance. Expectoration occurred in 169/655 (25.8%) patients in the cohort and was the sole prognostic factor for patients with cardiovascular complications, including hypertension. Shortness of breath, chest distress, muscle or joint ache, and dry cough, which occurred in 33 (5%), 83 (12.7%), 78 (11.9%), and 276 (42.1%) of the 655 patients, respectively, were significantly enriched among patients classified as severe. Stuffed nose and nausea were associated with favorable disease severity, especially among male patients. More female than male patients were documented as having muscle or joint ache. Headache was most enriched in patents aged 15 to 39 years, followed by those aged 40 to 64 years, with statistical significance. CONCLUSIONS: Fatigue and expectoration are signs of severe COVID-19 infection. Shortness of breath, chest distress, muscle or joint ache, and dry cough are prevalent in severe patients. Expectoration is commonly present in older individuals and patients with cardiovascular disorders, including hypertension. Shortness of breath is prognostic of severe infection in male patients. Stuffed nose and nausea are favorable prognostic factors of severe infection, especially among male patients.

positive: Diagnosis and treatment of 2019 novel coronavirus infection in children: a pressing issue

positive: Dermatologic findings in two patients with COVID-19

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

positive: SARS-CoV-2 induced diarrhoea as onset symptom in patient with COVID-19.

positive: Clinical features of 1487 COVID-19 patients with outpatient management in the Greater Paris: the COVID-call study Clinical features of COVID-19 have been mostly described in hospitalized patients with and without ICU admission. Yet, up to 80% of patients are managed in an outpatient setting. This population is poorly documented. In France, health authorities recommend outpatient management of patients presenting mild-to-moderate COVID-19 symptoms. The aim of this study was to describe their clinical characteristics. The study took place in an emergency medical dispatching center located in the Greater Paris region. Patients included in this survey met confirmed COVID-19 infection criteria according to the WHO definition. We investigated clinical features and classified symptoms as general, digestive, ear–nose–throat, thoracic symptoms, and eye disease. Patients were included between March 24 and April 6 2020. 1487 patients included: 700 (47%) males and 752 (51%) females, with a median age of 44 (32–57) years. In addition to dry cough and fever reported in more than 90% of cases, the most common symptoms were general symptoms: body aches/myalgia (N = 845; 57%), headache (N = 824; 55%), and asthenia (N = 886; 60%); shortness of breath (N = 479; 32%) and ear–nose–throat symptoms such as anosmia (N = 415; 28%) and ageusia (N = 422; 28%). Chest pain was reported in 320 (21%) cases and hemoptysis in 41 (3%) cases. The main difference between male and female patients was an increased prevalence of ear–nose–throat symptoms as well as diarrhea, chest pains, and headaches in female patients. General symptoms and ear–nose–throat symptoms were predominant in COVID-19 patients presenting mild-to-moderate symptoms. Shortness of breath and chest pain were remarkably frequent. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11739-020-02379-z) contains supplementary material, which is available to authorized users.

positive: Impact de l'épidémie de COVID-19 sur les demandes de prise en charge initiale pour cancer du sein Clinical characteristics and radiological features of children infected with the 2019 novel coronavirus AIM: To identify and summarise the common findings from 2019 novel coronavirus (2019-nCoV) infections in children MATERIALS AND METHODS: The clinical characteristics and radiological findings (chest radiography and chest computed tomography [CT]) of nine children infected with the 2019-nCoV were reviewed in this retrospective case series RESULTS: Among the children, six had fever (including two children with cough), one had only cough, one had a stuffy nose when initially diagnosed, and one was an asymptomatic carrier Chest radiographs seemed mostly normal in six cases whereas increased and/or disordered bilateral bronchovascular shadows and dense hilar shadows were seen in three cases Chest CT exhibited no obvious abnormal signs in four cases Typical CT findings included patchy, peripheral ground-grass opacities, subpleural lamellar dense shadows, and parenchymal bands Pleural effusions, mediastinal lymphadenopathy, cavitation, and pleural thickening were absent CONCLUSION: The clinical manifestations and radiological findings of the 2019-nCoV-infected children were mild and lacked a typical pattern

positive: Clinical Characteristics and Outcomes of 421 Patients with COVID-19 Treated in a Mobile Cabin Hospital Abstract Background In December 2019, a novel coronavirus-associated pneumonia (COVID-19) was first detected in Wuhan, China. To prevent the rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and treat patients with mild symptoms, sports stadiums and convention centers were reconstructed into mobile hospitals. Research Question Whether a mobile cabin hospital can provide a safe treatment site for patients with mild COVID-19 symptoms remains unknown. Study Design and Methods We retrospectively reviewed the medical records of 421 patients with COVID-19 admitted to a mobile cabin hospital in Wuhan from February 9th to March 5th, 2020. Clinical data comprised patient age, sex, clinical presentation, chest imaging, nucleic acid testing, length of hospitalization, and outcomes. Results The outcome was recovery and hospital discharge in 86% of patients, while 14.0% developed severe symptoms and were transferred to a designated hospital. The most common presenting symptoms were fever (60.6%) and cough (52.0%), while 5.2% showed no obvious symptoms. High fever (>39.0°C) was more common in severe cases than recovered cases (18.6% versus 6.6%). The distribution of lung lesions was peripheral in 85.0% of patients, multifocal in 69.4%, and bilateral in 68.2%. The most common pattern was ground-glass opacity (67.7%), followed by patchy shadowing (49.2%). The incidence of patchy shadowing was higher in severe patients (66.1%) than in those who recovered (31.8%, P<.0001). The median length of hospitalization was 17 (14–19) days, and the median time taken for positive real-time reverse transcriptase polymerase chain reaction results to become negative in recovered patients was 8 (6–10) days. Interpretation Mobile cabin hospitals provide a safe treatment site for patients with mild COVID-19 symptoms, and provide an effective isolation area to prevent the spread of SARS-CoV-2.

positive: Coronavirus Disease 2019 (COVID-19): A Perspective from China In December 2019, an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection occurred in Wuhan, Hubei Province, China and spread across China and beyond. On February 12, 2020, WHO officially named the disease caused by the novel coronavirus as Coronavirus Disease 2019 (COVID-19). Since most COVID-19 infected patients were diagnosed with pneumonia and characteristic CT imaging patterns, radiological examinations have become vital in early diagnosis and assessment of disease course. To date, CT findings have been recommended as major evidence for clinical diagnosis of COVID-19 in Hubei, China. This review focuses on the etiology, epidemiology, and clinical symptoms of COVID-19, while highlighting the role of chest CT in prevention and disease control. A full translation of this article in Chinese is available.

positive: Neurological Complications of Coronavirus Disease (COVID-19): Encephalopathy Coronavirus disease 2019 (COVID-19) is a pandemic. Neurological complications of COVID-19 have not been reported. Encephalopathy has not been described as a presenting symptom or complication of COVID-19. We report a case of a 74-year-old patient who traveled from Europe to the United States and presented with encephalopathy and COVID-19.

positive: Clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19 in Wuhan, China: a retrospective, single-centre, descriptive study Summary Background In December, 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China. The number of affected pregnant women is increasing, but scarce information is available about the clinical features of COVID-19 in pregnancy. This study aimed to clarify the clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19. Methods In this retrospective, single-centre study, we included all pregnant women with COVID-19 who were admitted to Tongji Hospital in Wuhan, China. Clinical features, treatments, and maternal and fetal outcomes were assessed. Findings Seven patients, admitted to Tongji Hospital from Jan 1, to Feb 8, 2020, were included in our study. The mean age of the patients was 32 years (range 29–34 years) and the mean gestational age was 39 weeks plus 1 day (range 37 weeks to 41 weeks plus 2 days). Clinical manifestations were fever (six [86%] patients), cough (one [14%] patient), shortness of breath (one [14%] patient), and diarrhoea (one [14%] patient). All the patients had caesarean section within 3 days of clinical presentation with an average gestational age of 39 weeks plus 2 days. The final date of follow-up was Feb 12, 2020. The outcomes of the pregnant women and neonates were good. Three neonates were tested for SARS-CoV-2 and one neonate was infected with SARS-CoV-2 36 h after birth. Interpretation The maternal, fetal, and neonatal outcomes of patients who were infected in late pregnancy appeared very good, and these outcomes were achieved with intensive, active management that might be the best practice in the absence of more robust data. The clinical characteristics of these patients with COVID-19 during pregnancy were similar to those of non-pregnant adults with COVID-19 that have been reported in the literature. Funding National Natural Science Foundation of China, Hubei Provincial Natural Science Foundation of China.

positive: CT findings of severe novel coronavirus disease (COVID-19): A case report of Heilongjiang Province, China 2019 novel coronavirus disease (COVED-19, previously known as novel coronavirus pneumonia) was first discovered in December 2019 and spread widely in China and all over the world in 2020 The initial symptoms of most patients include fever, cough, and fatigue Dyspnea may occur with the progress of the disease, and acute respiratory distress syndrome may occur in severe cases The CT manifestations of this disease are mainly ground-glass opacity (GGO) in the lung, which may be accompanied by patchy consolidation, and fibrous changes may appear in the lung at the later stage of the disease Combined with typical clinical and imaging findings and positive nucleic acid test results, the disease can be diagnosed We report the first case of novel coronavirus disease (COVED-19) in Heilongjiang Province, China The patient was seriously ill, who felt that he suffered from fever, fatigue, cough, and expectoration and sought medical treatment, with a history of contact with Wuhan The leukocyte count was normal, and the lymphocyte count was decreased CT imaging showed large GGO and partial patchy consolidation in both lungs The patient recovered and was discharged after 26 days of treatment This study is helpful for early diagnosis and timely clinical management by mastering the typical imaging of novel coronavirus disease (COVED-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: COVID-19 pandemic – A focused review for clinicians Abstract Background The COVID-19 pandemic caused by SARS-CoV-2 remains a significant issue for global health, economics and society. A wealth of data has been generated since its emergence in December 2019 and it is vital for clinicians to keep up with this data from across the world at a time of uncertainty and constantly evolving guidelines and clinical practice. Objectives Here we provide an update for clinicians on the recent developments about virology, diagnostics, clinical presentation, viral shedding, and treatment options for COVID-19 based on current literature. Sources We considered published peer-reviewed papers and non-peer-reviewed pre-print manuscripts on COVID19 and related aspects with an emphasis on clinical management aspects. Content We describe the virological characteristics of SARS-CoV-2 and clinical course of COVID-19 with an emphasis on diagnostic challenges, duration of viral shedding, severity markers and current treatment options. Implications The key challenge in managing COVID-19 remains the patient density. However, accurate diagnoses as well as early identification and management of high-risk severe cases are important for many clinicians. For improved management of cases, there is a need to understand test probability of serology, qRT-PCR and radiological testing, and the efficacy of available treatment options that could be used in severe cases with a high risk of mortality.

positive: 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.

positive: Uncommon Presentation Of Covid-19: Gastrointestinal Bleeding SUMMARY The COVID-19 outbreak has become a pandemic that is threatening global health. The typical clinical manifestations were fever, cough, dyspnea, and myalgia or fatigue. Digestive symptoms such as nausea, vomiting, diarrhea, abdominal pain usually accompany respiratory symptoms. However gastrointestinal bleeding as the first symptom is not reported. Here we reported a case of COVID-19 with gastrointestinal bleeding as the initial symptom to the emergency department with a real-time reverse transcriptase polymerase chain reaction test positive, and normal thorax tomography. The case demonstrate that; clinicians should be alerted to patients about COVID-19 when referring to atypical symptoms and every patient undergoing endoscopy should be considered potentially infected or can infect others.

positive: 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.

positive: Olfactory Dysfunction: A Highly Prevalent Symptom of COVID-19 With Public Health Significance OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a global pandemic affecting millions of individuals, killing hundreds of thousands. Although typically described with characteristic symptoms of fever, cough, and shortness of breath, greater understanding of COVID-19 has revealed myriad clinical manifestations. Olfactory dysfunction (OD)-hyposmia and anosmia-has recently been recognized as an important symptom of COVID-19 and increasingly gained traction as a public health tool for identifying COVID-19 patients, in particular otherwise asymptomatic carriers who, unawares, may be major drivers of disease spread. The objective of this study is to review the scientific evidence about anosmia in COVID-19. DATA SOURCES: PubMed, Google Scholar, and Web of Science. REVIEW METHODS: Comprehensive literature search of primary studies pertinent to the objectives of this review using the chosen data sources. CONCLUSIONS: Current evidence shows that OD is highly prevalent in COVID-19, with up to 80% of patients reporting subjective OD and objective olfactory testing potentially showing even higher prevalence. OD is frequently accompanied by taste dysfunction. Up to 25% of COVID-19 patients may experience sudden-onset OD as the first symptom. A large proportion of COVID-19 OD cases may resolve over the period of a few weeks. IMPLICATIONS FOR PRACTICE: Sudden anosmia should be considered a symptom of COVID-19. Assessing for sudden-onset anosmia may increase sensitivity of COVID-19 screening strategies, in particular for identifying patients at the earliest stages of disease. Since many cases of OD due to COVID-19 may resolve in the short term, conservative management, including observation, is reasonable, while advanced imaging is unnecessary.

positive: Involvement of digestive system in COVID-19: manifestations, pathology, management and challenges The pandemic of novel coronavirus disease (COVID-19) has developed as a tremendous threat to global health. Although most COVID-19 patients present with respiratory symptoms, some present with gastrointestinal (GI) symptoms like diarrhoea, loss of appetite, nausea/vomiting and abdominal pain as the major complaints. These features may be attributable to the following facts: (a) COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and its receptor angiotensin converting enzyme 2 (ACE2) was found to be highly expressed in GI epithelial cells, providing a prerequisite for SARS-CoV-2 infection; (b) SARS-CoV-2 viral RNA has been found in stool specimens of infected patients, and 20% of patients showed prolonged presence of SARS-CoV-2 RNA in faecal samples after the virus converting to negative in the respiratory system. These findings suggest that SARS-CoV-2 may be able to actively infect and replicate in the GI tract. Moreover, GI infection could be the first manifestation antedating respiratory symptoms; patients suffering only digestive symptoms but no respiratory symptoms as clinical manifestation have also been reported. Thus, the implications of digestive symptoms in patients with COVID-19 is of great importance. In this review, we summarise recent findings on the epidemiology of GI tract involvement, potential mechanisms of faecal–oral transmission, GI and liver manifestation, pathological/histological features in patients with COVID-19 and the diagnosis, management of patients with pre-existing GI and liver diseases as well as precautions for preventing SARS-CoV-2 infection during GI endoscopy procedures.

positive: Epidemiological and Clinical Characteristics of Children with Coronavirus Disease 2019 Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly identified pathogen which mainly spreads by droplets. Most published studies focused on adult patients with coronavirus disease 2019 (COVID-19), but data concerning pediatric patients is limited. This study aimed to determine epidemiological characteristics and clinical features of pediatric patients with COVID-19. Methods: We reviewed and analyzed data on pediatric patients with laboratory-confirmed COVID-19, including basic information, epidemiological history, clinical manifestations, laboratory and radiologic findings, treatment, outcome and follow-up results. Results: From January 20th to February 27th of 2020, a total of 74 pediatric patients with COVID-19 were included in this study. Of the 68 cases whose epidemiological data were complete, 65 (65/68, 95.59%) cases were household contacts of adults whose symptoms developed earlier. Forty (59.46%) of the infected children were male, and the median age and body weight are 6 (0.10-15.08) years and 24 (4.20-87.00) kg, respectively. Except for one critically ill case, 20 (27.03%) patients did not show any symptoms of infection, 24 (32.43%) patients had acute upper respiratory tract infection and 29 (39.19%) patients were diagnosed with mild pneumonia. Cough (24/74, 32.43%) and fever (20, 27.03%) were the predominant symptoms of 44 (59.46%) symptomatic patients at onset of the illness. Abnormalities in leukocyte count were found in 23 (31.08%) children and 10 (13.51%) children presented with abnormal lymphocyte count. Of the 34 (45.95%) patients who had nucleic acid testing results for common respiratory pathogens, 19 (19 / 34, 51.35%) showed co-infection with other pathogens other than SARS-CoV-2.Ten (13.51%) children had RT-PCR analysis of SARS-CoV-2 for fecal specimens and 8 of them showed prolonged existence of SARS-CoV-2 RNA 11 (5-23) days after nasopharynx swabs turning negative. Abnormalities in chest imaging were observed in 37 (50.00%) patients and 28 (37.84%) of them only presented with nontypical changes.All children had good prognosis with a median hospitalization duration of 11 days and follow-up period of 16.5 days. During the follow-up period, all the patients remained in quarantine at designated site and home for two 14-day obervation periods and showed no clinical manifestation,but 3 of the 8 cases with prolonged fecal shedding of SARS-CoV-2 still showed positive result of feces test.

positive: Epidemiologic and clinical characteristics of 91 hospitalized patients with COVID-19 in Zhejiang, China: a retrospective, multi-centre case series BACKGROUND: Recent studies have focused on initial clinical and epidemiological characteristics of the coronavirus disease 2019 (COVID-19), which is the mainly revealing situation in Wuhan, Hubei. AIM: This study aims to reveal more data on the epidemiological and clinical characteristics of COVID-19 patients outside of Wuhan, Zhejiang, China. DESIGN: This study was a retrospective case series. METHODS: Eighty-eight cases of laboratory-confirmed and three cases of clinically confirmed COVID-19 were admitted to five hospitals in Zhejiang province, China. Data were collected from 20 January 2020 to 11 February 2020. RESULTS AND DISCUSSION: Of all 91 patients, 88 (96.70%) were laboratory-confirmed COVID-19 with throat swab samples that tested positive for SARS-Cov-2, three (3.30%) cases were clinically diagnosed. The median age of the patients was 50 (36.5-57) years, and female accounted for 59.34%. In this sample, 40 (43.96%) patients had contracted the disease from local cases, 31 (34.07%) patients had been to Wuhan/Hubei, eight (8.79%) patients had contacted with people from Wuhan, and 11 (12.09%) patients were diagnosed after having flown together in the same flight with no passenger that could later be identified as the source of infection. In particular within the city of Ningbo, 60.52% cases can be traced back to an event held in a temple. The most common symptoms were fever (71.43%), cough (60.44%) and fatigue (43.96%). The median of incubation period was 6 (interquartile range 3-8) days and the median time from the first visit to a doctor to the confirmed diagnosis was 1 (1-2) days. According to the chest computed tomography scans, 67.03% cases had bilateral pneumonia. CONCLUSIONS: Social activity cluster, family cluster and flying alongside with persons already infected with COVID-19 were how people got infected with COVID-19 in Zhejiang.

positive: 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.

positive: Clinical characteristics and diagnostic challenges of pediatric COVID-19: A systematic review and meta-analysis Background/Purpose Current studies on pediatric coronavirus disease 2019 (COVID-19) are rare. The clinical characteristics and spectrum are still unknown. Facing this unknown and emerging pathogen, we aimed to collect current evidence about COVID-19 in children. Methods We performed a systematic review in PubMed and Embase to find relevant case series. Because some reports were published in Chinese journals, the journals and publications of the Chinese Medical Association related to COVID-19 were completely reviewed. A random effects model was used to pool clinical data in the meta-analysis. Results Nine case series were included. In the pooled data, most of patients (75%) had a household contact history. The disease severity was mainly mild to moderate (98%). Only 2 children (2%) received intensive care. Fever occurred in 59% of the patients, while cough in 46%. Gastrointestinal symptoms (12%) were uncommon. There are 26% children are asymptomatic. The most common radiographic finding was ground glass opacities (48%). Currently, there is no evidence of vertical transmission to neonates born to mothers with COVID-19. Compared with the most relevant virus, SARS-CoV, SARS-CoV-2 causes less severe disease. Conclusion COVID-19 has distinct features in children. The disease severity is mild. Current diagnosis is based mainly on typical ground glass opacities on chest CT, epidemiological suspicion and contact tracing.

positive: Coronavirus disease 2019 (COVID-19) in pregnant women: A report based on 116 cases Abstract Background The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global public health emergency. Data on the effect of COVID-19 in pregnancy are limited to small case series. Objectives To evaluate the clinical characteristics and outcomes in pregnancy and the vertical transmission potential of SARS-CoV-2 infection. Study Desigh Clinical records were retrospectively reviewed for 116 pregnant women with COVID-19 pneumonia from 25 hospitals in China between January 20 and March 24, 2020. Evidence of vertical transmission was assessed by testing for SARS-CoV-2 in amniotic fluid, cord blood, and neonatal pharyngeal swab samples. Results The median gestational age on admission was 38+0 (IQR 36+0-39+1) weeks. The most common symptoms were fever (50.9%, 59/116) and cough (28.4%, 33/116); 23.3% (27/116) patients presented without symptoms. Abnormal radiologic findings were found in 96.3% (104/108) of cases. There were eight cases (6.9%, 8/116) of severe pneumonia but no maternal deaths. One of eight patients (1/8) that presented in the first- and early-second-trimester had a missed spontaneous abortion. Twenty-one of 99 patients (21.2%, 21/99) that had delivered had preterm birth, including six with preterm premature ruptured of membranes. The rate of spontaneous preterm birth before 37 weeks was 6.1% (6/99). There was one case of severe neonatal asphyxia that resulted in neonatal death. Eighty-six of the 100 neonates that had testing for SARS-CoV-2 had negative results, of these ten neonates had paired amniotic fluid and cord blood samples that were tested negative for SARS-CoV-2. Conclusions SARS-CoV-2 infection during pregnancy is not associated with an increased risk of spontaneous abortion and spontaneous preterm birth. There is no evidence of vertical transmission of SARS-CoV-2 infection when the infection manifests during the third-trimester of pregnancy.

positive: ENT manifestation in COVID-19 patients OBJECTIVE: to detect, analyze and discuss the different ear nose throat (ENT) manifestations those were reported in COVID19 positive patients in the reviewed and published literatures. METHODS: We performed a search in the PubMed databases, Web of Science, LILACS, MEDLINE, SciELO, and Cochrane Library using the keywords; COVID-19, Novel coronavirus, corona, 2019-nCoV, SARS-CoV-2, ENT, ear, nose, throat, otorhinolaryngology, ORL, pharynx, ORL, smell, larynx, different ENT related symptoms. We reviewed published and peer reviewed studies that reported the ENT manifestations in COVID-19 laboratory-confirmed positive patients. RESULTS: within the included 1773 COVID-19 laboratory-confirmed positive patients, the most common ENT manifestations of COVID-19 were sore throat (11.3%) and headache (10.7%). While the other reported ENT manifestations were pharyngeal erythema (5.3%), nasal congestion (4.1%), runny nose or rhinorrhea (2.1%), upper respiratory tract infection (URTI) (1.9%), and tonsil enlargement (1.3%). CONCLUSION: ENT manifestations for COVID-19 are not common as fever and cough. But, a universal questionnaire using well-defined COVID-19 manifestations is needed to make the COVID-19 data precisely defined, complete and homogenous.

positive: 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.

positive: COVID-19 in a tertiary hospital from Romania: Epidemiology, preparedness and clinical challenges

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

positive: Neurological manifestations associated with COVID-19: a review and a call for action While the epidemic of Coronavirus disease 2019 (COVID-19) continues to spread globally, more and more evidences are collected about the presence of neurological manifestations and symptoms associated with it. A systematic review has been performed of papers published until 5 April 2020. 29 papers related to neurological manifestations associated with COVID-19 were examined. The results show presence of central and peripheral nervous system manifestations related to coronavirus. Neurological manifestations, or NeuroCOVID, are part of the COVID-19 clinical picture, but questions remain regarding the frequency and severity of CNS symptoms, the mechanism of action underlying neurological symptoms, and the relationship of symptoms with the course and severity of COVID-19. Further clinical, epidemiological, and basic science research is urgently needed to understand and address neurological sequalae of COVID-19. Concomitant risk factors or determinants (e.g. demographic factors, comorbidities, or available biomarkers) that may predispose a person with COVID-19 to neurological manifestations also need to be identified. The review shows that although more and more papers are reporting neurological manifestations associated with COVID-19; however, many items remain unclear and this uncertainty calls for a global action that requires close coordination and open-data sharing between hospitals, academic institutions and the fast establishment of harmonised research priorities and research consortia to face the NeuroCOVID-19 complications.

positive: Acute abdomen as an early symptom of COVID-19. A woman with acute abdominal pain was admitted to hospital with suspected cholecystitis. In addition to abdominal pain, she had vomiting, loss of appetite, diarrhoea and symptoms of pyrexia. She had no symptoms from the respiratory tract, but was later found to have COVID-19. A number of patients have presented with similar symptoms at our hospital. This has led to temporary changes in our procedures for handling and investigating patients with acute abdominal pain.

positive: Covid-19 in Critically Ill Patients in the Seattle Region — Case Series BACKGROUND: Community transmission of coronavirus 2019 (Covid-19) was detected in the state of Washington in February 2020. METHODS: We identified patients from nine Seattle-area hospitals who were admitted to the intensive care unit (ICU) with confirmed infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Clinical data were obtained through review of medical records. The data reported here are those available through March 23, 2020. Each patient had at least 14 days of follow-up. RESULTS: We identified 24 patients with confirmed Covid-19. The mean (±SD) age of the patients was 64±18 years, 63% were men, and symptoms began 7±4 days before admission. The most common symptoms were cough and shortness of breath; 50% of patients had fever on admission, and 58% had diabetes mellitus. All the patients were admitted for hypoxemic respiratory failure; 75% (18 patients) needed mechanical ventilation. Most of the patients (17) also had hypotension and needed vasopressors. No patient tested positive for influenza A, influenza B, or other respiratory viruses. Half the patients (12) died between ICU day 1 and day 18, including 4 patients who had a do-not-resuscitate order on admission. Of the 12 surviving patients, 5 were discharged home, 4 were discharged from the ICU but remained in the hospital, and 3 continued to receive mechanical ventilation in the ICU. CONCLUSIONS: During the first 3 weeks of the Covid-19 outbreak in the Seattle area, the most common reasons for admission to the ICU were hypoxemic respiratory failure leading to mechanical ventilation, hypotension requiring vasopressor treatment, or both. Mortality among these critically ill patients was high. (Funded by the National Institutes of Health.)

positive: SARS-CoV-2 infection in children: Transmission dynamics and clinical characteristics

positive: Neurosensory dysfunction: a diagnostic marker of early COVID-19 Abstract Objectives To detailly described the neurosensory dysfunction, including hyposmia, hypogeusia and tinnitus, in patients with COVID-19. Methods Clinical characteristics and oropharyngeal swabs were obtained from 86 patients with COVID-19 hospitalized in Guangzhou Eighth People’s Hospital. Chronological analysis method was used to detailly clarify the neurosensory dysfunction. The cycle threshold (Ct) values were used to approximately indicate viral load. Results Forth-four (51.2%) patients had neurosensory dysfunction: hyposmia (34, 39.5%), hypogeusia (33, 38.4%), and tinnitus (3, 3.5%). Neurosensory dysfunction was significantly more common in patients under 40 years old (p = 0.001) or women (p = 0.006). Hyposmia and hypogeusia coexisted in 23 (26.7%) patients. The interval between onset of hyposmia and hypogeusia was 0.7 ± 1.46 days. The interval from onset of hyposmia and hypogeusia to typical symptoms was 0.22 ± 4.57 and 0.75 ± 6.77 days; the interval from onset of hyposmia and hypogeusia to admission was 6.06 ± 6.68 and 5.76 ± 7.68 days; and the duration of hyposmia and hypogeusia was 9.09 ± 5.74 and 7.12 ± 4.66 days, respectively. The viral load was high since symptoms onset, peaked within the first week, and then gradually declined. Conclusions The neurosensory dysfunction tends to occur in the early stage of COVID-19, and it could be used as a marker for early diagnosis of COVID-19.

positive: Association of chemosensory dysfunction and Covid‐19 in patients presenting with influenza‐like symptoms BACKGROUND: Rapid spread of the SARS‐CoV‐2 virus and concern for viral transmission by ambulatory patients with minimal to no symptoms underline the importance of identifying early or subclinical symptoms of Covid‐19 infection. Two such candidate symptoms include anecdotally reported loss of smell and taste. Understanding the timing and association of smell/taste loss in Covid‐19 may help facilitate screening and early isolation of cases. METHODS: A single‐institution, cross‐sectional study evaluating patient‐reported symptoms with a focus on smell and taste was conducted using an internet‐based platform on adult subjects who underwent testing for Covid‐19. Logistic regression was employed to identify symptoms associated with Covid‐19 positivity. RESULTS: A total of 1480 patients with influenza‐like symptoms underwent Covid‐19 testing between March 3 through 29, 2020. Our study captured 59 of 102 (58%) Covid‐19‐positive patients and 203 of 1378 (15%) Covid‐19‐negative patients. Smell and taste loss were reported in 68% (40/59) and 71% (42/59) of Covid‐19‐positive subjects, respectively, compared to 16% (33/203) and 17% (35/203) of Covid‐19‐negative patients (p<0.001). Smell and taste impairment were independently and strongly associated with Covid‐19‐positivity (anosmia: adjusted odds ratio [aOR] 10.9, 95%CI:5.08‐23.5; ageusia: aOR 10.2 95%CI:4.74‐22.1); whereas, sore throat was associated with Covid‐19‐negativity (aOR 0.23, 95%CI:0.11‐0.50). Of patients who reported Covid‐19‐associated loss of smell, 74% (28/38) reported resolution of anosmia with clinical resolution of illness. CONCLUSIONS: In ambulatory individuals with influenza‐like symptoms, chemosensory dysfunction was strongly associated with Covid‐19 infection and should be considered when screening symptoms. Most will recover chemosensory function within weeks paralleling resolution of other disease‐related symptoms. This article is protected by copyright. All rights reserved

positive: COVID-19 and intracerebral haemorrhage: causative or coincidental? Pneumonia appears to be the most common manifestation of coronavirus disease 2019 (COVID-19), but some extrapulmonary involvement, such as gastrointestinal, cardiac and renal, has been reported. The limited clinical data about the virus's behavior to date, especially extrapulmonary symptoms, suggest that we should be aware of the possibility of initial cerebrovascular manifestations of COVID-19.

positive: Clinical characteristics of 51 patients discharged from hospital with COVID-19 in Chongqing，China Abstract Background：Since December 2019, Severe acute respiratory syndrome coronavirus 2（SARS-CoV-2）-infected disease (Coronavirus Disease 2019，COVID-19) emerged in Wuhan , China，and rapidly spread throughout China，even throughout the world. We try to describe the epidemiological and clinical characteristics of COVID-19 in non-Wuhan area，and explore its effective treatment. Methods：Retrospective, single-center case series of the 51 hospitalized patients with confirmed COVID-19 at Chongqing University Three Gorges Hospital in Chongqing, China, from January 20 to February 3, 2020；The discharge time was from January 29 to February 11, 2020. The main results and indicators of epidemiology, demography, clinical manifestation, laboratory examination, imaging data and treatment data of 51 patients with covid-19 were collected and analyzed. The changes of blood routine and biochemical indexes at discharge and admission were compared. Compare the clinical characteristics of severe patients (including severe and critical patients) and non- severe patients (general patients). Results： Of 51 hospitalized patients with COVID-19, the median age was 45 years (interquartile range, 34-51; range, 16-68 years) and 32 (62.7%) were men.43（84.3%）patients had been to Wuhan or Other Hubei areas outside Wuhan，and 4（7.7%） patients had a clear contact history of COVID-19 patients before the onset of the disease, and 4（7.7%） patients had no clear epidemiological history of COVID-19.Common symptoms included fever (43 [84.3%]), cough (38 [74.5%]) and fatigue (22 [43.1%]). Lymphopenia was observed in 26 patients (51.0%), and elevated C-reactive protein level in 32 patients (62.7%). Ground-glass opacity was the typical radiological finding on chest computed tomography (41 [80.4%])，Local consolidation of pneumonia in some patients(17 [33.3%]).Most of the patients were treated with traditional Chinese medicine decoction (28 [54.9%])，all of them received aerosol inhalation of recombinant human interferon a-1b for injection and oral antiviral therapy with Lopinavir and Ritonavir tablets (51 [100%]); Most of the patients were given Bacillus licheniformis capsules regulated intestinal flora treatment (44 [86.3%]). 10 patients (19.6%) received short-term (3-5 days) glucocorticoid treatment. Compared with non-severe patients (n = 44), severe patients (n = 7) were older (median age, 52 years vs 44 years), had a higher proportion of diabetes mellitus (4 [57.1%] vs 0 [0.0%]), most of them needed antibiotic treatment (7 [100%] vs 4 [9.1%], most of them needed nutritional diet (6 [85.7%) vs 0 [0.0%], and were more likely to have dyspnea (6 [85.7%] vs 5 [11.4%])，most of them needed noninvasive mechanical ventilation (6 [85.7%] vs 0 [0.0%]). Except one patient died, the remaining 50 patients were discharged according to the discharge standard, the common clinical symptoms disappeared basically, the lymphocyte increased significantly (P=0.008), CRP decreased significantly (P <0.001). The median length of stay was 12 days (IQR, 9-13). Conclusion：In 51 single center cases confirmed as COVID-19 and discharged from the hospital, 13.7% of the patients were severe. The main clinical symptoms of patients with COVID-19 were fever, cough and asthenia，Some patients had obvious dyspnea. They had clinical laboratory and radiologic characteristics. There is no specific drug treatment for the disease. For the treatment of COVID-19, in addition to oxygen inhalation and antiviral treatment, attention should be paid to the dialectical treatment of traditional Chinese medicine, regulation of intestinal flora, nutritional support treatment and other comprehensive treatment.

positive: AGA Institute Rapid Recommendations for Gastrointestinal Procedures During the COVID-19 Pandemic

positive: Keratoconjunctivitis as the initial medical presentation of the novel coronavirus disease 2019 (COVID-19) Abstract We present a case of coronavirus disease 2019 (COVID-19) with an initial medical presentation of keratoconjunctivitis, the first such reported case in North America. The patient's primary symptom was a red eye with watery discharge, though she did have mild respiratory symptoms, without fever. She was diagnosed with keratoconjunctivitis; evolving corneal findings were characterized through repeat visits to ophthalmology. A conjunctival swab of the affected eye was positive for the SAR-CoV-2 virus. This case emphasizes the importance of ensuring that first-line health care providers, including ophthalmologists, optometrists, emergency physicians, and family physicians, consider COVID-19 on the differential for any patient with recent travel who presents with acute conjunctivitis. Having a high index of suspicion with this presentation would allow for appropriate precautions to be taken to prevent further spread of COVID-19.

positive: Clinical features and management of severe COVID-19: A retrospective study in Wuxi, Jiangsu Province, China Objective: We aimed to investigate clinical features and management of 55 COVID-19 patients in Wuxi, especially severe COVID-19. Methods: Epidemiological, demographic, clinical, laboratory, imaging, treatment, and outcome data of patients were collected. Follow-up lasted until April 6, 2020. Results: All 55 patients included 47 (85.5%) non-severe patients and 8 (14.5%) severe patients. Common comorbidities were hypertension and diabetes. Common symptoms were fever, cough and sputum. Lymphopenia was a common laboratory finding, and ground-glass opacity was a common chest CT feature. All patients received antiviral therapy of α-interferon inhalation and lopinavir-ritonavir tablets. Common complications included acute liver injury and respiratory failure. All patients were discharged. No death was occurred and no medical staff got infected. Patients with severe COVID-19 showed significantly older age, decreased lymphocytes, increased C reactive protein, and higher frequency of bilateral lung infiltration compared to non-severe patients. Significantly more treatments including antibiotic therapy and mechanical ventilation, longer hospitalization stay and higher cost were shown on severe patients. Conclusions: Our study suggested that patients with severe COVID-19 may be more likely to have an older age, present with lymphopenia and bilateral lung infiltration, receive multiple treatments and stay longer in hospital.

positive: Children with coronavirus disease 2019: A review of demographic, clinical, laboratory, and imaging features in pediatric patients There is a current outbreak of coronavirus disease 2019 (COVID‐19), with a global spread. With the rapid increase in the number of infections, an increase is observed in the number of children with COVID‐19. Most research findings are regarding adult cases, which are not always transferrable to children. Evidence‐based studies are still expected to formulate clinical decisions for pediatric patients. In this review, we included 2597 pediatric patients that reported recently and evaluated the demographic, clinical, laboratory, and imaging features of children with COVID‐19. We found that even lymphopenia was the most common lab finding in adults; it infrequently occurred in children (9.8%). Moreover, elevated creatine kinase MB isoenzyme was much more commonly observed in children (27.0%) than that in adults, suggesting that heart injury would be more likely to occur in pediatric patients. Our analysis may contribute to determine the spectrum of disease in children and to develop strategies to control the disease transmission.

positive: Incidence, clinical characteristics and prognostic factor of patients with COVID-19: a systematic review and meta-analysis Background: Recently, Coronavirus Disease 2019 (COVID-19) outbreak started in Wuhan, China. Although the clinical features of COVID-19 have been reported previously, data regarding the risk factors associated with the clinical outcomes are lacking. Objectives: To summary and analyze the clinical characteristics and identify the predictors of disease severity and mortality. Methods: The PubMed, Web of Science Core Collection, Embase, Cochrane and MedRxiv databases were searched through February 25, 2020. Meta-analysis of Observational Studies in Epidemiology (MOOSE) recommendations were followed. We extracted and pooled data using random-effects meta-analysis to summary the clinical feature of the confirmed COVID-19 patients, and further identify risk factors for disease severity and death. Heterogeneity was evaluated using the I2 method and explained with subgroup analysis and meta-regression. Results: A total of 30 studies including 53000 patients with COVID-19 were included in this study, the mean age was 49.8 years (95% CI, 47.5-52.2 yrs) and 55.5% were male. The pooled incidence of severity and mortality were 20.2% (95% CI, 15.1-25.2%) and 3.1% (95% CI, 1.9-4.2%), respectively. The predictor for disease severity included old age (≥ 50 yrs, odds ratio [OR] = 2.61; 95% CI, 2.29-2.98), male (OR =1.348, 95% CI, 1.195-1.521), smoking (OR =1.734, 95% CI, 1.146-2.626) and any comorbidity (OR = 2.635, 95% CI, 2.098-3.309), especially chronic kidney disease (CKD, OR = 6.017; 95% CI, 2.192-16.514), chronic obstructive pulmonary disease (COPD, OR = 5.323; 95% CI, 2.613-10.847) and cerebrovascular disease (OR = 3.219; 95% CI, 1.486-6.972). In terms of laboratory results, increased lactate dehydrogenase (LDH), C-reactive protein (CRP) and D-dimer and decreased blood platelet and lymphocytes count were highly associated with severe COVID-19 (all for P < 0.001). Meanwhile, old age (≥ 60 yrs, RR = 9.45; 95% CI, 8.09-11.04), followed by cardiovascular disease (RR = 6.75; 95% CI, 5.40-8.43) hypertension (RR = 4.48; 95% CI, 3.69-5.45) and diabetes (RR = 4.43; 95% CI, 3.49-5.61) were found to be independent prognostic factors for the COVID-19 related death. Conclusions: To our knowledge, this is the first evidence-based medicine research to explore the risk factors of prognosis in patients with COVID-19, which is helpful to identify early-stage patients with poor prognosis and adapt effective treatment.

positive: Cutaneous manifestations in COVID-19: familial cluster of urticarial rash

positive: Coronavirus Disease (COVID-19): A primer for emergency physicians INTRODUCTION: Rapid worldwide spread of Coronavirus Disease 2019 (COVID-19) has resulted in a global pandemic. OBJECTIVE: This review article provides emergency physicians with an overview of the most current understanding of COVID-19 and recommendations on the evaluation and management of patients with suspected COVID-19. DISCUSSION: Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for causing COVID-19, is primarily transmitted from person-to-person through close contact (approximately 6 ft) by respiratory droplets. Symptoms of COVID-19 are similar to other viral upper respiratory illnesses. Three major trajectories include mild disease with upper respiratory symptoms, non-severe pneumonia, and severe pneumonia complicated by acute respiratory distress syndrome (ARDS). Emergency physicians should focus on identifying patients at risk, isolating suspected patients, and informing hospital infection prevention and public health authorities. Patients with suspected COVID-19 should be asked to wear a facemask. Respiratory etiquette, hand washing, and personal protective equipment are recommended for all healthcare personnel caring for suspected cases. Disposition depends on patient symptoms, hemodynamic status, and patient ability to self-quarantine. CONCLUSION: This narrative review provides clinicians with an updated approach to the evaluation and management of patients presenting to the emergency department with suspected COVID-19.

positive: Association between clinical manifestations and prognosis in patients with COVID-19 Abstract Purpose The purpose of this study was to find out risk factors associated with pneumonia, acute respiratory distress syndrome (ARDS) and clinical outcome among patients with 2019 novel coronavirus disease (COVID-19). Methods This was a cross-sectional multicenter clinical study. A total of 95 patients infected with COVID-19 were enrolled. The COVID-19 diagnostic standard was PCR detection of target genes of 2019 novel coronavirus(2019-nCoV). Clinical, laboratory, and radiological results as well as treatment outcome data were obtained. ARDS was defined as oxygenation index (PaO2/FiO2) ≤ 300mmHg. Findings Multivariate analysis showed that older age (OR=1.078, P=0.008) and high BMI (OR=1.327, P=0.024) were independent risk factor associated with patients with pneumonia. For patients with ARDS, multivariate analysis showed that only high systolic blood pressure (SBP) level (OR=1.046, P=0.025) and high lactate dehydrogenase (LDH) level (OR=1.010, P=0.021) were independent risk factors associated with ARDS. A total of 70 patients were conducted CT scan repeatedly after treatment. Patients were divided in disease exacerbation group (n=19) and disease relieve group (n=51). High BMI (OR=1.285, P=0.017) and tobacco smoking (OR=16.13, P=0.032) were independent risk factors associated with disease exacerbation after treatment. Implications Our results help to risk stratification in patients with 2019-nCoV infection. Patients with risk factors should be given timely intervention to avoid disease progression.

positive: COVID-19 symptoms predictive of healthcare workers’ SARS-CoV-2 PCR results BACKGROUND: Coronavirus 2019 disease (COVID-19) is caused by the virus SARS-CoV-2, transmissible both person-to-person and from contaminated surfaces. Early COVID-19 detection among healthcare workers (HCWs) is crucial for protecting patients and the healthcare workforce. Because of limited testing capacity, symptom-based screening may prioritize testing and increase diagnostic accuracy. METHODS AND FINDINGS: We performed a retrospective study of HCWs undergoing both COVID-19 telephonic symptom screening and nasopharyngeal SARS-CoV-2 assays during the period, March 9—April 15, 2020. HCWs with negative assays but progressive symptoms were re-tested for SARS-CoV-2. Among 592 HCWs tested, 83 (14%) had an initial positive SARS-CoV-2 assay. Fifty-nine of 61 HCWs (97%) who were asymptomatic or reported only sore throat/nasal congestion had negative SARS-CoV-2 assays (P = 0.006). HCWs reporting three or more symptoms had an increased multivariate-adjusted odds of having positive assays, 1.95 (95% CI: 1.10–3.64), which increased to 2.61 (95% CI: 1.50–4.45) for six or more symptoms. The multivariate-adjusted odds of a positive assay were also increased for HCWs reporting fever and a measured temperature ≥ 37.5°C (3.49 (95% CI: 1.95–6.21)), and those with myalgias (1.83 (95% CI: 1.04–3.23)). Anosmia/ageusia (i.e. loss of smell/loss of taste) was reported less frequently (16%) than other symptoms by HCWs with positive assays, but was associated with more than a seven-fold multivariate-adjusted odds of a positive test: OR = 7.21 (95% CI: 2.95–17.67). Of 509 HCWs with initial negative SARS-CoV-2 assays, nine had symptom progression and positive re-tests, yielding an estimated negative predictive value of 98.2% (95% CI: 96.8–99.0%) for the exclusion of clinically relevant COVID-19. CONCLUSIONS: Symptom and temperature reports are useful screening tools for predicting SARS-CoV-2 assay results in HCWs. Anosmia/ageusia, fever, and myalgia were the strongest independent predictors of positive assays. The absence of symptoms or symptoms limited to nasal congestion/sore throat were associated with negative assays.

positive: Acute urticaria with pyrexia as the first manifestations of a COVID‐19 infection The coronavirus disease 2019 (COVID‐19) affects principally the respiratory tract but recent studies described that COVID‐19 could present a broader clinical spectrum from the absence of any symptoms to heart (1), digestive (2) or Ear‐Nose‐Throat (including anosmia and ageusia) (3) manifestations. Here we report two cases of peculiar skin manifestation.

positive: CT imaging and clinical course of asymptomatic cases with COVID-19 pneumonia at admission in Wuhan, China Abstract Purpose Aimed to characterize the CT imaging and clinical course of asymptomatic cases with COVID-19 pneumonia. Methods Asymptomatic cases with COVID-19 pneumonia confirmed by SARS-COV-2 nucleic acid testing in Renmin Hospital of Wuhan University were retrospectively enrolled. The characteristics of CT imaging and clinical feature were collected and analyzed. Results 58 asymptomatic cases with COVID-19 pneumonia admitted to our hospital between Jan 1, 2020 and Feb 23, 2020 were enrolled. All patients had history of exposure to SARS-CoV-2. On admission, patients had no symptoms and laboratory findings were normal. The predominant feature of CT findings in this cohort was ground glass opacity (GGO) (55, 94.8%) with peripheral (44, 75.9%) distribution, unilateral location (34, 58.6%) and mostly involving one or two lobes (38, 65.5%), often accompanied by characteristic signs. After short-term follow-up, 16 patients (27.6%) presented symptoms with lower lymphocyte count and higher CRP, mainly including fever, cough and fatigue. The evolution of lesions on CT imaging were observed in 10 patients (17.2%). The average days of hospitalization was19.80±10.82 days, and was significantly longer in progression patients (28.60±7.55 day). Conclusion CT imaging of asymptomatic cases with COVID-19 pneumonia has definite characteristics. Since asymptomatic infections as “covert transmitter”, and some patients can progress rapidly in the short term. It is essential to pay attention to the surveillance of asymptomatic patients with COVID-19. CT scan has great value in screening and detecting patients with COVID-19 pneumonia, especially in the highly suspicious, asymptomatic cases with negative nucleic acid testing.

positive: Are Gastrointestinal Symptoms Specific for COVID-19 Infection? A Prospective Case-Control Study from the United States

positive: Caution: The clinical characteristics of COVID-19 patients at admission are changing Background With the emergence of 4rd generation transmission, the prevention and treatment of the novel coronavirus disease 2019 (COVID-19) has entered a new period. We aimed to report several changes in the clinical characteristics at admission of patients with COVID-19. Methods Clinical records and laboratory results of patients suffering from COVID-19 were retrospectively reviewed and matched with the admission dates to analyze the changes in characteristics at the onset of illness. Results Of the 89 affected patients, 31 [34.8%] patients were admitted from January 16 to 22, and 58 [65.2%] were admitted from January 23 to 29. Patients were admitted with more systemic symptoms, such as fever (21 [67.7%] of 31), fatigue (13 [41.9%] of 31), and myalgia (7 [22.6%] of 31), before January 23. More patients (10 [32.3%] of 31) admitted before January 23 had a small amount of sputum production compared with a smaller proportion (4 [6.9%] of 58) of the patients admitted after January 23. Other symptoms, such as cough, nausea, diarrhea, and chest tightness, were not significantly different between the two groups. In addition, the group admitted before January 23 had a larger proportion of patients with reduced lymphocyte (13 [54.2%] of 24), CD3 (11 [54.4%] of 21), and CD8 (9 [42.9%] of 21) counts and elevated serum amyloid A (SAA, 18 [75%] of 24). Conclusions The initial symptoms of recently infected patients seem more insidious, indicating that the new coronavirus may gradually evolve into a virus similar to influenza and latent in asymptomatic carriers for a long time.

positive: Clinical features of coronavirus disease 2019 (COVID-19) in a cohort of patients with disability due to spinal cord injury STUDY DESIGN: Cohort study of patients with spinal cord injury (SCI). OBJECTIVES: To describe the clinical and analytical features of a coronavirus disease 2019 (Covid-19) infected cohort with SCI to enable accurate diagnosis and to outline prevention measures. SETTING: This study was conducted at the National Hospital for Paraplegics (Toledo, Spain). METHODS: A cohort analysis of seven patients with SCI infected by Covid-19 was performed. Diagnosis was confirmed with reverse transcriptase polymerase chain reaction (RT-PCR) of nasal exudate or sputum samples. Clinical, analytical, and radiographic findings were registered. RESULTS: RT-PCR detected COVID-19 infection in all patients, affecting males and people with a cervical level of injury more often (five out of seven). The average delay for diagnostic confirmation was 4 days (interquartile range, 1-10). Fever was the most frequent symptom (six out of seven). The second most common symptom was asthenia (four out of seven), followed by dyspnea, cough, and expectoration (three out of seven for each symptom). The Modified Early Warning System score for Covid-19 severity rating was classified as severe in five out of seven cases. All but one patient showed radiological alterations evident in chest X-rays at the time of diagnosis. All patients recovered gradually. CONCLUSION: Our patients with SCI and Covid-19 infection exhibited fewer symptoms than the general population. Furthermore, they presented similar or greater clinical severity. The clinical evolution was not as pronounced as had been expected. This study recommends close supervision of the SCI population to detect early compatible signs and symptoms of Covid-19 infection.

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: 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).

positive: Neurological and Psychological Effects of Coronavirus (COVID-19): An Overview of the Current Era Pandemic Coronavirus disease 2019 (COVID 19) is a catastrophic illness that has significantly altered the world’s panoramic view of medicine. As the number of cases around the globe rise, the COVID-19 research writing has been immediately enhanced by professionals internationally. In this review, we focus on the neurological and psychological effects of COVID-19, which can determine both the severity of coronavirus and its related pandemic respectively. While it is critical to distinguish the neurological manifestations from the psychological effects, the latter is becoming more pervasive due to the fast-expanding outbreak. We conducted a systematic review and included observational retrospective, case-series studies, and surveys to establish the largest pool of valuable research. Articles on these approaches were conducted in PubMed, MEDLINE, and Google scholar. Some gray material was also selected because of the recent nature of the disease. Data collected from the studies have proposed that COVID-19 is not unusual in demonstrating the neurological symptoms, as it proved in the past by its sister coronaviruses such as severe acute respiratory syndrome coronavirus-1 (SARS-COV-1) and Middle Eastern respiratory syndrome coronavirus (MERS-COV). Studies have presented that some patients with COVID-19 also showed neurological signs, such as headache, nausea, vomiting, dizziness, loss of taste and smell, and impaired consciousness. However, it necessary to clarify that the invasion of severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) directly or indirectly affects the central nervous system (CNS). Contrarily, the COVID-19 pandemic has affected every single element of life. It has not only changed the individual’s health directly but also has significant psychological, economic, and sociological effects. These issues indicate the disease's extraordinary threat, and we must realize that another pandemic will shortly follow it: that of mental and behavioral illness. Thus, the long-lasting psychological implications of this outbreak deserve further investigation side by side.

positive: Anosmia and ageusia are emerging as symptoms in patients with COVID-19: What does the current evidence say? There have been several reports noting anosmia and ageusia as possible symptoms of COVID-19. This is of particular interest in oncology since patients receiving some cancer treatments such as chemotherapy or immune therapy often experience similar symptoms as side-effects. The purpose of this report was to summarise the evidence on the existence of anosmia and ageusia an emerging COVID-19 symptoms in order to better inform both oncology patients and clinicians. Currently, there is no published evidence or case reports noting anosmia or ageusia as symptoms of COVID-19. Nevertheless, experts in rhinology have suggested that the onset of such symptoms could either act as a trigger for testing for the disease where possible, or could be a new criterion to self-isolate. Whilst more data is currently needed to strengthen our knowledge of the symptoms of COVID-19, oncology patients who are concerned about anosmia or ageusia in the context of their systemic anti-cancer therapy should contact their acute oncology support line for advice.

positive: Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms OBJECTIVE: The SARS-CoV-2-infected disease (COVID-19) outbreak is a major threat to human beings. Previous studies mainly focused on Wuhan and typical symptoms. We analysed 74 confirmed COVID-19 cases with GI symptoms in the Zhejiang province to determine epidemiological, clinical and virological characteristics. DESIGN: COVID-19 hospital patients were admitted in the Zhejiang province from 17 January 2020 to 8 February 2020. Epidemiological, demographic, clinical, laboratory, management and outcome data of patients with GI symptoms were analysed using multivariate analysis for risk of severe/critical type. Bioinformatics were used to analyse features of SARS-CoV-2 from Zhejiang province. RESULTS: Among enrolled 651 patients, 74 (11.4%) presented with at least one GI symptom (nausea, vomiting or diarrhoea), average age of 46.14 years, 4-day incubation period and 10.8% had pre-existing liver disease. Of patients with COVID-19 with GI symptoms, 17 (22.97%) and 23 (31.08%) had severe/critical types and family clustering, respectively, significantly higher than those without GI symptoms, 47 (8.14%) and 118 (20.45%). Of patients with COVID-19 with GI symptoms, 29 (39.19%), 23 (31.08%), 8 (10.81%) and 16 (21.62%) had significantly higher rates of fever >38.5°C, fatigue, shortness of breath and headache, respectively. Low-dose glucocorticoids and antibiotics were administered to 14.86% and 41.89% of patients, respectively. Sputum production and increased lactate dehydrogenase/glucose levels were risk factors for severe/critical type. Bioinformatics showed sequence mutation of SARS-CoV-2 with m(6)A methylation and changed binding capacity with ACE2. CONCLUSION: We report COVID-19 cases with GI symptoms with novel features outside Wuhan. Attention to patients with COVID-19 with non-classic symptoms should increase to protect health providers.

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: Olfactory and Oral Manifestations of COVID-19: Sex-Related Symptoms—A Potential Pathway to Early Diagnosis OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic poses a threat to global health. Early diagnosis is an essential key to limit the outbreak of the virus. STUDY DESIGN: Case series, study conducted between March 25, 2020, and April 15, 2020. SETTING: Ambulatory, nonhospitalized patients who were quarantined in a designated hotel for COVID-19 patients and were recruited by an advertisement at the hotel. SUBJECTS AND METHODS: In total, 140 patients participated in a web-based questionnaire assessing initial symptoms of common viral diseases, olfactory and taste functions, xerostomia, and orofacial pain. RESULTS: A total of 58 men and 70 women participated. Initial symptoms were cough (59.4%), weakness (47.7%), myalgia (46.9%), fever (42.2%), headache (40.6%), impaired sense of smell (38.3%), impaired sense of taste (32.8%), sore throat (26.6%), runny nose (26.6%), and nasal congestion (22.7%). All symptoms were more frequent among women; however, only runny nose was statistically significant (P = .018). The most common combination of symptoms was cough and weakness (37.5%). A total of 25.8% reported olfactory and taste dysfunctions in the absence of other symptoms. In a comparison between the sexes, cough and runny nose were the most common combination in women (P = .018). A total of 38.3% of patients reported olfactory dysfunction as an initial symptom. Anosmia and facial pain were more common among women (P < .001 and P = .01, respectively), and 56% of patients reported xerostomia. CONCLUSION: A considerable number of patients presented with olfactory and oral disorders. Interestingly, women presented with a different cluster of symptoms than men, which may suggest a new clinical approach to diagnosing COVID-19 disease.

positive: Extrapulmonary and atypical clinical presentations of COVID‐19 The novel coronavirus (SARS‐CoV2) has led to outbreak of multiple cases of pneumonia in Wuhan city in December 2019. The disease caused by this virus was named coronavirus disease 2019 or “COVID‐19”, which was declared by WHO as a global pandemic in March 2020. It typically presents with respiratory symptoms and febrile illness. However, there are few reported extrapulmonary and atypical presentations, such as haemoptysis, cardiac, neurological, gastrointestinal, ocular and cutaneous manifestations, as well as venous and arterial thrombosis. Lack of awareness of these presentations might lead to misdiagnosis, delayed diagnosis and isolation of suspected patients which increases the risk of transmission of infection between patients and doctors. All these issues will be discussed in this review. This article is protected by copyright. All rights reserved.

positive: Diagnosis of patients with suspected COVID-19: What is the role of chest CT?()

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

negative: Epidemiologic characteristics of early cases with 2019 novel coronavirus (2019-nCoV) disease in Korea In about 20 days since the diagnosis of the first case of the 2019 novel coronavirus (2019-nCoV) in Korea on January 20, 2020, 28 cases have been confirmed. Fifteen patients (53.6%) of them were male and median age of was 42 years (range, 20-73). Of the confirmed cases, 16, 9, and 3 were index (57.2%), first-generation (32.1%), and second-generation (10.7%) cases, respectively. All first-generation and second-generation patients were family members or intimate acquaintances of the index cases with close contacts. Fifteen among 16 index patients had entered Korea from January 19 to 24, 2020 while 1 patient had entered Korea on January 31, 2020. The average incubation period was 3.9 days (median, 3.0), and the reproduction number was estimated as 0.48. Three of the confirmed patients were asymptomatic when they were diagnosed. Epidemiological indicators will be revised with the availability of additional data in the future. Sharing epidemiological information among researchers worldwide is essential for efficient preparation and response in tackling this new infectious disease.

negative: Modelling the epidemiological trend and behavior of COVID-19 in Italy As of March 16, 2020, over 185,000 across the world, Italy became the red hotspot for the COVID-19 pandemic after China. With over 35,000 cases and 2900 deaths reported in the month of March in Italy, it is necessary to stimulate epidemic trend to understand the behavior of COVID-19 in Italy. By S.E.I.R. simulation, we estimated the most representative epidemic parameters occurred from March 1 to 14, 2020, thus being able to evaluate the consistency of the containment rules and identify possible Sars-Cov-2 local mutations. Our estimations are based on some assumptions and limitations exited.

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

negative: Infectivity of Severe Acute Respiratory Syndrome during Its Incubation Period Objective To evaluate the infectivity of severe acute respiratory syndrome (SARS) during its incubation period by investigating chains of transmission and individuals isolated for medical observation with a view to providing scientific evidence for updating protocols of medical isolation. Methods Individuals related with the two SARS chains of transmission in Beijing in 2003 and a group of individuals isolated for medical observation in Haidian district of Beijing during the SARS outbreak were selected as subjects of study. Contactors with SARS patients and those with symptom development following the contacts were investigated via questionnaire. Serum samples were collected from super transmitters and tested for SARS-CoV antibody by neutralization test and enzyme linked immunosorbent assay (ELISA). Results A total of 1 112 contactors were investigated in three surveys. Of them, 669 had a history of close contact with symptomatic SARS patients, 101 developed symptoms with a rate of 15.1%, 363 had a history of close contact with patients in their incubation period, none of whom developed symptoms (0%). Serum samples were collected from 32 highly-exposed individuals, of whom 13 developing SARS symptoms after contact had serum samples positive for SARS-CoV antibody. Samples collected from the asymptomatic contactors were all negative for SARS-CoV antibody. Conclusion SARS cases are infectious only during their symptomatic period and are non-infectious during the incubation period. Isolation for medical observation should be placed for individuals who are in close contact with symptomatic SARS patients. The results of our study are of decisive significance for the Ministry of Health to the definition of SARS close contactor.

negative: Angiotensin receptor blockers as tentative SARS‐CoV‐2 therapeutics At the time of writing this commentary (February 2020), the coronavirus COVID‐19 epidemic has already resulted in more fatalities compared with the SARS and MERS coronavirus epidemics combined. Therapeutics that may assist to contain its rapid spread and reduce its high mortality rates are urgently needed. Developing vaccines against the SARS‐CoV‐2 virus may take many months. Moreover, vaccines based on viral‐encoded peptides may not be effective against future coronavirus epidemics, as virus mutations could make them futile. Indeed, new Influenza virus strains emerge every year, requiring new immunizations. A tentative suggestion based on existing therapeutics, which would likely be resistant to new coronavirus mutations, is to use available angiotensin receptor 1 (AT1R) blockers, such as losartan, as therapeutics for reducing the aggressiveness and mortality from SARS‐CoV‐2 virus infections. This idea is based on observations that the angiotensin‐converting enzyme 2 (ACE2) very likely serves as the binding site for SARS‐CoV‐2, the strain implicated in the current COVID‐19 epidemic, similarly to strain SARS‐CoV implicated in the 2002–2003 SARS epidemic. This commentary elaborates on the idea of considering AT1R blockers as tentative treatment for SARS‐CoV‐2 infections, and proposes a research direction based on datamining of clinical patient records for assessing its feasibility.

negative: Cough, Cold, and Congestion The common cold is a benign, self-limited, acute viral infection with associated symptoms of sneezing, rhinorrhea, nasal congestion, cough, and malaise. It is the most frequent acute illness in the industrialized world. Adults typically have two to three episodes of illness yearly while children can have up to five. The common cold is typically caused by viruses (including rhinovirus, RSV, coronavirus, and others), and often, no infecting organism is detected. Treatment is usually targeted at symptomatic relief. The differential diagnosis for cough, cold, and congestion is broad: ranging from non-emergent causes such as rhinitis to life-threatening illnesses such as pulmonary embolism. Careful assessment is necessary as misidentification can lead to inappropriate discharge of potentially lethal conditions.

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

negative: 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: The Place of Macrolides in the Treatment of Upper Respiratory Tract Infections The majority of all acute upper respiratory tract infections (URTIs) are viral in aetiology. Bacterial infection, either as a prime cause or secondary to the initial viral infection, can be effectively eradicated with appropriate drug therapy. A course of penicillin is usually effective in cases of acute tonsillitis, pharyngitis, otitis media and sinusitis. Macrolide antibiotics may be prescribed as an alternative, especially if β-lactamase-producing strains are present. Roxithromycin achieves high tissue concentrations, and cure rates between 85 and 100% have been reported in various URTIs.

negative: Pulmonary Manifestations of Predominantly Antibody Deficiencies Predominantly antibody deficiencies (PADs) are the most frequent forms of primary immunodeficiency diseases (PIDs). Commonly accompanied with complications involving several body systems, immunoglobulin substitution therapy along with prophylactic antibiotics remained the cornerstone of treatment for PADs and related complications. Patients with respiratory complications should be prescribed an appropriate therapy as soon as possible and have to be adhering to more and longer medical therapies. Recent studies identified a gap for screening protocols to monitor respiratory manifestations in patients with PADs. In the present chapter, the pulmonary manifestations of different PADs for each have been discussed. The chapter is mainly focused on X-linked agammaglobulinemia, common variable immunodeficiency, activated PI3K-δ syndrome, LRBA deficiency, CD19 complex deficiencies, CD20 deficiency, other monogenic defects associated with hypogammaglobulinemia, immunoglobulin class switch recombination deficiencies affecting B-cells, transient hypogammaglobulinemia of infancy, and selective IgA deficiency.

negative: Real-time tentative assessment of the epidemiological characteristics of novel coronavirus infections in Wuhan, China, as at 22 January 2020 A novel coronavirus (2019-nCoV) causing severe acute respiratory disease emerged recently in Wuhan, China. Information on reported cases strongly indicates human-to-human spread, and the most recent information is increasingly indicative of sustained human-to-human transmission. While the overall severity profile among cases may change as more mild cases are identified, we estimate a risk of fatality among hospitalised cases at 14% (95% confidence interval: 3.9–32%).

negative: Nucleocapsid Protein as Early Diagnostic Marker for SARS Serum samples from 317 patients with patients with severe acute respiratory syndrome (SARS) were tested for the nucleocapsid (N) protein of SARS-associated coronavirus, with sensitivities of 94% and 78% for the first 5 days and 6–10 days after onset, respectively. The specificity was 99.9%. N protein can be used as an early diagnostic maker for SARS.

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

negative: Development of Onchocerca volvulus in humanized NSG mice and detection of parasite biomarkers in urine and serum BACKGROUND: The study of Onchocerca volvulus has been limited by its host range, with only humans and non-human primates shown to be susceptible to the full life cycle infection. Small animal models that support the development of adult parasites have not been identified. METHODOLOGY/PRINCIPAL FINDINGS: We hypothesized that highly immunodeficient NSG mice would support the survival and maturation of O. volvulus and alteration of the host microenvironment through the addition of various human cells and tissues would further enhance the level of parasite maturation. NSG mice were humanized with: (1) umbilical cord derived CD34(+) stem cells, (2) fetal derived liver, thymus and CD34(+) stem cells or (3) primary human skeletal muscle cells. NSG and humanized NSG mice were infected with 100 O. volvulus infective larvae (L3) for 4 to 12 weeks. When necropsies of infected animals were performed, it was observed that parasites survived and developed throughout the infection time course. In each of the different humanized mouse models, worms matured from L3 to advanced fourth stage larvae, with both male and female organ development. In addition, worms increased in length by up to 4-fold. Serum and urine, collected from humanized mice for identification of potential biomarkers of infection, allowed for the identification of 10 O. volvulus-derived proteins found specifically in either the urine or the serum of the humanized O. volvulus-infected NSG mice. CONCLUSIONS/SIGNIFICANCE: The newly identified mouse models for onchocerciasis will enable the development of O. volvulus specific biomarkers, screening for new therapeutic approaches and potentially studying the human immune response to infection with O. volvulus.

negative: Severe Acute Respiratory Syndrome, Beijing, 2003 The largest outbreak of severe acute respiratory syndrome (SARS) struck Beijing in spring 2003. Multiple importations of SARS to Beijing initiated transmission in several healthcare facilities. Beijing’s outbreak began March 5; by late April, daily hospital admissions for SARS exceeded 100 for several days; 2,521 cases of probable SARS occurred. Attack rates were highest in those 20–39 years of age; 1% of cases occurred in children <10 years. The case-fatality rate was highest among patients >65 years (27.7% vs. 4.8% for those 20–64 years, p < 0.001). Healthcare workers accounted for 16% of probable cases. The proportion of case-patients without known contact to a SARS patient increased significantly in May. Implementation of early detection, isolation, contact tracing, quarantine, triage of case-patients to designated SARS hospitals, and community mobilization ended the outbreak.

negative: Buying Time—The Immune System Determinants of the Incubation Period to Respiratory Viruses Respiratory viruses cause disease in humans characterized by an abrupt onset of symptoms. Studies in humans and animal models have shown that symptoms are not immediate and appear days or even weeks after infection. Since the initial symptoms are a manifestation of virus recognition by elements of the innate immune response, early virus replication must go largely undetected. The interval between infection and the emergence of symptoms is called the incubation period and is widely used as a clinical score. While incubation periods have been described for many virus infections the underlying mechanism for this asymptomatic phase has not been comprehensively documented. Here we review studies of the interaction between human pathogenic respiratory RNA viruses and the host with a particular emphasis on the mechanisms used by viruses to inhibit immunity. We discuss the concept of the “stealth phase”, defined as the time between infection and the earliest detectable inflammatory response. We propose that the “stealth phase” phenomenon is primarily responsible for the suppression of symptoms during the incubation period and results from viral antagonism that inhibits major pathways of the innate immune system allowing an extended time of unhindered virus replication.

negative: Que doivent savoir les chirurgiens à propos des troubles digestifs et des anomalies paracliniques induits par le COVID 19? Resume Les symptômes liés au COVID-19 sont principalement caractérisés par la triade fièvre, toux sèche et dyspnée. Toutefois, des symptômes digestifs ont également été rapportés dont la fréquence initialement considérée comme faible semble toucher plus de la moitié des patients à des degrés divers. Ceux-ci se manifestent principalement par une anorexie, une diarrhée, des nausées et ou vomissements et des douleurs abdominales. Bien que le pronostic soit lié à l’atteinte pulmonaire, les troubles digestifs semblent significativement plus fréquents chez les patients ayant une infection sévère à COVID-19. Des formes digestives isolées ou pouvant précéder les symptômes pulmonaires sont désormais bien décrites avec de la diarrhée au premier plan clinique. Les principales anomalies biologiques pouvant orienter précocement vers une infection à COVID-19 sont la lymphopénie, une CRP augmentée et une augmentation des transaminases prédominant sur les ASAT. Le scanner thoraco-abdominal semble utile dans ce cas pour éliminer une pathologie digestive non liée au coronavirus et pour rechercher des images pulmonaires compatibles avec une infection à COVID-19. Il n’existe pas de données sur l’intérêt de l’endoscopie digestive en cas de symptômes digestifs persistants. Le risque de contamination de l’endoscopiste semble par ailleurs significatif. Un mode de transmission oro-fécale de l’infection est possible ce d’autant que l’excrétion virale dans les selles semblent fréquente et durer plus longtemps qu’au niveau ORL, y compris chez des patients avec prélèvement pharyngé négatif ou sans symptômes digestifs. Ainsi, dans certains cas douteux, une analyse virologique des selles peut permettre de porter un diagnostic de certitude. La contagiosité persistante d’un patient en cas d’excrétion virale prolongée dans les selles est possible mais pas parfaitement établi. L’avènement proche de la sérologie devrait permettre d’identifier les malades ayant été infectés par l’épidémie de COVID-19 notamment les sujets pauci-symptomatiques non détectés au sein du personnel de santé. La reprise de l’activité médico-chirurgicale devra faire l’objet d’une stratégie dédiée en amont du déconfinement. Abstract The symptoms associated with COVID-19 are mainly characterized by a triad composed of fever, dry cough and dyspnea. However, digestive symptoms have also been reported; at first considered as infrequent, they in fact seem to affect (to some extent) more than half of patients. The symptoms are mainly manifested by anorexia, diarrhea, nausea and/or vomiting and abdominal pain. Even though prognosis is associated with lung injury, digestive symptoms seem significantly more frequent in patients presenting with severe COVID-19 infection. Digestive forms, which may be isolated or which can precede pulmonary symptoms, have indeed been reported, with diarrhea as a leading clinical sign. The main biological abnormalities that can suggest COVID-19 infection at an early stage are lymphopenia, elevated CRP and heightened ASAT transaminases. Thoraco-abdominal scan seems useful as a means of on the one hand ruling out digestive pathology not connected with coronavirus and on the other hand searching for pulmonary images compatible with COVID-19 infection. No data exist on the interest of digestive endoscopy in cases of persistent digestive symptoms. Moreover, the endoscopic surgeons may themselves be at significant risk of contamination. Fecal-oral transmission of the infection is possible, especially insofar as viral shedding in stools seems frequent and of longer duration than at the ENT level, including in patients with negative throat swab and without digestive symptoms. In some doubtful cases, virologic assessment of stool samples can yield definitive diagnosis. In the event of prolonged viral shedding in stools, a patient’s persistent contagiousness is conceivable but not conclusively established. Upcoming serology should enable identification of the patients having been infected by the COVID-19 epidemic, particularly among previously undetected pauci-symptomatic members of a health care staff. Resumption of medico-surgical activity should be the object of a dedicated strategy preceding deconfinement.

negative: Multiple parameters required for diagnosis of COVID-19 in clinical practice

negative: In reply: Uncertainty in using chest computed tomography in early coronavirus disease (COVID-19)

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

negative: Headache medication and the COVID-19 pandemic The world is currently dominated by the Corona Virus Disease 2019 (COVID-19) pandemic. Besides the obvious concerns about limitation of virus spread and providing the best possible care to infected patients, a concomitant concern has now arisen in view of a putative link between the use of certain drugs, such as Renin-Angiotensin System (RAS) inhibitors and ibuprofen, and an increased risk for COVID-19 infection. We here discuss this concern in relation to headache treatment and conclude that, based on current evidence, there is no reason to abandon treatment of headache patients with RAS inhibitors or ibuprofen.

negative: Using ILI surveillance to estimate state-specific case detection rates and forecast SARS-CoV-2 spread in the United States Detection of SARS-CoV-2 infections to date has relied on RT-PCR testing. However, a failure to identify early cases imported to a country, bottlenecks in RT-PCR testing, and the existence of infections which are asymptomatic, sub-clinical, or with an alternative presentation than the standard cough and fever have resulted in an under-counting of the true prevalence of SARS-CoV-2. Here, we show how publicly available CDC influenza-like illness (ILI) outpatient surveillance data can be repurposed to estimate the detection rate of symptomatic SARS-CoV-2 infections. We find a surge of non-influenza ILI above the seasonal average and show that this surge is correlated with COVID case counts across states. By quantifying the number of excess ILI patients in March relative to previous years and comparing excess ILI to confirmed COVID case counts, we estimate the syndromic case detection rate of SARS-CoV-2 in the US to be less than 13%. If only 1/3 of patients infected with SARS-CoV-2 sought care, the ILI surge would correspond to more than 8.7 million new SARS-CoV-2 infections across the US during the three week period from March 8 to March 28. Combining excess ILI counts with the date of onset of community transmission in the US, we also show that the early epidemic in the US was unlikely to be doubling slower than every 4 days. Together these results suggest a conceptual model for the COVID epidemic in the US in which rapid spread across the US are combined with a large population of infected patients with presumably mild-to-moderate clinical symptoms. We emphasize the importance of testing these findings with seroprevalence data, and discuss the broader potential to use syndromic time series for early detection and understanding of emerging infectious diseases.

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

negative: Epidemiology and clinical presentation of the four human parainfluenza virus types BACKGROUND: Human parainfluenza viruses (HPIVs) are important causes of upper respiratory tract illness (URTI) and lower respiratory tract illness (LRTI). To analyse epidemiologic and clinical characteristics of the four types of human parainfluenza viruses (HPIVs), patients with acute respiratory tract illness (ARTI) were studied in Guangzhou, southern China. METHODS: Throat swabs (n=4755) were collected and tested from children and adults with ARTI over a 26-month period, and 4447 of 4755 (93.5%) patients’ clinical presentations were recorded for further analysis. RESULTS: Of 4755 patients tested, 178 (3.7%) were positive for HPIV. Ninety-nine (2.1%) samples were positive for HPIV-3, 58 (1.2%) for HPIV-1, 19 (0.4%) for HPIV-2 and 8 (0.2%) for HPIV-4. 160/178 (88.9%) HPIV-positive samples were from paediatric patients younger than 5 years old, but no infant under one month of age was HPIV positive. Seasonal peaks of HPIV-3 and HPIV-1 occurred as autumn turned to winter and summer turned to autumn. HPIV-2 and HPIV-4 were detected less frequently, and their frequency of isolation increased when the frequency of HPIV-3 and HPIV-1 declined. HPIV infection led to a wide spectrum of symptoms, and more “hoarseness” (p=0.015), “abnormal pulmonary breathing sound” (p<0.001), “dyspnoea” (p<0.001), “pneumonia” (p=0.01), and “diarrhoea” (p<0.001) presented in HPIV-positive patients than HPIV-negative patients. 10/10 (100%) HPIV-positive adult patients (≥14 years old) presented with systemic influenza-like symptoms, while 90/164 (54.9%) HPIV-positive paediatric patients (<14 years old) presented with these symptoms (p=0.005). The only significant difference in clinical presentation between HPIV types was “Expectoration” (p<0.001). Co-infections were common, with 33.3%–63.2% of samples positive for the four HPIV types also testing positive for other respiratory pathogens. However, no significant differences were seen in clinical presentation between patients solely infected with HPIV and patients co-infected with HPIV and other respiratory pathogens. CONCLUSIONS: HPIV infection led to a wide spectrum of symptoms, and similar clinical manifestations were found in the patients with four different types of HPIVs. The study suggested pathogenic activity of HPIV in gastrointestinal illness. The clinical presentation of HPIV infection may differ by patient age.

negative: Association of infected probability of COVID-19 with ventilation rates in confined spaces: a Wells-Riley equation based investigation Background: A growing number of epidemiological cases are proving the possibility of airborne transmission of coronavirus disease 2019 (COVID-19). Ensuring adequate ventilation rate is essential to reduce the risk of infection in confined spaces. Methods: We obtained the quantum generation rate by a COVID-19 infector with a reproductive number based fitting approach, and then estimated the association between infected probability and ventilation rate with the Wells-Riley equation. Results: The estimated quantum generation rate of COVID-19 is 14-48 /h. To ensure infected probabolity less than 1%, ventilation rate lareger than common values (100-350 m3/h and 1200-4000 m3/h for 15 minutes and 3 hours exposure, respectively) is required. If both the infector and susceptibles wear masks, the ventilation rate ensuring less than 1% infected probability is reduced to 50-180 m3/h and 600-2000 m3/h correspondingly, which is easier to be achieved by normal ventilation mode applied in some typical scenarios, including offices, classrooms, buses and aircraft cabins. Interpretation: The risk of potential airborne transmission in confined spaces cannot be ignored. Strict preventive measures that have been widely adopted should be effective in reducing the risk of airborne transmitted infection.

negative: Human Bocavirus, a Respiratory and Enteric Virus In Spain, human bocavirus (HBoV) was detected in 48 (9.1%) of 527 children with gastroenteritis at similar frequency as for children with respiratory illness (40/520, 7.7%). Fecal excretion adds new concern about the transmission of HBoV. To our knowledge, this report is the first to document HBoV in human feces.

negative: COVID-19: what is next for public health?

negative: Recommendations for Triage, Prioritization and Treatment of Breast Cancer Patients During the COVID-19 Pandemic Abstract The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) associated disease (COVID-19) outbreak seriously challenges globally all health care systems and professionals. Expert projections estimate that despite social distancing and lockdown being practiced, we have yet to feel the full impact of COVID-19. In this manuscript we provide guidance to prepare for the impact of COVID-19 pandemic on breast cancer patients and advise on how to triage, prioritize and organize diagnostic procedures, surgical, radiation and medical treatments.

negative: Author Response: Coronavirus Disease 2019 (COVID-19), Infectivity, and the Incubation Period

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

negative: Haematological parameters in severe acute respiratory syndrome Clinical presentation of severe acute respiratory syndrome (SARS) is non‐specific and isolation of all suspected patients is difficult because of the limited availability of isolation facilities. We studied changes in haematological parameters in SARS patients using median values analysed according to the day of symptom onset. White cell (WCC), absolute neutrophil, absolute lymphocyte (ALC) and platelet counts followed a v‐shaped trend with the nadir at day 6 or 7 after symptom onset except for ALC in the ICU group that had not reached the nadir by day 12. None of our patients had a platelet count < 80 × 10(9)/l and WCC < 2 × 10(9)/l in the first 5 days of symptoms and these parameters may allow early stratification of febrile patients into likely and unlikely SARS cases to allow effective utilization of isolation facilities. On multivariate analysis, age is the only independent predictor for ICU admission.

negative: Post-exposure Prophylaxis or Preemptive Therapy for SARS-Coronavirus-2: Study Protocol for a Pragmatic Randomized Controlled Trial Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 causing the coronavirus disease 2019 (COVID-19) pandemic. Currently, there are a lack of evidence-based therapies to prevent COVID-19 following exposure, or to prevent worsening of symptoms following confirmed infection. We describe the design of a clinical trial of hydroxychloroquine for post-exposure prophylaxis and pre-emptive therapy for COVID-19. Methods: We will conduct two nested multicenter international double-blind randomized placebo-controlled clinical trials of hydroxychloroquine for: 1) post-exposure prophylaxis (PEP) of asymptomatic household contacts or healthcare workers exposed to COVID-19 within the past four days, and 2) pre-emptive therapy (PET) for symptomatic outpatients with COVID-19 with a total symptom duration of less than 4 days. We will recruit 1500 patients for each the PEP and PET trials. Participants will be randomized 1:1 to receive 5 days of hydroxychloroquine or placebo. The primary PEP trial outcome will be the incidence of symptomatic COVID-19 disease. The primary PET trial outcome will be an ordinal scale of disease severity (not hospitalized; hospitalized without intensive care, hospitalization with intensive care, or death). Participant screening, informed consent, and follow up will be exclusively internet-based with appropriate regulatory and research ethics board approvals in Canada and the United States. Discussion: These complementary randomized control trials are innovatively designed and adequately powered to rapidly answer urgent questions regarding the effectiveness of hydroxychloroquine to reduce transmission and disease severity of COVID-19 during a pandemic. In-person participant follow-up will not be conducted in order to facilitate social distancing strategies and reduce risks of exposure to study personnel. Innovative trial approaches are needed to urgently assess therapeutic options to mitigate the global impact of this pandemic. Trials Registration: clinicaltrials.gov (NCT04308668); 16 March 2020.

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

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

negative: Targeting the Endocytic Pathway and Autophagy Process as a Novel Therapeutic Strategy in COVID-19 Coronaviruses (CoVs) are a group of enveloped, single-stranded positive genomic RNA viruses and some of them are known to cause severe respiratory diseases in human, including Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and the ongoing coronavirus disease-19 (COVID-19). One key element in viral infection is the process of viral entry into the host cells. In the last two decades, there is increasing understanding on the importance of the endocytic pathway and the autophagy process in viral entry and replication. As a result, the endocytic pathway including endosome and lysosome has become important targets for development of therapeutic strategies in combating diseases caused by CoVs. In this mini-review, we will focus on the importance of the endocytic pathway as well as the autophagy process in viral infection of several pathogenic CoVs inclusive of SARS-CoV, MERS-CoV and the new CoV named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and discuss the development of therapeutic agents by targeting these processes. Such knowledge will provide important clues for control of the ongoing epidemic of SARS-CoV-2 infection and treatment of COVID-19.

negative: Experiences of Patients With Rheumatic Diseases in the United States During Early Days of the COVID-19 Pandemic OBJECTIVE: Patients with rheumatic diseases such as rheumatoid arthritis (RA) and lupus have increased risk of infection and are treated with medications that may increase this risk yet are also hypothesized to help treat COVID-19. We set out to understand how the COVID-19 pandemic has impacted the lives of these patients in the United States. METHODS: Participants in a US-wide longitudinal observational registry responded to a supplemental COVID-19 questionnaire by e-mail on March 25, 2020, about their symptoms, COVID-19 testing, health care changes, and related experiences during the prior 2 weeks. Analysis compared responses by diagnosis, disease activity, and new onset of symptoms. Qualitative analysis was conducted on optional free-text comment fields. RESULTS: Of the 7061 participants invited to participate, 530 responded, with RA as the most frequent diagnosis (61%). Eleven participants met COVID-19 screening criteria, of whom two sought testing unsuccessfully. Six others sought testing, three of whom were successful, and all test results were negative. Not quite half of participants (42%) reported a change to their care in the prior 2 weeks. Qualitative analysis revealed four key themes: emotions in response to the pandemic, perceptions of risks from immunosuppressive medications, protective measures to reduce risk of COVID-19 infection, and disruptions in accessing rheumatic disease medications, including hydroxychloroquine. CONCLUSION: After 2 weeks, many participants with rheumatic diseases already had important changes to their health care, with many altering medications without professional consultation or because of hydroxychloroquine shortage. As evidence accumulates on the effectiveness of potential COVID-19 treatments, effort is needed to safeguard access to established treatments for rheumatic diseases.

negative: Prevalence and Influencing Factors of Anxiety and Depression Symptoms in the First-Line Medical Staff Fighting Against COVID-19 in Gansu BACKGROUND: The outbreak of novel coronavirus pneumonia (COVID-19) has brought enormous physical and psychological pressure on Chinese medical staff. It is extremely important to understand the prevalence and influencing factors of anxiety and depression symptoms in first-line anti-epidemic medical staff and their coping styles for these negative emotions. METHODS: A cross-sectional survey was conducted in Gansu (China), with a questionnaire packet which consisted of the self-rating anxiety scale (SAS), self-rating depression scale (SDS), and the simplified coping style questionnaire (SCSQ). A total of 79 doctors and 86 nurses participated in the survey. Correlation analysis was performed to explore the relationship between SAS, SDS, and SCSQ score. A linear regression model was used to determine the influencing factors for anxiety or depression symptoms. RESULTS: The prevalence rates of anxiety and depression symptoms among doctors was 11.4% and 45.6%, respectively. History of depression or anxiety (T=-2.644, p= 0.010, 95%CI: -10.514~-1.481) was shown to be a risk factor for anxiety symptoms in doctors, while being male (T=2.970, p=0.004, 95%CI: 2.667~13.521) was a protective factor for depression. The prevalence rate of anxiety and depression symptoms among nurses was 27.9% and 43.0%, respectively. History of depression or anxiety was a common risk factor for anxiety symptoms (T=-3.635, p=0.000, 95%CI: -16.360~-4.789) and depression symptoms (T=-2.835, p=0.005, 95%CI:-18.238~-3.254) in nurses. The results of partial correlation analysis (controlled for gender and history of depression or anxiety) indicated that the total score of positive coping was negatively correlated with the total score of anxiety (r=-0.182, p=0.002) and depression (r=-0.253, p=0.001). CONCLUSIONS: The first-line anti-epidemic medical staff have high anxiety and depression symptoms and adopting positive coping styles will help to improve their negative emotions.

negative: Continuity of Care and Outpatient Management for Patients with and at High Risk for Cardiovascular Disease during the COVID-19 Pandemic: A Scientific Statement from the American Society for Preventive Cardiology Abstract The coronavirus disease 2019 (COVID-19) pandemic has consumed our healthcare system, with immediate resource focus on the management of high numbers of critically ill patients. Those that fare poorly with COVID-19 infection more commonly have cardiovascular disease (CVD), hypertension and diabetes. There are also several other conditions that raise concern for the welfare of patients with and at high risk for CVD during this pandemic. Traditional ambulatory care is disrupted and many patients are delaying or deferring necessary care, including preventive care. New impediments to medication access and adherence have arisen. Social distancing measures can increase social isolation and alter physical activity and nutrition patterns. Virtually all facility based cardiac rehabilitation programs have temporarily closed. If not promptly addressed, these changes may result in delayed waves of vulnerable patients presenting for urgent and preventable CVD events. Here, we provide several recommendations to mitigate the adverse effects of these disruptions in outpatient care. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers should be continued in patients already taking these medications. Where possible, it is strongly preferred to continue visits via telehealth, and patients should be counselled about promptly reporting new symptoms. Barriers to medication access should be reviewed with patients at every contact, with implementation of strategies to ensure ongoing provision of medications. Team-based care should be leveraged to enhance the continuity of care and adherence to lifestyle recommendations. Patient encounters should include discussion of safe physical activity options and access to healthy food choices. Implementation of adaptive strategies for cardiac rehabilitation is recommended, including home based cardiac rehab, to ensure continuity of this essential service. While the practical implementation of these strategies will vary by local situation, there are a broad range of strategies available to ensure ongoing continuity of care and health preservation for those at higher risk of CVD during the COVID-19 pandemic.

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

negative: Validation of the Provincial Transfer Authorization Centre database: a comprehensive database containing records of all inter-facility patient transfers in the province of Ontario BACKGROUND: The Provincial Transfer Authorization Centre (PTAC) was established as a part of the emergency response in Ontario, Canada to the Severe Acute Respiratory Syndrome (SARS) outbreak in 2003. Prior to 2003, data relating to inter-facility patient transfers were not collected in a systematic manner. Then, in an emergency setting, a comprehensive database with a complex data collection process was established. For the first time in Ontario, population-based data for patient movement between healthcare facilities for a population of twelve million are available. The PTAC database stores all patient transfer data in a large database. There are few population-based patient transfer databases and the PTAC database is believed to be the largest example to house this novel dataset. A patient transfer database has also never been validated. This paper presents the validation of the PTAC database. METHODS: A random sample of 100 patient inter-facility transfer records was compared to the corresponding institutional patient records from the sending healthcare facilities. Measures of agreement, including sensitivity, were calculated for the 12 common data variables. RESULTS: Of the 100 randomly selected patient transfer records, 95 (95%) of the corresponding institutional patient records were located. Data variables in the categories patient demographics, facility identification and timing of transfer and reason and urgency of transfer had strong agreement levels. The 10 most commonly used data variables had accuracy rates that ranged from 85.3% to 100% and error rates ranging from 0 to 12.6%. These same variables had sensitivity values ranging from 0.87 to 1.0. CONCLUSION: The very high level of agreement between institutional patient records and the PTAC data for fields compared in this study supports the validity of the PTAC database. For the first time, a population-based patient transfer database has been established. Although it was created during an emergency situation and data collection is dependent on front-line medical workers, the PTAC data has achieved a high level of validity, perhaps even higher than many purpose built databases created during non-emergency settings.

negative: å¿ç«¥2019å ç¶ç æ¯ç æ£è çè¸é¨CTè¡¨ç°åä¸´åºç¹å¾./ å¿ç«¥2019å ç¶ç æ¯ç æ£è çè¸é¨CTè¡¨ç°åä¸´åºç¹å¾./ Chest CT findings and clinical features of coronavirus disease 2019 in children OBJECTIVES: To describe the CT features and clinical characteristics of pediatric patients with coronavirus disease 2019 (COVID-19). METHODS: A total of 9 COVID-19 infected pediatric patients were included in this study. Clinical history, laboratory examination, and detailed CT imaging features were analyzed. All patients underwent the first CT scanning on the same day of being diagnosed by real-time reverse-transcription polymerase chain reaction (rRT-PCR). A low-dose CT scan was performed during follow-up. RESULTS: All the child patients had positive results. Four patients had cough and one patient had fever. One patient presented both cough and fever. Two children presented other symptoms like sore throat and stuffy nose. One child showed no clinical symptom. Five patients had positive initial CT findings with subtle lesions like ground-glass opacity (GGO) or spot-like mixed consolidation. Three patients were reported with negative results in the initial and follow-up CT examination. One patient was reported with initial negative CT findings but turning positive during the first follow-up. All patients had absorbed lesions on follow-up CT images after treatment. CONCLUSIONS: Pediatric COVID-19 patients have certain imaging and clinical features as well as disease prognosis. Children with COVID-19 tend to have normal or subtle CT findings and relatively better outcome.

negative: The emergence of a novel coronavirus (SARS‐CoV‐2) disease and their neuroinvasive propensity may affect in COVID‐19 patients An outbreak of a novel coronavirus (SARS‐CoV‐2) infection has recently emerged and rapidly spreading in humans causing a significant threat to international health and the economy. Rapid assessment and warning are crucial for an outbreak analysis in response to serious public health. SARS‐CoV‐2 shares highly homological sequences with SARS‐CoVs causing highly lethal pneumonia with respiratory distress and clinical symptoms similar to those reported for SARS‐CoV and MERS‐CoV infections. Notably, some COVID‐19 patients also expressed neurologic signs like nausea, headache, and vomiting. Several studies have reported that coronaviruses are not only causing respiratory illness but also invade the central nervous system through a synapse‐connected route. SARS‐CoV infections are reported in both patients and experimental animals' brains. Interestingly, some COVID‐19 patients have shown the presence of SARS‐CoV‐2 virus in their cerebrospinal fluid. Considering the similarities between SARS‐CoV and SARS‐CoV‐2 in various aspects, it remains to clarify whether the potent invasion of SARS‐CoV‐2 may affect in COVID‐19 patients. All these indicate that more detailed criteria are needed for the treatment and the prevention of SARS‐CoV‐2 infected patients. In the absence of potential interventions for COVID‐19, there is an urgent need for an alternative strategy to control the spread of this disease.

negative: 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.

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

negative: Severe Acute Respiratory Syndrome (SARS) This article reviews the virology, history, pathology, epidemiology, clinical presentations, complications, radiology, laboratory testing, diagnosis, treatment, and prevention of severe respiratory distress syndrome, with reference to documented outbreaks of the disease.

negative: Corona Virus Disease 2019 (COVID-19) Presenting as Acute ST Elevation Myocardial Infarction Patients with Covid-19 disease commonly present with symptoms related to respiratory illness, and less commonly they develop cardiovascular complications either on presentation or during the course of the disease. The mortality/morbidity is high in these patients with cardiovascular involvement. Acute ST-elevation myocardial infarction (STEMI) is a medical emergency which needs immediate coronary re-perfusion for better patient outcomes. Here we present a patient who presented to the emergency room with acute STEMI and later tested positive for COVID-19. She was successfully treated with coronary revascularization and stent placement, and remains on the ventilator to date as she quickly developed acute respiratory distress syndrome. We need more research in Covid-19 patients with cardiovascular involvement for early diagnosis, prevention of exposure to health care workers and effective treatment.

negative: First reported nosocomial outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a pediatric dialysis unit BACKGROUND: Coronavirus disease 2019 (COVID-19) is a life-threatening respiratory condition caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was initially detected in China in December 2019. Currently, in Germany over 140,000 cases of COVID-19 are confirmed. Here we report a nosocomial outbreak of SARS-CoV-2 infections in the pediatric dialysis unit of the University Hospital of Münster (UHM). METHODS: Single-step real-time RT-PCR from nasopharyngeal swaps was used to diagnose the index patient and identify infected contacts. Epidemiological links were analyzed by patient interviews and chart reviews. In addition, each contact was assessed for exposure to the index case and monitored for clinical symptoms. Threshold cycle (C(t)) values of all positive test results were compared between symptomatic and asymptomatic cases. RESULTS: Forty-eight cases were involved in this nosocomial outbreak. Nine contact cases developed laboratory confirmed COVID-19 infections. Two SARS-CoV-2 positive cases remained clinically asymptomatic. Eleven cases reported flu-like symptoms without positive results. C(t) values were significantly lower in cases presenting typical COVID-19 symptoms, suggesting high viral shedding (p =0.007). CONCLUSION: Person-to-person transmission was at the heart of a hospital outbreak of SARS-CoV-2 between healthcare workers (HCWs) and patients in the pediatric dialysis unit at the UHM. Semi quantitative real-time RT-PCR results suggest that individuals with high viral load pose a risk to spread SARS-CoV-2 in the hospital setting. Our epidemiological observation highlights the need to develop strategies to trace and monitor SARS-CoV-2 infected HCWs in order to prevent COVID-19 outbreaks in the hospital setting.

negative: Multicenter initial guidance on use of antivirals for children with COVID-19/SARS-CoV-2 BACKGROUND: Although Coronavirus Disease 2019 (COVID-19) is mild in nearly all children, a small proportion of pediatric patients develops severe or critical illness. Guidance is therefore needed regarding use of agents with potential activity against severe acute respiratory syndrome coronavirus 2 in pediatrics. METHODS: A panel of pediatric infectious diseases physicians and pharmacists from 18 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of best available evidence and expert opinion. RESULTS: Given the typically mild course of pediatric COVID-19, supportive care alone is suggested for the overwhelming majority of cases. The panel suggests a decision-making framework for antiviral therapy that weighs risks and benefits based on disease severity as indicated by respiratory support needs, with consideration on a case-by-case basis of potential pediatric risk factors for disease progression. If an antiviral is used, the panel suggests remdesivir as the preferred agent. Hydroxychloroquine could be considered for patients who are not candidates for remdesivir or when remdesivir is not available. Antivirals should preferably be used as part of a clinical trial if available. CONCLUSIONS: Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For those rare children who develop severe or critical disease, this guidance offer an approach for decision-making regarding antivirals, informed by available data. As evidence continues to evolve rapidly, the need for updates to the guidance is anticipated.

negative: Factors Associated with Depression, Anxiety, and PTSD Symptomatology During the COVID-19 Pandemic: Clinical Implications for U.S. Young Adult Mental Health This study sought to identify factors associated with depression, anxiety, and PTSD symptomatology in U.S. young adults (18-30 years) during the COVID-19 pandemic. This cross-sectional online study assessed 898 participants from April 13, 2020 to May 19, 2020, approximately one month after the U.S. declared a state of emergency due to COVID-19 and prior to the initial lifting of restrictions across 50 U.S. states. Respondents reported high levels of depression (43.3%, PHQ-8 scores ≥ 10), high anxiety scores (45.4%, GAD-7 scores ≥ 10), and high levels of PTSD symptoms (31.8%, PCL-C scores ≥ 45). High levels of loneliness, high levels of COVID-19-specific worries, and low distress tolerance were significantly associated with clinical levels of depression, anxiety, and PTSD symptoms. Resilience was associated with low levels of depression and anxiety symptoms but not PTSD. Most respondents had high levels of social support; social support from family, but not from partner or peers, was associated with low levels of depression and PTSD. Compared to Whites, Asian Americans were less likely to report high levels across mental health symptoms, and Hispanic/Latinos were less likely to report high levels of anxiety. These factors provide initial guidance regarding clinical management for COVID-19-related mental health problems.

negative: Searching for MERS and Novel Flu with Limited Resources

negative: The pathogenesis of multiple sclerosis: Additional considerations Multiple sclerosis (MS) is acquired as a systemic “trait” by individuals who are genetically susceptible. This condition does not involve the central nervous system (CNS) and is characterized by a state of hyperactive immunocompetent responsiveness. It develops as the result of an antigenic challenge by a viral protein, either from a viral infection or a vaccination. In order for MS to become a disease affecting the CNS, it is necessary for the blood-brain barrier's (BBB) impermeability to be altered. This is now a fully recognized fact. As a result of this change, the MS lesion, which consists of edema and inflammation occurs. It may but need not lead to demyelination. Several mechanisms can cause this increased permeability of the BBB. The role of the immune system, and in particular of T lymphocytes in initiating and continuing the process of lesion formation remains extremely controversial. In fact, there are unanswered questions regarding the actual target of MS: is it the myelin sheath itself or its forming cell, the oligodendrocyte, or is it the BBB itself leading to bystander demyelination? The role of mild, concussional trauma to the CNS in producing the alteration of the BBB and therefore acting as a trigger or facilitator in the development or enlargement of MS lesions in the CNS, is based on considerable clinical, neuropathological and experimental evidence. Along with another viral infection, it must be one of the commonest causes of progression of MS, and quite often leads to the onset of the clinical manifestations of an hitherto asymptomatic condition.

negative: Risk factors for disease progression in COVID-19 patients BACKGROUND: Coronavirus disease (COVID-19) is rapidly spreading worldwide. Although 10–20% of patients with COVID-19 have severe symptoms, little is known about the risk factors related to the aggravation of COVID-19 symptoms from asymptomatic or mild to severe disease states. METHODS: This retrospective study included 211 patients who were asymptomatic or with mild presentations of COVID-19. We evaluated the differences in demographic and clinical data between the cured (discharged to home) and transferred (aggravated to severe-stage COVID-19) groups. RESULTS: A multivariate logistic analysis showed that body temperature, chills, initial chest X-ray findings, and the presence of diabetes were significantly associated with predicting the progression to severe stage of COVID-19 (p < 0.05). The odds ratio of transfer in patients with COVID-19 increased by 12.7-fold for abnormal findings such as haziness or consolidation in initial chest X-ray, 6.32-fold for initial symptom of chills, and 64.1-fold for diabetes. CONCLUSIONS: Even if patients are asymptomatic or have mild symptoms, clinicians should closely observe patients with COVID-19 presenting with chills, body temperature > 37.5 °C, findings of pneumonia in chest X-ray, or diabetes.

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: 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: BETS: The dangers of selection bias in early analyses of the coronavirus disease (COVID-19) pandemic The coronavirus disease 2019 (COVID-19) has quickly grown from a regional outbreak in Wuhan, China to a global pandemic. Early estimates of the epidemic growth and incubation period of COVID-19 may have been biased due to sample selection. Using detailed case reports from 14 locations in and outside mainland China, we obtained 378 Wuhan-exported cases who left Wuhan before an abrupt travel quarantine. We developed a generative model we call BETS for four key epidemiological events---Beginning of exposure, End of exposure, time of Transmission, and time of Symptom onset (BETS)---and derived explicit formulas to correct for the sample selection. We gave a detailed illustration of why some early and highly influential analyses of the COVID-19 pandemic were severely biased. All our analyses, regardless of which subsample and model were being used, point to an epidemic doubling time of 2 to 2.5 days during the early outbreak in Wuhan. A Bayesian nonparametric analysis further suggests that about 5% of the symptomatic cases may not develop symptoms within 14 days of infection and that men may be much more likely than women to develop symptoms within 2 days of infection.

negative: Lower respiratory tract infection in the community: associations between viral aetiology and illness course Abstract Objectives This study determined associations between respiratory viruses and subsequent illness course in primary care adult patients presenting with acute cough and/or suspected lower respiratory tract infection (LRTI). Methods A prospective European primary care study recruited adults with symptoms of lower respiratory tract infection between Nov-Apr 2007-2010. Real-time in-house polymerase chain reaction (PCR) was performed to test for six common respiratory viruses. In this secondary analysis, symptom severity (scored 1=no problem, 2=mild, 3=moderate, 4=severe) and symptom duration were compared between groups with different viral aetiologies using regression and Cox proportional hazard models, respectively. Additionally, associations between baseline viral load (cycle threshold (Ct) value) and illness course were assessed. Results The PCR tested positive for a common respiratory virus in 1,354 of the 2,957 (45.8%) included patients. The overall mean symptom score at presentation was 2.09 (95%CI 2.07-2.11) and the median duration until resolution of moderately bad or severe symptoms was 8.70 days (interquartile range 4.50-11.00). Patients with influenza virus, human metapneumovirus (hMPV), respiratory syncytial virus (RSV), coronavirus (CoV) or rhinovirus had a significantly higher symptom score than patients with no virus isolated (0.07-0.25 points or 2.3-8.3% higher symptom score). Time to symptom resolution was longer in RSV infections (adjusted hazard ratio (AHR) 0.80, 95%CI 0.65-0.96) and hMPV infections (AHR 0.77, 95%CI 0.62-0.94) than in infections with no virus isolated. Overall, baseline viral load was associated with symptom severity (difference 0.11, 95%CI 0.06-0.16 per 10 cycles decrease in Ct value), but not with symptom duration. Conclusions In healthy, working adults from the general community presenting at the general practitioner with acute cough and/or suspected LRTI respiratory viruses other than influenza impose an illness burden comparable to influenza. Hence, the public health focus for viral respiratory tract infections should be broadened.

negative: Type III interferons disrupt the lung epithelial barrier upon viral recognition Lower respiratory tract infections are a leading cause of mortality driven by infectious agents. RNA viruses such as influenza virus, respiratory syncytial virus and the new pandemic coronavirus SARS-CoV-2 can be highly pathogenic. Clinical and experimental evidence indicate that most severe and lethal cases do not depend on the viral burden and are, instead, characterized by an aberrant immune response. In this work we assessed how the innate immune response contributes to the pathogenesis of RNA virus infections. We demonstrate that type III interferons produced by dendritic cells in the lung in response to viral recognition cause barrier damage and compromise the host tissue tolerance. In particular, type III interferons inhibit tissue repair and lung epithelial cell proliferation, causing susceptibility to lethal bacterial superinfections. Overall, our data give a strong mandate to rethink the pathophysiological roles of this group of interferons and their possible use in the clinical practice against endemic as well as emerging viral infections.

negative: Immunosuppression And Experimental Virus Infection Of The Nervous System This chapter describes the current views of the pathogenesis of virus infections of the nervous system, with particular attention to certain aspects of virus-host interactions. Following invasion of the central nervous system, infection can follow a variety of patterns, as to number and distribution of neuronal and non-neuronal cells involved. There is a corresponding diversity in the pathological lesions of the central nervous system (CNS) produced by acute virus infection. Infection can be pictured as a race between virus and host defenses, where many factors, acting through different mechanisms, can influence the outcome. Outcome is always determined by multiple virus and host variables, although single variables can be independently studied under experimentally controlled conditions in the laboratory. The chapter demonstrates that in many virus-host combinations, the immune response plays an important role in recovery from primary infections. It mentions that an immunopathological process mediates the disease which follows certain CNS virus infections.

negative: Pathology of 2019 Novel Coronavirus Pneumonia: A Dynamic Disease Process

negative: Epidemiological characteristics of novel coronavirus infection: A statistical analysis of publicly available case data Following the first report of coronavirus disease 2019 (COVID-19) in Sapporo City, Hokkaido Prefecture, Japan on 14 February 2020, a surge of cases was observed in Hokkaido during February and March. As of 6 March, 90 cases were diagnosed in Hokkaido. Unfortunately, many infected persons may not have been recognized as cases due to having mild or no symptoms. We therefore estimated the actual number of COVID-19 cases in (i) Hokkaido Prefecture and (ii) Sapporo City using data on cases diagnosed outside these areas. The estimated cumulative incidence in Hokkaido as of 27 February was 2297 cases (95% confidence interval [CI]: 382, 7091) based on data on travelers outbound from Hokkaido. The cumulative incidence in Sapporo City as of 28 February was estimated at 2233 cases (95% CI: 0, 4893) based on the count of confirmed cases within Hokkaido. Both approaches resulted in similar estimates, indicating higher incidence of infections in Hokkaido than were detected by the surveillance system. This quantification of the gap between detected and estimated cases can help inform public health response as it provides insight into the possible scope of undetected transmission.

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: Containing 2019-nCoV (Wuhan) coronavirus The novel coronavirus 2019-nCoV first appeared in December 2019 in Wuhan, China. While most of the initial cases were linked to the Huanan Seafood Wholesale Market, person-to-person transmission has been verified. Given that a vaccine cannot be developed and deployed for at least a year, preventing further transmission relies upon standard principles of containment, two of which are the isolation of known cases and the quarantine of persons believed at high risk of exposure. This note presents probability models for assessing the effectiveness of case isolation and quarantine within a community during the initial phase of an outbreak with illustrations based on early observations from Wuhan.

negative: Acute disseminated encephalomyelitis: a call to the clinicians for keeping this rare condition on clinical radar Acute disseminated encephalomyelitis is a rare disease of central nervous system, which can present with a variety of clinical manifestations. That is why first attack of ADEM, in particular remains a diagnostic puzzle. Early anticipation and diagnosis is important for better outcomes. We present a case of acute disseminated encephalomyelitis which initially had atypical clinical features with cough, expectoration, fever and later manifested strange neurological features, diagnosed to be a case of acute disseminated encephalomyelitis based on radio-imaging.

negative: High risk of infection caused posttraumatic stress symptoms in individuals with poor sleep quality: A study on influence of coronavirus disease (COVID-19) in China The influence of the outbreak of coronavirus disease (COVID-19) on mental health was poorly understood. The present study aimed to exam sleep problems and posttraumatic stress symptoms (PTSS) in Chinese immediately after the massive outbreak of COVID-19. A total of 2027 Chinese participated in the present study. Wuhan-expose history, sleep quality and PTSS were measured with self-rating scales. Results showed that there were significant differences of PCL-5 and of sleep quality scores in different data-collection dates (ps<0.05). There were significant differences of PCL-5 scores (p<0.05) and latency onset of sleep (p<0.05) between participants with and without Wuhan-expose history. The interaction effect of Wuhan exposure history × sleep quality significantly influenced PCL-5 (ps<0.05). These results indicate that keeping good sleep quality in individuals with high infectious risk is a way to prevent PTSS.

negative: Evaluation of the potential incidence of COVID-19 and effectiveness of contention measures in Spain: a data-driven approach Our society is currently experiencing an unprecedented challenge, managing and containing an outbreak of a new coronavirus disease known as COVID-19. While China - were the outbreak started - seems to have been able to contain the growth of the epidemic, different outbreaks are nowadays being detected in multiple countries. Much is currently unknown about the natural history of the disease, such as a possible asymptomatic spreading or the role of age in both the susceptibility and mortality of the disease. Nonetheless, authorities have to take action and implement contention measures, even if not everything is known. To facilitate this task, we have studied the effect of different containment strategies that can be put into effect. Our work specifically refers to the situation in Spain as of February 28th, 2020, where a few dozens of cases have been detected. We implemented an SEIR-metapopulation model that allows tracing explicitly the spatial spread of the disease through data-driven stochastic simulations. Our results are in line with the most recent recommendations from the World Health Organization, namely, that the best strategy is the early detection and isolation of individuals with symptoms, followed by interventions and public recommendations aimed at reducing the transmissibility of the disease, which although not efficacious for disease eradication, would produce as a second-order effect a delay of several days in the raise of the number of infected cases

negative: Human Infected H7N9 Avian Influenza Human infected H7N9 avian influenza is an acute respiratory infectious disease caused by subtype H7N9 of avian influenza virus. Since the first case was reported in Yangzi River Delta of China in Feb. 2013, the total cases with definitive diagnosis had been up to 451 cases, including 176 cases of death, by Dec. 31, 2014, with a mortality rate of roughly 39 %.

negative: Clinical evaluation of an immunochromatographic IgM/IgG antibody assay and chest computed tomography for the diagnosis of COVID-19 Abstract Background We evaluated the clinical performance of an immunochromatographic (IC) IgM/IgG antibody assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) and chest computed tomography (CT) for the diagnosis of Coronavirus disease 2019 (COVID-19). Methods We examined 139 serum specimens collected from 112 patients with COVID-19 and 48 serum specimens collected from 48 non-COVID-19 patients. The presence of IgM/IgG antibody for SARS-CoV2 was determined using the One Step Novel Coronavirus (COVID-19) IgM/IgG Antibody Test. Chest CT was performed in COVID-19 patients on admission. Findings Of the139 COVID-19 serum specimens, IgM was detected in 27.8%, 48.0%, and 95.8% of the specimens collected within 1 week, 1-2 weeks, and >2 weeks after symptom onset and IgG was detected in 3.3%, 8.0%, and 62.5%, respectively. Among the 48 non-COVID-19 serum specimens, 1 generated a false-positive result for IgM. Thirty-eight of the 112 COVID-19 patients were asymptomatic, of whom 15 were positive for IgM, and 74 were symptomatic, of whom 22 were positive for IgM and 7 were positive for IgG. The diagnostic sensitivity of CT scan alone and in combination with the IC assay was 57.9 % (22/38) and 68.4% (26/38) for the asymptomatic patients and 74.3% (55/74) and 82.4% (61/74) for the symptomatic patients, respectively. Conclusion The IC assay had low sensitivity during the early phase of infection, and thus IC assay alone is not recommended for initial diagnostic testing for COVID-19. If RT-qPCR is not available, the combination of chest CT and IC assay may be useful for diagnosing COVID-19.

negative: The National Vaccine Advisory Committee at 30: Impact and opportunity Abstract Thirty years after passage of legislation that created the National Vaccine Advisory Committee (NVAC) “to achieve optimal prevention of human infectious diseases through immunization and to achieve optimal prevention against adverse reactions to vaccines,” this review reflects NVAC’s role and impact on the U.S. vaccine and immunization enterprise as an external advisor to the Department of Health and Human Services. We reviewed the history of NVAC in the context of the principles of its establishment, with a focus on its reports and recommendations. We performed a systematic literature review to identify NVAC reports published in widely-accessible public health journals, and we reviewed the available archives to identify other reports and resolutions approved by the committee not published in journals. We characterized key issues considered by NVAC according to the five goals of the 2010 National Vaccine Plan. The predominance of NVAC activities to date related to the implementation of immunization across the lifespan and the many aspects of the system needed to foster the goal of full immunization. Reflecting on the impacts of NVAC to date, this review identified 30 NVAC approved reports published in journals, 22 stand-alone resolutions, and 26 unique unpublished reports. The development of new and improved vaccines continues to represent a significant priority for NVAC, and we identified several challenges related to future vaccine innovation. Given the many factors that impact on policy changes in the vaccine and immunization enterprise, we encountered challenges associated with demonstrating attribution of specific policy changes to NVAC recommendations. Although difficult to quantify, this review suggests that NVAC played an important role in the improvements in the U.S. immunization enterprise over the past 30 years and that NVAC can and will continue to play an important role supporting U.S. immunization going forward.

negative: Multiple organ failure – the discrepancy between our scientific knowledge and understanding and the management of our patients The excitement of molecular biology and of genetic knowledge and their possibilities must be balanced against our limitations in using this information for the care of our patients. There is a great discrepancy between what we know and what we can do. There are many reasons for this. A major one is that science must simplify/reduce the variables in experimentation and then generalize in terms of a specific factor or effect, whereas patients are complex with variables that we do not yet understand completely. This powerful science is now teaching us about the genetic diversity in both susceptibility and outcome of disease, and the diversity in life experiences and antigen exposures. Clinicians have tried to lump together and treat in a similar way many diverse human diseases. This has not worked well. Pancreatitis and perforated diverticulitis both produce inflammation and sepsis, but they are different processes and may both lead to multiple organ failure. This lumping together has contributed to the failure of so-called magic bullets. There are new contributors to organ damage. Gender, lifestyle and prior disease differences also complicate the care of patients. Despite this, we are slowly and gradually improving the care of our surgical patients by careful pre-, intra- and postoperative support and better, simpler and safer operations.

negative: Standard and AEGIS nicking molecular beacons detect amplicons from the Middle East respiratory syndrome coronavirus Abstract This paper combines two advances to detect MERS-CoV, the causative agent of Middle East Respiratory Syndrome, that have emerged over the past few years from the new field of “synthetic biology”. Both are based on an older concept, where molecular beacons are used as the downstream detection of viral RNA in biological mixtures followed by reverse transcription PCR amplification. The first advance exploits the artificially expanded genetic information systems (AEGIS). AEGIS adds nucleotides to the four found in standard DNA and RNA (xNA); AEGIS nucleotides pair orthogonally to the A:T and G:C pairs. Placing AEGIS components in the stems of molecular beacons is shown to lower noise by preventing unwanted stem invasion by adventitious natural xNA. This should improve the signal-to-noise ratio of molecular beacons operating in complex biological mixtures. The second advance introduces a nicking enzyme that allows a single target molecule to activate more than one beacon, allowing “signal amplification”. Combining these technologies in primers with components of a self-avoiding molecular recognition system (SAMRS), we detect 50 copies of MERS-CoV RNA in a multiplexed respiratory virus panel by generating fluorescence signal visible to human eye and/or camera.

negative: Identifiability of infection model parameters early in an epidemic It is known that the parameters in the deterministic and stochastic SEIR epidemic models are structurally identifiable. For example, from knowledge of the infected population time series I(t) during the entire epidemic, the parameters can be successfully estimated. In this article we observe that estimation will fail in practice if only infected case data during the early part of the epidemic (pre-peak) is available. This fact can be explained using a long-known phenomenon called dynamical compensation. We use this concept to derive an unidentifiability manifold in the parameter space of SEIR that consists of parameters indistinguishable to I(t) early in the epidemic. Thus, identifiability depends on the extent of the system trajectory that is available for observation. Although the existence of the unidentifiability manifold obstructs the ability to exactly determine the parameters, we suggest that it may be useful for uncertainty quantification purposes. A variant of SEIR recently proposed for COVID-19 modeling is also analyzed, and an analogous unidentifiability surface is derived.

negative: COVID-19 and Diabetic Foot: Will the Lamp Burn Bright?

negative: A Simple and Multiplex Loop-Mediated Isothermal Amplification (LAMP) Assay for Rapid Detection of SARS-CoV The current diagnosis of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) relies on laboratory-based tests since its clinical features are nonspecific, unlike other respiratory pathogens. Therefore, the development of a rapid and simple method for on-site detection of SARS-CoV is crucial for the identification and prevention of future SARS outbreaks. In this study, a simple colorimetric and multiplex loop-mediated isothermal amplification (LAMP) assay was developed to rapid screening of severe acute respiratory syndrome-associated coronavirus (SARS-CoV). It can be visually detected based on color change and monitored in real-time with fluorescent signals. The performance of this assay, based on six primers targeting open reading frame (ORF1b) and nucleocapsid (N) genes located in different regions of the SARS-CoV, was compared with real-time RT-PCR assay using various concentrations of target genes. The detection limit of the LAMP assay was comparable to that of real-time RT-PCR assay and therefore a few target RNA to 10(4)-10(5) copies could be detected within a short period of time (20–25 min). In addition, we established a multiplex real-time LAMP assay to simultaneously detect two target regions within the SARS-CoV genome. Two target sequences were amplified by specific primers in the same reaction tube and revealed that it was able to detect down to 10(5) copies. The standard curve had a linear relationship with similar amplification efficiencies. The LAMP assay results in shorter “sample-to-answer” time than conventional PCR method. Therefore, it is suitable not only for diagnosis of clinical test, but also for surveillance of SARS virus in developing countries. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s13206-019-3404-3 and is accessible for authorized users.

negative: Transmission dynamics of 2019 novel coronavirus (2019-nCoV) Background Since December 29, 2019, pneumonia infection with 2019-nCoV has rapidly spread out from Wuhan, Hubei Province, China to most others provinces and other counties. However, the transmission dynamics of 2019-nCoV remain unclear. Methods Data of confirmed 2019-nCoV cases before January 23, 2020 were collected from medical records, epidemiological investigations or official websites. Data of severe acute respiratory syndrome (SARS) cases in Guangdong Province during 2002-2003 were obtained from Guangdong Provincial Center for Disease Control and Prevention (GDCDC). Exponential Growth (EG) and maximum likelihood estimation (ML) were applied to estimate the reproductive number (R) of 2019-nCoV and SARS. Findings As of January 23, 2020, a total of 830 confirmed 2019-nCoV cases were identified across China, and 9 cases were reported overseas. The average incubation duration of 2019-nCoV infection was 4.8days. The average period from onset of symptoms to isolation of 2019-nCoV and SARS cases were 2.9 and 4.2 days, respectively. The R values of 2019-nCoV were 2.90 (95%CI: 2.32-3.63) and 2.92 (95%CI: 2.28-3.67) estimated using EG and ML respectively, while the corresponding R values of SARS-CoV were 1.77 (95%CI: 1.37-2.27) and 1.85 (95%CI: 1.32-2.49). We observe a decreasing trend of the period from onset to isolation and R values of both 2019-nCoV and SARS-CoV. Interpretation The 2019-nCoV may have a higher pandemic risk than SARS broken out in 2003. The implemented public-health efforts have significantly decreased the pandemic risk of 2019-nCoV. However, more rigorous control and prevention strategies and measures to contain its further spread. Funding National Key Research and Development Program of China, Science and Technology Program of Guangdong Province, and Guangzhou Science and technology Plan Project.

negative: Detection of Nucleocapsid Antibody to SARS-CoV-2 is More Sensitive than Antibody to Spike Protein in COVID-19 Patients Background: SARS-CoV-2, the cause of coronavirus disease 2019 (COVID-19), is associated with respiratory-related morbidity and mortality. Assays to detect virus-specific antibodies are important to understand the prevalence of infection and the course of the immune response. Methodology: Quantitative measurements of plasma or serum antibodies by luciferase immunoprecipitation assay systems (LIPS) to the nucleocapsid and spike proteins were analyzed in 100 cross-sectional or longitudinal samples from SARS-CoV-2-infected patients. A subset of samples was tested with and without heat inactivation. Results: Fifteen or more days after symptom onset, antibodies against SARS-CoV-2 nucleocapsid protein showed 100% sensitivity and 100% specificity, while antibodies to spike protein were detected with 91% sensitivity and 100% specificity. Neither antibody levels nor the rate of seropositivity were significantly reduced by heat inactivation of samples. Analysis of daily samples from six patients with COVID-19 showed anti-nucleocapsid and spike antibodies appearing between day 8 to day 14 after initial symptoms. Immunocompromised patients generally had a delayed antibody response to SARS-CoV-2 compared to immunocompetent patients. Conclusions: Antibody to the nucleocapsid protein of SARS-CoV-2 is more sensitive than spike protein antibody for detecting early infection. Analyzing heat-inactivated samples by LIPS is a safe and sensitive method for detecting SARS-CoV-2 antibodies.

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

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

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

negative: CXCL13 promotes isotype-switched B cell accumulation to the central nervous system during viral encephalomyelitis Elevated CXCL13 within the central nervous system (CNS) correlates with humoral responses in several neuroinflammatory diseases, yet its role is controversial. During coronavirus encephalomyelitis CXCL13 deficiency impaired CNS accumulation of memory B cells and antibody-secreting cells (ASC) but not naïve/early-activated B cells. However, despite diminished germinal center B cells and follicular helper T cells in draining lymph nodes, ASC in bone marrow and antiviral serum antibody were intact in the absence of CXCL13. The data demonstrate that CXCL13 is not essential in mounting effective peripheral humoral responses, but specifically promotes CNS accumulation of differentiated B cells.

negative: Public health might be endangered by possible prolonged discharge of SARS-CoV-2 in stool • The published data, which showed the COVID-19 patients with low digestive. • manifestation, might be misleading. Case with negative URT test showed positive in. • rectal scarab which challenge the isolation protocol. • As fomite transmission caused clusters of infection of SARS, adequate disinfection. • operations should be adopted in SARS-CoV-2 outbreak.

negative: Prolonged viral shedding in feces of pediatric patients with coronavirus disease 2019 Abstract Objective To determine the dynamic changes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in respiratory and fecal specimens in children with coronavirus disease 2019 (COVID-19). Methods From January 17, 2020 to February 23, 2020, three paediatric cases of COVID-19 were reported in Qingdao, Shandong Province, China. Epidemiological, clinical, laboratory, and radiological characteristics and treatment data were collected. Patients were followed up to March 10, 2020, and dynamic profiles of nucleic acid testing results in throat swabs and fecal specimens were closely monitored. Results Clearance of SARS-CoV-2 in respiratory tract occurred within two weeks after abatement of fever, whereas viral RNA remained detectable in stools of pediatric patients for longer than 4 weeks. Two children had fecal SARS-CoV-2 undetectable 20 days after throat swabs showing negative, while that of another child lagged behind for 8 days. Conclusions SARS-CoV-2 may exist in children's gastrointestinal tract for a longer time than respiratory system. Persistent shedding of SARS-CoV-2 in stools of infected children raises the possibility that the virus might be transmitted through contaminated fomites. Massive efforts should be made at all levels to prevent spreading of the infection among children after reopening of kindergartens and schools.

negative: Evolving reporting criteria of COVID-19 in Taiwan during the epidemic

negative: Radiologic chest CT findings from COVID‐19 in Orleans Parish, Louisiana Orleans Parish in Louisiana is in the midst of an exponentially increasing number of patient admissions with COVID‐19 and respiratory symptoms. Patients have been described having CT findings most consistent with an early‐stage (<7 days from symptoms onset) or an advanced stage (8‐14 days from symptoms onset). We describe and illustrate those early and advanced stage CT findings from patients with documented COVID‐19 who have been admitted to University Medical Center in New Orleans, Louisiana.

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

negative: Posterior Reversible Encephalopathy Syndrome: A Manifestation of COVID-19 Cytokine Storm Neuroimaging manifestations of COVID-19 are being reported with increasing frequency with recent reports of associated atypical leukoencephalopathies. We add to this literature by describing a COVID-19 + patient who demonstrated imaging findings typical for posterior reversible encephalopathy syndrome (PRES). The inflammatory syndrome associated with novel corona virus infection has shown markedly increased levels of cytokines and inflammatory markers. This has also been described in a proposed mechanism for PRES, where elevated inflammatory markers result in endothelial injury causing interstitial fluid extravasation typical of PRES. We expect that other cases of PRES will be observed in this population given the scope of the Covid-19 pandemic.

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

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: A comprehensive Chinese experience against SARS-CoV-2 in ophthalmology The 2019 novel coronavirus disease (COVID-19) has now swept through the continents and poses a global threat to public health. Several investigations have been conducted to identify whether COVID-19 can be transmitted through the ocular route, and the conclusion is that it is a potential route but remains uncertain. Due to the face-to-face communication with patients, frequent exposure to tears and ocular discharge, and the unavoidable use of equipment which requires close proximity, ophthalmologists carry a high risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on 33 articles published by Chinese scholars, guidelines and clinical practice experience in domestic hospitals, we have summarized the Chinese experience through the lens of ophthalmology, hoping to make a contribution to protecting ophthalmologists and patients around the world.

negative: The establishment of reference sequence for SARS‐CoV‐2 and variation analysis Starting around December 2019, an epidemic of pneumonia, which was named COVID‐19 by the World Health Organization, broke out in Wuhan, China, and is spreading throughout the world. A new coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) by the Coronavirus Study Group of the International Committee on Taxonomy of Viruses was soon found to be the cause. At present, the sensitivity of clinical nucleic acid detection is limited, and it is still unclear whether it is related to genetic variation. In this study, we retrieved 95 full‐length genomic sequences of SARAS‐CoV‐2 strains from the National Center for Biotechnology Information and GISAID databases, established the reference sequence by conducting multiple sequence alignment and phylogenetic analyses, and analyzed sequence variations along the SARS‐CoV‐2 genome. The homology among all viral strains was generally high, among them, 99.99% (99.91%‐100%) at the nucleotide level and 99.99% (99.79%‐100%) at the amino acid level. Although overall variation in open‐reading frame (ORF) regions is low, 13 variation sites in 1a, 1b, S, 3a, M, 8, and N regions were identified, among which positions nt28144 in ORF 8 and nt8782 in ORF 1a showed mutation rate of 30.53% (29/95) and 29.47% (28/95), respectively. These findings suggested that there may be selective mutations in SARS‐COV‐2, and it is necessary to avoid certain regions when designing primers and probes. Establishment of the reference sequence for SARS‐CoV‐2 could benefit not only biological study of this virus but also diagnosis, clinical monitoring and intervention of SARS‐CoV‐2 infection in the future.

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

negative: 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: Rational Design of an Epstein-Barr Virus Vaccine Targeting the Receptor-Binding Site Epstein-Barr virus (EBV) represents a major global health problem. Though it is associated with infectious mononucleosis and over 200,000 cancers annually worldwide, a vaccine is not available. The major target of immunity is EBV glycoprotein 350/220 (gp350) that mediates attachment to B cells through complement receptor 2 (CR2/CD21). Here, we created self-assembling nanoparticles that displayed different domains of gp350 in a symmetric array. By focusing presentation of the CR2-binding domain on nanoparticles, potent neutralizing antibodies were elicited in mice and non-human primates. The structurally designed nanoparticle vaccine improved vaccine-induced protection in a mouse model by targeting a functionally conserved site of vulnerability with 10- to 100-fold increased neutralization compared to soluble gp350. This rational approach to EBV vaccine design elicited potent neutralizing antibody responses by focusing on a conserved viral entry domain, a strategy that can be applied to other viruses.

negative: Chest CT Findings in Coronavirus Disease-19 (COVID-19): Relationship to Duration of Infection In this retrospective study, chest CTs of 121 symptomatic patients infected with coronavirus disease-19 (COVID-19) from four centers in China from January 18, 2020 to February 2, 2020 were reviewed for common CT findings in relationship to the time between symptom onset and the initial CT scan (i.e. early, 0-2 days (36 patients), intermediate 3-5 days (33 patients), late 6-12 days (25 patients)). The hallmarks of COVID-19 infection on imaging were bilateral and peripheral ground-glass and consolidative pulmonary opacities. Notably, 20/36 (56%) of early patients had a normal CT. With a longer time after the onset of symptoms, CT findings were more frequent, including consolidation, bilateral and peripheral disease, greater total lung involvement, linear opacities, “crazy-paving” pattern and the “reverse halo” sign. Bilateral lung involvement was observed in 10/36 early patients (28%), 25/33 intermediate patients (76%), and 22/25 late patients (88%).

negative: Initial otolaryngological manifestations of severe acute respiratory syndrome in Taiwan. OBJECTIVE To provide a clue for screening severe acute respiratory syndrome (SARS), a highly transmissible disease with health care workers at particular risk, in the early stage from an otolaryngological perspective. DESIGN Prospective study. SETTING Community hospital. PATIENTS Between April 17 and April 26, 2003, 32 consecutive patients with SARS were encountered. Investigation consisted of local examination of ear, nose, and throat fields; palpation of the nuchal areas; and plain chest radiography. Analyses of throat swab samples using reverse transcription-polymerase chain reaction were conducted. RESULTS Clinical manifestations included fever in 31 patients (97%), followed by cough, dyspnea, chill, headache, sore throat, diarrhea, rhinorrhea, and otalgia. Neither the pharyngeal wall nor the tonsillar area demonstrated hyperemia. There was no lymphadenopathy in the neck. Plain chest radiographs revealed consolidation in 25 (78%) of 32 patients. Results of reverse transcription-polymerase chain reaction analysis targeting the novel coronavirus present in throat swab samples were positive in 19 (66%) of 29 patients tested. Twenty-eight patients required supplemental oxygen, and 14 patients were intubated with mechanical ventilation. Twenty-eight patients survived and 4 patients died. CONCLUSIONS When presented with a patient with flulike symptoms such as fever and/or cough, but no pharyngeal hyperemia or neck lymphadenopathy, physicians should be alerted to the possibility of SARS. In contrast, evidence of inflammatory signs in the otolaryngological field may explain the flulike symptoms, and serve as a differential diagnostic tool between influenza and SARS.

negative: Deciphering the power of isolation in controlling COVID-19 outbreaks

negative: Sleep problems among Chinese adolescents and young adults during the coronavirus-2019 pandemic OBJECTIVE: To assess the prevalence and sociodemographic correlates of insomnia symptoms among Chinese adolescents and young adults affected by the outbreak of coronavirus disease-2019 (COVID-19). METHODS: This cross-sectional study included Chinese adolescents and young adults 12–29 years of age during part of the COVID-19 epidemic period. An online survey was used to collect demographic data, and to assess recognition of COVID-19, insomnia, depression, and anxiety symptoms using the Pittsburgh Sleep Quality Index (PSQI), the Patient Health Questionnaire (PHQ-9), and the Generalized Anxiety Disorder (GAD-7) questionnaires, respectively. The Social Support Rate Scale was used to assess social support. RESULTS: Among 11,835 adolescents and young adults included in the study, the prevalence of insomnia symptoms during part of the COVID-19 epidemic period was 23.2%. Binomial logistic regression analysis revealed that female sex and residing in the city were greater risk factors for insomnia symptoms. Depression or anxiety were risk factors for insomnia symptoms; however, social support, both subjective and objective, was protective factors against insomnia symptoms. Furthermore, anxiety and depression symptoms were mediators of social support and insomnia symptoms. CONCLUSIONS: Results of this study revealed a high prevalence of sleep problems among adolescents and young adults during the COVID-19 epidemic, especially senior high school and college students, which were negatively associated with students’ projections of trends in COVID-19. The adverse impact of COVID-19 was a risk factor for insomnia symptoms; as such, the government must devote more attention to sleep disorders in this patient population while combating COVID-19.

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: 2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus 2019 Novel Coronavirus (2019-nCoV) is an emerging infectious disease closely related to MERS-CoV and SARS-CoV that was first reported in Wuhan City, Hubei Province, China in December 2019. As of January 2020, cases of 2019-nCoV are continuing to be reported in other Eastern Asian countries as well as in the United States, Europe, Australia, and numerous other countries. An unusually high volume of domestic and international travel corresponding to the beginning of the 2020 Chinese New Year complicated initial identification and containment of infected persons. Due to the rapidly rising number of cases and reported deaths, all countries should be considered at risk of imported 2019-nCoV. Therefore, it is essential for prehospital, clinic, and emergency department personnel to be able to rapidly assess 2019-nCoV risk and take immediate actions if indicated. The Identify-Isolate-Inform (3I) Tool, originally conceived for the initial detection and management of Ebola virus and later adjusted for other infectious agents, can be adapted for any emerging infectious disease. This paper reports a modification of the 3I Tool for use in the initial detection and management of patients under investigation for 2019-nCoV. After initial assessment for symptoms and epidemiological risk factors, including travel to affected areas and exposure to confirmed 2019-nCoV patients within 14 days, patients are classified in a risk-stratified system. Upon confirmation of a suspected 2019-nCoV case, affected persons must immediately be placed in airborne infection isolation and the appropriate public health agencies notified. This modified 3I Tool will assist emergency and primary care clinicians, as well as out-of-hospital providers, in effectively managing persons with suspected or confirmed 2019-nCoV.

negative: Lack of association between genetic variants at ACE2 and TMPRSS2 genes involved in SARS-CoV-2 infection and human quantitative phenotypes Coronavirus disease 2019 (COVID-19) shows a wide variation in expression and severity of symptoms, from very mild or no symptomes, to flu-like symptoms, and in more severe cases, to pneumonia, acute respiratory distress syndrome and even death. Large differences in outcome have also been observed between males and females. The causes for this variability are likely to be multifactorial, and to include genetics. The SARS-CoV-2 virus responsible for the infection uses the human receptor angiotensin converting enzyme 2 (ACE2) for cell invasion, and the serine protease TMPRSS2 for S protein priming. Genetic variation in these two genes may thus modulate an individual's genetic predisposition to infection and virus clearance. While genetic data on COVID-19 patients is being gathered, we carried out a phenome-wide association scan (PheWAS) to investigate the role of these genes in other human phenotypes in the general population. We examined 178 quantitative phenotypes including cytokines and cardio-metabolic biomarkers, as well as 58 medications in 36,339 volunteers from the Lifelines population biobank, in relation to 1,273 genetic variants located in or near ACE2 and TMPRSS2. While none reached our threshold for significance, we observed a suggestive association of polymorphisms within the ACE2 gene with (1) the use of ARBs combination therapies (p=5.7x10-4), an association that is significantly stronger in females (pdiff=0.01), and (2) with the use of non-steroid anti-inflammatory and antirheumatic products (p=5.5x10-4). While these associations need to be confirmed in larger sample sizes, they suggest that these variants play a role in diseases such as hypertension and chronic inflammation that are often observed in the more severe COVID-19 cases. Further investigation of these genetic variants in the context of COVID-19 is thus promising for better understanding of disease variability. Full results are available at https://covid19research.nl.

negative: Coronavirus disease 2019 (COVID-19) in the radiology department: What radiographers need to know OBJECTIVES: The aim is to review current literature related to the diagnosis, management, and follow-up of suspected and confirmed Covid-19 cases. KEY FINDINGS: Medical Imaging plays an important auxiliary role in the diagnosis of Covid-19 patients, mainly those most seriously affected. Practice differs widely among different countries, mainly due to the variability of access to resources (viral testing and imaging equipment, specialised staff, protective equipment). It has been now well-documented that chest radiographs should be the first-line imaging tool and chest CT should only be reserved for critically ill patients, or when chest radiograph and clinical presentation may be inconclusive. CONCLUSION: As radiographers work on the frontline, they should be aware of the potential risks associated with Covid-19 and engage in optimal strategies to reduce these. Their role in vetting, conducting and often reporting the imaging examinations is vital as well as their contribution in patient safety and care. Medical Imaging should be limited to critically ill patients, and where it may have an impact on the patient management plan. IMPLICATIONS FOR PRACTICE: At the time of publication, this review offers the most up-to-date recommendations for clinical practitioners in radiology departments, including radiographers. Radiography practice has to significantly adjust to these new requirements to support optimal and safe imaging practices for the diagnosis of Covid-19. The adoption of low dose CT, rigorous infection control protocols and optimal use of personal protective equipment may reduce the potential risks of radiation exposure and infection, respectively, within Radiology departments.

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

negative: Serological and molecular findings during SARS-CoV-2 infection: the first case study in Finland, January to February 2020 The first case of coronavirus disease (COVID-19) in Finland was confirmed on 29 January 2020. No secondary cases were detected. We describe the clinical picture and laboratory findings 3–23 days since the first symptoms. The SARS-CoV-2/Finland/1/2020 virus strain was isolated, the genome showing a single nucleotide substitution to the reference strain from Wuhan. Neutralising antibody response appeared within 9 days along with specific IgM and IgG response, targeting particularly nucleocapsid and spike proteins.

negative: Spatial-temporal variations of atmospheric factors contribute to SARS-CoV-2 outbreak The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19) reached over two million confirmed cases worldwide, and numbers are still growing at a fast rate. The majority of new infections are now being reported outside of China, where the outbreak officially originated in December 2019 in Wuhan. Despite the wide outbreak of the infection, a remarkable asymmetry is observed in the number of cases and in the distribution of the severity of the COVID-19 symptoms in patients with respect to the countries/regions. In the early stages of a new pathogen outbreak, it is critical to understand the dynamics of the infection transmission, in order to follow contagion over time and project the epidemiological situation in the near future. While it is possible to reason that observed variation in the number and severity of cases stem from the initial number of infected individuals, the difference in the testing policies and social aspects of community transmissions, the factors that could explain high discrepancy in areas with a similar level of healthcare still remain unknown. Here we introduce a binary classifier based on an artificial neural network that can help in explaining those differences and that can be used to support the design of containment policies. We propose that air pollutants, and specifically particulate matter (PM) 2.5 and ozone, are oppositely related with the SARS-CoV-2 infection frequency and could serve as surrogate markers to complement the infection outbreak anticipation.

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

negative: An update on COVID-19 for the otorhinolaryngologist – a Brazilian Association of Otolaryngology and Cervicofacial Surgery (ABORL-CCF) Position Statement Abstract Introduction We are facing a pandemic with a great impact worldwide, as a result of the rapid spread of the novel coronavirus (COVID-19). The medical community is still getting to know behavior of this virus and the consequences from a population point of view. All this knowledge is extremely dynamic, so some behaviors are still not well established. Otorhinolaryngologists have a central role in the management of this situation, in which they must assess the patient, avoid contamination to and by health professionals and other patients. Thus, the recommendations of the Brazilian Association of Otorhinolaryngology and Cervical-Facial Surgery (ABORL-CCF) have the main objective of reducing the spread of the new coronavirus during otorhinolaryngological care and assisting in the management of these patients. Methods Review of the main recommendations of national and international scientific societies, decisions by government agencies and class councils. The topics will be related to the general aspects of COVID-19, personal protective equipment, care in patient assistance, endoscopic exam routines and the management of sinonasal, otological and pediatric evaluations related to COVID-19. Results The use of personal protective equipment is considered crucial in routine ENT care. We recommend postponing appointments, exams and elective surgeries to reduce the spread of COVID-19. Similarly, we recommend changing routines in several areas of otolaryngology. Additionally, guidance is provided on the use of telemedicine resources during the pandemic period. Conclusions We are still at the beginning of the COVID-19 pandemic and scientific evidence is still scarce and incomplete, so these ABORL-CCF recommendations for otorhinolaryngologists may be updated based on new knowledge and the pattern of the new coronavirus spread.

negative: National Institute for the Infectious Diseases “L. Spallanzani”, IRCCS. Recommendations for COVID-19 clinical management On January 9 2020, the World Health Organization (WHO) declared the identification, by Chinese Health authorities, of a novel coronavirus, further classified as SARS-CoV-2 responsible of a disease (COVID-19) ranging from asymptomatic cases to severe respiratory involvement. On March 9 2020, WHO declared COVID-19 a global pandemic. Italy is the second most affected country by COVID-19 infection after China. The “L. Spallanzani” National Institute for the Infectious Diseases, IRCCS, Rome, Italy, has been the first Italian hospital to admit and manage patients affected by COVID-19. Hereby, we show our recommendations for the management of COVID-19 patients, based on very limited clinical evidences; they should be considered as expert opinions, which may be modified according to newly produced literature data.

negative: Middle East Respiratory Syndrome Coronavirus Transmission in Dialysis Unit and Infection Control Interventions in Korea

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: Factors Associated With Mental Health Outcomes Among Health Care Workers Exposed to Coronavirus Disease 2019 IMPORTANCE: Health care workers exposed to coronavirus disease 2019 (COVID-19) could be psychologically stressed. OBJECTIVE: To assess the magnitude of mental health outcomes and associated factors among health care workers treating patients exposed to COVID-19 in China. DESIGN, SETTINGS, AND PARTICIPANTS: This cross-sectional, survey-based, region-stratified study collected demographic data and mental health measurements from 1257 health care workers in 34 hospitals from January 29, 2020, to February 3, 2020, in China. Health care workers in hospitals equipped with fever clinics or wards for patients with COVID-19 were eligible. MAIN OUTCOMES AND MEASURES: The degree of symptoms of depression, anxiety, insomnia, and distress was assessed by the Chinese versions of the 9-item Patient Health Questionnaire, the 7-item Generalized Anxiety Disorder scale, the 7-item Insomnia Severity Index, and the 22-item Impact of Event Scale–Revised, respectively. Multivariable logistic regression analysis was performed to identify factors associated with mental health outcomes. RESULTS: A total of 1257 of 1830 contacted individuals completed the survey, with a participation rate of 68.7%. A total of 813 (64.7%) were aged 26 to 40 years, and 964 (76.7%) were women. Of all participants, 764 (60.8%) were nurses, and 493 (39.2%) were physicians; 760 (60.5%) worked in hospitals in Wuhan, and 522 (41.5%) were frontline health care workers. A considerable proportion of participants reported symptoms of depression (634 [50.4%]), anxiety (560 [44.6%]), insomnia (427 [34.0%]), and distress (899 [71.5%]). Nurses, women, frontline health care workers, and those working in Wuhan, China, reported more severe degrees of all measurements of mental health symptoms than other health care workers (eg, median [IQR] Patient Health Questionnaire scores among physicians vs nurses: 4.0 [1.0-7.0] vs 5.0 [2.0-8.0]; P = .007; median [interquartile range {IQR}] Generalized Anxiety Disorder scale scores among men vs women: 2.0 [0-6.0] vs 4.0 [1.0-7.0]; P < .001; median [IQR] Insomnia Severity Index scores among frontline vs second-line workers: 6.0 [2.0-11.0] vs 4.0 [1.0-8.0]; P < .001; median [IQR] Impact of Event Scale–Revised scores among those in Wuhan vs those in Hubei outside Wuhan and those outside Hubei: 21.0 [8.5-34.5] vs 18.0 [6.0-28.0] in Hubei outside Wuhan and 15.0 [4.0-26.0] outside Hubei; P < .001). Multivariable logistic regression analysis showed participants from outside Hubei province were associated with lower risk of experiencing symptoms of distress compared with those in Wuhan (odds ratio [OR], 0.62; 95% CI, 0.43-0.88; P = .008). Frontline health care workers engaged in direct diagnosis, treatment, and care of patients with COVID-19 were associated with a higher risk of symptoms of depression (OR, 1.52; 95% CI, 1.11-2.09; P = .01), anxiety (OR, 1.57; 95% CI, 1.22-2.02; P < .001), insomnia (OR, 2.97; 95% CI, 1.92-4.60; P < .001), and distress (OR, 1.60; 95% CI, 1.25-2.04; P < .001). CONCLUSIONS AND RELEVANCE: In this survey of heath care workers in hospitals equipped with fever clinics or wards for patients with COVID-19 in Wuhan and other regions in China, participants reported experiencing psychological burden, especially nurses, women, those in Wuhan, and frontline health care workers directly engaged in the diagnosis, treatment, and care for patients with COVID-19.

negative: Estimation of Infection Rate and Prediction of Initial Infected Individuals of COVID-19 We consider the pandemic spreading of COVID-19 for some selected countries after the outbreak of the coronavirus in Wuhan City, China. We estimated the infection rate and the initial infected individuals of COVID-19 by using the officially reported data at the early stage of the epidemic for the susceptible (S), infectable (I), quarantined (Q), and the cofirmed recovered (Rk) population model, so called SIQRk model. In the reported data we know the quarantined cases and the recovered cases. We can not know the recovered cases from the asymptomatic cases. In the SIQRk model we can estimated the model parameters and the initial infecting cases (confirmed ans asymtomatic cases) from the data fits. We obtained the infection rate in the range between 0.233 and 0.462, the basic reproduction number Ro in the range between 1.8 and 3.5, and the initial number of infected individuals in the range betwee 10 and 8409 for some selected countries. By using fitting parameters we estimated the maximum time of the infection for Germany when the government are performing the quarantine policy. The disease is undergoing to the calm state about six months after first patients were identified.

negative: Perinatal Considerations in the Hospital Disaster Management Process ABSTRACT Nurses play a vital role in providing care to mothers and infants during a disaster, yet few are fully prepared for the challenges they will encounter under extreme conditions. The ability to provide the best possible care for families begins with understanding the perinatal issues in relation to each phase of the disaster management process. This article reviews the hospital and perinatal nursing role in the mitigation, preparedness, response, and recovery phases of disaster management.

negative: A novel coronavirus (2019-nCoV) causing pneumonia-associated respiratory syndrome

negative: Clinical and High-Resolution CT Features of the COVID-19 Infection: Comparison of the Initial and Follow-up Changes OBJECTIVES: In late December 2019, an outbreak of coronavirus disease (COVID-19) in Wuhan, China was caused by a novel coronavirus, newly named severe acute respiratory syndrome coronavirus 2. We aimed to quantify the severity of COVID-19 infection on high-resolution chest computed tomography (CT) and to determine its relationship with clinical parameters. MATERIALS AND METHODS: From January 11, 2020, to February 5, 2020, the clinical, laboratory, and high-resolution CT features of 42 patients (26-75 years, 25 males) with COVID-19 were analyzed. The initial and follow-up CT, obtained a mean of 4.5 days and 11.6 days from the illness onset were retrospectively assessed for the severity and progression of pneumonia. Correlations among clinical parameters, initial CT features, and progression of opacifications were evaluated with Spearman correlation and linear regression analysis. RESULTS: Thirty-five patients (83%) exhibited a progressive process according to CT features during the early stage from onset. Follow-up CT findings showed progressive opacifications, consolidation, interstitial thickening, fibrous strips, and air bronchograms, compared with initial CT (all P < 0.05). Before regular treatments, there was a moderate correlation between the days from onset and sum score of opacifications (R = 0.68, P < 0.01). The C-reactive protein, erythrocyte sedimentation rate, and lactate dehydrogenase showed significantly positive correlation with the severity of pneumonia assessed on initial CT (Rrange, 0.36-0.75; P < 0.05). The highest temperature and the severity of opacifications assessed on initial CT were significantly related to the progression of opacifications on follow-up CT (P = 0.001-0.04). CONCLUSIONS: Patients with the COVID-19 infection usually presented with typical ground glass opacities and other CT features, which showed significant correlations with some clinical and laboratory measurements. Follow-up CT images often demonstrated progressions during the early stage from illness onset.

negative: Systematic literature review on novel corona virus SARS-CoV-2: a threat to human era Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the seventh-generation coronavirus family causing viral pandemic coronavirus disease (COVID-19) across globe affecting millions of people. The objectives of this study are to (1) identify the major research themes in COVID-19 literature, (2) determine the origin, symptoms and modes of transmission of COVID, (3) recommend the intervention and mitigation strategies adopted by the Governments globally against the spread of COVID-19 and the traumatization among the public? and (4) study the possible drugs/treatment plans against COVID-19. A systematic literature review and comprehensive analysis of 38 research articles on COVID-19 are conducted. An integrated Research focus parallel-ship network and keyword co-occurrence analysis are carried out to visualize the three research concepts in COVID-19 literature. Some of our observations include: (1) as SARS-CoV-2’s RNA matches ~ 96% to SARS-CoV, it is assumed to be transmitted from the bats. (2) The common symptoms are high fever, dry cough, fatigue, sputum production, shortness of breath, diarrhoea etc. (3) A lockdown across 180 affected counties for more than a month with social-distancing and the precautions taken in SARS and MERS are recommended by the Governments. (4) Researchers’ claim that nutrition and immunity enhancers and treatment plans such as arbidol, lopinavir/ritonavir, convalescent plasma and mesenchymal stem cells and drugs including remdesivir, hydroxychloroquine, azithromycin and favipiravir are effective against COVID-19. This complied report serves as guide to help the administrators, researchers and the medical officers to adopt recommended intervention strategies and the optimal treatment/drug against COVID-19. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13337-020-00604-z) contains supplementary material, which is available to authorized users.

negative: COVID-19 and biologics for psoriasis: a high-epidemic area experience - Bergamo, Lombardy, Italy

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

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

negative: Integrated infection control strategy to minimize nosocomial infection of coronavirus disease 2019 among ENT healthcare workers

negative: The Importance of Diagnostic Testing during a Viral Pandemic: Early Lessons from Novel Coronavirus Disease (COVID-19) The Importance of Diagnostic Testing during a Viral Pandemic: Early Lessons from Novel Coronavirus Disease (COVID-19).

negative: Controversies about COVID-19 and anticancer treatment with immune checkpoint inhibitors

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 artificial intelligence-based first-line defence against COVID-19: digitally screening citizens for risks via a chatbot To combat the pandemic of the coronavirus disease (COVID-19), numerous governments have established phone hotlines to prescreen potential cases. These hotlines have struggled with the volume of callers, leading to wait times of hours or, even, an inability to contact health authorities. Symptoma is a symptom-to-disease digital health assistant that can differentiate more than 20,000 diseases with an accuracy of more than 90%. We tested the accuracy of Symptoma to identify COVID-19 using a set of diverse clinical cases combined with case reports of COVID-19. We showed that Symptoma can accurately distinguish COVID-19 in 96.32% of clinical cases. When considering only COVID-19 symptoms and risk factors, Symptoma identified 100% of those infected when presented with only three signs. Lastly, we showed that Symptoma’s accuracy far exceeds that of simple “yes-no” questionnaires widely available online. In summary, Symptoma provides unparalleled accuracy in systematically identifying cases of COVID-19 while also considering over 20,000 other diseases. Furthermore, Symptoma allows free text input, furthered with disease-specific follow up questions, in 36 languages. Combined, these results and accessibility give Symptoma the potential to be a key tool in the global fight against COVID-19. The Symptoma predictor is freely available online at https://www.symptoma.com.

negative: Clinical education of ethicists: the role of a clinical ethics fellowship BACKGROUND: Although clinical ethicists are becoming more prevalent in healthcare settings, their required training and education have not been clearly delineated. Most agree that training and education are important, but their nature and delivery remain topics of debate. One option is through completion of a clinical ethics fellowship. METHOD: In this paper, the first four fellows to complete a newly developed fellowship program discuss their experiences. They describe the goals, structure, participants and activities of the fellowship. They identify key elements for succeeding as a clinical ethicist and sustaining a clinical ethics program. They critically reflect upon the challenges faced in the program. RESULTS: The one-year fellowship provided real-time clinical opportunities that helped them to develop the necessary knowledge and skills, gain insight into the role and scope of practice of clinical ethicists and hone valuable character traits. CONCLUSION: The fellowship enabled each of the fellows to assume confidently and competently a position as a clinical ethicist upon completion.

negative: Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease BACKGROUND: Since early December 2019, the 2019 novel coronavirus disease (COVID-19) has caused pneumonia epidemic in Wuhan, Hubei province of China. This study aims to investigate the factors affecting the progression of pneumonia in COVID-19 patients. Associated results will be used to evaluate the prognosis and to find the optimal treatment regimens for COVID-19 pneumonia. METHODS: Patients tested positive for the COVID-19 based on nucleic acid detection were included in this study. Patients were admitted to 3 tertiary hospitals in Wuhan between December 30, 2019, and January 15, 2020. Individual data, laboratory indices, imaging characteristics, and clinical data were collected, and statistical analysis was performed. Based on clinical typing results, the patients were divided into a progression group or an improvement/stabilization group. Continuous variables were analyzed using independent samples t-test or Mann-Whitney U test. Categorical variables were analyzed using Chi-squared test or Fisher's exact test. Logistic regression analysis was performed to explore the risk factors for disease progression. RESULTS: Seventy-eight patients with COVID-19-induced pneumonia met the inclusion criteria and were included in this study. Efficacy evaluation at 2 weeks after hospitalization indicated that 11 patients (14.1%) had deteriorated, and 67 patients (85.9%) had improved/stabilized. The patients in the progression group were significantly older than those in the disease improvement/stabilization group (66 [51, 70] vs. 37 [32, 41] years, U = 4.932, P = 0.001). The progression group had a significantly higher proportion of patients with a history of smoking than the improvement/stabilization group (27.3% vs. 3.0%, χ(2) = 9.291, P = 0.018). For all the 78 patients, fever was the most common initial symptom, and the maximum body temperature at admission was significantly higher in the progression group than in the improvement/stabilization group (38.2 [37.8, 38.6] vs. 37.5 [37.0, 38.4]°C, U = 2.057, P = 0.027). Moreover, the proportion of patients with respiratory failure (54.5% vs. 20.9%, χ(2) = 5.611, P = 0.028) and respiratory rate (34 [18, 48] vs. 24 [16, 60] breaths/min, U = 4.030, P = 0.004) were significantly higher in the progression group than in the improvement/stabilization group. C-reactive protein was significantly elevated in the progression group compared to the improvement/stabilization group (38.9 [14.3, 64.8] vs. 10.6 [1.9, 33.1] mg/L, U = 1.315, P = 0.024). Albumin was significantly lower in the progression group than in the improvement/stabilization group (36.62 ± 6.60 vs. 41.27 ± 4.55 g/L, U = 2.843, P = 0.006). Patients in the progression group were more likely to receive high-level respiratory support than in the improvement/stabilization group (χ(2) = 16.01, P = 0.001). Multivariate logistic analysis indicated that age (odds ratio [OR], 8.546; 95% confidence interval [CI]: 1.628–44.864; P = 0.011), history of smoking (OR, 14.285; 95% CI: 1.577–25.000; P = 0.018), maximum body temperature at admission (OR, 8.999; 95% CI: 1.036–78.147, P = 0.046), respiratory failure (OR, 8.772, 95% CI: 1.942–40.000; P = 0.016), albumin (OR, 7.353, 95% CI: 1.098–50.000; P = 0.003), and C-reactive protein (OR, 10.530; 95% CI: 1.224−34.701, P = 0.028) were risk factors for disease progression. CONCLUSIONS: Several factors that led to the progression of COVID-19 pneumonia were identified, including age, history of smoking, maximum body temperature at admission, respiratory failure, albumin, C-reactive protein. These results can be used to further enhance the ability of management of COVID-19 pneumonia.

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

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

negative: Cytokine storm intervention in the early stages of COVID-19 pneumonia Abstract Clinical intervention in patients with corona virus disease 2019 (COVID-19) has demonstrated a strong upregulation of cytokine production in patients who are critically ill with SARS-CoV2-induced pneumonia. In a retrospective study of 41 patients with COVID-19, most patients with SARS-CoV-2 infection developed mild symptoms, whereas some patients later developed aggravated disease symptoms, and eventually passed away because of multiple organ dysfunction syndrome (MODS), as a consequence of a severe cytokine storm. Guidelines for the diagnosis and treatment of SARS-CoV-2 infected pneumonia were first published January 30th, 2020; these guidelines recommended for the first time that cytokine monitoring should be applied in severely ill patients to reduce pneumonia related mortality. The cytokine storm observed in COVID-19 illness is also an important component of mortality in other viral diseases, including SARS, MERS and influenza. In view of the severe morbidity and mortality of COVID-19 pneumonia, we review the current understanding of treatment of human coronavirus infections from the perspective of a dysregulated cytokine and immune response.

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: Characteristic ECG Manifestations in Patients with COVID-19 Abstract Cardiac involvement has been reported in patients with COVID-19, which may be reflected by ECG changes. Two COVID-19 cases in our report exhibited different ECG manifestations as the disease caused deterioration. The first case presented temporary SIQIIITIII morphology followed by reversible nearly complete atrioventricular block, while the second demonstrated ST segment elevation accompanied by multifocal ventricular tachycardia. The underlying mechanisms of these electrocardiographic abnormalities in the severe stage of COVID-19 may be attributed to hypoxia and inflammatory damage incurred by the virus.

negative: A Health System Response to COVID‐19 in Long‐Term Care and Post‐Acute Care: A Three‐Phase Approach BACKGROUND: The Seattle, WA, area was ground zero for coronavirus disease 2019 (COVID‐19). Its initial emergence in a skilled nursing facility (SNF) not only highlighted the vulnerability of its patients and residents, but also the limited clinical support that led to national headlines. Furthermore, the coronavirus pandemic heightened the need for improved collaboration among healthcare organizations and local and state public health. METHODS: The University of Washington Medicine's (UWM's) Post‐Acute Care (PAC) Network developed and implemented a three‐phase approach within its pre‐existing network of SNFs to help slow the spread of the disease, support local area SNFs from becoming overwhelmed when inundated with COVID‐19 cases or persons under investigation, and help decrease the burden on area hospitals, clinics, and emergency medical services. RESULTS: Support of local area SNFs consisted of the following phases that were implemented at various times as COVID‐19 impacted each facility at different times. Initial Phase: This phase was designed to (1) optimize communication, (2) review infection control practices, and (3) create a centralized process to track and test the target population. Delayed Phase: The goals of the Delayed Phase were to slow the spread of the disease once it is present in the SNF by providing consistent education and reinforcing infection prevention and control practices to all staff. Surge Phase: This phase aimed to prepare facilities in response to an outbreak by deploying a "Drop Team" within 24 hours to the facility to expeditiously test patients and exposed employees, triage symptomatic patients, and coordinate care and supplies with local public health authorities. CONCLUSIONS: The COVID‐19 Three‐Phase Response Plan provides a standardized model of care that may be implemented by other health systems and SNFs to help prepare and respond to COVID‐19.

negative: Novel Coronavirus Pneumonia Outbreak in 2019: Computed Tomographic Findings in Two Cases Since the 2019 novel coronavirus (2019-nCoV or officially named by the World Health Organization as COVID-19) outbreak in Wuhan, Hubei Province, China in 2019, there have been a few reports of its imaging findings. Here, we report two confirmed cases of 2019-nCoV pneumonia with chest computed tomography findings of multiple regions of patchy consolidation and ground-glass opacities in both lungs. These findings were characteristically located along the bronchial bundle or subpleural lungs.

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

negative: PNEUMONIA | Atypical ‘Atypical pneumonia’ refers to a clinical syndrome associated with pneumonia (typically mild, nonlobar) and diverse upper respiratory tract and extrapulmonary manifestations. Clinical features overlap with bacterial pneumonia, and co-infection with both typical (e.g., Streptococcus pneumoniae or other bacteria) and atypical pathogens may occur. ‘Atypical’ pathogens include Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella spp. In large epidemiological studies, Mycoplasma pneumoniae has been implicated in 2–18% of community-acquired pneumonias; Chlamydia pneumoniae, in 2–8%; Legionella sp., 1–4%. Atypical pathogens lack cell walls and are resistant to β-lactam antibiotics but are usually susceptible to tetracyclines, macrolides, ketolides, and fluoroquinolone antibiotics. In this article, we also review other unusual causes of pneumonia which are transmitted by insects or vectors (e.g., Rocky Mountain spotted fever, cat scratch fever, Q fever, ehrlichiosis, Lyme disease, and tularemia). These diverse organisms are not found on Gram stain, and diagnosis requires special culture techniques or serological assays. We review the salient clinical and laboratory features of these various disorders, and discuss diagnostic and therapeutic strategies.

negative: Diagnostic delays in 537 symptomatic cases of Middle East respiratory syndrome coronavirus infection in Saudi Arabia Abstract Background Although the literature indicates that patient delays in seeking medical support for Middle East respiratory syndrome coronavirus (MERS-CoV) infections are associated with poor clinical outcomes, delays in the diagnosis itself remain poorly understood in these patients. This study aimed to determine the median time interval from symptom onset to a confirmed diagnosis and to identify the potential predictors of this interval in Saudi Arabian MERS patients. Methods This was a retrospective study of patients with confirmed MERS who were publicly reported by the World Health Organization (WHO). Results Five hundred and thirty-seven symptomatic cases of MERS-CoV infection were included. The median time interval between symptom onset and confirmation of the MERS diagnosis was 4 days (interquartile range 2–7 days), ranging from 0 to 36 days. According to the negative binomial model, the unadjusted rate ratio (RR) of delays in the diagnosis was significantly higher in older patients (>65 years) (RR 1.42), non-healthcare workers (RR 1.74), patients with severe illness (RR 1.22), those with an unknown source of infection (RR 1.84), and those who had been in close contact with camels (RR 1.74). After accounting for confounders, the adjusted rate ratio (aRR) of delays in the diagnosis was independently associated with unknown source of infection (aRR 1.68) and close contact with camels (aRR 1.58). Conclusions The time interval from symptom onset to diagnosis was greater in older patients, non-healthcare workers, patients with severe illness, patients with an unknown source of infection, and patients who had been in close contact with camels. The findings warrant educational interventions to raise general public awareness of the importance of early symptom notification.

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: Recomendaciones sobre el manejo clínico de la infección por el «nuevo coronavirus¼ SARS-CoV2. Grupo de trabajo de la Asociación Española de Pediatría (AEP)./ [Recommendations on the clinical management of the COVID-19 infection by the «new coronavirus¼ SARS-CoV2. Spanish Paediatric Association working group] 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 coronavirus¼, 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: 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: 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.

negative: Early experience with COVID-19 in kidney transplantation recipients: update and review. INTRODUCTION little is known on the risk factors, clinical presentation, therapeutic protocols, and outcomes of kidney transplantation recipients (KTRs) who become infected by SARS-CoV-2. PURPOSE to provide an updated view regarding the early experience obtained from the management of KTRs with COVID-19. MATERIALS AND METHODS A narrative review was conducted using PubMed database to identify relevant articles written in English/Spanish, and published through May 15, 2020. Search terms included: "coronavirus", "severe acute respiratory syndrome coronavirus 2", "SARS-CoV-2", "COVID-19", "COVID", "renal transplantation", and "kidney transplantation". Case series were considered eligible, and case reports excluded. Thirty-four articles were included in the review. RESULTS KTRs should be considered immunocompromised hosts: potential risk for infection, non-negligible comorbidity, and exposure to long-term immunosuppression. Only single center small retrospective experiences are still available regarding KTRs with COVID-19. SARS-CoV-2 symptoms in KTRs are similar to that observed for the general population, being fever and cough the most frequently observed. Mild-to-moderate symptomatic KTRs can be managed in an outpatient setting, while patients exhibiting severe symptoms must be addmited to hospital. More rapid clinical progression, and higher complication and death rates have been observed for hospitalized KTRs, requiring hemodyalisis or ventilatory support. Lymphopenia, elevated serum markers (C-reactive protein, procalcitonin, IL-6, D-dimer), and chest-X-ray findings consistent with pneumonia are linked to worse prognosis. A number of antiviral therapies have been used. However, it is difficult to draw meaningful conclusions regarding their efficacy at this point. Baseline immunosupression regimen should be adjusted in a case-by-case manner. However, it poses a significant challenge.

negative: Infection with SARS-CoV-2 causes abnormal laboratory results of multiple organs in patients Aim: To evaluate the clinical value of abnormal laboratory results of multiple organs in patients with coronavirus disease 2019 (COVID-2019) and to help clinicians perform correct treatment. Results: Elevated neutrophil-to-LYM ratio (NLR), D-dimer(D-D), interleukin (IL)-6, IL-10, IL-2, interferon-Y, and age were significantly associated with the severity of illness. However, significant and sustained decreases were observed in the LYM subset (p<0.05). D-D, T cell counts, and cytokine levels in severe COVID-19 patients who survived the disease gradually recovered at later time points to levels that were comparable to those of mild cases. Second, D-D increased from 0.5 to 8, and the risk ratio increased from 2.75 to 55, eventually leading to disseminated intravascular coagulation. Moreover, the acute renal function damage occurred earlier than abnormal heart and liver functions (p<0.05). Conclusions: The degrees of lymphopenia and proinflammatory cytokine storm were higher in severe COVID-19 patients than in mild cases. The degree was associated with the disease severity. Advanced age, NLR, D-D, and cytokine levels may serve as useful prognostic factors for the early identification of severe COVID-19 cases. Methods: Peripheral blood samples were collected from 93 confirmed COVID-19 patients. The samples were examined for lymphocyte (LYM) subsets by flow cytometry and cytokine profiles by specific immunoassays. The receiver operating characteristic curve was applied to determine the best diagnostic thresholds for laboratory results, and principal component analysis was used to screen the major risk factors. The prognostic values were assessed using the Kaplan–Meier curve and univariate and multivariate COX regression models.

negative: Post-exposure prophylaxis or pre-emptive therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): study protocol for a pragmatic randomized-controlled trial BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 causing the coronavirus disease (COVID-19) pandemic. Currently, there is a lack of evidence-based therapies to prevent COVID-19 following exposure to the virus, or to prevent worsening of symptoms following confirmed infection. We describe the design of a clinical trial of hydroxychloroquine for post-exposure prophylaxis (PEP) and pre-emptive therapy (PET) for COVID-19. METHODS: We will conduct two nested multicentre international double-blind randomized placebo-controlled clinical trials of hydroxychloroquine for: 1) PEP of asymptomatic household contacts or healthcare workers exposed to COVID-19 within the past four days, and 2) PET for symptomatic outpatients with COVID-19 showing symptoms for less than four days. We will recruit 1,500 patients each for the PEP and PET trials. Participants will be randomized 1:1 to receive five days of hydroxychloroquine or placebo. The primary PEP trial outcome will be the incidence of symptomatic COVID-19. The primary PET trial outcome will be an ordinal scale of disease severity (not hospitalized, hospitalized without intensive care, hospitalization with intensive care, or death). Participant screening, informed consent, and follow-up will be exclusively internet-based with appropriate regulatory and research ethics board approvals in Canada and the United States. DISCUSSION: These complementary randomized-controlled trials are innovatively designed and adequately powered to rapidly answer urgent questions regarding the effectiveness of hydroxychloroquine to reduce virus transmission and disease severity of COVID-19 during a pandemic. In-person participant follow-up will not be conducted to facilitate social distancing strategies and reduce risks of exposure to study personnel. Innovative trial approaches are needed to urgently assess therapeutic options to mitigate the global impact of this pandemic. TRIALS REGISTRATION: clinicaltrials.gov (NCT04308668); registered 16 March, 2020.

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

negative: Chapter 7 Pathogenesis of Virus Infections Abstract Pathogenesis encompasses all the sequence of events accompanying acute and persistent infections. It includes entry of the virus into the body, multiplication and spread, the development of tissue damage, and the production of an immune response; the latter may contribute to the pathology of an infection. It includes the appearance of clinical signs and symptoms, the eventual resolution of the infection and, in most cases, virus elimination. Understanding viral disease pathogenesis requires knowledge of each of the stages of infection and an awareness of the underlying mechanisms. There may be variation from individual to individual in the severity and/or the duration of these events, but a sound working knowledge of a typical sequence associated with each infection is crucial in both making an accurate diagnosis and recommending the appropriate treatment.

negative: Acute Rhinosinusitis in Children Acute rhinosinusitis in children is a common disorder that is characterized by some or all of the following symptoms: fever, rhinorrhea, nasal congestion, cough, postnasal drainage, and facial pain/headache. It often starts as an upper respiratory tract infection that is complicated by a bacterial infection in which the symptoms worsen, persist, or are particularly severe. The accurate diagnosis of acute rhinosinusitis is challenging because of the overlap of symptoms with other common diseases, heavy reliance on subjective reporting of symptoms by the parents, and difficulties related to the physical examination of the child. Antibiotics are the mainstay of treatment. There is no strong evidence for the use of ancillary therapy. Orbital and intracranial complications may occur and are best treated early and aggressively. This article reviews the diagnosis, pathophysiology, bacteriology, treatment, and complications of acute rhinosinusitis in children.

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: Application and optimization of RT-PCR in diagnosis of SARS-CoV-2 infection Background: Coronavirus Disease 2019 (COVID-19) caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global threat to public health. Aiming to construct an efficient screening pattern, we comprehensively evaluated the performances of RT-PCR and chest CT in diagnosing COVID-19. Methods: The records including demographics, RT-PCR, and CT from 87 confirmed COVID-19 cases and 481 exclusion cases were collected. The diagnostic accuracy of the pharyngeal swab RT-PCR, CT, combination with the second pharyngeal swab RT-PCR or with CT were evaluated individually. Besides, all the stool RT-PCR results were plotted by time to explore the value of stool RT-PCR. Findings: Combination of RT-PCR and CT has the higher sensitivity (91.9%,79/86) than RT-PCR alone (78.2%，68/87) or CT alone (66.7%, 54 of 81) or combination of two RT-PCR tests (86.2%,75/87). There was good agreement between RT-PCR and CT (kappa-value, 0.430). In 34 COVID-19 cases with inconsistent results, 94.1% (n=32) are mild infection, 62.5% of which (20/32) showed positive RT-PCR. 46.7% (35/75) COVID-19 patients had at least one positive stool during the course. Two cases had positive stool earlier than the pharyngeal swabs. Importantly, one patient had consecutive positive stool but negative pharyngeal swabs. Interpretation: Combination of RT-PCR and CT with the highest sensitivity is an optimal pattern to screen COVID-19. RT-PCR is superior to CT in diagnosing mild infections. Stool RT-PCR should be considered as an item for improving discovery rate and hospital discharge. This study shed light for optimizing scheme of screening and monitoring of SARS-CoV-2 infection.

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: Ultra-High-Resolution CT Follow-Up in Patients with Imported Early-Stage Coronavirus Disease 2019 (COVID-19) Related Pneumonia Background: An ongoing outbreak of mystery pneumonia in Wuhan was caused by coronavirus disease 2019 (COVID-19). The infectious disease has spread globally and become a major threat to public health. Purpose: We aim to investigate the ultra-high-resolution CT (UHR-CT) findings of imported COVID-19 related pneumonia from the initial diagnosis to early-phase follow-up. Methods: This retrospective study included confirmed cases with early-stage COVID-19 related pneumonia imported from the epicenter. Initial and early-phase follow-up UHR-CT scans (within 5 days) were reviewed for characterizing the radiological findings. The normalized total volumes of ground-glass opacities (GGOs) and consolidations were calculated and compared during the radiological follow-up by artificial-intelligence-based methods. Results: Eleven patients (3 males and 8 females, aged 32-74 years) with confirmed COVID-19 were evaluated. Subpleural GGOs with inter/intralobular septal thickening were typical imaging findings. Other diagnostic CT features included distinct margins (8/11, 73%), pleural retraction or thickening (7/11, 64%), intralesional vasodilatation (6/11, 55%). Normalized volumes of pulmonary GGOs (p=0.003) and consolidations (p=0.003) significantly increased during the CT follow-up. Conclusions: The abnormalities of GGOs with peripleural distribution, consolidated areas, septal thickening, pleural involvement and intralesional vasodilatation on UHR-CT indicate the diagnosis of COVID-19. COVID-19 cases could manifest significantly progressed GGOs and consolidations with increased volume during the early-phase CT follow-up.

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: Immune phenotyping based on neutrophil-to-lymphocyte ratio and IgG predicts disease severity and outcome for patients with COVID-19 Background: A recently emerging respiratory disease named coronavirus disease 2019 (COVID-19) has quickly spread across the world. This disease is initiated by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and uncontrolled cytokine storm, but it remains unknown as to whether a robust antibody response is related to clinical deterioration and poor outcome in laboratory-confirmed COVID-19 patients. Methods: Anti-SARS-CoV-2 IgG and IgM antibodies were determined by chemiluminescence analysis (CLIA) in COVID-19 patients from a single center in Wuhan. Median IgG and IgM levels in acute and convalescent-phase sera (within 35 days) for all included patients were calculated and compared among severe and nonsevere patients. Immune response phenotyping based on late IgG levels and neutrophil-to-lymphocyte ratio (NLR) was characterized to stratify patients with different disease severities and outcome. Laboratory parameters in patients with different immune response phenotypes and disease severities were analyzed. Findings: A total of 222 patients were included in this study. IgG was first detected on day 4 of illness, and its peak levels occurred in the fourth week. Severe cases were more frequently found in patients with high IgG levels, compared to those who with low IgG levels (51.8% versus 32.3%; p=0.008). Severity rates for patients with NLRhiIgGhi, NLRhiIgGlo, NLRloIgGhi, and NLRloIgGlo phenotype was 72.3%, 48.5%, 33.3%, and 15.6%, respectively (p<0.0001). Furthermore, severe patients with NLRhiIgGhi, NLRhiIgGlo had higher proinflammatory cytokines levels including IL-2, IL-6 and IL-10, and decreased CD4+ T cell count compared to those with NLRloIgGlo phenotype (p<0.05). Recovery rate for severe patients with NLRhiIgGhi, NLRhiIgGlo, NLRloIgGhi, and NLRloIgGlo phenotype was 58.8% (20/34), 68.8% (11/16), 80.0% (4/5), and 100% (12/12), respectively (p=0.0592). Dead cases only occurred in NLRhiIgGhi and NLRhiIgGlo phenotypes. Interpretation: COVID-19 severity is associated with increased IgG response, and an immune response phenotyping based on late IgG response and NLR could act as a simple complementary tool to discriminate between severe and nonsevere COVID-19 patients, and further predict their clinical outcome.

negative: Isolation and contact tracing can tip the scale to containment of COVID-19 in populations with social distancing Background: Novel coronavirus (SARS-CoV-2) has extended its range of transmission in all parts of the world, with substantial variation in rates of transmission and severity of associated disease. Many countries have implemented social distancing as a measure to control further spread. Methods: We evaluate whether and under which conditions containment or slowing down COVID-19 epidemics are possible by isolation and contact tracing in settings with various levels of social distancing. We use a stochastic transmission model in which every person generates novel infections according to a probability distribution that is affected by the incubation period distribution (time from infection to symptoms), distribution of the latent period (time from infection to onset of infectiousness), and overall transmissibility. The model distinguishes between close contacts (e.g., within a household) and other contacts in the population. Social distancing affects the number of contacts outside but not within the household. Findings: The proportion of asymptomatic or unascertained cases has a strong impact on the controllability of the disease. If the proportion of asymptomatic infections is larger than 30%, contact tracing and isolation cannot achieve containment for an R0 of 2.5. Achieving containment by social distancing requires a reduction of numbers of non-household contacts by around 90%. Depending on the realized level of contact reduction, tracing and isolation of only household contacts, or of household and non-household contacts are necessary to reduce the effective reproduction number to below 1. A combination of social distancing with isolation and contact tracing leads to synergistic effects that increase the prospect of containment. Interpretation: Isolation and contact tracing can be an effective means to slow down epidemics, but only if the majority of cases are ascertained. In a situation with social distancing, contact tracing can act synergistically and tip the scale towards containment, and can therefore be a tool for controlling COVID-19 epidemics as part of an exit strategy from current lockdown measures.

negative: Two X-linked agammaglobulinemia patients develop pneumonia as COVID-19 manifestation but recover BACKGROUND: The recent SARS-CoV-2 pandemic, which has recently affected Italy since February 21, constitutes a threat to normal subjects, as the coronavirus disease-19 (COVID-19) can manifest with a broad spectrum of clinical phenotypes ranging from asymptomatic cases to pneumonia or even death. There is evidence that older age and several comorbidities can affect the risk to develop severe pneumonia and possibly the need of mechanic ventilation in subjects infected with SARS-CoV-2. Therefore, we evaluated the outcome of SARS-CoV-2 infection in patients with inborn errors of immunity (IEI) such as X-linked agammaglobulinemia (XLA). METHODS: When the SARS-CoV-2 epidemic has reached Italy, we have activated a surveillance protocol of patients with IEI, to perform SARS-CoV-2 search by nasopharyngeal swab in patients presenting with symptoms that could be a manifestation of COVID-19, such as fever, cough, diarrhea, or vomiting. RESULTS: We describe two patients with X-linked agammaglobulinemia (XLA) aged 34 and 26 years with complete absence of B cells from peripheral blood who developed COVID-19, as diagnosed by SARS-CoV-2 detection by nasopharyngeal swab, while receiving immunoglobulin infusions. Both patients developed interstitial pneumonia characterized by fever, cough, and anorexia and associated with elevation of CRP and ferritin, but have never required oxygen ventilation or intensive care. CONCLUSION: Our report suggests that XLA patients might present with high risk to develop pneumonia after SARS-CoV-2 infection, but can recover from infection, suggesting that B-cell response might be important, but is not strictly required to overcome the disease. However, there is a need for larger observational studies to extend these conclusions to other patients with similar genetic immune defects.

negative: The management of coronavirus disease 2019 (COVID‐19) In December 2019, a novel coronavirus causing severe acute respiratory disease occurred in Wuhan, China. It is an emerging infectious disease with widespread and rapid infectiousness. The World Health Organization declared the coronavirus outbreak to be a public health emergency of international concern on 31 January 2020. Severe COVID‐19 patients should be managed and treated in a critical care unit. Performing a chest X‐ray/CT can judge the severity of the disease. The management of COVID‐19 patients includes epidemiological risk and patient isolation; treatment entails general supportive care, respiratory support, symptomatic treatment, nutritional support, psychological intervention, etc. The prognosis of the patients depends upon the severity of the disease, the patient's age, the underlying diseases of the patients, and the patient's overall medical condition. The management of COVID‐19 should focus on early diagnosis, immediate isolation, general and optimized supportive care, and infection prevention and control.

negative: Epidemiological Investigation of the Outbreak of Acute Respiratory Infection caused by Adenovirus Type B55 in a Physical Education School in 2017 BACKGROUND: On May 19, 2017, the cluster of 6 acute respiratory infections due to adenovirus in the swimming department of a physical education school (School J) was reported to Korea Centers for Disease Control and Prevention. An epidemiological investigation was conducted to identify the transmission route of the infection and to control the outbreak. MATERIALS AND METHODS: A retrospective cohort study (Study 1) was conducted on students and teachers of the athletic departments using the swimming pool, and a prospective surveillance (Study 2) was conducted on all students and teachers of the School J. A case was defined as any student and school personnel who developed more than two of the following symptoms from April 10 to July 2, 2017: fever, sore throat, cough, rhinorrhea, or headache. Relative risks (RRs) were calculated to compare the attack rates according to potential risk factors. Multivariable logistic regression was performed to identify the risk factors for infection in the outbreak. RESULTS: 47 cases were identified: 33 (55.9%) cases occurred among 59 students and teachers in Study 1 and 14 (3.9%) among 362 students and school personnel in Study 2. There were 18 laboratory confirmed adenovirus infection cases. The common symptoms were headache (71.7%), fever (69.6%), rhinorrhea (63.0%), sputum (56.5%), and sore throat (54.3%). 23.9% of the cases were accompanied with diarrhea and 19.6% with eye congestion. None of the cases developed pneumonia. 32.6% of the cases were hospitalized. In Study 1, attack rate in the swimming department was higher than that in others (RR: 1.90; 95% confidence interval [CI]: 1.01-3.60). In Study 2, being a member of the shooting department (RR: 20.70; 95% CI: 4.90-87.47) and being a first year high school student (RR: 10.95; 95% CI: 2.90-41.33) were identified as risk factors for the infections. Genetic analyses of the adenoviruses showed 100% identical sequence in homology and confirmed the human adenovirus B55 (HAdV-B55). No adenovirus was detected at examining the water and environment of the swimming pool and dormitory. CONCLUSION: The outbreak is inferred to be occurred via propagated transmission among the students in the same athletic department, while the students with symptoms of respiratory infection continued performing school activities without any restrictions. Infection control measures such as early detection of symptoms of respiratory infection and restriction of group activity are necessary to prevent respiratory infection outbreak in the communal living setting.

negative: Tocilizumab, an anti-IL6 receptor antibody, to treat Covid-19-related respiratory failure: a case report

negative: Medical Management of Hospitalized Patients with Asthma or Chronic Obstructive Pulmonary Disease

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

negative: Importance of respiratory airway management as well as psychological and rehabilitative treatments to COVID-19 patients Abstract The clinical therapy for severe 2019 coronavirus disease (i.e., COVID-19) sufferers is relatively challenging. Herein, the processes involving salvage of a critical COVID-19 patient were retrospectively analyzed. The condition of an obese female critical COVID-19 sufferer progressively worsened in the initial period after admission. According to her symptoms and examination reports, endotracheal intubation and mechanical ventilation were timely conducted and meanwhile high-dose sedatives and analgesics were administrated. In the later therapeutic phase, however, sedative and analgesic dosages were gradually reduced, and psychological and rehabilitative therapies were conducted, concomitantly with enhancement of airway care to facilitate sputum expectoration. Eventually, the endotracheal tube was feasibly removed after intubation for 18 days and subsequently replaced with noninvasive ventilation and a high-flow nasal cannula oxygen therapy. Intensive airway care alongside psychological and rehabilitative therapies can shorten the mechanical ventilation time and improve the prognosis of COVID-19 sufferers.

negative: SOGC Committee Opinion – COVID-19 in Pregnancy

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

negative: Hematological findings in coronavirus disease 2019: indications of progression of disease Coronavirus disease 2019 (COVID-19) is a new human infectious disease. The etiology for this outbreak is a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus far, related research on COVID-19 is still in preliminary stage. This paper summarized the latest outcomes of corresponding study from Chinese centers and clarified the hematopoietic abnormality caused by SARS-CoV-2 and potential mechanism. Lymphopenia was common in the early stage after the onset of COVID-19. A significant decrease was observed in peripheral CD4+ and CD8+ T lymphocytes. As the illness progressed, neutrophilia emerged in several cases, and patients with severe critical pulmonary conditions showed higher neutrophils than common type. Thrombocytopenia was resulting from the consumption and/or the reduced production of platelets in damaged lungs. Anemia was not observed notably, but the decrease in hemoglobin was frequent. The activation of monocyte-macrophage system aggravates the immune damage of lung and other tissues, which leads to the increase of D-dimer, prothrombin time, and platelet consumption.

negative: Enteric involvement of coronaviruses: is faecal–oral transmission of SARS-CoV-2 possible?

negative: Assessment of returning travellers with fever Millions of people travel to the tropics each year and a significant minority of them become ill, either during their stay or shortly after their return. Most have mild, self-limiting illnesses, but a few have a life-threatening condition. This article outlines how to evaluate fever in the returning traveller and discusses important infection control and public health measures. A detailed travel history, which takes into account travel destinations, specific activities and risk factors in relation to the onset of symptoms, is essential for constructing a comprehensive list of differential diagnoses and guiding appropriate investigations. Importantly, all travellers returning from the tropics with a fever should be investigated for malaria.

negative: Pathogens and epidemiologic feature of severe fever with thrombocytopenia syndrome in Hubei province, China Abstract To evaluate the aetiological agents and epidemiologic features of severe fever with thrombocytopenia syndrome (SFTS) in Hubei province, China, sera from patients were collected from January to December 2011. All cases occurred from April to December, and the epidemic peaked from May to August. The ages of patients ranged from 10 to 86 years (median=55years), and the incidence of SFTS increased with age. The female:male ratio of cases was 1.008:1, and 54.6% (77/141) and 1.4% (2/141) of the cases were confirmed by qPCR to be SFTSV and Hantavirus (HV) infection, respectively. No case of simultaneous infection with two or more pathogens was found. The research in this paper showed that some suspected SFTS cases are confused with HV infection due to similar symptoms. The analysis showed that the distribution of SFTSV has a marked regional aggregation in Hubei province.

negative: The clinical and immunological features of pediatric COVID-19 patients in China Abstract In December 2019, the corona virus disease 2019 (COVID-19) caused by novel coronavirus (SARS-CoV-2) emerged in Wuhan, China and rapidly spread worldwide. Few information on clinical features and immunological profile of COVID-19 in paediatrics. The clinical features and treatment outcomes of twelve paediatric patients confirmed as COVID-19 were analyzed. The immunological features of children patients was investigated and compared with twenty adult patients. The median age was 14.5-years (range from 0.64 to 17), and six of the patients were male. The average incubation period was 8 days. Clinically, cough (9/12, 75%) and fever (7/12, 58.3%) were the most common symptoms. Four patients (33.3%) had diarrhea during the disease. As to the immune profile, children had higher amount of total T cell, CD8+ T cell and B cell but lower CRP levels than adults (P < 0.05). Ground-glass opacity (GGO) and local patchy shadowing were the typical radiological findings on chest CT scan. All patients received antiviral and symptomatic treatment and the symptom relieved in 3–4 days after admitted to hospital. The paediatric patients showed mild symptom but with longer incubation period. Children infected with SARS-CoV-2 had different immune profile with higher T cell amount and low inflammatory factors level, which might ascribed to the mild clinical symptom. We advise that nucleic acid test or examination of serum IgM/IgG antibodies against SARS-CoV-2 should be taken for children with exposure history regardless of clinical symptom.

negative: Febrile seizures: an overview BACKGROUND: Febrile seizures are the most common neurologic disorder in childhood. Physicians should be familiar with the proper evaluation and management of this common condition. OBJECTIVE: To provide an update on the current understanding, evaluation, and management of febrile seizures. METHODS: A PubMed search was completed in Clinical Queries using the key terms ‘febrile convulsions’ and ‘febrile seizures’. The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. RESULTS: Febrile seizures, with a peak incidence between 12 and 18 months of age, likely result from a vulnerability of the developing central nervous system to the effects of fever, in combination with an underlying genetic predisposition and environmental factors. The majority of febrile seizures occur within 24 hours of the onset of the fever. Febrile seizures can be simple or complex. Clinical judgment based on variable presentations must direct the diagnostic studies which are usually not necessary in the majority of cases. A lumbar puncture should be considered in children younger than 12 months of age or with suspected meningitis. Children with complex febrile seizures are at risk of subsequent epilepsy. Approximately 30–40% of children with a febrile seizure will have a recurrence during early childhood. The prognosis is favorable as the condition is usually benign and self-limiting. Intervention to stop the seizure often is unnecessary. CONCLUSION: Continuous preventative antiepileptic therapy for the prevention of recurrent febrile seizures is not recommended. The use of intermittent anticonvulsant therapy is not routinely indicated. Antipyretics have no role in the prevention of febrile seizures.

negative: Rethinking antiviral effects for COVID-19 in clinical studies: early initiation is key to successful treatment Development of an effective antiviral drug for COVID-19 is a global health priority. Although several candidate drugs have been identified through in vitro and in vivo models, consistent and compelling evidence for effective drugs from clinical studies is limited. The lack of evidence could be in part due to heterogeneity of virus dynamics among patients and late initiation of treatment. We first quantified the heterogeneity of viral dynamics which could be a confounder in compassionate use programs. Second, we demonstrated that an antiviral drug is unlikely to be effective if initiated after a short period following symptom onset. For accurate evaluation of the efficacy of an antiviral drug for COVID-19, antiviral treatment should be initiated before or soon after symptom onset in randomized clinical trials.

negative: Propagation of program control: A tool for distributed disease surveillance Abstract Purpose The purpose of the study was (1) to identify the requirements for syndromic, disease surveillance and epidemiology systems arising from events such as the SARS outbreak in March 2003, and the deliberate spread of Bacillus anthracis, or anthrax, in the US in 2001; and (2) to use these specifications as input to the construction of a system intended to meet these requirements. An important goal was to provide information about the diffusion of a communicable disease without being dependent on centralised storage of information about individual patients or revealing patient-identifiable information. Methods The method applied is rooted in the engineering paradigm involving phases of analysis, system specification, design, implementation, and testing. The requirements were established from earlier projects’ conclusions and analysis of disease outbreaks. The requirements were validated by a literature study of syndromic and disease surveillance systems. The system was tested on simulated EHR databases generated from microbiology laboratory data. Results A requirements list that a syndromic and disease surveillance system should meet, and an open source system, “The Snow Agent system”, has been developed. The Snow Agent system is a distributed system for monitoring the status of a population's health by distributing processes to, and extracting epidemiological data directly from, the electronic health records (EHR) system in a geographic area. Conclusions Syndromic and disease surveillance tools should be able to operate at all levels in the health systems and across national borders. Such systems should avoid transferring patient identifiable data, support two-way communications and be able to define and incorporate new and unknown diseases and syndrome definitions that should be reported by the system. The initial tests of the Snow Agent system shows that it will easily scale to national level in Norway.

negative: Novel Coronavirus (COVID-19) Knowledge and Perceptions: A Survey of Healthcare Workers Background: During the first week of March, the surge of coronavirus disease 2019 (COVID-19) cases reached over 100 countries with more than 100,000 cases. Healthcare authorities have already initiated awareness and preparedness activities beyond borders. A poor understanding of the disease among healthcare workers (HCWs) may result in delayed treatment and the rapid spread of infection. This study aimed to investigate the knowledge and perceptions of HCWs about COVID-19. Methods: A cross-sectional, web-based study was conducted among HCWs about COVID-19 during the first week of March 2020. A 23-item survey instrument was developed and distributed randomly to HCWs using social media; it required 5 minutes to complete. A chi-square test was used to investigate the level of association among variables at the significance level of p<0.05. Results: Of 529 participants, a total of 453 HCWs completed the survey (response rate: 85.6%); 51.6% were males, 32.1% were aged 25-34 years, and most were doctors (30.2%) and medical students (29.6%). Regarding COVID-19, most of the participants used social media to obtain information (61%), and a significant proportion of HCWs had poor knowledge of its transmission (61%) and symptom onset (63.6%) and showed positive perceptions of COVID-19 prevention and control. Factors such as age and profession were associated with inadequate knowledge and poor perception of COVID-19. Conclusion: As the global threat of COVID-19 continues to emerge, it is critical to improve the knowledge and perceptions of HCWs. Educational interventions are urgently needed to reach HCWs beyond borders, and further studies are warranted.

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: Detection of SARS-CoV-2 Among Residents and Staff Members of an Independent and Assisted Living Community for Older Adults — Seattle, Washington, 2020 In the Seattle, Washington metropolitan area, where the first case of novel coronavirus 2019 disease (COVID-19) in the United States was reported (1), a community-level outbreak is ongoing with evidence of rapid spread and high morbidity and mortality among older adults in long-term care skilled nursing facilities (SNFs) (2,3). However, COVID-19 morbidity among residents of senior independent and assisted living communities, in which residents do not live as closely together as do residents in SNFs and do not require skilled nursing services, has not been described. During March 5-9, 2020, two residents of a senior independent and assisted living community in Seattle (facility 1) were hospitalized with confirmed COVID-19 infection; on March 6, social distancing and other preventive measures were implemented in the community. UW Medicine (the health system linked to the University of Washington), Public Health - Seattle & King County, and CDC conducted an investigation at the facility. On March 10, all residents and staff members at facility 1 were tested for SARS-CoV-2, the virus that causes COVID-19, and asked to complete a questionnaire about their symptoms; all residents were tested again 7 days later. Among 142 residents and staff members tested during the initial phase, three of 80 residents (3.8%) and two of 62 staff members (3.2%) had positive test results. The three residents had no symptoms at the time of testing, although one reported an earlier cough that had resolved. A fourth resident, who had negative test results in the initial phase, had positive test results 7 days later. This resident was asymptomatic on both days. Possible explanations for so few cases of COVID-19 in this residential community compared with those in several Seattle SNFs with high morbidity and mortality include more social distancing among residents and less contact with health care providers. In addition, early implementation of stringent isolation and protective measures after identification of two COVID-19 cases might have been effective in minimizing spread of the virus in this type of setting. When investigating a potential outbreak of COVID-19 in senior independent and assisted living communities, symptom screening is unlikely to be sufficient to identify all persons infected with SARS-CoV-2. Adherence to CDC guidance to prevent COVID-19 transmission in senior independent and assisted living communities (4) could be instrumental in preventing a facility outbreak.

negative: 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.

negative: Ecosystem approaches to the risk for schizophrenia

negative: Prevalence of SARS-CoV-2 infection in the Luxembourgish population: the CON-VINCE study. BACKGROUND: After the World Health Organization declared the outbreak of coronavirus disease to be a public health emergency of international concern on January 30, 2020, the first SARS-CoV-2 infection was detected in Luxembourg on February 29, 2020. Representative population-based data, including asymptomatic individuals for assessing the viral spread and immune response were, however, lacking worldwide. METHODS: Using a panel-based method, we implemented a representative sample of the Luxembourgish population based on age, gender and residency for testing for SARS-CoV-2 infection and antibody status in order to define prevalence irrespective of clinical symptoms. Participants were contacted via email to fill an online questionnaire before biosampling at local laboratories. All participants provided information related to clinical symptoms, epidemiology, socioeconomic and psychological assessments and underwent biosampling, rRT-PCR testing and serology for SARS-CoV-2. RESULTS: We included a total of 1862 individuals in our representative sample of the general Luxembourgish population. Of these, 5 individuals had a current positive result for infection with SARS-CoV-2 based on rRT-PCR. Four of these individuals were oligosymptomatic and one was asymptomatic. Overall we found a positive IgG antibody status in 35 individuals (1.97%), of which 11 reported to be tested positive by rRT-PCR for SARS-CoV-2 previously and showed in addition their IgG positive status also a positive status for IgA. Our data indicate a prevalence of 0.3% for active SARS-CoV-2 infection and an infection rate of 2.15% in the Luxembourgish population between 18 and 79 years of age. CONCLUSIONS: Luxembourgish residents show a low rate of acute infections after 7 weeks of confinement and present with an antibody profile indicative of a more recent immune response to SARS-CoV-2. All infected individuals were oligo- or asymptomatic. Bi-weekly follow-up visits over the next 2 months will inform about the viral spread by a- and oligosymptomatic carriers and the individual changes in the immune profile.

negative: Four point-of-care lateral flow immunoassays for diagnosis of COVID-19 and for assessing dynamics of antibody responses to SARS-CoV-2 OBJECTIVES: We aimed to evaluate the role of rapid serological tests in the management of coronavirus disease 2019 (COVID-19) patients. METHODS: This retrospective study enrolled 16 real-time reverse transcription polymerase chain reaction-confirmed symptomatic patients with COVID-19 and 58 COVID-19 negative patients at a medical center in Taiwan over a 3-month period. Serial serum samples were collected and tested for antibody response using four point-of-care (POC) lateral flow immunoassays (LFIA) (ALLTEST 2019-nCoV IgG/IgM Rapid Test, Dynamiker 2019-nCoV IgG/IgM Rapid Test, ASK COVID-19 IgG/IgM Rapid Test, and Wondfo SARS-CoV-2 Antibody Test). Time-dependent detection sensitivity and timeliness of seroconversion were determined and compared between the four POC rapid tests. RESULTS: The overall sensitivity and specificity of the four tests for detecting anti-SARS-CoV-2 antibodies after 3 weeks of symptom onset were 100% and 100%, respectively. There was no significant difference between the rapid tests used for detection of IgM and IgG separately and those used for detection of combined total antibody (mainly IgM/IgG). There was no significant difference between the four POC rapid tests in terms of time required for determining seroconversion of COVID-19. Patients with COVID-19 with pneumonia demonstrated shorter seroconversion time than those without pneumonia. CONCLUSION: Though the POC antibody rapid tests based on LFIA showed reliable performance in the detection of SARS-CoV-2-specific antibodies, the results of these tests should be interpreted and applied appropriately in the context of antibody dynamic of COVID-19 infection. COVID-19 patients complicated with pneumonia exhibited earlier anti-SARS-CoV-2 antibody response than COVID-19 patients without pneumonia.

negative: International Expert Consensus Statement on Chest Imaging in Pediatric COVID-19 Patient Management: Imaging Findings, Imaging Study Reporting and Imaging Study Recommendations The coronavirus disease 2019 (COVID-19) has quickly spread since it was first detected in December of 2019 to a global pandemic with over 1.7 million confirmed cases in over 200 countries around the world at the time this document is being prepared. Due to the novel nature of the virus and the rapidly evolving understanding of the disease, there is a great deal of uncertainty surrounding the diagnosis and management of COVID-19 pneumonia in pediatric patients. Chest imaging plays an important role in evaluation of pediatric patients with COVID-19, however there is currently little information available describing imaging manifestations of pediatric COVID-19 and even less discussing utilization of imaging studies in pediatric patients. To specifically address these concerns, a group of international experts in pediatric thoracic imaging from 5 continents convened to create a consensus statement describing the imaging manifestations of COVID-19 in the pediatric population, discussing the potential utility of structured reporting during the coronavirus 2019 pandemic, and generating consensus recommendations for utilization of chest radiographs (CXR) and computed tomography (CT) in the evaluation of pediatric patients with COVID-19. The results were compiled into 2 structured reporting algorithms (one for CXR and one for chest CT) and 8 consensus recommendations for utilization of chest imaging in pediatric COVID-19 infection.

negative: Coronavirus (COVID‐19) in the United Kingdom: A personality‐based perspective on concerns and intention to self‐isolate OBJECTIVES: Public behaviour change is necessary to contain the spread of coronavirus (COVID‐19). Based on the reinforcement sensitivity theory (RST) framework, this study presents an examination of individual differences in some relevant psychological factors. DESIGN: Cross‐sectional psychometric. METHODS: UK respondents (N = 202) completed a personality questionnaire (RST‐PQ), measures of illness attitudes, concerns about the impact of coronavirus on health services and socio‐economic infrastructures, personal safety, and likelihood of voluntary self‐isolation. RESULTS: Respondents most concerned were older, had negative illness attitudes, and scored higher on reward reactivity (RR), indicating the motivation to take positive approach action despite prevailing worry/anxiety. Personal safety concerns were highest in those with negative illness attitudes and higher fight–flight–freeze system (FFFS, reflecting fear/avoidance) scores. Results suggest people are experiencing psychological conflict: between the urge to stay safe (FFFF‐related) and the desire to maintain a normal, pleasurable (RR‐related) life. Ways of ameliorating conflict may include maladaptive behaviours (panic buying), reflecting reward‐related displacement activity. Intended self‐isolation related to FFFS, but also low behavioural inhibition system (related to anxiety) scores. Older people reported themselves less likely to self‐isolate. CONCLUSIONS: Interventions need to consider individual differences in psychological factors in behaviour change, and we discuss relevant literature to inform policy makers and communicators. STATEMENT OF CONTRIBUTION: What is already known on this subject? Reinforcement sensitivity theory (RST) personality systems can influence perception of persuasive health messages. However, there is limited evidence for their direct effects on health concerns and behaviours, and none relating to specific infectious diseases. What does this study add? Reward reactivity (RR) is associated with concern about impact of coronavirus on the NHS and other social infrastructures, indicating the motivation to take positive‐approach action despite worry/anxiety. Personal safety concerns are related to fight–flight–freeze system traits (FFFS, reflecting fear/avoidance). Intended self‐isolation related to FFFS, but also low behavioural inhibition system (related to anxiety) scores. Older people reported themselves less likely to self‐isolate. Results suggest psychological conflict: between the urge to stay safe (FFFF‐related) and the desire to maintain a normal, pleasurable life (RR‐related). Ways of ameliorating conflict may include maladaptive behaviours (panic buying), reflecting reward‐related displacement activity;

negative: A screen of the NIH Clinical Collection small molecule library identifies potential anti-coronavirus drugs Abstract With the recent emergence of Middle East Respiratory Syndrome coronavirus in humans and the outbreak of devastating porcine epidemic diarrhea coronavirus in swine, therapeutic intervention is urgently needed. However, anti-coronavirus drugs currently are not available. In an effort to assist rapid development of anti-coronavirus drugs, here we screened the NIH Clinical Collection in cell culture using a luciferase reporter-expressing recombinant murine coronavirus. Of the 727 compounds screened, 84 were found to have a significant anti-coronavirus effect. Further experiments revealed that 51 compounds blocked virus entry while 19 others inhibited viral replication. Additional validation studies with the top 3 inhibitors (hexachlorophene, nitazoxanide and homoharringtonine) demonstrated robust anti-coronavirus activities (a reduction of 6 to 8log10 in virus titer) with an IC50 ranging from 11nM to 1.2μM. Furthermore, homoharringtonine and hexachlorophene exhibited broad antiviral activity against diverse species of human and animal coronaviruses. Since the NIH Clinical Collection consists of compounds that have already been through clinical trials, these small molecule inhibitors have a great potential for rapid development as anti-coronavirus drugs.

negative: Out-of-Hospital Cohort Treatment of Coronavirus Disease 2019 Patients with Mild Symptoms in Korea: an Experience from a Single Community Treatment Center The outbreak of Coronavirus Disease 2019 (COVID-19) caused a worldwide pandemic. Less than 6 weeks after the first confirmed cases in Korea, the patient number exceeded 5,000, which overcrowded limited hospital resources and forced confirmed patients to stay at home. To allocate medical resources efficiently, Korea implemented a novel institution for the purpose of treating patients with cohort isolation out of hospital, namely the Community Treatment Center (CTC). Herein, we report results of the initial management of patients at one of the largest CTC in Korea. A total of 309 patients were admitted to our CTC. During the first two weeks, 7 patients were transferred to the hospital because of symptom aggravation and 107 patients were discharged without any complication. Although it is a novel concept and may have some limitations, CTC may be a very cost-effective and resource-saving strategy in managing massive cases of COVID-19 or other emerging infectious diseases.

negative: SARS molecular epidemiology: a Chinese fairy tale of controlling an emerging zoonotic disease in the genomics era. Severe acute respiratory syndrome (SARS) was the first natural disaster that challenged the Chinese people at the beginning of the twenty-first century. It was caused by a novel animal coronavirus, never recognized or characterized before. This SARS coronavirus (SARS-CoV) exploited opportunities provided by 'wet markets' in southern China to adapt to the palm civet and human. Under the positive selection pressure of human host, certain mutated lineages of the virus became readily transmissible between humans and thus caused the epidemic of 2002-2003. This review will provide first-hand information, particularly from Guangdong, China, about the initial epidemiology, the identification of the aetiological agent of the disease, the molecular evolution study of the virus, the finding of SARS-like CoV in horseshoe bats and the mechanistic analysis for the cross-host tropism transition. The substantial scientific contributions made by the Chinese scientists towards understanding the virus and the disease will be emphasized. Along with the description of the scientific discoveries and analyses, the significant impact of these researches upon the public health measurement or regulations will be highlighted. It is aimed to appreciate the concerted and coordinated global response that controlled SARS within a short period of time as well as the research strategy and methodology developed along with this process, which can be applied in response to other public health challenges, particularly the future emerging/re-merging infectious diseases.

negative: Asymptomatic Shedding of Respiratory Virus among an Ambulatory Population across Seasons Most observation of human respiratory virus carriage is derived from medical surveillance; however, the infections documented by this surveillance represent only a symptomatic fraction of the total infected population. As the role of asymptomatic infection in respiratory virus transmission is still largely unknown and rates of asymptomatic shedding are not well constrained, it is important to obtain more-precise estimates through alternative sampling methods. We actively recruited participants from among visitors to a New York City tourist attraction. Nasopharyngeal swabs, demographics, and survey information on symptoms, medical history, and recent travel were obtained from 2,685 adults over two seasonal arms. We used multiplex PCR to test swab specimens for a selection of common respiratory viruses. A total of 6.2% of samples (168 individuals) tested positive for at least one virus, with 5.6% testing positive in the summer arm and 7.0% testing positive in the winter arm. Of these, 85 (50.6%) were positive for human rhinovirus (HRV), 65 (38.7%) for coronavirus (CoV), and 18 (10.2%) for other viruses (including adenovirus, human metapneumovirus, influenza virus, and parainfluenza virus). Depending on the definition of symptomatic infection, 65% to 97% of infections were classified as asymptomatic. The best-fit model for prediction of positivity across all viruses included a symptom severity score, Hispanic ethnicity data, and age category, though there were slight differences across the seasonal arms. Though having symptoms is predictive of virus positivity, there are high levels of asymptomatic respiratory virus shedding among the members of an ambulatory population in New York City. IMPORTANCE Respiratory viruses are common in human populations, causing significant levels of morbidity. Understanding the distribution of these viruses is critical for designing control methods. However, most data available are from medical records and thus predominantly represent symptomatic infections. Estimates for asymptomatic prevalence are sparse and span a broad range. In this study, we aimed to measure more precisely the proportion of infections that are asymptomatic in a general, ambulatory adult population. We recruited participants from a New York City tourist attraction and administered nasal swabs, testing them for adenovirus, coronavirus, human metapneumovirus, rhinovirus, influenza virus, respiratory syncytial virus, and parainfluenza virus. At recruitment, participants completed surveys on demographics and symptomology. Analysis of these data indicated that over 6% of participants tested positive for shedding of respiratory virus. While participants who tested positive were more likely to report symptoms than those who did not, over half of participants who tested positive were asymptomatic.

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

negative: The Diagnosis and Treatment of Elderly Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease and Chronic Bronchitis The syndrome of chronic obstructive pulmonary disease (COPD) consists of chronic bronchitis (CB), bronchiectasis, emphysema, and reversible airway disease that combine uniquely in an individual patient. Older patients are at risk for COPD and its components—emphysema, CB, and bronchiectasis. Bacterial and viral infections play a role in acute exacerbations of COPD (AECOPD) and in acute exacerbations of CB (AECB) without features of COPD. Older patients are at risk for resistant bacterial organisms during their episodes of AECOPD and AECB. Organisms include the more‐common bacteria implicated in AECOPD/AECB such as Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. Less‐common nonenteric, gram‐negative organisms including Pseudomonas aeruginosa, gram‐positive organisms including Staphylococcus aureus, and strains of nontuberculosis Mycobacteria are more often seen in AECOPD/AECB episodes involving elderly patients with frequent episodes of CB or those with bronchiectasis. Risk‐stratified antibiotic treatment guidelines appear useful for purulent episodes of AECOPD and episodes of AECB. These guidelines have not been prospectively validated for the general population and especially not for the elderly population. Using a risk‐stratification approach for elderly patients, first‐line antibiotics (e.g., amoxicillin, ampicillin, pivampicillin, trimethoprim/sulfamethoxazole, and doxycycline), with a more‐limited spectrum of antibacterial coverage, are used in patients who are likely to have a low probability of resistant organisms during AECOPD/AECB. Second‐line antibiotics (e.g., amoxicillin/clavulanic acid, second‐ or third‐generation cephalosporins, and respiratory fluoroquinolones) with a broader spectrum of coverage are reserved for patients with significant risk factors for resistant organisms and those who have failed initial antibiotic treatment.

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: Early Clinical Features of Dengue Virus Infection in Nicaraguan Children: A Longitudinal Analysis BACKGROUND: Tens of millions of dengue cases and approximately 500,000 life-threatening complications occur annually. New tools are needed to distinguish dengue from other febrile illnesses. In addition, the natural history of pediatric dengue early in illness in a community-based setting has not been well-defined. METHODS: Data from the multi-year, ongoing Pediatric Dengue Cohort Study of approximately 3,800 children aged 2–14 years in Managua, Nicaragua, were used to examine the frequency of clinical signs and symptoms by day of illness and to generate models for the association of signs and symptoms during the early phase of illness and over the entire course of illness with testing dengue-positive. Odds ratios (ORs) and 95% confidence intervals were calculated using generalized estimating equations (GEE) for repeated measures, adjusting for age and gender. RESULTS: One-fourth of children who tested dengue-positive did not meet the WHO case definition for suspected dengue. The frequency of signs and symptoms varied by day of illness, dengue status, and disease severity. Multivariable GEE models showed increased odds of testing dengue-positive associated with fever, headache, retro-orbital pain, myalgia, arthralgia, rash, petechiae, positive tourniquet test, vomiting, leukopenia, platelets ≤150,000 cells/mL, poor capillary refill, cold extremities and hypotension. Estimated ORs tended to be higher for signs and symptoms over the course of illness compared to the early phase of illness. CONCLUSIONS: Day-by-day analysis of clinical signs and symptoms together with longitudinal statistical analysis showed significant associations with testing dengue-positive and important differences during the early phase of illness compared to the entire course of illness. These findings stress the importance of considering day of illness when developing prediction algorithms for real-time clinical management.

negative: Human immunodeficiency virus infection (HIV)–associated rheumatic manifestations in thepre- and post-HAART eras Rheumatic manifestations remain an important clinical manifestation associated to HIV. To date after 4 decades of the onset of the HIV/AIDS pandemic, almost 37 million individuals are living with the infection, including close to 2 million of newly infected individuals. The status, however, of a considerable proportion of HIV/AIDS patients has changed from a near fatal disorder secondary to opportunistic infections to a chronic disease in which renal cardiovascular, diabetes, malignancy, and autoimmune co-morbid disorders have become prevalent and relevant. In addition, the spectrum of rheumatic disorders also has changed since the introduction of HAART and its diagnosis and treatment represents a challenge. The purpose of this review is to define and discuss the HIV-related rheumatic manifestations in the pre- and post-HAART eras.

negative: Data Mining and Content Analysis of the Chinese Social Media Platform Weibo During the Early COVID-19 Outbreak: Retrospective Observational Infoveillance Study BACKGROUND: The coronavirus disease (COVID-19) pandemic, which began in Wuhan, China in December 2019, is rapidly spreading worldwide with over 1.9 million cases as of mid-April 2020. Infoveillance approaches using social media can help characterize disease distribution and public knowledge, attitudes, and behaviors critical to the early stages of an outbreak. OBJECTIVE: The aim of this study is to conduct a quantitative and qualitative assessment of Chinese social media posts originating in Wuhan City on the Chinese microblogging platform Weibo during the early stages of the COVID-19 outbreak. METHODS: Chinese-language messages from Wuhan were collected for 39 days between December 23, 2019, and January 30, 2020, on Weibo. For quantitative analysis, the total daily cases of COVID-19 in Wuhan were obtained from the Chinese National Health Commission, and a linear regression model was used to determine if Weibo COVID-19 posts were predictive of the number of cases reported. Qualitative content analysis and an inductive manual coding approach were used to identify parent classifications of news and user-generated COVID-19 topics. RESULTS: A total of 115,299 Weibo posts were collected during the study time frame consisting of an average of 2956 posts per day (minimum 0, maximum 13,587). Quantitative analysis found a positive correlation between the number of Weibo posts and the number of reported cases from Wuhan, with approximately 10 more COVID-19 cases per 40 social media posts (P<.001). This effect size was also larger than what was observed for the rest of China excluding Hubei Province (where Wuhan is the capital city) and held when comparing the number of Weibo posts to the incidence proportion of cases in Hubei Province. Qualitative analysis of 11,893 posts during the first 21 days of the study period with COVID-19-related posts uncovered four parent classifications including Weibo discussions about the causative agent of the disease, changing epidemiological characteristics of the outbreak, public reaction to outbreak control and response measures, and other topics. Generally, these themes also exhibited public uncertainty and changing knowledge and attitudes about COVID-19, including posts exhibiting both protective and higher-risk behaviors. CONCLUSIONS: The results of this study provide initial insight into the origins of the COVID-19 outbreak based on quantitative and qualitative analysis of Chinese social media data at the initial epicenter in Wuhan City. Future studies should continue to explore the utility of social media data to predict COVID-19 disease severity, measure public reaction and behavior, and evaluate effectiveness of outbreak communication.

negative: The Natural History of Influenza Infection in the Severely Immunocompromised vs Nonimmunocompromised Hosts Introduction. Medical advances have led to an increase in the world's population of immunosuppressed individuals. The most severely immunocompromised patients are those who have been diagnosed with a hematologic malignancy, solid organ tumor, or who have other conditions that require immunosuppressive therapies and/or solid organ or stem cell transplants. Materials and methods. Medically attended patients with a positive clinical diagnosis of influenza were recruited prospectively and clinically evaluated. Nasal washes and serum were collected. Evaluation of viral shedding, nasal and serum cytokines, clinical illness, and clinical outcomes were performed to compare severely immunocompromised individuals to nonimmunocompromised individuals with influenza infection. Results. Immunocompromised patients with influenza had more severe disease/complications, longer viral shedding, and more antiviral resistance while demonstrating less clinical symptoms and signs on clinical assessment. Conclusions. Immunocompromised patients are at risk for more severe or complicated influenza induced disease, which may be difficult to prevent with existing vaccines and antiviral treatments. Specific issues to consider when managing a severely immunocompromised host include the development of asymptomatic shedding, multi-drug resistance during prolonged antiviral therapy, and the potential high risk of pulmonary involvement. Clinical trials registration, ClinicalTrials.gov identifier NCT00533182.

negative: Virological assessment of hospitalized patients with COVID-2019. Coronavirus disease 2019 (COVID-19) is an acute respiratory tract infection that emerged in late 20191,2. Initial outbreaks in China involved 13.8% cases with severe, and 6.1% with critical courses3. This severe presentation corresponds to the usage of a virus receptor that is expressed predominantly in the lung2,4. By causing an early onset of severe symptoms, this same receptor tropism is thought to have determined pathogenicity, but also aided the control, of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of COVID-19 cases with mild upper respiratory tract symptoms, suggesting the potential for pre- or oligosymptomatic transmission6-8. There is an urgent need for information on body site-specific virus replication, immunity, and infectivity. Here we provide a detailed virological analysis of nine cases, providing proof of active virus replication in upper respiratory tract tissues. Pharyngeal virus shedding was very high during the first week of symptoms (peak at 7.11 × 108 RNA copies per throat swab, day 4). Infectious virus was readily isolated from throat- and lung-derived samples, but not from stool samples, in spite of high virus RNA concentration. Blood and urine never yielded virus. Active replication in the throat was confirmed by viral replicative RNA intermediates in throat samples. Sequence-distinct virus populations were consistently detected in throat and lung samples from the same patient, proving independent replication. Shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (14 days in all), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild upper respiratory tract illness. Active virus replication in the upper respiratory tract puts the prospects of COVID-19 containment in perspective.

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

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

negative: Iron metabolism and lymphocyte characterisation during Covid-19 infection in ICU patients: an observational cohort study BACKGROUND: Iron metabolism and immune response to SARS-CoV-2 have not been described yet in intensive care patients, although they are likely involved in Covid-19 pathogenesis. METHODS: We performed an observational study during the peak of pandemic in our intensive care unit, dosing D-dimer, C-reactive protein, troponin T, lactate dehydrogenase, ferritin, serum iron, transferrin, transferrin saturation, transferrin soluble receptor, lymphocyte count and NK, CD3, CD4, CD8 and B subgroups of 31 patients during the first 2 weeks of their ICU stay. Correlation with mortality and severity at the time of admission was tested with the Spearman coefficient and Mann–Whitney test. Trends over time were tested with the Kruskal–Wallis analysis. RESULTS: Lymphopenia is severe and constant, with a nadir on day 2 of ICU stay (median 0.555 10(9)/L; interquartile range (IQR) 0.450 10(9)/L); all lymphocytic subgroups are dramatically reduced in critically ill patients, while CD4/CD8 ratio remains normal. Neither ferritin nor lymphocyte count follows significant trends in ICU patients. Transferrin saturation is extremely reduced at ICU admission (median 9%; IQR 7%), then significantly increases at days 3 to 6 (median 33%, IQR 26.5%, p value 0.026). The same trend is observed with serum iron levels (median 25.5 μg/L, IQR 69 μg/L at admission; median 73 μg/L, IQR 56 μg/L on days 3 to 6) without reaching statistical significance. Hyperferritinemia is constant during intensive care stay: however, its dosage might be helpful in individuating patients developing haemophagocytic lymphohistiocytosis. D-dimer is elevated and progressively increases from admission (median 1319 μg/L; IQR 1285 μg/L) to days 3 to 6 (median 6820 μg/L; IQR 6619 μg/L), despite not reaching significant results. We describe trends of all the abovementioned parameters during ICU stay. CONCLUSIONS: The description of iron metabolism and lymphocyte count in Covid-19 patients admitted to the intensive care unit provided with this paper might allow a wider understanding of SARS-CoV-2 pathophysiology.

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: Coronavirus disease 2019: new things to know! We have read with interest the review of Feng et al. “Coronavirus Disease 2019 (COVID‐19): What we know?” 1 which report the clinical features, diagnosis and treatment of the novel Coronavirus Disease 2019 (COVID‐19). This article is protected by copyright. All rights reserved.

negative: Approach to a Child with Sore Throat Sore throat is one of the common reasons for outpatient and emergency visits among children. It could be because of several etiologies; of these bacterial pharyngitis is the most important. Major challenge for the clinician is to diagnose group A beta hemolytic streptococcus (GABHS) pharyngitis and diphtheria, which are associated with serious complications. Throat swab smear with culture and rapid antigen tests are useful for making the diagnosis but the later may not be available in resource poor settings. Many clinical scores have been devised to diagnose GABHS with variable success but usually clinical features, epidemiological criteria and expert clinical judgment with or without supportive investigations indicate need for antibiotics. A child with sore throat and toxic look may have diphtheria or parapharyngeal/retropharyngeal abscess, and therefore should be hospitalized.

negative: Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases BACKGROUND: Chest CT is used for diagnosis of 2019 novel coronavirus disease (COVID-19), as an important complement to the reverse-transcription polymerase chain reaction (RT-PCR) tests. PURPOSE: To investigate the diagnostic value and consistency of chest CT as compared with comparison to RT-PCR assay in COVID-19. METHODS: From January 6 to February 6, 2020, 1014 patients in Wuhan, China who underwent both chest CT and RT-PCR tests were included. With RT-PCR as reference standard, the performance of chest CT in diagnosing COVID-19 was assessed. Besides, for patients with multiple RT-PCR assays, the dynamic conversion of RT-PCR results (negative to positive, positive to negative, respectively) was analyzed as compared with serial chest CT scans for those with time-interval of 4 days or more. RESULTS: Of 1014 patients, 59% (601/1014) had positive RT-PCR results, and 88% (888/1014) had positive chest CT scans. The sensitivity of chest CT in suggesting COVID-19 was 97% (95%CI, 95-98%, 580/601 patients) based on positive RT-PCR results. In patients with negative RT-PCR results, 75% (308/413) had positive chest CT findings; of 308, 48% were considered as highly likely cases, with 33% as probable cases. By analysis of serial RT-PCR assays and CT scans, the mean interval time between the initial negative to positive RT-PCR results was 5.1 ± 1.5 days; the initial positive to subsequent negative RT-PCR result was 6.9 ± 2.3 days). 60% to 93% of cases had initial positive CT consistent with COVID-19 prior (or parallel) to the initial positive RT-PCR results. 42% (24/57) cases showed improvement in follow-up chest CT scans before the RT-PCR results turning negative. CONCLUSION: Chest CT has a high sensitivity for diagnosis of COVID-19. Chest CT may be considered as a primary tool for the current COVID-19 detection in epidemic areas. A translation of this abstract in Farsi is available in the supplement. - ترجمه چکیده این مقاله به فارسی، در ضمیمه موجود است.

negative: Vaccines for emerging pathogens: prospects for licensure Globally, there are a number of emerging pathogens. For most, there are no licensed vaccines available for human use, although there is ongoing research and development. However, given the extensive and increasing list of emerging pathogens and the investment required to bring vaccines into clinical use, the task is huge. Overlaid on this task is the risk of anti‐microbial resistance (AMR) acquisition by micro‐organisms which can endow a relatively harmless organism with pathogenic potential. Furthermore, climate change also introduces a challenge by causing some of the insect vectors and environmental conditions prevalent in tropical regions to begin to spread out from these traditional areas, thus increasing the risk of migration of zoonotic disease. Vaccination provides a defence against these emerging pathogens. However, vaccines for pathogens which cause severe, but occasional, disease outbreaks in endemic pockets have suffered from a lack of commercial incentive for development to a clinical standard, encompassing Phase III clinical trials for efficacy. An alternative is to develop such vaccines to request US Emergency Use Authorization (EUA), or equivalent status in the United States, Canada and the European Union, making use of a considerable number of regulatory mechanisms that are available prior to licensing. This review covers the status of vaccine development for some of the emerging pathogens, the hurdles that need to be overcome to achieve EUA or an equivalent regional or national status and how these considerations may impact vaccine development for the future, such that a more comprehensive stockpile of promising vaccines can be achieved.

negative: Predictors of Initial Smear-Negative Active Pulmonary Tuberculosis with Acute Early Stage Lung Injury by High-Resolution Computed Tomography and Clinical Manifestations: An Auxiliary Model in Critical Patients This study evaluated the diagnostic use of high-resolution computed tomography (HRCT), chest X-ray (CXR), and clinical manifestations (CM) to identify initial smear-negative (iSN) active pulmonary tuberculosis (aPTB) [iSN-aPTB] in patients with iSN-pulmonary diseases (PD) and acute lung injury (ALI). In the derivation cohort, the [iSN-PD] with ALI patients were divided into the [iSN-aPTB] (G1, n = 26) and [non-aPTB-PD] (G2, n = 233) groups. Lung morphology, number, and lobar (segmental) distribution were evaluated using CXR and HRCT. A multivariate analysis was performed to identify independent variables associated with G1, which were used to generate predictive score models for G1. The predictive model was validated in a separate population of patients (n = 372) with [iSN-PD] and (ALI). The validated model for [HRCT (CXR + Hypoalbuminemia)] had 93.5% (25.8%) sensitivity, 99.5% (89.4%) specificity, and a negative predictive value of 99.5% (93.0%). For [iSN-aPTB], the post-test probability in the derivation cohort (prevalence = 10%), validation cohort (prevalence = 8.3%), and the given prevalence (prevalence = 1%) was 88.7%, 94.4%, and 41.5%, respectively. The HRCT model effectively identified the [iSN-aPTB] subjects among the [iSN-PD] with ALI, regardless of CM. The [non-aPTB-PD] were also correctly classified by the HRCT and [CXR + Hypoalbuminemia] models.

negative: A Machine Learning Model to Identify Early Stage Symptoms of SARS-Cov-2 Infected Patients The recent outbreak of the respiratory ailment COVID-19 caused by novel coronavirus SARS-Cov2 is a severe and urgent global concern. In the absence of effective treatments, the main containment strategy is to reduce the contagion by the isolation of infected individuals; however, isolation of unaffected individuals is highly undesirable. To help make rapid decisions on treatment and isolation needs, it would be useful to determine which features presented by suspected infection cases are the best predictors of a positive diagnosis. This can be done by analyzing patient characteristics, case trajectory, comorbidities, symptoms, diagnosis, and outcomes. We developed a model that employed supervised machine learning algorithms to identify the presentation features predicting COVID-19 disease diagnoses with high accuracy. Features examined included details of the individuals concerned, e.g., age, gender, observation of fever, history of travel, and clinical details such as the severity of cough and incidence of lung infection. We implemented and applied several machine learning algorithms to our collected data and found that the XGBoost algorithm performed with the highest accuracy (>85%) to predict and select features that correctly indicate COVID-19 status for all age groups. Statistical analyses revealed that the most frequent and significant predictive symptoms are fever (41.1%), cough (30.3%), lung infection (13.1%) and runny nose (8.43%). While 54.4% of people examined did not develop any symptoms that could be used for diagnosis, our work indicates that for the remainder, our predictive model could significantly improve the prediction of COVID-19 status, including at early stages of infection.

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

negative: SARS-CoV and Emergent Coronaviruses: Viral Determinants of Interspecies Transmission Most new emerging viruses are derived from strains circulating in zoonotic reservoirs. Coronaviruses, which had an established potential for cross-species transmission within domesticated animals, suddenly became relevant with the unexpected emergence of the highly pathogenic human SARS-CoV strain from zoonotic reservoirs in 2002. SARS-CoV infected approximately 8000 people worldwide before public health measures halted the epidemic. Supported by robust time-ordered sequence variation, structural biology, well-characterized patient pools, and biological data, the emergence of SARS-CoV represents one of the best studied natural models of viral disease emergence from zoonotic sources. This review article summarizes previous and more recent advances into the molecular and structural characteristics, with particular emphasis on host-receptor interactions, that drove this remarkable virus disease outbreak in human populations.

negative: Revisiting the dangers of the coronavirus in the ophthalmology practice

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

negative: Chest CT Findings in Coronavirus Disease-19 (COVID-19): Relationship to Duration of Infection In this retrospective study, chest CTs of 121 symptomatic patients infected with coronavirus disease-19 (COVID-19) from four centers in China from January 18, 2020 to February 2, 2020 were reviewed for common CT findings in relationship to the time between symptom onset and the initial CT scan (i.e. early, 0-2 days (36 patients), intermediate 3-5 days (33 patients), late 6-12 days (25 patients)). The hallmarks of COVID-19 infection on imaging were bilateral and peripheral ground-glass and consolidative pulmonary opacities. Notably, 20/36 (56%) of early patients had a normal CT. With a longer time after the onset of symptoms, CT findings were more frequent, including consolidation, bilateral and peripheral disease, greater total lung involvement, linear opacities, "crazy-paving" pattern and the "reverse halo" sign. Bilateral lung involvement was observed in 10/36 early patients (28%), 25/33 intermediate patients (76%), and 22/25 late patients (88%).

negative: 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.

negative: The Impact of Host-Based Early Warning on Disease Outbreaks Objective: The detection of communicable pathogens responsible for major outbreaks relies on health care professionals recognition of symptoms manifesting in infectious individuals. Early warning of such communicable diseases before the onset of symptoms could improve both patient care and public health responses. However, the potential impact of such a host-based early warning system on containing the spread of an outbreak and in steering public health response is unknown. Methods: We extend the deterministic SEIR (Susceptible, Exposed, Infectious, Recovered) model to simulate disease outbreak scenarios and to quantify the potential impact of a host-based early warning capability to mitigate pathogen transmission during an outbreak. In particular, we compare and contrast the performance of five different policies: Self-monitoring and reporting (baseline SEIR model), Quarantining the entire population, Quarantine-on-alert (with high sensitivity early warning), Quarantine-on-alert (with high specificity early warning), and Quarantine-on-alert (ideal early warning). We further evaluate these five policy options against four different outbreak scenarios with high or low disease transmission and high or low initial population exposures. Results: For all scenarios, a quarantine-on-alert policy coupled with the near-ideal early warning capability reduces quarantine needs with only a small increase in the number of additional infections. The cost of a highly specific early detection system (i.e., a reduction in false alarms and thus quarantine costs) is an increase in additional infections relative to the near-ideal system. Conversely, a highly sensitive early detection system increases the percentage of the population in quarantine compared to both the ideal and high-specificity early detection system while also reducing the number of additional infections to nearly the numbers seen by quarantining the entire population a priori. Conclusions: Our simulations demonstrate the utility of host-based early warning systems in controlling an outbreak under various outbreak conditions. Our tools also provide a simulation capability for evaluating public health policies enabling quantitative evaluation of their impacts prior to implementation.

negative: Acquisition of respiratory viruses and presence of respiratory symptoms in French pilgrims during the 2016 Hajj: A prospective cohort study Abstract Background Viral respiratory tract infections are frequent among Hajj pilgrims. However, it is still not known whether viruses are responsible for the symptoms observed in sick pilgrims or whether they only colonize sick and asymptomatic pilgrims. Patients and methods A prospective cohort study was conducted among French Hajj pilgrims in 2016. Medical follow-up and systematic nasal swabbing were performed pre- and post-Hajj. Additional samples were obtained per-Hajj, at symptom onset in ill pilgrims. Viruses were identified using the BioFire FilmArray® Respiratory multiplex qualitative PCR panel. Results 109 pilgrims were included. 83.5% presented respiratory symptoms during Hajj and 39.5% were still symptomatic on return. 5.5% of pre-Hajj, 95.2% of per-Hajj (at symptom onset) and 46.5% of post-Hajj samples tested positive (p < 0.0001). Acquisition rates of rhinovirus/enterovirus, coronavirus 229E and influenza A virus were respectively 38.6%, 19.8% and 2.0%. Although rhinovirus/enterovirus, coronavirus 229E and influenza A clearance were respectively 70.6%, 71.4% and 100% on return, overall virus carriage proportion on return was 75.0% in pilgrims with influenza-like illness and 44.0% in those who have never experienced this symptoms or resolved it (OR = 4.05, 95% CI [1.02–16.02]). Conclusions Viruses likely play some role in the pathogenesis of the respiratory tract infections at the Hajj. Point of care-rapid multiplex PCR assays are valuable diagnosis tools in this context when used at respiratory symptom onset or soon after.

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: 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: Two deletion variants of Middle East respiratory syndrome coronavirus found in a patient with characteristic symptoms Significant sequence variation of Middle East respiratory syndrome coronavirus (MERS CoV) has never been detected since it was first reported in 2012. A MERS patient came from Korea to China in late May 2015. The patient was 44 years old and had symptoms including high fever, dry cough with a little phlegm, and shortness of breath, which are roughly consistent with those associated with MERS, and had had close contact with individuals with confirmed cases of MERS.After one month of therapy with antiviral, anti-infection, and immune-enhancing agents, the patient recovered in the hospital and was discharged. A nasopharyngeal swab sample was collected for direct sequencing, which revealed two deletion variants of MERS CoV. Deletions of 414 and 419 nt occurred between ORF5 and the E protein, resulting in a partial protein fusion or truncation of ORF5 and the E protein. Functional analysis by bioinformatics and comparison to previous studies implied that the two variants might be defective in their ability to package MERS CoV. However, the mechanism of how these deletions occurred and what effects they have need to be further investigated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-017-3361-x) contains supplementary material, which is available to authorized users.

negative: Age-dependent effects in the transmission and control of COVID-19 epidemics The COVID-19 pandemic has shown a markedly low proportion of cases among children. Age disparities in observed cases could be explained by children having lower susceptibility to infection, lower propensity to show clinical symptoms, or both. We evaluate these possibilities by fitting an age-structured mathematical model to epidemic data from six countries. We estimate that clinical symptoms occur in 25% (95% CrI: 19-32%) of infections in 10-19-year-olds, rising to 76% (68-82%) in over-70s, and that susceptibility to infection in under-20s is approximately half that of older adults. Accordingly, we find that interventions aimed at children may have a relatively small impact on total cases, particularly if the transmissibility of subclinical infections is low. The age-specific clinical fraction and susceptibility we have estimated has implications for the expected global burden of COVID-19 because of demographic differences across settings: in younger populations, the expected clinical attack rate would be lower, although it is likely that comorbidities in low-income countries will affect disease severity. Without effective control measures, regions with older populations may see disproportionally more clinical cases, particularly in the later stages of the pandemic.

negative: Clinical Course and Outcomes of Patients with Severe Acute Respiratory Syndrome Coronavirus 2 Infection: a Preliminary Report of the First 28 Patients from the Korean Cohort Study on COVID-19 BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pneumonia emerged in Wuhan, China in December 2019. In this retrospective multicenter study, we investigated the clinical course and outcomes of novel coronavirus disease 2019 (COVID-19) from early cases in Republic of Korea. METHODS: All of the cases confirmed by real time polymerase chain reaction were enrolled from the 1st to the 28th patient nationwide. Clinical data were collected and analyzed for changes in clinical severity including laboratory, radiological, and virologic dynamics during the progression of illness. RESULTS: The median age was 40 years (range, 20–73 years) and 15 (53.6%) patients were male. The most common symptoms were cough (28.6%) and sore throat (28.6%), followed by fever (25.0%). Diarrhea was not common (10.7%). Two patients had no symptoms. Initial chest X-ray (CXR) showed infiltration in 46.4% of the patients, but computed tomography scan confirmed pneumonia in 88.9% (16/18) of the patients. Six patients (21.4%) required supplemental oxygen therapy, but no one needed mechanical ventilation. Lymphopenia was more common in severe cases. Higher level of C-reactive protein and worsening of chest radiographic score was observed during the 5–7 day period after symptom onset. Viral shedding was high from day 1 of illness, especially from the upper respiratory tract (URT). CONCLUSION: The prodromal symptoms of COVID-19 were mild and most patients did not have limitations of daily activity. Viral shedding from URT was high from the prodromal phase. Radiological pneumonia was common from the early days of illness, but it was frequently not evident in simple CXR. These findings could be plausible explanations for the easy and rapid spread of SARS-CoV-2 in the community.

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

negative: Highly Pathogenic Avian Influenza Highly pathogenic avian influenza is an acute respiratory infectious disease caused by some viral strains of avian influenza virus A. Its severity is highly diverse ranging from common cold-like symptoms to septicemia, shock, multiple organ failure, Reye syndrome, pulmonary hemorrhage, and other complications leading to death. According to the laws, human infection of highly pathogenic avian influenza has been legally listed as class B infectious diseases in China. And it has been stipulated that it should be managed according to class A infectious diseases in China.

negative: Chest CT for detecting COVID-19: a systematic review and meta-analysis of diagnostic accuracy OBJECTIVE: The purpose of this article was to perform a systematic review and meta-analysis regarding the diagnostic test accuracy of chest CT for detecting coronavirus disease 2019 (COVID-19). METHODS: PubMed, Embase, Web of Science, and CNKI were searched up to March 12, 2020. We included studies providing information regarding diagnostic test accuracy of chest CT for COVID-19 detection. The methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Sensitivity and specificity were pooled. RESULTS: Sixteen studies (n = 3186 patients) were included. The risks of bias in all studies were moderate in general. Pooled sensitivity was 92% (95% CI = 86–96%), and two studies reported specificity (25% [95% CI = 22–30%] and 33% [95% CI = 23–44%], respectively). There was substantial heterogeneity according to Cochran’s Q test (p < 0.01) and Higgins I(2) heterogeneity index (96% for sensitivity). After dividing the studies into two groups based on the study site, we found that the sensitivity of chest CT was great in Wuhan (the most affected city by the epidemic) and the sensitivity values were very close to each other (97%, 96%, and 99%, respectively). In the regions other than Wuhan, the sensitivity varied from 61 to 98%. CONCLUSION: Chest CT offers the great sensitivity for detecting COVID-19, especially in a region with severe epidemic situation. However, the specificity is low. In the context of emergency disease control, chest CT provides a fast, convenient, and effective method to early recognize suspicious cases and might contribute to confine epidemic. KEY POINTS: • Chest CT has a high sensitivity for detecting COVID-19, especially in a region with severe epidemic, which is helpful to early recognize suspicious cases and might contribute to confine epidemic.

negative: 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.

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: Evaluation the auxiliary diagnosis value of antibodies assays for detection of novel coronavirus (SARS-Cov-2) causing an outbreak of pneumonia (COVID-19) Background: The spread of an novel coronavirus (SARS-CoV-2, previously named 2019-nCoV) has already taken on pandemic proportions, affecting over 100 countries in a matter of weeks. Elucidating the diagnostic value of different methods, especially the auxiliary diagnosis value of antibodies assays for SARS-CoV-2 infection is helpful for improving the sensitivities of pathogenic-diagnosis, providing timely treatment, and differentiating the infected cases from the healthy, thus preventing further epidemics. Methods: Medical records from 38 patients with confirmed SARS-CoV-2 infection in the Second People's Hospital of Fuyang from January 22, 2020 to February 28, 2020 were collected and retrospectively analyzed. Specimens including throat swabs, sputum and serum were collected during the hospitalization period, viral RNAs and serum IgM-IgG antibodies to SARS-CoV-2 were measured respectively. The detectability of different methods as well as the auxiliary diagnosis value of antibodies test for SARS-CoV-2 infection were analyzed. Results: Among 38 patients, the total seropositive rate for IgM and IgG was 50.0% and 92.1%, respectively. Two patients remained seronegative throughout the course of illness. In the early phase of illness, the RNA test for sputum specimens possessed the highest detectability(92.3%), followed by the the RNA test for throat swabs (69.2%), and the antibodies assays presented lower positive rates(IgM, 23.0%, IgG, 53.8%). While, the sensitivity of antibodies assays overtook that of RNA test since day 8 after onset (IgM, 50.0%; IgG, 87.5%). Of note, the positive rate of throat swabs was only 13.0% for cases in later phase(≥15 d.a.o), and the sensitivities of IgM and IgG rose to 52.2% and 91.3%, respectively. Combined use of antibodies assay and qRT-PCR at the same time was able to improve the sensitivities of pathogenic-diagnosis, especially for the throat swabs group at the later stage of illness. Moreover, most of these cases with undetectable viral RNA in throat swabs specimens at the early stage of illness were able to be IgM/IgG seropositive after 7 days. Conclusions: The antibodies detection against SARS-CoV-2 offers vital clinical information for physicians, and could be used as an effective supplementary indicator for suspected cases of negative viral nucleic acid detection or in conjunction with nucleic acid detection in the diagnosis of suspected cases.

negative: Impacts of Social and Economic Factors on the Transmission of Coronavirus Disease 2019 (COVID-19) in China This paper examines the role of various socioeconomic factors in mediating the local and cross-city transmissions of the novel coronavirus 2019 (COVID-19) in China. We implement a machine learning approach to select instrumental variables that strongly predict virus transmission among the rich exogenous weather characteristics. Our 2SLS estimates show that the stringent quarantine, massive lockdown and other public health measures imposed in late January significantly reduced the transmission rate of COVID-19. By early February, the virus spread had been contained. While many socioeconomic factors mediate the virus spread, a robust government response since late January played a determinant role in the containment of the virus. We also demonstrate that the actual population flow from the outbreak source poses a higher risk to the destination than other factors such as geographic proximity and similarity in economic conditions. The results have rich implications for ongoing global efforts in containment of COVID-19.

negative: 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.

negative: 15 Respiratory medicine ●. Upper respiratory infections are commonplace, especially in young people, and are often contagious; ●. Lower respiratory infections are often contagious and some are potentially fatal; ●. Asthma is common and may be life-threatening; ●. Chronic obstructive pulmonary disease is common and disabling; ●. Tuberculosis worldwide is an important infection, affecting people with HIV/AIDS or malnutrition particularly; ●. Lung cancer is common and usually has a poor prognosis.

negative: Diagnosis and treatment of community‐acquired pneumonia in adults: 2016 clinical practice guidelines by the Chinese Thoracic Society, Chinese Medical Association Community‐acquired pneumonia (CAP) in adults is an infectious disease with high morbidity in China and the rest of the world. With the changing pattern in the etiological profile of CAP and advances in medical techniques in diagnosis and treatment over time, Chinese Thoracic Society of Chinese Medical Association updated its CAP guideline in 2016 to address the standard management of CAP in Chinese adults. Extensive and comprehensive literature search was made to collect the data and evidence for experts to review and evaluate the level of evidence. Corresponding recommendations are provided appropriately based on the level of evidence. This updated guideline covers comprehensive topics on CAP, including aetiology, antimicrobial resistance profile, diagnosis, empirical and targeted treatments, adjunctive and supportive therapies, as well as prophylaxis. The recommendations may help clinicians manage CAP patients more effectively and efficiently. CAP in pediatric patients and immunocompromised adults is beyond the scope of this guideline. This guideline is only applicable for the immunocompetent CAP patients aged 18 years and older. The recommendations on selection of antimicrobial agents and the dosing regimens are not mandatory. The clinicians are recommended to prescribe and adjust antimicrobial therapies primarily based on their local etiological profile and results of susceptibility testing, with reference to this guideline.

negative: How best to use limited tests? Improving COVID-19 surveillance in long-term care Background: Long-term care facilities (LTCFs) are particularly vulnerable to nosocomial outbreaks of coronavirus disease 2019 (COVID-19), with high rates of transmission and mortality. Timely epidemiological surveillance is essential to detect and respond to outbreaks, but testing resources are highly limited in the current pandemic context. Methods: We used an individual-based transmission model to simulate COVID-19 spread along inter-individual contact networks in the LTCF setting. A range of surveillance strategies were evaluated for their ability to detect simulated outbreaks, assuming limited availability of standard RT-PCR tests. Various epidemiological scenarios were considered, including COVID-19 importation from patient transfers or staff members infected in the community. Findings: We estimated a median delay of 7 (95% uncertainty interval: 2-15) days from importation of an asymptomatic COVID-19-infected patient to first presentation of COVID-19 symptoms among any patients or staff, at which point an additional 7 (0-25) individuals were infected but did not (yet) show symptoms. Across a range of scenarios, the reference surveillance strategy (testing individuals with COVID-like symptoms with signs of severity) took a median 11-21 days to detect an outbreak. Group testing (pooling specimens from multiple individuals for a single RT-PCR test) patients and staff with any COVID-like symptoms was both the most timely and efficient strategy, detecting outbreaks up to twice as quickly as the reference, and more quickly than other considered strategies while using fewer tests. Maximizing use of available tests via testing cascades was more effective than group testing only when substantial testing resources were available (on the order of 1 test/20 beds/day). Including not merely those with symptoms but also newly admitted patients in group tests and testing cascades reduced delays in outbreak detection for LTCFs actively admitting patients potentially already infected with COVID-19. Interpretation: Improving COVID-19 surveillance can alert healthcare institutions to emerging outbreaks before they escalate, informing a need for urgent public health intervention in settings with ongoing nosocomial transmission.

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: The Natural Viral Load Profile of Patients With Pandemic 2009 Influenza A(H1N1) and the Effect of Oseltamivir Treatment Background The natural history of viral shedding from the upper respiratory tract of the new pandemic 2009 influenza A(H1N1) and the effect of oseltamivir treatment were uncertain. Methods A retrospective cohort study involving 145 consecutive patients with specimens positive by reverse transcriptase-polymerase chain reaction for the matrix and new H1 genes was conducted. Results The nontreated and oseltamivir-treated patients were comparable in their viral load at presentation, demography, and the presenting symptoms. No correlation was observed between viral load with age and number of symptoms. Viral load of nasopharyngeal aspirate (NPA) was significantly lower in treated than in nontreated patients at day 5 after symptom onset. When oseltamivir was initiated ≤ 2 days after symptom onset, a greater rate of viral load reduction in NPA of treated patients than that of nontreated patients was observed (−0.638 [95% CI, −0.809 to −0.466] vs −0.409 [95% CI, −0.663 to −0.185] log10 copies/mL/d post-symptom onset), and the viral load was undetectable at day 6 after oseltamivir initiation, which was 1 day earlier than that of those whose treatment was initiated > 2 days of symptom onset. The viral load was inversely correlated with concomitant absolute lymphocyte count in nontreated patients (Pearson correlation coefficient [r] = −0.687, P = .001) and treated patients (Pearson r = −0.365, P < .001). Resolution of fever was 1.4 days later in nontreated than treated patients (P = .012) Conclusions The natural viral load profile was described. Oral oseltamivir suppresses viral load more effectively when given early in mild cases of pandemic 2009 influenza A(H1N1) infections.

negative: Achievements and highlights for Infection, Disease and Health

negative: First Case of Coronavirus Disease 2019 in Childhood Leukemia in China We report the first case of coronavirus disease 2019 (COVID-19) comorbid with leukemia in a patient hospitalized in Beijing, China. The patient showed a prolonged manifestation of symptoms and a protracted diagnosis period of COVID-19. It is necessary to extend isolation time, increase the number of nucleic acid detections and conduct early symptomatic treatment for children with both COVID-19 and additional health problems.

negative: Cardiac surgery in patients with confirmed COVID‐19 infection: Early experience The novel coronavirus, now termed SARS‐CoV‐2, has caused a significant global impact in the space of 4 months. Almost all elective cardiac surgical operations have been postponed in order to reduce transmission and to allocate resources adequately. Urgent and emergency cardiac surgery is still taking place during the pandemic. The decision to operate in urgent patients with active/recent COVID‐19 infection is difficult to make, particularly as it is still an unknown disease entity in the setting of emergent cardiac surgery. We present a case series of three patients who underwent urgent cardiac surgery and who have had recent or active COVID‐19 infection.

negative: Comorbidity and its impact on 1590 patients with Covid-19 in China: A Nationwide Analysis BACKGROUND: The coronavirus disease 2019 (Covid-19) outbreak is evolving rapidly worldwide. OBJECTIVE: To evaluate the risk of serious adverse outcomes in patients with coronavirus disease 2019 (Covid-19) by stratifying the comorbidity status. METHODS: We analysed the data from 1590 laboratory-confirmed hospitalised patients 575 hospitals in 31 province/autonomous regions/provincial municipalities across mainland China between December 11(th), 2019 and January 31(st), 2020. We analyse the composite endpoints, which consisted of admission to intensive care unit, or invasive ventilation, or death. The risk of reaching to the composite endpoints was compared according to the presence and number of comorbidities. RESULTS: The mean age was 48.9 years. 686 patients (42.7%) were females. 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. The most prevalent comorbidity was hypertension (16.9%), followed by diabetes (8.2%). 130 (8.2%) patients reported having two or more comorbidities. After adjusting for age and smoking status, COPD [hazards ratio (HR) 2.681, 95% confidence interval (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 risk factors of reaching to the composite endpoints. The HR 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: Among laboratory-confirmed cases of Covid-19, patients with any comorbidity yielded poorer clinical outcomes than those without. A greater number of comorbidities also correlated with poorer clinical outcomes.

negative: Direct Measurement of Rates of Asymptomatic Infection and Clinical Care-Seeking for Seasonal Coronavirus The pandemic potential of the novel coronavirus (nCoV) that emerged in Wuhan, China, during December 2019 is strongly tied to the number and contagiousness of undocumented human infections. Here we present findings from a proactive longitudinal sampling study of acute viral respiratory infections that documents rates of asymptomatic infection and clinical care seeking for seasonal coronavirus. We find that the majority of infections are asymptomatic by most symptom definitions and that only 4% of individuals experiencing a seasonal coronavirus infection episode sought medical care for their symptoms. These numbers indicate that a very high percentage of seasonal coronavirus infections are undocumented and provide a reference for understanding the spread of the emergent nCoV.

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

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

negative: Mapping of medical acronyms and initialisms to Medical Subject Headings (MeSH) across selected systems. INTRODUCTION Given the common use of acronyms and initialisms in the health sciences, searchers may be entering these abbreviated terms rather than full phrases when searching online systems. The purpose of this study is to evaluate how various MEDLINE Medical Subject Headings (MeSH) interfaces map acronyms and initialisms to the MeSH vocabulary. METHODS The interfaces used in this study were: the PubMed MeSH database, the PubMed Automatic Term Mapping feature, the NLM Gateway Term Finder, and Ovid MEDLINE. Acronyms and initialisms were randomly selected from 2 print sources. The test data set included 415 randomly selected acronyms and initialisms whose related meanings were found to be MeSH terms. Each acronym and initialism was entered into each MEDLINE MeSH interface to determine if it mapped to the corresponding MeSH term. Separately, 46 commonly used acronyms and initialisms were tested. RESULTS While performance differed widely, the success rates were low across all interfaces for the randomly selected terms. The common acronyms and initialisms tested at higher success rates across the interfaces, but the differences between the interfaces remained. CONCLUSION Online interfaces do not always map medical acronyms and initialisms to their corresponding MeSH phrases. This may lead to inaccurate results and missed information if acronyms and initialisms are used in search strategies.

negative: Assessing Viral Shedding and Infectivity of Tears in Coronavirus Disease 2019 (COVID-19) Patients

negative: Sofosbuvir protects human brain organoids against SARS-CoV-2 COVID-19 was rapidly declared a pandemic by the World Health Organization, only three months after the initial outbreak in Wuhan, China. Early clinical care mainly focused on respiratory illnesses. However, a variety of neurological manifestations in both adults and newborns are also emerging. To determine whether SARS-CoV-2 could target the human brain, we infected iPSC-derived human brain organoids. Our findings show that SARS-CoV-2 was able to infect and kill neural cells, including cortical neurons. This phenotype was accompanied by impaired synaptogenesis. Finally, Sofosbuvir, an FDA-approved antiviral drug, was able to rescue these alterations. Given that there are currently no vaccine or antiviral treatments available, urgent therapies are needed. Our findings put Sofosbuvir forward as a potential treatment to alleviate COVID-19-related neurological symptoms. One Sentence Summary SARS-CoV-2 infection causes neuronal death and impaired synaptogenesis, both rescued by Sofosbuvir treatment.

negative: Surgery during the COVID-19 pandemic: A comprehensive overview and perioperative care Abstract COVID-19 disease is a pandemic disease caused by a single-stranded RNA virus that belongs to the coronavirus family known as 2019-nCoV (SARS-CoV-2). The disease is highly contagious and transmitted mainly by droplets or close contact. As the global incidence of COVID-19 disease is increasing dramatically, health systems worldwide started to suffer in terms of its capability to manage affected people and the ability to provide standard treatment for critically ill patients in a safe environment. As Medical staff has extensive contact with patients, families as well as other health care providers, they are very likely to cause cross-infection. This paper aims to provide a comprehensive overview of COVID-19 disease as well as to highlight essential measures that healthcare providers and surgeons need to take into consideration during their management of the patient during the COVID-19 pandemic.

negative: COVID-19 in Great Britain: epidemiological and clinical characteristics of the first few hundred (FF100) cases: a descriptive case series and case control analysis Objectives: Following detection of the first virologically-confirmed cases of COVID-19 in Great Britain, an enhanced surveillance study was initiated by Public Health England to describe the clinical presentation, course of disease and identify risk factors for infection of the first few hundred cases. Methods: Information was collected on the first COVID-19 cases according to the First Few X WHO protocol. Case-control analyses of the sensitivity, specificity and predictive value of symptoms and risk factors for infection were conducted. Point prevalences of underlying health conditions among the UK general population were presented. Findings: The majority of FF100 cases were imported (51.4%), of which the majority had recent travel to Italy (71.4%). 24.7% were secondary cases acquired mainly through household contact (40.4%). Children had lower odds of COVID-19 infection compared with the general population. The clinical presentation of cases was dominated by cough, fever and fatigue. Non-linear relationships with age were observed for fever, and sensitivity and specificity of symptoms varied by age. Conditions associated with higher odds of COVID-19 infection (after adjusting for age and sex) were chronic heart disease, immunosuppression and multimorbidity. Conclusion: This study presents the first epidemiological and clinical summary of COVID-19 cases in Great Britain. The FFX study design enabled systematic data collection. The study was able to characterize the risk factors for infection with population prevalence estimates setting these relative risks into a public health context. It also provides important evidence for generating case definitions to support public health risk assessment, clinical triage and diagnostic algorithms.

negative: SARS Severe acute respiratory syndrome (SARS) is an acute respiratory tract infectious disease induced by SARS-CoV and mainly transmitted through the short-distance air droplets and close contact. Its main clinical characteristics is abrupt onset of the disease and the initial symptom is fever accompanied with systematic symptoms of headache, soreness and fatigue, and respiratory tract symptoms such as cough, chest dullness, and dyspnea. A few cases may progress to acute respiratory distress syndrome (ARDS). Due to its self-limiting feature, the prognosis is predominantly good but may be poor in severe cases, with mortality about 9.3 %. Some patients may develop such complications such as lung fibrosis and necrosis of the head of femur. On April 8, 2003, SARS was defined as a legal infectious disease by the Ministry of Heath of China.

negative: Large artery ischaemic stroke in severe acute respiratory syndrome (SARS) Of the 206 patients who contracted Severe Acute Respiratory Syndrome (SARS) in Singapore five developed large artery cerebral infarctions. Four patients were critically-ill and three died. Intravenous immunoglobulin was given to three patients. An increased incidence of deep venous thrombosis and pulmonary embolism was also observed among the critically-ill patients. We believe our experience warrants an increased vigilance against stroke and other thrombotic complications among critically-ill SARS patients in future outbreaks, especially if treatment such as intravenous immunoglobulin, that increases pro-thrombotic tendency, is contemplated.

negative: Analysis and Prediction of False Negative Results for SARS-CoV-2 Detection with Pharyngeal Swab Specimen in COVID-19 Patients: A Retrospective Study Background: False negative results of SARS-CoV-2 nucleic acid detection pose threats to COVID-19 patients and medical workers alike. Objective: To develop multivariate models to determine clinical characteristics that contribute to false negative results of SARS-CoV-2 nucleic acid detection, and use them to predict false negative results as well as time windows for testing positive. Design: Retrospective Cohort Study (Ethics number of Tongji Hospital: No. IRBID: TJ-20200320) Setting: A database of outpatients in Tongji Hospital (University Hospital) from 15 January 2020 to 19 February 2020. Patients: 1,324 outpatients with COVID-19 Measurements: Clinical information on CT imaging reports, blood routine tests, and clinic symptoms were collected. A multivariate logistic regression was used to explain and predict false negative testing results of SARS-CoV-2 detection. A multivariate accelerated failure model was used to analyze and predict delayed time windows for testing positive. Results: Of the 1,324 outpatients who diagnosed of COVID-19, 633 patients tested positive in their first SARS-CoV-2 nucleic acid test (47.8%), with a mean age of 51 years (SD=14.9); the rest, which had a mean age of 47 years (SD=15.4), tested negative in the first test. Ground glass opacity in a CT imaging report was associated with a lower chance of false negatives (aOR, 0.56), and reduced the length of time window for testing positive by 26%. Consolidation was associated with a higher chance of false negatives (aOR, 1.57), and extended the length of time window for testing positive by 44%. In blood routine tests, basophils (aOR, 1.28) and eosinophils (aOR, 1.29) were associated with a higher chance of false negatives, and were found to extend the time window for testing positive by 23% and 41%, respectively. Age and gender also affected the significantly. Limitation: Data were generated in a large single-center study. Conclusion: Testing outcome and positive window of SARS-CoV-2 detection for COVID-19 patients were associated with CT imaging results, blood routine tests, and clinical symptoms. Taking into account relevant information in CT imaging reports, blood routine tests, and clinical symptoms helped reduce a false negative testing outcome. The predictive AFT model, what we believe to be one of the first statistical models for predicting time window of SARS-CoV-2 detection, could help clinicians improve the accuracy and efficiency of the diagnosis, and hence, optimizes the timing of nucleic acid detection and alleviates the shortage of nucleic acid detection kits around the world. Primary Funding Source: None.

negative: Diagnostic performance between CT and initial real-time RT-PCR for clinically suspected 2019 coronavirus disease (COVID-19) patients outside Wuhan, China Abstract Introduction Chest CT is thought to be sensitive but less specific in diagnosing the 2019 coronavirus disease (COVID-19). The diagnostic value of CT is unclear. We aimed to compare the performance of CT and initial RT-PCR for clinically suspected COVID-19 patients outside the epicentre—Wuhan, China. Materials and methods Patients clinically suspected of COVID-19 infection who underwent initial RT-PCR and chest CT at the same time were retrospectively enrolled. Two radiologists with specific training reviewed the CT images independently and final diagnoses of the presence or absence of COVID-19 was reached by consensus. With serial RT-PCR as reference standard, the performance of initial RT-PCR and chest CT was analysed. A strategy of combining initial RT-PCR and chest CT was analysed to study the additional benefit. Results 82 patients admitted to hospital between Jan 10, 2020 to Feb 28, 2020 were enrolled. 34 COVID-19 and 48 non-COVID-19 patients were identified by serial RT-PCR. The sensitivity, specificity was 79% (27/34) and 100% (48/48) for initial RT-PCR and 77% (26/34) and 96% (46/48) for chest CT. The image readers had a good interobserver agreement with Cohen's kappa of 0.69. No statistical difference was found in the diagnostic performance between initial RT-PCR and chest CT. The comprehensive strategy had a higher sensitivity of 94% (32/34). Conclusions Initial RT-PCR and chest CT had comparable diagnostic performance in identification of suspected COVID-19 patients outside the epidemic center. To compensate potential risk of false-negative PCR, chest CT should be applied for clinically suspected patients with negative initial RT-PCR.

negative: SARS-associated Coronavirus Transmission, United States To better assess the risk for transmission of the severe acute respiratory syndrome–associated coronavirus (SARS-CoV), we obtained serial specimens and clinical and exposure data from seven confirmed U.S. SARS patients and their 10 household contacts. SARS-CoV was detected in a day-14 sputum specimen from one case-patient and in five stool specimens from two case-patients. In one case-patient, SARS-CoV persisted in stool for at least 26 days after symptom onset. The highest amounts of virus were in the day-14 sputum sample and a day-14 stool sample. Residual respiratory symptoms were still present in recovered SARS case-patients 2 months after illness onset. Possible transmission of SARS-CoV occurred in one household contact, but this person had also traveled to a SARS-affected area. The data suggest that SARS-CoV is not always transmitted efficiently. Laboratory diagnosis of SARS-CoV infection is difficult; thus, sputum and stool specimens should be included in the diagnostic work-up for SARS-CoV infection.

negative: 66 Incidence of Burkholderia cepacia complex infection in a Cystic Fibrosis Centre in Buenos Aires City, Argentina, from 2004 to 2014 Burkholderia cepacia complex (Bcc) is recognized as a significant respiratory pathogen in Cystic Fibrosis (CF) patients. The identification at species level among the 18 established Bcc members is an essential tool for epidemiological studies and infection control policies. In the early 2000s the epidemiology of Burkholderia cepacia (Bcc) in Argentina was characterized by the occurrence of a B. contaminans outbreak that took place in major CF centres. This situation was quite different from other countries where B. cenocepacia and B. multivorans have been the most frequent Bcc infecting species in CF patients. Although B. contaminans outbreak was studied, little is known about the evolution of Bcc epidemiology during the last years. The aim of this study was to analyse Bcc infections in CF patients (pt) attending Hospital de Niños “R. Gutiérrez” in 3 different periods between 2004 and 2014. Incidence and distribution of Bcc species have been described. 2004–2005: Incidence 13.5% (22/163 pt). B. contaminans 55.6% (10/18), B. cepacia 16.7% (3/18), B. cenocepacia and B. seminalis 11.1% (2/18), B. multivorans 5.6% (1/18), 4 nonviable strains. 2007–2009: Incidence 6.6% (12/181 pt). B. contaminans 72.7% (8/11), B. cepacia 27.3% (3/11), 1 nonviable strain. 2012–2014: Incidence 5.4% (10/184 pt). B. contaminans 90% (9/10), B. cepacia 10% (1/10). CONCLUSION: B. contaminans remains the most frequent isolated species among the new cases of infection. Although incidence values have decreased, these results suggest the situation with B. contaminans hasn't been solved yet. More studies specially focusing on the transmission of these bacteria and the possible sources of infection are needed.

negative: Perinatal depressive and anxiety symptoms of pregnant women during the coronavirus disease 2019 outbreak in China BACKGROUND: On January 20, 2020, a new coronavirus epidemic with human-to-human transmission was officially declared by the Chinese government, which caused significant public panic in China. In light of the coronavirus disease 2019 outbreak, pregnant women may be particularly vulnerable and in special need for preventive mental health strategies. Thus far, no reports exist to investigate the mental health response of pregnant women to the coronavirus disease 2019 outbreak. OBJECTIVE: This study aimed to examine the impact of coronavirus disease 2019 outbreak on the prevalence of depressive and anxiety symptoms and the corresponding risk factors among pregnant women across China. STUDY DESIGN: A multicenter, cross-sectional study was initiated in early December 2019 to identify mental health concerns in pregnancy using the Edinburgh Postnatal Depression Scale. This study provided a unique opportunity to compare the mental status of pregnant women before and after the declaration of the coronavirus disease 2019 epidemic. A total of 4124 pregnant women during their third trimester from 25 hospitals in 10 provinces across China were examined in this cross-sectional study from January 1, 2020, to February 9, 2020. Of these women, 1285 were assessed after January 20, 2020, when the coronavirus epidemic was publicly declared and 2839 were assessed before this pivotal time point. The internationally recommended Edinburgh Postnatal Depression Scale was used to assess maternal depression and anxiety symptoms. Prevalence rates and risk factors were compared between the pre- and poststudy groups. RESULTS: Pregnant women assessed after the declaration of coronavirus disease 2019 epidemic had significantly higher rates of depressive symptoms (26.0% vs 29.6%, P=.02) than women assessed before the epidemic declaration. These women were also more likely to have thoughts of self-harm (P=.005). The depressive rates were positively associated with the number of newly confirmed cases of coronavirus disease 2019 (P=.003), suspected infections (P=.004), and deaths per day (P=.001). Pregnant women who were underweight before pregnancy, primiparous, younger than 35 years, employed full time, in middle income category, and had appropriate living space were at increased risk for developing depressive and anxiety symptoms during the outbreak. CONCLUSION: Major life-threatening public health events such as the coronavirus disease 2019 outbreak may increase the risk for mental illness among pregnant women, including thoughts of self-harm. Strategies targeting maternal stress and isolation such as effective risk communication and the provision of psychological first aid may be particularly useful to prevent negative outcomes for women and their fetuses.

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

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

negative: sOptimizing screening strategies for coronavirus disease 2019: A study from Middle China Abstract Background Coronavirus disease 2019 (COVID-19) has been highly epidemic in China since January 2020. Rapid detection of the causative agent, severe acute respiratory coronavirus-2 (SARS-CoV-2), is very important due to its high rate of infectivity. This study aimed to clarify the epidemiology and clinical characteristics of COVID-19 outside of Hubei province, China, and to optimize screening strategies for COVID-19 in attempts to contain spread of the virus. Methods This retrospective study included all confirmed cases of COVID-19 in Hunan Provincial People's Hospital (Changsha, China) between January 22 and February 15, 2020. All cases were detected using a real-time reverse transcription polymerase chain reaction assay. The epidemiology and clinical characteristic of these cases were investigated according to outcome in attempts to optimize screening strategies for COVID-19. Results There were 24 confirmed cases of COVID-19 in the fever outpatient department of Hunan Provincial People's Hospital. Three patients were asymptomatic, and 3 exhibited mild and 3 moderate disease. There was a family cluster phenomenon. Conclusion Individuals with COVID-19 can be asymptomatic or exhibit mild manifestations of disease. Close monitoring and an optimized screening strategy for COVID-19 could help deter spread of the virus.

negative: Epidemiology and transmission of COVID-19 in 391 cases and 1286 of their close contacts in Shenzhen, China: a retrospective cohort study Summary Background Rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, prompted heightened surveillance in Shenzhen, China. The resulting data provide a rare opportunity to measure key metrics of disease course, transmission, and the impact of control measures. Methods From Jan 14 to Feb 12, 2020, the Shenzhen Center for Disease Control and Prevention identified 391 SARS-CoV-2 cases and 1286 close contacts. We compared cases identified through symptomatic surveillance and contact tracing, and estimated the time from symptom onset to confirmation, isolation, and admission to hospital. We estimated metrics of disease transmission and analysed factors influencing transmission risk. Findings Cases were older than the general population (mean age 45 years) and balanced between males (n=187) and females (n=204). 356 (91%) of 391 cases had mild or moderate clinical severity at initial assessment. As of Feb 22, 2020, three cases had died and 225 had recovered (median time to recovery 21 days; 95% CI 20–22). Cases were isolated on average 4·6 days (95% CI 4·1–5·0) after developing symptoms; contact tracing reduced this by 1·9 days (95% CI 1·1–2·7). Household contacts and those travelling with a case were at higher risk of infection (odds ratio 6·27 [95% CI 1·49–26·33] for household contacts and 7·06 [1·43–34·91] for those travelling with a case) than other close contacts. The household secondary attack rate was 11·2% (95% CI 9·1–13·8), and children were as likely to be infected as adults (infection rate 7·4% in children <10 years vs population average of 6·6%). The observed reproductive number (R) was 0·4 (95% CI 0·3–0·5), with a mean serial interval of 6·3 days (95% CI 5·2–7·6). Interpretation Our data on cases as well as their infected and uninfected close contacts provide key insights into the epidemiology of SARS-CoV-2. This analysis shows that isolation and contact tracing reduce the time during which cases are infectious in the community, thereby reducing the R. The overall impact of isolation and contact tracing, however, is uncertain and highly dependent on the number of asymptomatic cases. Moreover, children are at a similar risk of infection to the general population, although less likely to have severe symptoms; hence they should be considered in analyses of transmission and control. Funding Emergency Response Program of Harbin Institute of Technology, Emergency Response Program of Peng Cheng Laboratory, US Centers for Disease Control and Prevention.

negative: Acute febrile respiratory infection symptoms in Australian Hajjis at risk of exposure to Middle East respiratory syndrome coronavirus

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: Intestinal Health – Key to Maximise Growth Performance in Livestock, Theo Niewold (Ed.), Wageningen Academic Publishers, Wageningen, The Netherlands (2015). 276 pp., Hardcover, Price: 89 €; 108.49 US$; £ 69.65; Hardback ISBN: 978-90-76998-91 6; e-book ISBN: 978-90-8686-792-9 Unknown

negative: Difficulty of downscaling the precautions for coronavirus disease-19 based on negative throat polymerase chain results in the early phase of infection Abstract We here report a case of coronavirus disease-19 (COVID-19) in Japan in which the initial throat swab polymerase chain reaction result was negative The possibility of false-negative results in the early phase of disease suggest reconsideration of the feasibility of a community or national infection control framework to prevent transmission. We recommend establishing an alternative feasible system, such as self-isolation by contact history in non-endemic community and by symptoms in endemic community, not relying on the PCR examination, to minimize this ongoing COVID-19 outbreak. Further rapid accumulation of knowledge including incubation period, clinical course and types of transmission is warranted to control this outbreak.

negative: Global challenges to urology practice during the COVID‐19 pandemic Since the first report of coronavirus commonly termed as COVID-19 in China, it has progressed into a pandemic and Italy has been one of the countries worst hit. Coronaviruses are enveloped ribonucleic acid (RNA) viruses that cause respiratory, entero-hepatic, and neurologic diseases in humans and mammals. More specifically the coronavirus causing the current pandemic is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The common symptoms include a dry continuous cough, fever and shortness of breath; severe cases involve pneumonia which may require ventilatory support.

negative: Chapter 3 Chemical and Biological Aspects of Narcissus Alkaloids Publisher Summary This chapter discusses the chemical and biological aspects of Narcissus alkaloids. Numerous alkaloids have been isolated from Narcissus speciesasaresult of the continuing search for novel alkaloids with pharmacological activity in the Amaryllidaceae family. The alkaloids isolated from this genus, classified in relation to the different skeleton types. The different Narcissus wild species and intersectional hybrids, grouped into subgenera and sections, with their corresponding alkaloids, arranged according to their ring system are listed. The biosynthetic pathways of Narcissus alkaloids includes: (1) enzymatic preparation of the precursors, (2) primary cyclization mechanisms, (3) enzymatic preparation of intermediates, (4) secondary cyclization, diversification, and restructuring. The chapter discusses proton nuclear magnetic resonance (1H NMR), carbon nuclear magnetic resonance (13C NMR), and mass spectrometry (MS) for Narcissus alkaloids. A list of the different Narcissus alkaloids, their spectroscopic properties, and literature with the most recent spectroscopic data is given. Several Narcissus extracts shows the following activities: antiviral, prophage induction, antibacterial, antifungal, antimalarial, insecticidal, cytotoxic, antitumor, antimitotic, antiplatelet, hypotensive, emetic, acetylcholine esterase inhibitory, antifertility, antinociceptive, chronotropic, pheromone, plant growth inhibitor, and allelopathic.

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: Human Immunodeficiency Virus Infection: Spectrum of Rheumatic Manifestations Emerging and reemerging viral infections have been a characteristic feature of the past several decades, with HIV infection being the most important example of an emergent viral infection. To date, the status of a considerable proportion of HIV/AIDS patients has changed from a near-fatal disorder secondary to opportunistic infections to a chronic disease in which a variety of co-morbid conditions have become prevalent and relevant. Arthralgia and myalgias are the most common symptoms. The rate of spondyloarthritis varies according to the geographic area, genetic and mode of transmission. Most RA and SLE patients might go into remission after the development of AIDS, but also there are patients that continue with active disease. Prevalence of DILS is highest among African Americans in less advanced stages. PAN is clinically less aggressive and peripheral neuropathy is the most common clinical manifestation. Anti-phospholipid syndrome (APS), systemic sclerosis and poly-dermatomyositis are uncommon. After the introduction of combination antiretroviral therapy (cART), a decline of spondyloarthritis disorders and of DILS and development of new syndromes such as IRIS, osteoporosis and avascular bone necrosis have occurred. The treatment of patients with rheumatic diseases and HIV infection remains a challenge.

negative: Clinical data analysis of 19 cases of community-acquired adenovirus pneumonia in immunocompetent adults. The aim of this study was to investigate the characteristics of clinical manifestations, laboratory tests and imaging changes of community-acquired adenovirus pneumonia in immunocompetent adults. A retrospective study was performed on 19 adult community-acquired adenovirus pneumonia cases in Yantai, whereby the clinical data were collected and analyzed. Of 19 cases, 14 (73.68%) had fever and 17 (89.47%) had cough symptoms. Moreover, 14 cases (73.68%) had normal white blood cell counts, while 11 cases (57.89%) exhibited a reduction in lymphocyte proportion. Among the 19 cases, 17 cases exhibited lesions in a single lung, while 2 cases involved bilateral lungs. The lesions predominantly exhibited ground glass-like changes. The clinical manifestations of adult community-acquired adenovirus pneumonia patients with normal immune functions were mild, with such presenting symptoms as fever, cough, and sputum; most patients did not exhibit high levels of white blood cells or low lymphocyte counts, and the imaging features (ground glass-like effusion) were indicative of single-lung involvement.

negative: Coupling infectious diseases, human preventive behavior, and networks – A conceptual framework for epidemic modeling Human-disease interactions involve the transmission of infectious diseases among individuals and the practice of preventive behavior by individuals. Both infectious diseases and preventive behavior diffuse simultaneously through human networks and interact with one another, but few existing models have coupled them together. This article proposes a conceptual framework to fill this knowledge gap and illustrates the model establishment. The conceptual model consists of two networks and two diffusion processes. The two networks include: an infection network that transmits diseases and a communication network that channels inter-personal influence regarding preventive behavior. Both networks are composed of same individuals but different types of interactions. This article further introduces modeling approaches to formulize such a framework, including the individual-based modeling approach, network theory, disease transmission models and behavioral models. An illustrative model was implemented to simulate a coupled-diffusion process during an influenza epidemic. The simulation outcomes suggest that the transmission probability of a disease and the structure of infection network have profound effects on the dynamics of coupled-diffusion. The results imply that current models may underestimate disease transmissibility parameters, because human preventive behavior has not been considered. This issue calls for a new interdisciplinary study that incorporates theories from epidemiology, social science, behavioral science, and health psychology.

negative: A comparison study of SARS-CoV-2 IgG antibody between male and female COVID-19 patients: a possible reason underlying different outcome between gender. Objective: To compare the difference of SARS-CoV-2 IgG antibody between male and female COVID-19 patients and figure out a possible explanation for different outcome between male and female patients. Methods: A total number of 331 patients confirmed SARS-CoV-2 infection were enrolled. The plasma of these patients were collected during hospitalization and were detected for SARS-CoV-2 IgG antibody. Afterwards, the difference of IgG antibody between male and female patients was analyzed. Results: The level of IgG antibody in mild, general and recovering patients showed on difference between male and female. In severe status, the average IgG antibody level in female patients tended to be higher than that of in male patients. Compared with male patients, most of the female patients generated a relatively high level of SARS-CoV-2 IgG antibody in severe status. In addition, the generation of IgG antibody in female tended to be stronger than male patients in disease early phase. Conclusions: The inconsistent of SARS-CoV-2 IgG antibody generation in male and female patients may account for the different outcome of COVID-19 between gender.

negative: Preliminary Assessment of the COVID-19 Outbreak Using 3-Staged Model e-ISHR The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan has aroused widespread concern and attention from all over the world. Many articles have predicted the development of the epidemic. Most of them only use very basic SEIR model without considering the real situation. In this paper, we build a model called e-ISHR model based on SEIR model. Then we add hospital system and time delay system into the original model to simulate the spread of COVID-19 better. Besides, in order to take the government’s control and people’s awareness into consideration, we change our e-ISHR model into a 3-staged model which effectively shows the impact of these factors on the spread of the disease. By using this e-ISHR model, we fit and predict the number of confirmed cases in Wuhan and China except Hubei. We also change some of parameters in our model. The results indicate the importance of isolation and increasing the number of beds in hospital.

negative: Asymptomatic SARS-CoV-2 infections: What do we need to know?

negative: Perspectives on therapeutic neutralizing antibodies against the Novel Coronavirus SARS-CoV-2 A newly identified novel coronavirus (SARS-CoV-2) is causing pneumonia-associated respiratory syndrome across the world. Epidemiology, genomics, and pathogenesis of the SARS-CoV-2 show high homology with that of SARS-CoV. Current efforts are focusing on development of specific antiviral drugs. Therapeutic neutralizing antibodies (NAbs) against SARS-CoV-2 will be greatly important therapeutic agents for the treatment of coronavirus disease 2019 (COVID-19). Herein, the host immune responses against SARS-CoV discussed in this review provide implications for developing NAbs and understanding clinical interventions against SARS-CoV-2. Further, we describe the benefits, challenges and considerations of NAbs against SARS-CoV-2. Although many challenges exist, NAbs still offer a therapeutic option to control the current pandemic and the possible re-emergence of the virus in the future, and their development therefore remains a high priority.

negative: First 12 patients with coronavirus disease 2019 (COVID-19) in the United States Introduction: More than 93,000 cases of coronavirus disease (COVID-19) have been reported worldwide. We describe the epidemiology, clinical course, and virologic characteristics of the first 12 U.S. patients with COVID-19. Methods: We collected demographic, exposure, and clinical information from 12 patients confirmed by CDC during January 20-February 5, 2020 to have COVID-19. Respiratory, stool, serum, and urine specimens were submitted for SARS-CoV-2 rRT-PCR testing, virus culture, and whole genome sequencing. Results: Among the 12 patients, median age was 53 years (range: 21-68); 8 were male, 10 had traveled to China, and two were contacts of patients in this series. Commonly reported signs and symptoms at illness onset were fever (n=7) and cough (n=8). Seven patients were hospitalized with radiographic evidence of pneumonia and demonstrated clinical or laboratory signs of worsening during the second week of illness. Three were treated with the investigational antiviral remdesivir. All patients had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2-3 weeks after illness onset, with lowest rRT-PCR Ct values often detected in the first week. SARS-CoV-2 RNA was detected after reported symptom resolution in seven patients. SARS-CoV-2 was cultured from respiratory specimens, and SARS-CoV-2 RNA was detected in stool from 7/10 patients. Conclusions: In 12 patients with mild to moderately severe illness, SARS-CoV-2 RNA and viable virus were detected early, and prolonged RNA detection suggests the window for diagnosis is long. Hospitalized patients showed signs of worsening in the second week after illness onset.

negative: Comparisons of viral shedding time of SARS-CoV-2 of different samples in ICU and non-ICU patients • Dynamic RT-PCR test samples of nasal swabs, blood, fecal, urine, saliva and tears. • Nasal swab had a longer viral shedding time of SARS-CoV-2 than blood and saliva. • Viral shedding time of SARS-CoV-2 in ICU was longer than non-ICU patients.

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: Diffuse parenchymal lung disease as first clinical manifestation of GATA-2 deficiency in childhood BACKGROUND: GATA-2 transcription factor deficiency has recently been described in patients with a propensity towards myeloid malignancy associated with other highly variable phenotypic features: chronic leukocytopenias (dendritic cell-, monocyto-, granulocyto-, lymphocytopenia), increased susceptibility to infections, lymphatic vasculature abnormalities, and sensorineural deafness. Patients often suffer from opportunistic respiratory infections; chronic pulmonary changes have been found in advanced disease. CASE PRESENTATION: We present a case of a 17-year-old previously healthy Caucasian male who was admitted to the hospital with fever, malaise, headache, cough and dyspnea. A chest X-ray revealed bilateral interstitial infiltrates and pneumonia was diagnosed. Despite prompt clinical improvement under antibiotic therapy, interstitial changes remained stable. A high resolution computer tomography showed severe diffuse parenchymal lung disease, while the patient’s pulmonary function tests were normal and he was asymptomatic. Lung tissue biopsy revealed chronic reparative and resorptive reaction with organizing vasculitis. At the time of the initial presentation to the hospital, serological signs of acute infection with Epstein-Barr virus (EBV) were present; EBV viremia with atypical serological response persisted during two-year follow up. No other infectious agents were found. Marked monocytopenia combined with B-cell lymphopenia led to a suspicion of GATA-2 deficiency. Diagnosis was confirmed by detection of the previously published heterozygous mutation in GATA2 (c.1081 C > T, p.R361C). The patient’s brother and father were both carriers of the same genetic defect. The brother had no clinically relevant ailments despite leukocyte changes similar to the index patient. The father suffered from spondylarthritis, and apart from B-cell lymphopenia, no other changes within the leukocyte pool were seen. CONCLUSION: We conclude that a diagnosis of GATA-2 deficiency should be considered in all patients with diffuse parenchymal lung disease presenting together with leukocytopenia, namely monocyto-, dendritic cell- and B-lymphopenia, irrespective of severity of the clinical phenotype. Genetic counseling and screening for GATA2 mutations within the patient’s family should be provided as the phenotype is highly variable and carriers without apparent immunodeficiency are still in danger of developing myeloid malignancy. A prompt recognition of this rare condition helps to direct clinical treatment strategies and follow-up procedures.

negative: The SARS-CoV-2 epidemic outbreak: a review of plausible scenarios of containment and mitigation for Mexico We present here several variants of a mathematical model to explore three main issues related to SARS-CoV-2 spread in scenarios similar to those present in Mexico and elsewhere in Latin America. We explore the consequences for travel inside a given region, in this case Mexico, particularly focusing on airplane transportation but attempting to give a gross approximation to terrestrial movement since this is the main form of population movement across geographical areas in the country; then we proceed to study the effect of behavioral changes required to lower transmission by lowering the contact rate and infection probability and lastly, we explore the consequences of disease spread in a population subject to social isolation.These models are not suitable for predictive purposes although some rough predictions can be extracted from them. They are presented as a tool that can serve to explore plausible scenarios of spread and impact, effectiveness and consequences of contention and mitigation policies. Given the early stage at which the epidemic is at the date of writing in Mexico, we hope these ideas can be helpful for the understanding of the importance of isolation, social distancing and screening of the general population.

negative: Use of siltuximab in patients with COVID-19 pneumonia requiring ventilatory support COVID-19 is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SAR-CoV-2), resulting in symptoms, such as fever, cough, and shortness of breath. The SARS-CoV-2 virus has also been suggested to initiate a cytokine storm in patients with COVID-19 evidenced by elevated cytokines, such as interleukin-6 (IL-6) and C-reactive protein (CRP). We report preliminary data from 21 patients with COVID-19 who developed pneumonia/acute respiratory distress syndrome (ARDS) and participated in a compassionate-use program at Papa Giovanni XXIII hospital in Bergamo, Italy. All 21 patients received intravenous siltuximab, a chimeric mAb that binds to and blocks the effect of IL-6, at a dose ranging between 700 to 1,200 mg (median 900 mg). The median age of patients treated was 64 years, and all patients were followed for a median of eight days. Serum CRP levels reduced in all 16 patients with available data following treatment. An improvement in the clinical condition was observed in 33% (7/21) of patients, 43% (9/21) of patients stabilized as evidenced by no clinically relevant change in their condition, and 24% (5/21) experienced a worsening in their condition. Of those patients who experienced a worsening in their condition, one patient died, and one patient experienced a cerebrovascular event. This analysis is presented to inform the medical community of the potential role of siltuximab in treating patients with ARDS secondary to SARS-CoV-2 infection, and a cohort study with patients treated with standard therapy in our hospital is ongoing, and will report the 30-day mortality rates upon completion.

negative: Prevalence of COVID-19-like symptoms in Italy and Lombardy, March–April 2020, and their implications on cancer prevention, diagnosis and management Two population-based surveys on coronavirus disease-2019 (Covid-19)-like symptoms were conducted by BVA-Doxa on representative samples of the general population from Italy and its largest region, Lombardy, with over 10 million inhabitants and heavily struck by Covid-19, on 27–30 March and 3–7 April, on a total of 2000 individuals – 353 from Lombardy. Overall, 14.2% of Italians – and 19.6% in Lombardy – reported Covid-19-like symptoms. The estimated prevalence was higher in the young, in smokers, and in Lombardy over the period 20 March to 7 April. Although the influenza season was ended by mid-March, at least part of the symptoms may be not Covid-19 related. Even assuming that only half are, at least 7% of Italians and 10% in Lombardy had been affected by Covid-19. To these, asymptomatic or paucisymptomatic cases have to be added. These estimates are at least one or two orders of magnitude larger than official registered cases. This has major implications for cancer prevention, management and treatment.

negative: Impact of antibacterials on subsequent resistance and clinical outcomes in adult patients with viral pneumonia: an opportunity for stewardship INTRODUCTION: Respiratory viruses are increasingly recognized as significant etiologies of pneumonia among hospitalized patients. Advanced technologies using multiplex molecular assays and polymerase-chain reaction increase the ability to identify viral pathogens and may ultimately impact antibacterial use. METHOD: This was a single-center retrospective cohort study to evaluate the impact of antibacterials in viral pneumonia on clinical outcomes and subsequent multidrug-resistant organism (MDRO) infections/colonization. Patients admitted from March 2013 to November 2014 with positive respiratory viral panels (RVP) and radiographic findings of pneumonia were included. Patients transferred from an outside hospital or not still hospitalized 72 hours after the RVP report date were excluded. Patients were categorized based on exposure to systemic antibacterials: less than 3 days representing short-course therapy and 3 to 10 days being long-course therapy. RESULTS: A total of 174 patients (long-course, n = 67; short-course, n = 28; mixed bacterial-viral infection, n = 79) were included with most being immunocompromised (56.3 %) with active malignancy the primary etiology (69.4 %). Rhinovirus/Enterovirus (23 %), Influenza (19 %), and Parainfluenza (15.5 %) were the viruses most commonly identified. A total of 13 different systemic antibacterials were used as empiric therapy in the 95 patients with pure viral infection for a total of 466 days-of-therapy. Vancomycin (50.7 %), cefepime (40.3 %), azithromycin (40.3 %), meropenem (23.9 %), and linezolid (20.9 %) were most frequently used. In-hospital mortality did not differ between patients with viral pneumonia in the short-course and long-course groups. Subsequent infection/colonization with a MDRO was more frequent in the long-course group compared to the short-course group (53.2 vs 21.1 %; P = 0.027). CONCLUSION: This study found that long-course antibacterial use in the setting of viral pneumonia had no impact on clinical outcomes but increased the incidence of subsequent MDRO infection/colonization.

negative: Chapter 3 Immunobiological aspects of vaccines in pregnancy: Maternal perspective Abstract Immunization during pregnancy is an efficient strategy to protect both the mother and the newborn infant against infectious pathogens. Pregnant women have an increased susceptibility to severe infections caused by some pathogens, but the mechanisms involved remain poorly understood. Pregnancy is associated with dynamic changes in maternal immune system that are critical for tolerance of the fetus. These changes could also play an important role in shaping maternal immune components that are transferred to the newborn infant following natural infection or vaccination to prevent infectious diseases in early life. As the momentum for maternal immunization is growing, there is a need to increase our understanding of the immunobiology of maternal immunization in order to better prevent infectious diseases in the pregnant women and the young infant.

negative: Analysis of clinical features and early warning signs in patients with severe COVID-19: A retrospective cohort study Coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China, in December 2019. Although previous studies have described the clinical aspects of COVID-19, few studies have focused on the early detection of severe COVID-19. Therefore, this study aimed to identify the predictors of severe COVID-19 and to compare clinical features between patients with severe COVID-19 and those with less severe COVID-19. Patients admitted to designated hospital in the Henan Province of China who were either discharged or died prior to February 15, 2020 were enrolled retrospectively. Additionally, patients who underwent at least one of the following treatments were assigned to the severe group: continuous renal replacement therapy, high-flow oxygen absorption, noninvasive and invasive mechanical ventilation, or extracorporeal membrane oxygenation. The remaining patients were assigned to the non-severe group. Demographic information, initial symptoms, and first visit examination results were collected from the electronic medical records and compared between the groups. Multivariate logistic regression analysis was performed to determine the predictors of severe COVID-19. A receiver operating characteristic curve was used to identify a threshold for each predictor. Altogether,104 patients were enrolled in our study with 30 and 74 patients in the severe and non-severe groups, respectively. Multivariate logistic analysis indicated that patients aged ≥63 years (odds ratio = 41.0; 95% CI: 2.8, 592.4), with an absolute lymphocyte value of ≤1.02×10(9)/L (odds ratio = 6.1; 95% CI = 1.5, 25.2) and a C-reactive protein level of ≥65.08mg/L (odds ratio = 8.9; 95% CI = 1.0, 74.2) were at a higher risk of severe illness. Thus, our results could be helpful in the early detection of patients at risk for severe illness, enabling the implementation of effective interventions and likely lowering the morbidity of COVID-19 patients.

negative: Early-Life Exposure to Clostridium leptum Causes Pulmonary Immunosuppression INTRODUCTION: Low Clostridium leptum levels are a risk factor for the development of asthma. C. leptum deficiency exacerbates asthma; however, the impact of early-life C. leptum exposure on cesarean-delivered mice remains unclear. This study is to determine the effects of early-life C. leptum exposure on asthma development in infant mice. METHODS: We exposed infant mice to C. leptum (fed-CL) and then induced asthma using the allergen ovalbumin (OVA). RESULTS: Fed-CL increased regulatory T (Treg) cells in cesarean-delivered mice compared with vaginally delivered mice. Compared with OVA-exposed mice, mice exposed to C. leptum + OVA did not develop the typical asthma phenotype, which includes airway hyper-responsiveness, cell infiltration, and T helper cell subset (Th1, Th2, Th9, Th17) inflammation. Early-life C. leptum exposure induced an immunosuppressive environment in the lung concurrent with increased Treg cells, resulting in the inhibition of Th1, Th2, Th9, and Th17 cell responses. CONCLUSION: These findings demonstrate a mechanism whereby C. leptum exposure modulates adaptive immunity and leads to failure to develop asthma upon OVA sensitization later in life.

negative: Adaptive evolution of the spike gene of SARS coronavirus: changes in positively selected sites in different epidemic groups BACKGROUND: It is believed that animal-to-human transmission of severe acute respiratory syndrome (SARS) coronavirus (CoV) is the cause of the SARS outbreak worldwide. The spike (S) protein is one of the best characterized proteins of SARS-CoV, which plays a key role in SARS-CoV overcoming species barrier and accomplishing interspecies transmission from animals to humans, suggesting that it may be the major target of selective pressure. However, the process of adaptive evolution of S protein and the exact positively selected sites associated with this process remain unknown. RESULTS: By investigating the adaptive evolution of S protein, we identified twelve amino acid sites (75, 239, 244, 311, 479, 609, 613, 743, 765, 778, 1148, and 1163) in the S protein under positive selective pressure. Based on phylogenetic tree and epidemiological investigation, SARS outbreak was divided into three epidemic groups: 02–04 interspecies, 03-early-mid, and 03-late epidemic groups in the present study. Positive selection was detected in the first two groups, which represent the course of SARS-CoV interspecies transmission and of viral adaptation to human host, respectively. In contrast, purifying selection was detected in 03-late group. These indicate that S protein experiences variable positive selective pressures before reaching stabilization. A total of 25 sites in 02–04 interspecies epidemic group and 16 sites in 03-early-mid epidemic group were identified under positive selection. The identified sites were different between these two groups except for site 239, which suggests that positively selected sites are changeable between groups. Moreover, it was showed that a larger proportion (24%) of positively selected sites was located in receptor-binding domain (RBD) than in heptad repeat (HR)1-HR2 region in 02–04 interspecies epidemic group (p = 0.0208), and a greater percentage (25%) of these sites occurred in HR1–HR2 region than in RBD in 03-early-mid epidemic group (p = 0.0721). These suggest that functionally different domains of S protein may not experience same positive selection in each epidemic group. In addition, three specific replacements (F360S, T487S and L665S) were only found between 03-human SARS-CoVs and strains from 02–04 interspecies epidemic group, which reveals that selective sweep may also force the evolution of S genes before the jump of SARS-CoVs into human hosts. Since certain residues at these positively selected sites are associated with receptor recognition and/or membrane fusion, they are likely to be the crucial residues for animal-to-human transmission of SARS-CoVs, and subsequent adaptation to human hosts. CONCLUSION: The variation of positive selective pressures and positively selected sites are likely to contribute to the adaptive evolution of S protein from animals to humans.

negative: A model for the emergence of drug resistance in the presence of asymptomatic infections Abstract An analysis of a mathematical model, which describes the dynamics of an aerially transmitted disease, and the effects of the emergence of drug resistance after the introduction of treatment as an intervention strategy is presented. Under explicit consideration of asymptomatic and symptomatic infective individuals for the basic model without intervention the analysis shows that the dynamics of the epidemic is determined by a basic reproduction number R 0 . A disease-free and an endemic equilibrium exist and are locally asymptotically stable when R 0 < 1 and R 0 > 1 respectively. When treatment is included the system has a basic reproduction number, which is the largest of the two reproduction numbers that characterise the drug-sensitive ( R 1 ) or resistant ( R 2 ) strains of the infectious agent. The system has a disease-free equilibrium, which is stable when both R 1 and R 2 are less than unity. Two endemic equilibria also exist and are associated with treatment and the development of drug resistance. An endemic equilibrium where only the drug-resistant strain persists exists and is stable when R 2 > 1 and R 1 < R 2 . A second endemic equilibrium exists when R 1 > 1 and R 1 > R 2 and both drug-sensitive and drug-resistant strains are present. The analysis of the system provides insights about the conditions under which the infection will persist and whether sensitive and resistant strains will coexist or not.

negative: Measuring Icebergs: Using Different Methods to Estimate the Number of COVID-19 Cases in Portugal and Spain The world is suffering from a pandemic called COVID-19, caused by the SARS-CoV-2 virus. The different national governments have problems evaluating the reach of the epidemic, having limited resources and tests at their disposal. Hence, any means to evaluate the number of persons with symptoms compatible with COVID-19 with reasonable level of accuracy is useful. In this paper we present the initial results of the @CoronaSurveys project. The objective of this project is the collection and publication of data concerning the number of people that show symptoms compatible with COVID-19 in different countries using open anonymous surveys. While this data may be biased, we conjecture that it is still useful to estimate the number of infected persons with the COVID-19 virus at a given point in time in these countries, and the evolution of this number over time. We show here the initial results of the @CoronaSurveys project in Spain and Portugal.

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: Strong effect of socioeconomic levels on the spread and treatment of the 2019 novel coronavirus (COVID-19) in China Background: Global response to the COVID-19 epidemic presents strengths and weaknesses in national and regional social governance capacities to address public health challenges. The emergence, detection, spread, treatment and containment of infectious diseases shows the considerable political and economic impacts in a highly interconnected world. We aimed to estimate the effects of socioeconomic levels on the spread and treatment of COVID-19 in China. Methods: We obtained daily COVID-19 cases at a city level in China. We used migration data from the major cities in Hubei Province, and macroeconomic data at city and province levels. We obtained social management measures in response to COVID-19 outbreak. We assessed the association between measures, migration and COVID-19 spread, and the association between socioeconomic levels and COVID-19 treatment capacity. Findings: On January 1, 2020, COVID-19 spread that affected by management measures and migration started across China. After Wuhan lockdown, the case number reached peak in 12 days, and COVID-19 outbreak was basically contained in China in four weeks due to intensive measures. Guangdong, Jiangsu and Zhejiang Provinces showed the most excellent COVID-19 treatment capacities. Socioeconomic levels in these provinces ranked top in China. Guangdong achieved the largest decline in severe case rate by 22.1%. Jiangsu had the lowest average rate of severe cases (1.7%) and zero death. Among the regions with top case number, Zhejiang showed the highest rate of cured cases on confirmed cases (96.3%), the lowest average rate of severe cases (7.7%), and one death. The COVID-19 treatment capacities were strongly affected by regional economics and measures on control, detection and treatment. Interpretation: Socioeconomic levels had strong effect on the spread and treatment of COVID-19 in China. Further investigations are needed on the effectiveness of Chinese measures and the effects of socioeconomic levels on COVID-19 treatment outside China. Fund Guangdong Natural Science Foundation

negative: Estimating the Asymptomatic Proportion of 2019 Novel Coronavirus onboard the Princess Cruises Ship, 2020 The potential infectiousness of asymptomatic COVID-19 cases together with a substantial fraction of asymptomatic infections among all infections, have been highlighted in clinical studies. We conducted statistical modeling analysis to derive the delay-adjusted asymptomatic proportion of the positive COVID-19 infections onboard the Princess Cruises ship along with the timeline of infections. We estimated the asymptomatic proportion at 17.9% (95% CrI: 15.5%-20.2%), with most of the infections occurring before the start of the 2-week quarantine.

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

negative: Seasonality of infectious diseases and severe acute respiratory syndrome–what we don't know can hurt us Summary The novel severe acute respiratory syndrome (SARS) coronavirus caused severe disease and heavy economic losses before apparently coming under complete control. Our understanding of the forces driving seasonal disappearance and recurrence of infectious diseases remains fragmentary, thus limiting any predictions about whether, or when, SARS will recur. It is true that most established respiratory pathogens of human beings recur in wintertime, but a new appreciation for the high burden of disease in tropical areas reinforces questions about explanations resting solely on cold air or low humidity. Seasonal variation in host physiology may also contribute. Newly emergent zoonotic diseases such as ebola or pandemic strains of influenza have recurred in unpredictable patterns. Most established coronaviruses exhibit winter seasonality, with a unique ability to establish persistent infections in a minority of infected animals. Because SARS coronavirus RNA can be detected in the stool of some individuals for at least 9 weeks, recurrence of SARS from persistently shedding human or animal reservoirs is biologically plausible.

negative: Understanding the mechanisms of viral induced asthma: New therapeutic directions Asthma is a common and debilitating disease that has substantially increased in prevalence in Western Societies in the last 2 decades. Respiratory tract infections by respiratory syncytial virus (RSV) and rhinovirus (RV) are widely implicated as common causes of the induction and exacerbation of asthma. These infections in early life are associated with the induction of wheeze that may progress to the development of asthma. Infections may also promote airway inflammation and enhance T helper type 2 lymphocyte (Th2 cell) responses that result in exacerbations of established asthma. The mechanisms of how RSV and RV induce and exacerbate asthma are currently being elucidated by clinical studies, in vitro work with human cells and animal models of disease. This research has led to many potential therapeutic strategies and, although none are yet part of clinical practise, they show much promise for the prevention and treatment of viral disease and subsequent asthma.

negative: A Novel CDC42 Mutation in an 11-Year Old Child Manifesting as Syndromic Immunodeficiency, Autoinflammation, Hemophagocytic Lymphohistiocytosis, and Malignancy: A Case Report Background: The CDC42 (Cell Division Cycle 42) gene product, CDC42, is a member of the family of small Rho GTPases, which are implicated in a broad spectrum of physiological functions in cell cycle regulation, including establishing and controlling of the cell actin cytoskeleton, vesicle trafficking, cell polarity, proliferation, motility and migration, transcription activation, reactive oxygen species production, and tumorigenesis. The CDC42 gene mutations are associated with distinct clinical phenotypes characterized by neurodevelopmental, growth, hematological, and immunological disturbances. Case presentation: We report the case of an 11-year-old boy with syndromic features, immunodeficiency, and autoinflammation who developed hemophagocytic lymphohistiocytosis and malignant lymphoproliferation. In this patient, a novel heterozygous p.Cys81Tyr mutation in the CDC42 gene was found by whole exome sequencing. Conclusions: The Cdc42 molecule plays a pivotal role in cell cycle regulation and a wide array of tissue-specific functions, and its deregulation may result in a broad spectrum of molecular and cellular dysfunctions, making patients with CDC42 gene mutations susceptible to infections, immune dysregulation, and malignancy. In the patient studied, a syndromic phenotype with facial dysmorphism, neurodevelopmental delay, immunodeficiency, autoinflammation, and hemophagocytic lymphohistiocytosis shares common features with Takenouchi–Kosaki syndrome and with C-terminal variants in CDC42. It is important to emphasize that Hodgkin's lymphoma is described for the first time in the medical literature in a pediatric patient with the novel p.Cys81Tyr mutation in the CDC42 gene. Further studies are required to delineate precisely the CDC42 genotype–phenotype correlations.

negative: Coronavirus disease 2019: initial chest CT findings OBJECTIVES: To systematically analyze CT findings during the early and progressive stages of natural course of coronavirus disease 2019 and also to explore possible changes in pulmonary parenchymal abnormalities during these two stages. METHODS: We retrospectively reviewed the initial chest CT data of 62 confirmed coronavirus disease 2019 patients (34 men, 28 women; age range 20-91 years old) who did not receive any antiviral treatment between January 21 and February 4, 2020, in Chongqing, China. Patients were assigned to the early-stage group (onset of symptoms within 4 days) or progressive-stage group (onset of symptoms within 4-7 days) for analysis. CT characteristics and the distribution, size, and CT score of pulmonary parenchymal abnormalities were assessed. RESULTS: In our study, the major characteristic of coronavirus disease 2019 was ground-glass opacity (61.3%), followed by ground-glass opacity with consolidation (35.5%), rounded opacities (25.8%), a crazy-paving pattern (25.8%), and an air bronchogram (22.6%). No patient presented cavitation, a reticular pattern, or bronchial wall thickening. The CT scores of the progressive-stage group were significantly greater than those of the early-stage group (p = 0.004). CONCLUSIONS: Multiple ground-glass opacities with consolidations in the periphery of the lungs were the primary CT characteristic of coronavirus disease 2019. CT score can be used to evaluate the severity of the disease. If these typical alterations are found, then the differential diagnosis of coronavirus disease 2019 must be considered. KEY POINTS: â¢ Multiple GGOs with consolidations in the periphery of the lungs were the primary CT characteristic of COVID-19. â¢ The halo sign may be a special CT feature in the early-stage COVID-19 patients. â¢ Significantly increased CT score may indicate the aggravation of COVID-19 in the progressive stage.

negative: Uncertainty in using chest computed tomography in early coronavirus disease (COVID-19)

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

negative: Effect of the Wet Market on the coronavirus disease (COVID-19) transmission dynamics in China, 2019-2020 Abstract Objectives The novel coronavirus (SARS-CoV-2) originating from Wuhan rapidly spread throughout China. While its origin remains uncertain, accumulating evidence links a wet market for the early SARS-CoV-2 spread in Wuhan. Similarly, the influence of the marketplace on the early transmission dynamics is yet to be investigated. Methods Using the daily series of COVID-19 incidence stratified according to contact history with the market, we have conducted quantitative modeling analyses to estimate the reproduction numbers (R) for the market-to-human and human-to-human transmission, the reporting probability and the early effects of public health interventions. Results We estimated R at 0.24 (95%CrI: 0.01-1.38) for market-to-human transmission, and 2.37 (95%CrI: 2.08-2.71) for human-to-human transmission during the early spread in China (2019-2020). Moreover, we estimated that the reporting rate for cases stemming from market-to-human transmission was 2-34 fold higher than that for cases stemming from human-to-human transmission, suggesting that contact history with the wet market played a key role in identifying COVID-19 cases. Conclusions Our R estimate tied to market-to-human transmission has substantial uncertainty, but it was significantly lower compared to the reproduction number driving human-to-human transmission. Our results also suggest that asymptomatic and subclinical infections constitute a substantial component of the COVID-19 morbidity burden.

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: Effect of prior receipt of antibiotics on the pathogen distribution: a retrospective observational cohort study on 27,792 patients BACKGROUND: There have been no systematic studies of microbiological differences before and after antibiotics treatment. The aim of this study was to evaluate the effect of prior receipt of antibiotics on the microorganism distribution. METHODS: A retrospective, observational cohort study was conducted in a 3200-bed tertiary, referral, teaching hospital in eastern China. During a 2-year period, all hospitalized patients treated with antimicrobial agents were enrolled in this study. Among 48,692 patients evaluated, the 27,792 (57.1%) who were sampled within 2 days before or after administration of the first dose of antimicrobial agents were included. Distribution of clinical specimens and the microorganism were compared between before and after antibiotic drug treatment groups. RESULTS: Compared to specimens taken after antibiotics exposure, specimens taken before antibiotics exposure had a higher proportion of blood and urine specimens and a higher culture positive rate (all P < 0.001). Higher percentages of Staphylococcus aureus (9.9% vs. 8.5%, P = 0.041), non-fermenting bacteria (27.7% vs. 19.9%, P < 0.001), and fungi (8.4% vs. 4.0%, P < 0.001) were isolated from the group after antibiotics exposure, while the percentages of Streptococcus spp. (4.8% vs. 2.7%, P < 0.001), Haemophilus influenzae (2.3% vs. 0.8%, P < 0.001), and Moraxella catarrhalis (0.7% vs. 0.1%, P < 0.001) were higher in the group before antibiotics exposure. Further analysis found significant differences of microbes derived from respiratory secretions, blood or urine samples. We found, after antibiotics exposure, the separation rate of non-fermenting bacteria was significantly increased (all P < 0.05), and the separation rate of Candida spp. was higher, with statistical significance in airway secretion and urine samples (both P < 0.05), but the separation rate of Staphylococcus aureus among the three groups was not affected by antibiotics. In addition, the isolation rate of Streptococcus spp. in blood and urine samples decreased significantly (both P < 0.05) after antibiotics exposure. Interestingly, no statistical difference was found for microbes isolated from body fluid specimens between the two groups. CONCLUSIONS: The outcome revealed that antibiotic-insensitive organisms such as non-fermentative bacteria and fungi were more frequently isolated after antibiotics exposure. However, this trend might be specimen dependent and was not obvious in body fluid specimens.

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

negative: 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: From SARS to COVID-19: What we have learned about children infected with COVID-19 Abstract Coronaviruses, both SARS-CoV and SARS-CoV-2 were firstly appeared in China. They have certain similarities in biological, epidemiological and pathological. To data, the researches have shown that their gene exhibit 79% of identical sequence and the receptor-binding domain structure is also very similar. There have been extensive research performed on SARS, however, the understanding of pathophysiology impact of Corona Virus Disease 2019(COVID-19) is still limited. In the review, we draw upon the lessons learnt from SARS in the epidemiology, clinical characteristics and pathogenesis for further understand the features of COVID-19. By comparing these two diseases, we found, COVID-19 has quicker and wider transmission, obvious family agglomeration, higher morbidity and mortality. Newborns, asymptomatic children and normal chest imaging cases were emerged in COVID-19. Children started with gastrointestinal symptoms may progress to severe condition and newborn whose mother was infected with COVID-19 could have severe complications. The laboratory test data showed, the percentage of neutrophils and the level of LDH is higher, otherwise the number of CD4+ and CD8+T cells is decreased in children's COVID-19 cases. Based on these early observations, as pediatrician, we put forward some thoughts on children's COVID-19 and give some recommendations to contain the disease.

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

negative: Computed Tomography Findings and Short-term follow-up with Novel Coronavirus Pneumonia Objective: To assess the characteristics of computed tomography (CT) features and changes in CT monitoring in patients with novel coronavirus pneumonia (NCP) . Methods: In this retrospective, two-center study, we reviewed the medical records of 57 patients with NCP in CT from January 21 to February 12, 2020. Cases were confirmed by the results of nucleic acid test positive, and were analyzed for demographic, clinical, and CT features. Results: Of the 57 patients, 31cases were male, and 45.6% were female. The average age was 46.5 years. Patients had fever (84.2%), cough (49.1%), weak (31.6%), muscle ache (17.5%), shortness of breath (12.3%). The distribution of abnormality was a subpleural lesions in 51 cases, with 96.5% ground-glass opacity (GGO) and 68.4% consolidation. Another observation reveals 45.6% fibrosis, 33.3% lymph node enlargement, 21.1% pleural thickening, 17.5% small nodule, 7.0% white lung, 5.3% emphysema, and 3.5% bronchiectasis. Importantly, the group of men had more septal thickening and air trapping than the female group (p < 0.05); Compared with the younger, the elderly had higher of subpleural lesion, interlobular septal thickening and pleural thickening (p < 0.05). In the first monitoring, there were 37.3% improvement, 60.8% progress. In the second monitoring, there were 55% improvement, 35% progress. The improvement rate during the third follow-up visit was 100%. Conclusions: CT features and CT dynamic observation play a vital role in the diagnosis and treatment with NCP. It is conducive to early diagnosis, deepen the knowledge of NCP and accumulate experience.

negative: CT Features of Coronavirus Disease 2019 (COVID-19) Pneumonia in 62 Patients in Wuhan, China. OBJECTIVE. The purpose of this study was to investigate 62 subjects in Wuhan, China, with laboratory-confirmed coronavirus disease (COVID-19) pneumonia and describe the CT features of this epidemic disease. MATERIALS AND METHODS. A retrospective study of 62 consecutive patients with laboratory-confirmed COVID-19 pneumonia was performed. CT images and clinical data were reviewed. Two thoracic radiologists evaluated the distribution and CT signs of the lesions and also scored the extent of involvement of the CT signs. The Mann-Whitney U test was used to compare lesion distribution and CT scores. The chi-square test was used to compare the CT signs of early-phase versus advanced-phase COVID-19 pneumonia. RESULTS. A total of 62 patients (39 men and 23 women; mean [± SD] age, 52.8 ± 12.2 years; range, 30-77 years) with COVID-19 pneumonia were evaluated. Twenty-four of 30 patients who underwent routine blood tests (80.0%) had a decreased lymphocyte count. Of 27 patients who had their erythrocyte sedimentation rate and high-sensitivity C-reactive protein level assessed, 18 (66.7%) had an increased erythrocyte sedimentation rate, and all 27 (100.0%) had an elevated high-sensitivity C-reactive protein level. Multiple lesions were seen on the initial CT scan of 52 of 62 patients (83.9%). Forty-eight of 62 patients (77.4%) had predominantly peripheral distribution of lesions. The mean CT score for the upper zone (3.0 ± 3.4) was significantly lower than that for the middle (4.5 ± 3.8) and lower (4.5 ± 3.7) zones (p = 0.022 and p = 0.020, respectively), and there was no significant difference in the mean CT score of the middle and lower zones (p = 1.00). The mean CT score for the anterior area (4.4 ± 4.1) was significantly lower than that for the posterior area (7.7 ± 6.3) (p = 0.003). CT findings for the patients were as follows: 25 patients (40.3%) had ground-glass opacities (GGO), 21 (33.9%), consolidation; 39 (62.9%), GGO plus a reticular pattern; 34 (54.8%), vacuolar sign; 28 (45.2%), microvascular dilation sign; 35 (56.5%), fibrotic streaks; 21 (33.9%), a subpleural line; and 33 (53.2%), a subpleural transparent line. With regard to bronchial changes seen on CT, 45 patients (72.6%) had air bronchogram, and 11 (17.7%) had bronchus distortion. In terms of pleural changes, CT showed that 30 patients (48.4%) had pleural thickening, 35 (56.5%) had pleural retraction sign, and six (9.7%) had pleural effusion. Compared with early-phase disease (≤ 7 days after the onset of symptoms), advanced-phase disease (8-14 days after the onset of symptoms) was characterized by significantly increased frequencies of GGO plus a reticular pattern, vacuolar sign, fibrotic streaks, a subpleural line, a subpleural transparent line, air bronchogram, bronchus distortion, and pleural effusion; however, GGO significantly decreased in advanced-phase disease. CONCLUSION. CT examination of patients with COVID-19 pneumonia showed a mixed and diverse pattern with both lung parenchyma and the interstitium involved. Identification of GGO and a single lesion on the initial CT scan suggested early-phase disease. CT signs of aggravation and repair coexisted in advanced-phase disease. Lesions presented with a characteristic multifocal distribution in the middle and lower lung regions and in the posterior lung area. A decreased lymphocyte count and an increased high-sensitivity C-reactive protein level were the most common laboratory findings.

negative: Sensitivity of Chest CT for COVID-19: Comparison to RT-PCR

negative: Influenza Influenza, briefly known as flu, is an acute respiratory infectious disease caused by influenza virus. It spreads via droplets, with strong infectivity. Its incident rate ranks first in legal infectious diseases, with occurrences of outbreaks or pandemics. Its clinical symptoms are characterized by acute onset of high fever, fatigue, systemic muscular soreness and pain, as well as mild respiratory tract symptoms. Influenza more commonly occurs in autumns and winters. Although it has a short disease course and is self-limited, it may be complicated by pneumonia and other serious complications in populations including the elderly, infants and young children, patients with cardiac or pulmonary diseases, patients with other chronic diseases, and patients with compromised immunity. In some serious cases, death may even occur.

negative: Novel Coronavirus Outbreak in Wuhan, China, 2020: Intense Surveillance Is Vital for Preventing Sustained Transmission in New Locations The outbreak of pneumonia originating in Wuhan, China, has generated 24,500 confirmed cases, including 492 deaths, as of 5 February 2020. The virus (2019-nCoV) has spread elsewhere in China and to 24 countries, including South Korea, Thailand, Japan and USA. Fortunately, there has only been limited human-to-human transmission outside of China. Here, we assess the risk of sustained transmission whenever the coronavirus arrives in other countries. Data describing the times from symptom onset to hospitalisation for 47 patients infected early in the current outbreak are used to generate an estimate for the probability that an imported case is followed by sustained human-to-human transmission. Under the assumptions that the imported case is representative of the patients in China, and that the 2019-nCoV is similarly transmissible to the SARS coronavirus, the probability that an imported case is followed by sustained human-to-human transmission is 0.41 (credible interval [0.27, 0.55]). However, if the mean time from symptom onset to hospitalisation can be halved by intense surveillance, then the probability that an imported case leads to sustained transmission is only 0.012 (credible interval [0, 0.099]). This emphasises the importance of current surveillance efforts in countries around the world, to ensure that the ongoing outbreak will not become a global pandemic.

negative: Preliminary Results of Initial Testing for Coronavirus (COVID-19) in the Emergency Department INTRODUCTION: On March 10, 2020, the World Health Organization declared a global pandemic due to widespread infection of the novel coronavirus 2019 (COVID-19). We report the preliminary results of a targeted program of COVID-19 infection testing in the ED in the first 10 days of its initiation at our institution. METHODS: We conducted a review of prospectively collected data on all ED patients who had targeted testing for acute COVID-19 infection at two EDs during the initial 10 days of testing (March 10-19, 2020). During this initial period with limited resources, testing was targeted toward high-risk patients per Centers for Disease Control and Prevention guidelines. Data collected from patients who were tested included demographics, clinical characteristics, and test qualifying criteria. We present the data overall and by test results with descriptive statistics. RESULTS: During the 10-day study period, the combined census of the study EDs was 2157 patient encounters. A total of 283 tests were ordered in the ED. The majority of patients were 18-64 years of age, male, non-Hispanic white, had an Emergency Severity Index score of three, did not have a fever, and were discharged from the ED. A total of 29 (10.2%) tested positive. Symptoms-based criteria most associated with COVID-19 were the most common criteria identified for testing (90.6%). All other criteria were reported in 5.51-43.0% of persons being tested. Having contact with a person under investigation was significantly more common in those who tested positive compared to those who tested negative (63% vs 24.5%, respectively). The majority of patients in both results groups had at least two qualifying criteria for testing (75.2%). CONCLUSION: In this review of prospectively collected data on all ED patients who had targeted testing for acute COVID-19 infection at two EDs in the first 10 days of testing, we found that 10.2% of those tested were identified as positive. The continued monitoring of testing and results will help providers understand how COVID-19 is progressing in the community.

negative: Clinical Features, Epidemiology, and Climatic Impact of Genotype-specific Human Metapneumovirus Infections: Long-term Surveillance of Hospitalized Patients in South Korea BACKGROUND: Human metapneumovirus (hMPV) commonly causes upper and lower respiratory tract infections. Here, we performed long-term retrospective surveillance of hMPV infection among patients hospitalized in South Korea between 2007 and 2016 and investigated seasonal dynamics and clinical characteristics associated with each virus subtype/genotype. METHODS: Patient specimens were tested for hMPV and other respiratory viruses by commercial molecular assays. Medical records of hMPV-positive patients were reviewed, and hMPV subtype/genotype analysis was performed. We also collected meteorological data and analyzed relationships with hMPV activity. RESULTS: Of 23 694 specimens, 1275 (5.4%) were positive; among them, 94.0% were classified into 5 subtypes (A1, A2a, A2b, B1, and B2). Some clinical manifestations differed according to hMPV genotype; however, there was no correlation between hMPV subtype and clinical outcome. Viral activity peaked at 13–20 weeks (April and May) and was associated with climate-specific factors, including temperature, relative humidity, diurnal temperature variation, wind speed, and sunshine duration. CONCLUSIONS: This large-scale, 10-year study provides valuable information about the clinical characteristics associated with hMPV subtypes and climate factors contributing to virus transmission.

negative: End-to-End AI-Based Point-of-Care Diagnosis System for Classifying Respiratory Illnesses and Early Detection of COVID-19 Respiratory symptoms can be a caused by different underlying conditions, and are often caused by viral infections, such as Influenza-like illnesses or other emerging viruses like the Coronavirus. These respiratory viruses, often, have common symptoms, including coughing, high temperature, congested nose, and difficulty breathing. However, early diagnosis of the type of the virus, can be crucial, especially in cases such as the recent COVID-19 pandemic. One of the factors that contributed to the spread of the pandemic, was the late diagnosis or confusing it with regular flu-like symptoms. Science has proved that one of the possible differentiators of the underlying causes of these different respiratory diseases is coughing, which comes in different types and forms. Therefore, a reliable lab-free tool for early and more accurate diagnosis that can differentiate between different respiratory diseases is very much needed. This paper proposes an end-to-end portable system that can record data from patients with symptom, including coughs (voluntary or involuntary) and translate them into health data for diagnosis, and with the aid of machine learning, classify them into different respiratory illnesses, including COVID-19. With the ongoing efforts to stop the spread of the COVID-19 disease everywhere today, and against similar diseases in the future, our proposed low cost and user-friendly solution can play an important part in the early diagnosis.

negative: A considerable proportion of individuals with asymptomatic SARS-CoV-2 infection in Tibetan population Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) quickly became a major epidemic threat in the whole China. We analysed SARS-Cov-2 infected cases from Tibetan Autonomous Prefecture, and noted divergent characteristics of these Tibetans infected cases compared to Han Chinese, characterizing by a considerable proportion of asymptomatic carriers (21.7%), and few symptomatic patients with initial symptom of fever (7.7%). Here, we did a descriptive study on clinical characteristics of 18 asymptomatic individuals with SARS-CoV-2 infection. The median age of these asymptomatic carriers was 31 years and one third of them were students, aged under 20 years. Notably, some of asymptomatic carriers had recognizable changes in radiological and laboratory indexes. Our finding indicates a potentially big number of SARS-CoV-2 asymptomatic carriers in prevalent area, highlighting a necessity of screening individuals with close contact of infected patients, for a better control on the spread of SARS-CoV-2 infection.

negative: The association of SARS-CoV-2 infection and acute disseminated encephalomyelitis without prominent clinical pulmonary symptoms • We describe a patient with acute disseminated encephalitis and COVID-19. • CNS manifestations primarily occurred without evident pulmonary symptoms. • Brain MRI of the patient indicated diffuse confluent white matter hyperintensities. • The patient initially responded to steroids but lastly, died of status epilepticus. • The occurrence of acute disseminated encephalitis may have been immune-mediated.

negative: Coronavirus and Other Respiratory Illnesses Comparing Older with Young Adults Abstract Background Study of human coronavirus and other virus-associated respiratory illnesses is needed to describe their clinical effects on chronically ill, older adults. Methods A prospective study during 2009 to 2013 clinically assessed acute respiratory illnesses soon after onset and 3 to 4 weeks later in patients aged ≥60 years with chronic lung and heart diseases (group 1, 100 subjects) and healthy adults aged 18 to 40 years (group 2, 101 subjects). Respiratory secretions were tested for nucleic acids of a panel of respiratory viruses. An increase in antibody titer was assessed for 4 coronavirus strains. Results Virus-associated illnesses (29 [39.1%] of 74 illnesses in group 1 and 59 [48.7%] of 121 illnesses in group 2) occurred in all calendar quarters, most commonly in the first and fourth quarters. Coronaviruses (group 1: 14 [18.9%] illnesses; group 2: 26 [21.5%] illnesses) and enteroviruses/rhinoviruses (group 1: 14 [18.9%] illnesses; group 2: 37 [30.6%] illnesses) were most common. Virus co-infections occurred in 10 illnesses. Illnesses with 9 to 11 symptoms were more common in group 1 (17 [23.0%]) than in group 2 (15 [12.4%]) (P < .05). Compared with group 2, more group 1 subjects reported dyspnea, more severe disease of longer duration, and treatment for acute illness with prednisone and antibiotics. Coronavirus-associated illnesses (percent of illnesses, group 1 vs group 2) were characterized by myalgias (21% vs 68%, P < .01), chills (50% vs 52%), dyspnea (71% vs 24%, P < .01), headache (64% vs 72%), malaise (64% vs 84%), cough (86% vs 68%), sputum production (86% vs 60%), sore throat (64% vs 80%), and nasal congestion (93% vs 96%). Conclusions Respiratory illnesses were commonly associated with coronaviruses and enteroviruses/rhinoviruses affecting chronically ill, older patients more than healthy, young adults.

negative: COVID-19: Global radiation oncology’s targeted response for pandemic preparedness Abstract As the global COVID-19 pandemic escalates there is a need within radiation oncology to work to support our patients in the best way possible. Measures are required to reduce infection spread between patients and within the workforce. Departments need contingency planning to create capacity and continue essential treatments despite a reduced workforce. The #radonc community held an urgent online journal club on Twitter in March 2020 to discuss these issues and create some consensus on crucial next steps. There were 121 global contributors. This document summarises these discussions around themes of infection prevention, rationalisation of workload and working practice in the presence of infection.

negative: Evaluation and Management of Bacterial and Fungal Infections Occurring in Patients with a Hematological Malignancy: A 2011 Update Patients with a hematological malignancy are a heterogeneous patient population who are afflicted with diseases that range from rapidly fatal acute leukemia to indolent lymphoma or chronic leukemia. Treatment options for these patients range from observation to hematopoietic stem cell transplantation (HSCT), but all patients are more susceptible to infection. The problem of infection is dynamic with continued shifts in pathogenic organisms and microbial susceptibilities, new treatment regimens that further diminish immune function, and patients receiving treatment who are now older and frailer. The classic patterns of immunodeficiency for patients with a hematological malignancy include: periods of profound neutropenia, increased iatrogenic risks (i.e., central vascular catheters), and cellular immune suppression that affects HSCT recipients, patients with lymphoid malignancies, and those receiving treatment with corticosteroids or agents like alemtuzumab [1–4]. Recent advances in antimicrobial drug development, new technology, clinical trial results, and further clinical experience have enhanced the database on which to make infection prophylaxis and treatment decisions. However, the practicing clinician must remember that the majority of basic infection management principles for patients who are neutropenic remain unchanged.

negative: Combining Clinical and Epidemiologic Features for Early Recognition of SARS Early recognition and rapid initiation of infection control precautions are currently the most important strategies for controlling severe acute respiratory syndrome (SARS). No rapid diagnostic tests currently exist that can rule out SARS among patients with febrile respiratory illnesses. Clinical features alone cannot with certainty distinguish SARS from other respiratory illnesses rapidly enough to inform early management decisions. A balanced approach to screening that allows early recognition of SARS without unnecessary isolation of patients with other respiratory illnesses will require clinicians not only to look for suggestive clinical features but also to routinely seek epidemiologic clues suggestive of SARS coronavirus exposure. Key epidemiologic risk factors include 1) exposure to settings where SARS activity is suspected or documented, or 2) in the absence of such exposure, epidemiologic linkage to other persons with pneumonia (i.e., pneumonia clusters), or 3) exposure to healthcare settings. When combined with clinical findings, these epidemiologic features provide a possible strategic framework for early recognition of SARS.

negative: Characteristics of patients with coronavirus disease (COVID‐19) confirmed using an IgM‐IgG antibody test Coronavirus disease (COVID‐19), caused by a novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has rapidly developed into a pandemic since it was first reported in December 2019. Nucleic acid testing is the standard method for the diagnosis of viral infections. However, this method reportedly has a low positivity rate. To increase the sensitivity of COVID‐19 diagnoses, we developed an IgM‐IgG combined assay and tested it in patients with suspected SARS‐CoV‐2 infection. In total, 56 patients were enrolled in this study and SARS‐CoV‐2 was detected by using both IgM‐IgG antibody and nucleic acid tests. Clinical and laboratory data were collected and analyzed. Our findings suggest that patients who develop severe illness might experience longer virus exposure times and develop a more severe inflammatory response. The IgM‐IgG test is an accurate and sensitive diagnostic method. A combination of nucleic acid and IgM‐IgG testing is a more sensitive and accurate approach for diagnosis and early treatment of COVID‐19.

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

negative: [COVID-19 Crisis: Early Observations on a Pandemic's Psychiatric Problems]. We have recently observed several clusters of psychiatric symptoms in the context of COVID-19: (1) increased anxiety in psychiatric in- and outpatients with different diagnoses; (2) more cases of domestic violence often associated with increased drug- or alcohol-consumption in offenders and victims; (3) a nihilistic "apocalyptic" syndrome of elderly patients cut-off from their families; (4) visual and acoustic hallucinoses due to pneumonia and sepsis-related confusional states. Cases of chloroquine-related toxicity have been reported elsewhere, but have not been observed in our hospital so far. Mental issues related to COVID-19 reported from China and practical recommendations are briefly summarized. Many patients with serious mental disorders will suffer world-wide due to a reallocation of medical, social and financial ressources.

negative: The role of asymptomatic SARS-CoV-2 infections: rapid living systematic review and meta-analysis Background: There is substantial disagreement about the level of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a population. The disagreement results, in part, from the interpretation of studies that report a proportion of asymptomatic people with SARS-CoV-2 detected at a single point. Review questions: 1. Amongst people who become infected with SARS-CoV-2, what proportion does not experience symptoms at all during their infection? 2. Amongst people with SARS-CoV-2 infection who are asymptomatic when diagnosed, what proportion will develop symptoms later? 3. What proportion of SARS-CoV-2 transmission is accounted for by people who are either asymptomatic throughout infection, or pre-symptomatic? Methods: Rapid living systematic review (protocol https://osf.io/9ewys/). We searched Pubmed, Embase, bioRxiv and medRxiv using a living evidence database of SARS-CoV-2 literature on 25.03.2020. We included studies of people with SARS-CoV-2 diagnosed by reverse transcriptase PCR (RT-PCR) that documented follow-up and symptom status at the beginning and end of follow-up and modelling studies. Study selection, data extraction and bias assessment were done by one reviewer and verified by a second, with disagreement resolved by discussion or a third reviewer. We used a common-effect model to synthesise proportions from comparable studies. Results: We screened 89 studies and included 11. We estimated an upper bound for the proportion of asymptomatic SARS-CoV-2 infections of 29% (95% confidence interval 23 to 37%) in eight studies. Selection bias and likely publication bias affected the family case investigation studies. One statistical modelling study estimated the true proportion of asymptomatic infections at 18% (95% credibility interval 16 to 20%). Estimates of the proportions of pre-symptomatic individual in four studies were too heterogeneous to combine. In modelling studies, 40-60% of all SARS-CoV-2 infections are the result of transmission from pre-symptomatic individuals, with a smaller contribution from asymptomatic individuals. Conclusions: An intermediate contribution of pre-symptomatic and asymptomatic infections to overall SARS-CoV-2 transmission means that combination prevention, with enhanced hand and respiratory hygiene, testing tracing and isolation strategies and social distancing, will continue to be needed. The findings of this systematic review of publications early in the pandemic suggests that most SARS-CoV-2 infections are not asymptomatic throughout the course of infection.

negative: Liver Disease Associated with Non-Hepatitis Viruses Abstract Hepatitis is commonly associated with certain viruses labeled as “Hepatitis” viruses. However, many other viral infections can also affect the liver ranging from mild asymptomatic elevations of aminotransferases to fulminant hepatic failure. This article will provide a brief overview on a variety of different viral infections that may be associated with significant liver pathology at least under certain conditions, for example, immunosuppression. This overview discusses key virological features, clinical presentation of associated liver disease and provides some information on diagnosis and an outline of treatment options. Thus, the overview can provide first orientation when infectious hepatitis is encountered in a patient that cannot be explained by the usual hepatitis viruses.

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: Labor and delivery guidance for COVID-19 This document addresses the current coronavirus disease 2019 (COVID-19) pandemic for providers and patients in labor and delivery (L&D). The goals are to provide guidance regarding methods to appropriately screen and test pregnant patients for COVID-19 prior to, and at admission to L&D reduce risk of maternal and neonatal COVID-19 disease through minimizing hospital contact and appropriate isolation; and provide specific guidance for management of L&D of the COVID-19–positive woman, as well as the critically ill COVID-19–positive woman. The first 5 sections deal with L&D issues in general, for all women, during the COVID-19 pandemic. These include Section 1: Appropriate screening, testing, and preparation of pregnant women for COVID-19 before visit and/or admission to L&D Section 2: Screening of patients coming to L&D triage; Section 3: General changes to routine L&D work flow; Section 4: Intrapartum care; Section 5: Postpartum care; Section 6 deals with special care for the COVID-19–positive or suspected pregnant woman in L&D and Section 7 deals with the COVID-19–positive/suspected woman who is critically ill. These are suggestions, which can be adapted to local needs and capabilities.

negative: Core Outcome Set for Clinical Trials on Coronavirus Disease 2019 (COS-COVID) Abstract Since its outbreak in December 2019, a series of clinical trials on Coronavirus Disease 2019 (COVID-19) have been registered or carried out. However, the significant heterogeneity and less critical outcomes of such trials may be leading to a waste of research resources. This study aimed to develop a core outcome set (COS) for clinical trials on COVID-19 in order to tackle the outcome issues. The study was conducted according to the Core Outcome Measures in Effectiveness Trials (COMET) handbook (version 1.0), a guideline for COS development. A research group was set up that included experts in respiratory and critical medicine, traditional Chinese medicine, evidence-based medicine, clinical pharmacology, and statistics, in addition to medical journal editors. Clinical trial registry websites (chictr.org.cn and clinicaltrials.gov) were searched to retrieve clinical trial protocols and outcomes in order to form an outcome pool. A total of 78 clinical trial protocols on COVID-19 were included and 259 outcomes were collected. After standardization, 132 outcomes were identified within seven different categories, of which 58 were selected to develop a preliminary outcome list for further consensus. After two rounds of Delphi survey and one consensus meeting, the most important outcomes for the different clinical classifications of COVID-19 were identified and determined to constitute the COS for clinical trials on COVID-19 (COS-COVID). The COS-COVID includes one outcome for the mild type (time to 2019-nCoV reverse transcription-polymerase chain reaction (RT-PCR) negativity), four outcomes for the ordinary type (length of hospital stay, composite events, score of clinical symptoms, and time to 2019-nCoV RT-PCR negativity), five outcomes for the severe type (composite events, length of hospital stay, arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (FiO2), duration of mechanical ventilation, and time to 2019-nCoV RT-PCR negativity), one outcome for critical type (all-cause mortality), and one outcome for rehabilitation period (pulmonary function). The COS-COVID is currently the most valuable and practical clinical outcome set for the evaluation of intervention effect, and is useful for evidence assessment and decision-making. With a deepening understanding of COVID-19 and application feedback, the COS-COVID should be continuously updated.

negative: Broadly targeted multiprobe QPCR for detection of coronaviruses: Coronavirus is common among mallard ducks (Anas platyrhynchos) Abstract Coronaviruses (CoVs) can cause trivial or fatal disease in humans and in animals. Detection methods for a wide range of CoVs are needed, to understand viral evolution, host range, transmission and maintenance in reservoirs. A new concept, “Multiprobe QPCR”, which uses a balanced mixture of competing discrete non- or moderately degenerated nuclease degradable (TaqMan®) probes was employed. It provides a broadly targeted and rational single tube real-time reverse transcription PCR (“NQPCR”) for the generic detection and discovery of CoV. Degenerate primers, previously published, and the new probes, were from a conserved stretch of open reading frame 1b, encoding the replicase. This multiprobe design reduced the degree of probe degeneration, which otherwise decreases the sensitivity, and allowed a preliminary classification of the amplified sequence directly from the QPCR trace. The split probe strategy allowed detection of down to 10 viral nucleic acid equivalents of CoV from all known CoV groups. Evaluation was with reference CoV strains, synthetic targets, human respiratory samples and avian fecal samples. Infectious-Bronchitis-Virus (IBV)-related variants were found in 7 of 35 sample pools, from 100 wild mallards (Anas platyrhynchos). Ducks may spread and harbour CoVs. NQPCR can detect a wide range of CoVs, as illustrated for humans and ducks.

negative: Consistency analysis of COVID-19 nucleic acid tests and the changes of lung CT Abstract Background COVID-19, the latest outbreak of infectious disease, has caused huge medical challenges to China and the entire globe. No unified diagnostic standard has been formulated. The initial diagnosis remains based on the positive of nucleic acid tests. However, early nucleic acid tests were identified to be negative in some patients, whereas the patients exhibited characteristic CT changes of lung, and positive test results appeared after repeated nucleic acid tests, having caused the failure to diagnose these patients early. The study aimed to delve into the relationships between initial nucleic acid testing and early lung CT changes in patients with COVID-19. Method In accordance with the latest COVID-19 diagnostic criteria, 69 patients diagnosed with COVID-19 treated in the infected V ward of Xiaogan Central Hospital from 2020/1/25 to 2020/2/6 were retrospectively analyzed. The consistency between the first COVID-19 nucleic acid test positive and lung CT changes was studied. In addition, the sensitivity and specificity of CT and initial nucleic acid were studied. Result The Kappa coefficient of initial nucleic acid positive changes and lung CT changes was −1.52. With a positive nucleic acid test as the gold standard, the sensitivity of lung CT was 12.00 %, 95 % CI: 4.6–24.3; with the changes of CT as the gold standard, the sensitivity of nucleic acid positive was 30.16 %, 95 % CI: 19.2−43.0. Conclusion The consistency between the initial positive nucleic acid test and the CT changes in the lungs is poor; low sensitivity was achieved for initial nucleic acid detection and CT changes.

negative: Acute care issues in internationally adopted children Over the past decade there has been a dramatic increase in international adoptions in the United States. While most adopted children will have common illnesses, others may have unique medical issues as a result of the conditions in their birth country requiring a broadened differential diagnosis. Knowledge of these issues is essential in the management of these patients. This review will predominately focus on infectious disease issues commonly seen in international adoptees but will also discuss other medical conditions and some of the psychosocial issues which may be encountered by caregivers in the emergency department.

negative: Diagnosis of COVID-19: Considerations, controversies and challenges Coronavirus disease 2019 (COVID-19) due to a novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic that has resulted in over 1.5 million confirmed cases and close to 100 000 deaths. In the majority of symptomatic cases, COVID-19 results in a mild disease predominantly characterised by upper respiratory tract symptoms. Reverse transcription polymerase chain reaction (RT-PCR) using a nasopharyngeal sample is the mainstay of diagnosis, but there is an ~30% false negative rate early in the disease and in patients with mild disease, and therefore repeat testing may be required. RT-PCR positivity can persist for several days after resolution of symptoms. IgM and IgG antibody responses become positive several days after the onset of symptoms, and robust antibody responses are detectable in the second week of illness. Antibody-based immunoassays have a limited role in the diagnosis of early symptomatic disease. However, their incremental benefit over RT-PCR in the first 2 weeks of illness is currently being clarified in ongoing studies. Such assays may be useful for surveillance purposes. However, their role in potentially selecting individuals who may benefit from vaccination, or as a biomarker identifying persons who could be redeployed into essential employment roles, is being investigated. Rapid antibody-based immunoassays that detect viral antigen in nasopharyngeal samples are being developed and evaluated.

negative: Detecting specific infections in children through host responses: a paradigm shift. PURPOSE OF REVIEW There is a need for improved diagnosis and for optimal classification of patients with infectious diseases. An alternative approach to the pathogen-detection strategy is based on a comprehensive analysis of the host response to the infection. This review focuses on the value of transcriptome analyses of blood leukocytes for the diagnosis and management of patients with infectious diseases. RECENT FINDINGS Initial studies showed that RNA from blood leukocytes of children with acute viral and bacterial infections carried pathogen-specific transcriptional signatures. Subsequently, transcriptional signatures for several other infections have been described and validated in humans with malaria, dengue, salmonella, melioidosis, respiratory syncytial virus, influenza, tuberculosis, and HIV. In addition, transcriptome analyses represent an invaluable tool to understand disease pathogenesis and to objectively classify patients according to the clinical severity. SUMMARY Microarray studies have been shown to be highly reproducible using different platforms, and in different patient populations, confirming the value of blood transcriptome analyses to study pathogen-specific host immune responses in the clinical setting. Combining the detection of the pathogen with a comprehensive assessment of the host immune response will provide a new understanding of the correlations between specific causative agents, the host response, and the clinical manifestations of the disease.

negative: Recently Discovered Human Coronaviruses In marked contrast to their historical classification as relatively harmless, common cold-causing, respiratory pathogens, human coronaviruses (HCoVs) are associated with more severe clinical complications, as emphasized by the discovery of severe acute respiratory syndrome-associated CoV (SARS-CoV) in 2003. Still, their precise pathogenic potential is largely unknown, particularly regarding the most recently identified strains HCoV-NL63 and HCoV-HKU1, and definite proof for their etiology remains a major challenge. This article focuses on the characteristics of the five HCoVs that are known, and summarizes current knowledge of their pathogenic potential in people, with an emphasis on the interactions between these viruses and their cognate receptors on susceptible target cells.

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: 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: COVID-19 Drug Discovery Using Intensive Approaches Since the infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in China during December 2019, the coronavirus disease 2019 (COVID-19) has spread on a global scale, causing the World Health Organization (WHO) to issue a warning. While novel vaccines and drugs that target SARS-CoV-2 are under development, this review provides information on therapeutics which are under clinical trials or are proposed to antagonize SARS-CoV-2. Based on the information gained from the responses to other RNA coronaviruses, including the strains that cause severe acute respiratory syndrome (SARS)-coronaviruses and Middle East respiratory syndrome (MERS), drug repurposing might be a viable strategy. Since several antiviral therapies can inhibit viral replication cycles or relieve symptoms, mechanisms unique to RNA viruses will be important for the clinical development of antivirals against SARS-CoV-2. Given that several currently marketed drugs may be efficient therapeutic agents for severe COVID-19 cases, they may be beneficial for future viral pandemics and other infections caused by RNA viruses when standard treatments are unavailable.

negative: 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.

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

negative: Can Unconventional Immunomodulatory Agents Help Alleviate COVID-19 Symptoms and Severity? Severe acute respiratory syndrome coronavirus 2 (SARS coronavirus 2, or SARS-CoV-2) is the cause of the respiratory infection known as COVID-19. From an immunopathological standpoint, coronaviruses such as SARS-CoV-2 induce increased levels of a variety of T-helper 1 (Th1) and inflammatory cytokines and chemokines, including interleukin-1 (IL-1), IL-6, CCL2 protein, and CXCL10 protein. In the absence of proven antiviral agents or an effective vaccine, substances with immunomodulatory activity may be able to inhibit inflammatory and Th1 cytokines and/or yield an anti-inflammatory and/or Th2 immune response to counteract COVID-19 symptoms and severity. This report briefly describes the following four unconventional but commercially accessible immunomodulatory agents that can be employed in clinical trials to evaluate their effectiveness at alleviating disease symptoms and severity: low-dose oral interferon alpha, microdose DNA, low-dose thimerosal, and phytocannabinoids.

negative: A Practical Approach to the Management of Cancer Patients During the Novel Coronavirus Disease 2019 (COVID‐19) Pandemic: An International Collaborative Group The outbreak of coronavirus disease 2019 (COVID‐19) has rapidly spread globally since being identified as a public health emergency of major international concern and has now been declared a pandemic by the World Health Organization (WHO). In December 2019, an outbreak of atypical pneumonia, known as COVID‐19, was identified in Wuhan, China. The newly identified zoonotic coronavirus, severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), is characterized by rapid human‐to‐human transmission. Many cancer patients frequently visit the hospital for treatment and disease surveillance. They may be immunocompromised due to the underlying malignancy or anticancer therapy and are at higher risk of developing infections. Several factors increase the risk of infection, and cancer patients commonly have multiple risk factors. Cancer patients appear to have an estimated twofold increased risk of contracting SARS‐CoV‐2 than the general population. With the WHO declaring the novel coronavirus outbreak a pandemic, there is an urgent need to address the impact of such a pandemic on cancer patients. This include changes to resource allocation, clinical care, and the consent process during a pandemic. Currently and due to limited data, there are no international guidelines to address the management of cancer patients in any infectious pandemic. In this review, the potential challenges associated with managing cancer patients during the COVID‐19 infection pandemic will be addressed, with suggestions of some practical approaches. IMPLICATIONS FOR PRACTICE: The main management strategies for treating cancer patients during the COVID‐19 epidemic include clear communication and education about hand hygiene, infection control measures, high‐risk exposure, and the signs and symptoms of COVID‐19. Consideration of risk and benefit for active intervention in the cancer population must be individualized. Postponing elective surgery or adjuvant chemotherapy for cancer patients with low risk of progression should be considered on a case‐by‐case basis. Minimizing outpatient visits can help to mitigate exposure and possible further transmission. Telemedicine may be used to support patients to minimize number of visits and risk of exposure. More research is needed to better understand SARS‐CoV‐2 virology and epidemiology.

negative: The outlook for diagnostic purposes of the 2019‐novel coronavirus disease At the end of December 2019, a novel acute respiratory syndrome coronavirus 2 (SARS‐CoV2) appeared as the third unheard of outbreak of human coronavirus infection in the 21st century. First, in Wuhan, China, the novel SARS‐CoV2 was named by the World Health Organization (WHO), as 2019‐nCOV (COVID‐19), and spread extremely all over the world. SARS‐CoV2 is transmitted to individuals by human‐to‐human transmission leading to severe viral pneumonia and respiratory system injury. SARS‐CoV2 elicits infections from the common cold to severe conditions accompanied by lung injury, acute respiratory distress syndrome, and other organ destruction. There is a possibility of virus transmission from asymptomatic cases as active carriers, in addition to symptomatic ones, which is a crucial crisis of COVID‐19 that should be considered. Hence, paying more attention to the accurate and immediate diagnosis of suspected and infected cases can be a great help in preventing the rapid spread of the virus, improving the disease prognosis, and controlling the pandemic. In this review, we provide a comprehensive and up‐to‐date overview of the different types of Clinical and Para‐clinical diagnostic methods and their practical features, which can help understand better the applications and capacities of various diagnostic approaches for COVID‐19 infected cases.

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

negative: Early outcomes of tocilizumab in adults hospitalized with severe COVID19. An initial report from the Vall dHebron COVID19 prospective cohort study. Background: Modulation of the immune system to prevent lung injury is being widely used against the new coronavirus disease (COVID19) despite the scarcity of evidence. Methods: We report preliminary results from the Vall dHebron prospective cohort study at Vall dHebron University Hospital, in Barcelona (Spain), including all consecutive patients who had a confirmed infection with the severe acute respiratory syndrome coronavirus2 (SARSCoV2) and who were treated with tocilizumab until March 25th. The primary endpoint was mortality at 7 days after tocilizumab administration. Secondary endpoints were admission to the intensive care unit, development of ARDS and respiratory insufficiency among others. Results: 82 patients with COVID19 received at least one dose of tocilizumab. The mean (SD) age was 59.1 (19.8) years, 63% were male, 22% were of non Spanish ancestry, and the median (IQR) ageadjusted Charlson index at baseline was 3 (1 to 4) points. Respiratory failure and ARDS developed in 62 (75.6%) and 45 (54.9%) patients, respectively. Median time from symptom onset to ARDS development was 8 (5 to 11) days. The median time from symptom onset to the first dose of tocilizumab was 9 (7 to 11) days. Mortality at 7 days was 26.8%. Hazard ratio for mortality was 3.3; 95% CI, 1.3 to 8.5 (age adjusted hazard ratio for mortality 2.1; 95% CI, 0.8 to 5.8) if tocilizumab was administered after the onset of ARDS. Conclusion: Time from lung injury onset to tocilizumab administration may be critical to patient recovery. Our preliminary data could inform bedside decisions until more data from clinical trials becomes available.

negative: Determination of host proteins composing the microenvironment of coronavirus replicase complexes by proximity-labeling Positive-sense RNA viruses hijack intracellular membranes that provide niches for viral RNA synthesis and a platform for interactions with host proteins. However, little is known about host factors at the interface between replicase complexes and the host cytoplasm. We engineered a biotin ligase into a coronaviral replication/transcription complex (RTC) and identified >500 host proteins constituting the RTC microenvironment. siRNA-silencing of each RTC-proximal host factor demonstrated importance of vesicular trafficking pathways, ubiquitin-dependent and autophagy-related processes, and translation initiation factors. Notably, detection of translation initiation factors at the RTC was instrumental to visualize and demonstrate active translation proximal to replication complexes of several coronaviruses. Collectively, we establish a spatial link between viral RNA synthesis and diverse host factors of unprecedented breadth. Our data may serve as a paradigm for other positive-strand RNA viruses and provide a starting point for a comprehensive analysis of critical virus-host interactions that represent targets for therapeutic intervention.

negative: Severe pneumonia due to infection with Candida krusei in a case of suspected Middle East respiratory syndrome: A case report and literature review. Candida krusei (C. krusei) pneumonia is a rare infection that is frequently associated with a poor outcome. The present study reports an unusual case of C. krusei pneumonia that was initially suspected to be a Middle East respiratory syndrome (MERS) case. A 64-year-old Saudi Arabian male patient was admitted to our hospital with complaints of cough and dyspnea that persisted for 6 days. The patient presented fever (oral temperature, 38.5°C) and slight tachypnea (25 respirations/min). A chest computerized tomography demonstrated unclear lung fields, diffuse pathological changes in the two lungs and multiple lymphadenectasis in the retrocaval and para-aortic arch area. The patient received 95-98% oxygen (6 l/min) for 24 h, as well as sulbactam sodium/cefoperazone sodium (1:1) injection (3.0 g) every 12 h, oral oseltamivir capsules (75 mg/time) twice a day, medaron injection (80 mg/time) and 750 ml fluid infusion; however, he succumbed to the disease on day 2 after admission. The infection was diagnosed by sputum smear and culture subsequent to patient mortality. A sputum smear showed a large fungal infection and sputum culture revealed the presence of C. krusei infection. Serum procalcitonin concentrations were 4.73 µg/l and 7.23 µg/l on days 2 and 3 after admission, respectively. In conclusion, the diagnosis of Candida pneumonia should be strongly considered in the presence of growth of Candida from a sputum culture and based on a suggestive computed tomography image. Tumescent diaphragmatic lymph nodes may also be an important symptom of Candida pneumonia. Treatment should be initiated immediately to improve tissue oxygenation, restore cardiovascular function and improve other organ functions.

negative: Cardiopulmonary Resuscitation for Ebola patients: Ethical considerations

negative: Perinatal depressive and anxiety symptoms of pregnant women along with COVID-19 outbreak in China Abstract Background On January 20, 2020, a new coronavirus epidemic with “human-to-human” transmission was officially announced by the Chinese government, which caused significant public panic in China. Pregnant women may be particularly vulnerable and in special need for preventative mental health strategies. Thus far, no reports exist to investigate the mental health response of pregnant women to the COVID-19 outbreak. Objective The aim of the present study is to examine the impact of COVID-19 outbreak on the prevalence of depressive and anxiety symptoms and the corresponding risk factors among pregnant women across China. Study Design A multi-center cross-sectional study was initiated in early December 2019 to identify mental health concerns in pregnancy using the Edinburgh Postnatal Depression Scale (EPDS). This study provided a unique opportunity to compare the mental status of pregnant women before and after the announcement of the COVID-19 epidemic. A total of 4124 pregnant women during their third trimester from 25 hospitals in 10 provinces across China were examined in this cross-sectional study from January 1 to February 9, 2020. Of these women, 1285 were assessed after January 20, 2020 when the coronavirus epidemic was publically announced and 2839 were assessed before this pivotal time point. The internationally recommended EPDS was used to assess maternal depression and anxiety symptoms. Prevalence rates and risk factors were compared between the pre and post study groups. Results Pregnant women assessed after the declaration of COVID-19 epidemic had significantly higher rates of depressive symptoms (26.0% vs 29.6%, P=0.02) than women assess pre-epidemic announcement. These women were also more likely to endorse thoughts of self-harm (P=0.005). The depressive rates were positively associated with the number of newly-confirmed COVID-19 cases (P=0.003), suspected infections (P=0.004), and death cases per day (P=0.001). Pregnant women who were underweight pre-pregnancy, primiparous, < 35 years old, employed full-time, middle income, and had appropriate living space were at increased risk to develop depressive and anxiety symptoms during the outbreak. Conclusion Major life-threatening public health events such as the COVID-19 outbreak may increase the risk for mental illness among pregnant women including thoughts of self-harm. Strategies targeting maternal stress and isolation such as effective risk communication and the provision of psychological first aid may be particularly useful to prevent negative outcomes for women and their fetuses.

negative: Tick-Borne Bacterial, Rickettsial, Spirochetal, and Protozoal Diseases Approximately 900 tick species exist worldwide, parasitizing a broad array of mammals, including humans, and thereby playing a significant role in the transmission of infectious diseases (1). In the United States, tick-borne diseases are generally seasonal and geographically distributed. They occur mostly during the spring and summer but can occur throughout the year.

negative: Antiviral activity of dried extract of Stevia The biological (antiviral) activity of a dried purified extract of Stevia was evaluated in vitro. Tests were performed using Teschen disease virus, infectious rhinotracheitis virus, and human coronavirus.

negative: Case Studies Ms A was a 28 year old woman in her second pregnancy (she had one previous termination of pregnancy) who booked-in at 19 weeks’ gestation. She was known to have sickle cell disease (specifically sickle cell anaemia [HbSS]), and her last crisis had occurred 3 years before this pregnancy.

negative: Prevention of Experimental Coronavirus Colds with Intranasal α-2b Interferon Fifty-five volunteers treated with either intranasal recombinant interferon (rIFN; 2 × 10(6) IU/day) or placebo for 15 days were exposed to coronavirus by direct intranasal inoculation on the eighth day of treatment. Symptom scores were recorded, and cultures of virus were taken daily for all volunteers for seven days after inoculation. Nineteen (73%) of the 26 placebo recipients met symptom-score criteria for a cold, compared with 12 (41%) of the IFN recipients (P = .02). The mean nasal symptom scores in the placebo and IFN groups were 9.2 and 5.4, respectively (P = .03), and the mean total symptom scores in the two groups were 23.2 and 9.4, respectively (P = .003). The mean number of days with a total symptom score >4 was 1.6 in the placebo recipients and 0.5 in the rIFN recipients (P = .02). Prophylactic intranasal rIFN effectively shortened the duration and reduced the severity of coronavirus cold symptoms.

negative: Assessing the anxiety level of Iranian general population during COVID-19 outbreak Abstract This study is aimed to assess the anxiety level of Iranian general population during COVID-19 outbreak. The online questionnaire surveyed 10,754 individuals from the general population of 31 provinces of Iran who completed the questionnaire on social networks from March 1 to March 9, 2020. The inferential statistics suggests that the level of anxiety was higher among women (95 % CI [0.1, 81.36], p < 0.001), people who more followed corona-related news (p < 0.001) and the age group of 21–40 years (p < 0.001). Ultimately, the level of anxiety was significantly higher among people who had at least one family member, relative, or friend who contracted COVID-19 disease (95 % CI [1.2, 35.03], p < 0.001). The health care system should adopt a package of psychosocial interventions to reduce the anxiety of high risk groups.

negative: Characteristics of Ocular Findings of Patients With Coronavirus Disease 2019 (COVID-19) in Hubei Province, China IMPORTANCE: While the outbreak of coronavirus disease 2019 (COVID-19) has resulted in more than 100 000 infected individuals in China and worldwide, there are few reports on the association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with ocular abnormalities. Understanding ocular manifestations of patients with COVID-19 by ophthalmologists and others may facilitate the diagnosis and prevention of transmission of the disease. OBJECTIVE: To investigate ocular manifestations and viral prevalence in the conjunctiva of patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: In this case series, patients with COVID-19 treated from February 9 to 15, 2020, at a hospital center in Hubei province, China, were retrospectively reviewed for ocular manifestations. During the period of treatment, the ocular signs and symptoms as well as results of blood tests and reverse transcriptase–polymerase chain reaction (RT-PCR) from nasopharyngeal and conjunctival swabs for SARS-CoV-2 were noted and analyzed. MAIN OUTCOMES AND MEASURES: Ocular signs and symptoms as well as results of blood tests and RT-PCR for SARS-CoV-2. RESULTS: Of the 38 included patients with clinically confirmed COVID-19, 25 (65.8%) were male, and the mean (SD) age was 65.8 (16.6) years. Among them, 28 patients (73.7%) had positive findings for COVID-19 on RT-PCR from nasopharyngeal swabs, and of these, 2 patients (5.2%) yielded positive findings for SARS-CoV-2 in their conjunctival as well as nasopharyngeal specimens. A total of 12 of 38 patients (31.6%; 95% CI, 17.5-48.7) had ocular manifestations consistent with conjunctivitis, including conjunctival hyperemia, chemosis, epiphora, or increased secretions. By univariate analysis, patients with ocular symptoms were more likely to have higher white blood cell and neutrophil counts and higher levels of procalcitonin, C-reactive protein, and lactate dehydrogenase than patients without ocular symptoms. In addition, 11 of 12 patients with ocular abnormalities (91.7%; 95% CI, 61.5-99.8) had positive results for SARS-CoV-2 on RT-PCR from nasopharyngeal swabs. Of these, 2 (16.7%) had positive results for SARS-CoV-2 on RT-PCR from both conjunctival and nasopharyngeal swabs. CONCLUSIONS AND RELEVANCE: In this study, one-third of patients with COVID-19 had ocular abnormalities, which frequently occurred in patients with more severe COVID-19. Although there is a low prevalence of SARS-CoV-2 in tears, it is possible to transmit via the eyes.

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

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

negative: Multiple Presentations of LRBA Deficiency: a Single-Center Experience INTRODUCTION: LPS-responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency categorized as common variable immunodeficiency associated with autoimmune manifestations and inflammatory bowel diseases; however, the clinical spectrum has been extended. Here, we present our cohort of Turkish LRBA-deficient patients from a single center, demonstrating a diversity of clinical manifestations. METHOD: Seven affected individuals from five families were assessed retrospectively in this study. RESULTS: Of the seven patients with LRBA deficiency, four had homozygous, and two had compound heterozygous mutations. One patient remained disease free until the last follow-up (age 17 years). The most common clinical manifestations of the six symptomatic patients were organomegaly (6/6), autoimmunity (6/6), and chronic diarrhea (5/6). Recurrent infectious episodes were observed in three patients. None of the patients had hypogammaglobulinemia at presentation. B cell subpopulation analysis revealed low numbers of switched-memory B cell numbers in two of the four tested patients. During the disease course, three of the patients died, two of them underwent successful hematopoietic stem cell transplantation (HSCT) from matched sibling donors, and one is under abatacept therapy. CONCLUSION: LRBA defects should always be kept in mind as a differential diagnosis for patients with autoimmune disease affecting multiple organs, chronic diarrhea, and organomegalies. In our experience, early HSCT is a life-saving therapeutic strategy.

negative: Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication Coronaviruses are of veterinary and medical importance and include highly pathogenic zoonotic viruses, such as SARS-CoV and MERS-CoV. They are known to efficiently evade early innate immune responses, manifesting in almost negligible expression of type-I interferons (IFN-I). This evasion strategy suggests an evolutionary conserved viral function that has evolved to prevent RNA-based sensing of infection in vertebrate hosts. Here we show that the coronavirus endonuclease (EndoU) activity is key to prevent early induction of double-stranded RNA (dsRNA) host cell responses. Replication of EndoU-deficient coronaviruses is greatly attenuated in vivo and severely restricted in primary cells even during the early phase of the infection. In macrophages we found immediate induction of IFN-I expression and RNase L-mediated breakdown of ribosomal RNA. Accordingly, EndoU-deficient viruses can retain replication only in cells that are deficient in IFN-I expression or sensing, and in cells lacking both RNase L and PKR. Collectively our results demonstrate that the coronavirus EndoU efficiently prevents simultaneous activation of host cell dsRNA sensors, such as Mda5, OAS and PKR. The localization of the EndoU activity at the site of viral RNA synthesis–within the replicase complex—suggests that coronaviruses have evolved a viral RNA decay pathway to evade early innate and intrinsic antiviral host cell responses.

negative: Comparative Impact of Individual Quarantine vs. Active Monitoring of Contacts for the Mitigation of COVID-19: a modelling study BACKGROUND: Voluntary individual quarantine and voluntary active monitoring of contacts are core disease control strategies for emerging infectious diseases, such as COVID-19. Given the impact of quarantine on resources and individual liberty, it is vital to assess under what conditions individual quarantine can more effectively control COVID-19 than active monitoring. As an epidemic grows, it is also important to consider when these interventions are no longer feasible, and broader mitigation measures must be implemented. METHODS: To estimate the comparative efficacy of these case-based interventions to control COVID-19, we fit a stochastic branching model to reported parameters for the dynamics of the disease. Specifically, we fit to the incubation period distribution and each of two sets of the serial interval distribution: a shorter one with a mean serial interval of 4.8 days and a longer one with a mean of 7.5 days. To assess variable resource settings, we consider two feasibility settings: a high feasibility setting with 90% of contacts traced, a half-day average delay in tracing and symptom recognition, and 90% effective isolation; and low feasibility setting with 50% of contacts traced, a two-day average delay, and 50% effective isolation. FINDINGS: Our results suggest that individual quarantine in high feasibility settings where at least three-quarters of infected contacts are individually quarantined contains an outbreak of COVID-19 with a short serial interval (4.8 days) 84% of the time. However, in settings where this performance is unrealistically high and the outbreak continues to grow, so too will the burden of the number of contacts traced for active monitoring or quarantine. When resources are prioritized for scalable interventions such as social distancing, we show active monitoring or individual quarantine of high-risk contacts can contribute synergistically to mitigation efforts. INTERPRETATION: Our model highlights the urgent need for more data on the serial interval and the extent of presymptomatic transmission in order to make data-driven policy decisions regarding the cost-benefit comparisons of individual quarantine vs. active monitoring of contacts. To the extent these interventions can be implemented they can help mitigate the spread of COVID-19.

negative: Respiratory Viruses Respiratory viruses are the most frequent causative agents of disease in humans, with significant impact on morbidity and mortality worldwide. Common respiratory agents from several virus families are well adapted to efficient person-to-person transmission and circulate in a global scale, and community-based studies conducted over the past five decades or so confirm that these viruses are the predominant etiological agents of acute respiratory infections (ARIs). The respiratory viruses that most commonly circulate in all continents as endemic or epidemic agents are influenza virus, respiratory syncytial virus, parainfluenza viruses, metapneumovirus, rhinovirus, coronaviruses, adenoviruses, and bocaviruses. Although vaccines and effective antiviral drugs are not yet available for most of these viruses, much progress has been made in the understanding of their biology and fundamental issues of host–parasite relationship. This article is a summary of the current knowledge about these viruses.

negative: Coronavirus Disease (COVID-19) Pandemic: An Overview of Systematic Reviews Background: Navigating the rapidly growing body of scientific literature on the SARS-CoV-2 pandemic is challenging and ongoing critical appraisal of this output is essential. We aimed to collate and summarize all published systematic reviews on the coronavirus disease (COVID-19). Methods: Nine databases (Medline, EMBASE, Cochrane Library, CINAHL, Web of Sciences, PDQ-Evidence, WHO's Global Research, LILACS and Epistemonikos) were searched from December 1, 2019 to March 24, 2020. Systematic reviews analyzing primary studies of COVID-19 were included. Two authors independently undertook screening, selection, extraction (data on clinical symptoms, prevalence, pharmacological and non-pharmacological interventions, diagnostic test assessment, laboratory and radiological findings) and quality assessment (AMSTAR 2). Meta-analysis on prevalence of clinical outcomes was performed. Results: Eighteen systematic reviews were included; one was empty. Using AMSTAR 2, confidence in the results of 13 reviews was rated as "critically low", one as "low", one as "moderate" and two as "high". Symptoms of COVID-19 were (range values of point estimates): fever (82-95%), cough with or without sputum (58-72%), dyspnea (26-59%), myalgia or muscle fatigue (29-51%), sore throat (10-13%), headache (8-12%) and gastrointestinal complaints (5-9%). Severe symptoms were more common in men. Elevated C-reactive protein (associated with lymphocytopenia) and lactate dehydrogenase, and slightly elevated aspartate and alanine aminotransferase, were commonly described. Thrombocytopenia and elevated levels of procalcitonin and cardiac troponin I were associated with severe disease. Chest imaging described a frequent pattern of uni- or bilateral multilobar ground-glass opacity. Only one review investigated the impact of medication (chloroquine) but found no verifiable clinical data. All-cause mortality ranged from 0.3% to 14%. Conclusions: Confidence in the results of most reviews was "critically low". Future studies and systematic reviews should adhere to established methodologies. The majority of included systematic reviews were hampered by imprecise search strategy and no previous protocol submission. Protocol registration: This is an extension of a PROSPERO protocol (CRD42020170623); protocol available on Open Science Framework (https://osf.io/6xtyw).

negative: Coronavirus Disease 2019 (COVID-19): Protecting Hospitals From the Invisible Coronavirus disease 2019 (COVID-19) is optimized to spread widely: Its signs and symptoms are largely indistinguishable from those of other respiratory viruses. This commentary specifically addresses best ways to protect our hospitals against COVID-19.

negative: Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia BACKGROUND: The initial cases of novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP. METHODS: We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number. RESULTS: Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). CONCLUSIONS: On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.)

negative: COVID-19 pneumonia: what has CT taught us?

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

negative: Genome Sequence of SARS-CoV-2 Isolate Cali-01, from Colombia, Obtained Using Oxford Nanopore MinION Sequencing We report the genome sequence of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolate obtained from a patient with symptoms of coronavirus disease 2019 (COVID-19) who was infected in Cali, Colombia. The patient had no recent travel record and did not require hospitalization. The virus genome was obtained using Oxford Nanopore MinION sequencing.

negative: Docetaxel induces moderate ovarian toxicity in mice, primarily affecting granulosa cells of early growing follicles Advances in cancer therapy have focused attention on the quality of life of cancer survivors. Since infertility is a major concern following chemotherapy, it is important to characterize the drug-specific damage to the reproductive system to help find appropriate protective strategies. This study investigates the damage on neonatal mouse ovary maintained in vitro for 6 days, and exposed for 24 h (on Day 2) to clinically relevant doses of Docetaxel (DOC; low: 0.1 µM, mid: 1 µM, high: 10 µM). Furthermore, the study explores the putative protective action exerted by Tri-iodothyronine (T3; 10(−7) M). At the end of culture, morphological analyses and follicle counts showed that DOC negatively impacts on early growing follicles, decreasing primary follicle number and severely affecting health at the transitional and primary stages. Poor follicle health was mainly due to effects on granulosa cells, indicating that the effects of DOC on oocytes were likely to be secondary to granulosa cell damage. DOC damages growing follicles specifically, with no direct effect on the primordial follicle reserve. Immunostaining and western blotting showed that DOC induces activation of intrinsic, type II apoptosis in ovarian somatic cells; increasing the levels of cleaved caspase 3, cleaved caspase 8, Bax and cleaved poly(ADP-ribose) polymerase, while also inducing movement of cytochrome C from mitochondria into the cytosol. T3 did not prevent the damage induced by the low dose of DOC. These results demonstrated that DOC induces a gonadotoxic effect on the mouse ovary through induction of somatic cell apoptosis, with no evidence of direct effects on the oocyte, and that the damaging effect is not mitigated by T3.

negative: Temporal dynamics in viral shedding and transmissibility of COVID-19 We report temporal patterns of viral shedding in 94 laboratory-confirmed COVID-19 patients and modelled COVID-19 infectiousness profile from a separate sample of 77 infector-infectee transmission pairs. We observed the highest viral load in throat swabs at the time of symptom onset, and inferred that infectiousness peaked on or before symptom onset. We estimated that 44% of transmission could occur before first symptoms of the index. Disease control measures should be adjusted to account for probable substantial pre-symptomatic transmission.

negative: Diagnostic Imaging of Chest Influenza A(H1N1) is caused by the conflict of interest between giant organisms and microorganisms. Influenza A and B viruses are single stranded RNA envelope virus composed of 890–2,341 nucleic acids in eight segmented genomes. Presently, only the virus subtypes of H1N1 and H3N2 still spread from human to human. The viruses spread and replicate under the following conditions: (1) the viruses enter the human body and duplicate there; (2) the viruses cause diseases; and (3) the viruses can easily spread from person to person. The H1N1 influenza viruses replicate is within only respiratory epithelial cells. The virus entering into the cells causes complex pathological changes of the cells. The columnar epithelial cells stop the self-synthesis of cellular component proteins. Therefore, the cells die due to their lack of necessary cell component proteins.

negative: The spread of the COVID‐19 coronavirus: Health agencies worldwide prepare for the seemingly inevitability of the COVID‐19 coronavirus becoming endemic While it is too late to confine the COVID‐19 coronovirus outbreak to China, a wealth of data spurs epidemiological and vaccine research. [Image: see text]

negative: Diagnosis of COVID-19: Considerations, Controversies and Challenges in South Africa Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 is a global pandemic that has resulted in over 1.5 million confirmed cases and close to 100,000 deaths. In the majority of symptomatic cases COVID-19 results in a mild disease predominantly characterised by upper respiratory tract symptoms. Reverse transcription polymerase chain reaction (RT-PCR), using a nasopharyngeal sample, is the mainstay of diagnosis, but there is an ~30% false negative rate early in the disease and in patients with mild disease. RT-PCR positivity can persist for several days after a resolution of symptoms. IgM and IgG antibody responses become positive several days after the onset of symptoms, and robust antibody responses are detectable in the second week of illness. Antibody-based immunoassays have a limited role in the diagnosis of early symptomatic disease. However, their incremental benefit over RT-PCR in the first 2 weeks of illness is currently being clarified in ongoing studies. Such assays may be useful for surveillance purposes. However, their role in potentially selecting individuals that may benefit from vaccination, or as a biomarker identifying persons that could be redeployed into essential employment roles are being investigated. Rapid antibody-based immunoassays that detect viral antigen in nasopharyngeal samples are being developed and evaluated.

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: Early Detection and Assessment of Covid-19 Background: Since the Covid-19 global pandemic emerged, developing countries have been facing multiple challenges over its diagnosis. We aimed to establish a relationship between the signs and symptoms of COVID-19 for early detection and assessment to reduce the transmission rate of SARS-Cov-2. Methods: We collected published data on the clinical features of Covid-19 retrospectively and categorized them into physical and blood biomarkers. Common features were assigned scores by the Borg scoring method with slight modifications and were incorporated into a newly-developed Hashmi-Asif Covid-19 assessment Chart. Correlations between signs and symptoms with the development of Covid-19 was assessed by Pearson correlation and Spearman Correlation coefficient (rho). Linear regression analysis was employed to assess the highest correlating features. The frequency of signs and symptoms in developing Covid-19 was assessed through Chi-square test two tailed with Cramer's V strength. Changes in signs and symptoms were incorporated into a chart that consisted of four tiers representing disease stages. Results: Data from 10,172 Covid-19 laboratory confirmed cases showed a correlation with Fever in 43.9% (P = 0.000) cases, cough 54.08% and dry mucus 25.68% equally significant (P = 0.000), Hyperemic pharyngeal mucus membrane 17.92% (P = 0.005), leukopenia 28.11% (P = 0.000), lymphopenia 64.35% (P = 0.000), thrombopenia 35.49% (P = 0.000), elevated Alanine aminotransferase 50.02% (P = 0.000), and Aspartate aminotransferase 34.49% (P = 0.000). The chart exhibited a maximum scoring of 39. Normal tier scoring was ≤ 12/39, mild state scoring was 13–22/39, and star values scoring was ≥7/15; this latter category on the chart means Covid-19 is progressing and quarantine should be adopted. Moderate stage scored 23–33 and severe scored 34–39 in the chart. Conclusion: The Hashmi-Asif Covid-19 Chart is significant in assessing subclinical and clinical stages of Covid-19 to reduce the transmission rate.

negative: Influence of socio-ecological factors on COVID-19 risk: a cross-sectional study based on 178 countries/regions worldwide BACKGROUND: The initial outbreak of COVID-19 caused by SARS-CoV-2 in China in 2019 has been severely tested in other countries worldwide. We aimed to describe the spatial distribution of the COVID-19 pandemic worldwide and assess the effects of various socio-ecological factors on COVID-19 risk. METHODS: We collected COVID-19 pandemic infection data and social-ecological data of 178 countries/regions worldwide from three database. We used spatial econometrics method to assess the global and local correlation of COVID-19 risk indicators for COVID-19. To estimate the adjusted incidence rate ratio (IRR), we modelled negative binomial regression analysis with spatial information and socio-ecological factors. FINDINGS: The study indicated that 37, 29 and 39 countries/regions were strongly opposite from the IR, CMR and DCI index "spatial autocorrelation hypothesis", respectively. The IRs were significantly positively associated with GDP per capita, the use of at least basic sanitation services and social insurance program coverage, and were significantly negatively associated with the proportion of the population spending more than 25% of household consumption or income on out-of-pocket health care expenses and the poverty headcount ratio at the national poverty lines. The CMR was significantly positively associated with urban populations, GDP per capita and current health expenditure, and was significantly negatively associated with the number of hospital beds, number of nurses and midwives, and poverty headcount ratio at the national poverty lines. The DCI was significantly positively associated with urban populations, population density and researchers in R&D, and was significantly negatively associated with the number of hospital beds, number of nurses and midwives and poverty headcount ratio at the national poverty lines. We also found that climatic factors were not significantly associated with COVID-19 risk. CONCLUSION: Countries/regions should pay more attention to controlling population flow, improving diagnosis and treatment capacity, and improving public welfare policies.

negative: 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: Infección por coronavirus (COVID-19) en Anales de Pediatría

negative: COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-up Abstract Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, due to excessive inflammation, platelet activation, endothelial dysfunction, and stasis. In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy. Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease. Herein, we review the current understanding of the pathogenesis, epidemiology, management and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, and of those with preexisting thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.

negative: Severe respiratory failure in the course of COVID-19, treated with extracorporeal membrane oxygenation (ECMO)

negative: Crisis Symptom Management and Patient Communication Protocols Are Important Tools for All Clinicians Responding to COVID-19 Abstract Symptom management and skilled communication with patients and families are essential clinical services in the midst of the COVID-19 pandemic. While palliative care specialists have training in these skills, many front-line clinicians from other specialties do not. It is imperative that all clinicians responding to the COVID-19 crisis have access to clinical tools to support symptom management and difficult patient and family communication.

negative: Current evidence for directed and supportive investigational therapies against COVID-19 Coronavirus disease 2019 (COVID-19) is a global health crisis. There is currently a great need for effective and safe therapies directed at the disease, but no drugs are presently registered for use in COVID-19. Several directed therapies have been proposed, and most are still in clinical trials. Currently available published, peer-reviewed results mostly involve small sample sizes with study limitations restricting the interpretation of the findings. Many trials currently published also do not have a control group, limiting the interpretation of the effect of the intervention. Investigational directed therapies as well as investigational supportive therapies against COVID-19 are reviewed here. Chloroquine and hydroxychloroquine show promise as directed therapies, but current trial results are conflicting. Lopinavir/ritonavir also shows potential, but was started late in the disease course in most trials. No randomised controlled evidence is currently available for remdesivir and favipiravir. Corticosteroid use is not recommended for directed therapy against COVID-19, and the role of tocilizumab is currently unclear, based on limited evidence. Early initiation of investigational directed therapies may provide benefit in selected patients. The results from larger randomised controlled trials will clarify the place of these therapies in COVID-19 treatment.

negative: Assessing the interactions between COVID-19 and influenza in the United States The 2019–2020 influenza sentinel surveillance data exhibits unexpected trends. Typical influenza seasons have a small herald wave, followed by a decrease due to school closure during holidays, and then a main post-holiday peak that is significantly larger than the pre-holiday wave. During the 2019–2020 influenza season, influenza-like illness data in the United States appears to have a markedly lower main epidemic peak compared to what would be expected based on the pre-holiday peak. We hypothesize that the 2019–2020 influenza season does have a lower than expected burden and that this deflation is due to a behavioral or ecological interaction with COVID-19. We apply an intervention analysis to assess if this influenza season deviates from expectations, then we compare multiple hypothesized drivers of the decrease in influenza in a spatiotemporal regression model. Lastly, we develop a mechanistic metapopulation model, incorporating transmission reduction that scales with COVID-19 risk perception. We find that the 2019–2020 ILI season is smaller and decreases earlier than expected based on prior influenza seasons, and that the increase in COVID-19 risk perception is associated with this decrease. Additionally, we find that a 5% average reduction in transmission is sufficient to reproduce the observed flu dynamics. We propose that precautionary behaviors driven by COVID-19 risk perception or increased isolation driven by undetected COVID-19 spread dampened the influenza season. We suggest that when surveillance for a novel pathogen is limited, surveillance streams of co-circulating infections may provide a signal.

negative: Estimation of the asymptomatic ratio of novel coronavirus infections (COVID-19) A total of 565 Japanese citizens were evacuated from Wuhan, China to Japan. All passengers were screened for symptoms and also undertook reverse transcription polymerase chain reaction testing, identifying 5 asymptomatic and 7 symptomatic passengers testing positive for 2019-nCoV. We show that the screening result is suggestive of the asymptomatic ratio at 41.6%.

negative: Life-Threatening Viral Disease and Its Treatment

negative: Clinical and epidemiological characteristics of 320 deceased Covid‐19 patients in an Italian Province: a retrospective observational study BACKGROUND: Studies have described clinical features of Covid‐19 patients. However, limited data concerning the clinical characteristics of the Italian deaths are available. We aim to describe the clinical and epidemiological characteristics of 320 deceased from the Italian experience. METHODS: We retrospectively collected all consecutive non‐survivor patients with laboratory‐confirmed Covid‐19 infection admitted to the Emergency Rooms (ER) Piacenza Hospital Network during the first month of Covid‐19 pandemic in Italy. Clinical history, comorbidities, laboratory findings and treatment were recorded for each patient. RESULTS: A total of 1050 patients with confirmed Covid‐19 pneumonia were admitted to the ERs between 24 February,2020, and 22 March,2020. 320 (30.5%) patients died with a median age of 78.0 years, 205 (64%) non‐survivors were above 65 years old, 230 (71.9 %) were male. Non‐survivor patients showed frequently several coexisting medical conditions, with hypertension being the most common comorbidity (235 patients, 73.4%). The in‐hospital mortality did not change during the progression of the pandemic. CONCLUSION: In this retrospective Italian study, most of Covid‐19 deceased patients were elderly male aged over than 65 years. Hypertension was the most common coexisting disease. In‐hospital mortality was high and showed no variation during the first month of the Covid‐19 italian epidemic. This article is protected by copyright. All rights reserved.

negative: Lung involvement in patients with coronavirus disease-19 (COVID-19): a retrospective study based on quantitative CT findings PURPOSE: To explore lung involvement in patients with coronavirus disease-19 (COVID-19) using quantitative computed tomography (QCT). METHODS: A total of 52 patients with COVID-19 who were admitted to three hospitals in China from January 23, 2020 to February 1, 2020 were retrospectively analyzed using QCT. The accuracy of QCT segmentation was assessed. The relationship between the time from symptom onset to initial CT and QCT parameters acquired on the initial CT were explored. RESULTS: First, the ability of QCT to detect and segment lesions was investigated and it was unveiled that results of segmentation of the majority of cases (42/52) were satisfactory and for 8 out of 52 patients, the images depicted lesions with miss-segmentation; besides, 2 out of 52 cases had negative finding on chest CT achieved by both radiologists and QCT. QCT-related parameters showed to have a relationship with the time from symptom onset to initial CT. In the early-stage (0–3 days), the percentage of lung involvement was 4%, with a mean density of − 462 ± 99 HU. The peak density of lesions appeared at the range of − 500 to − 700 HU on density histogram. In the intermediate-stage (4–6 days), the mean percentage of lung involvement noticeably increased compared with that in early stage (7%, p < 0.05). In late stage (7–14 days), the percentage of lung involvement decreased to 5%. The mean density of lesions was the highest (− 430 ± 80), and heterogeneity density distribution showed a dual-peak on density histogram. CONCLUSION: COVID-19 can be promptly detected by QCT. In addition, the QCT-related parameters can highly facilitate assessment of pulmonary involvement.

negative: Corticosteroid treatment of patients with coronavirus disease 2019 (COVID‐19) OBJECTIVES: To assess the efficacy of corticosteroid treatment of patients with coronavirus disease 2019 (COVID‐19). DESIGN, SETTING: Observational study in the two COVID‐19‐designated hospitals in Wuhu, Anhui province, China, 24 January – 24 February 2020. PARTICIPANTS: Thirty‐one patients infected with the severe acute respiratory coronavirus 2 (SARS‐CoV‐2) treated at the two designated hospitals. MAIN OUTCOME MEASURES: Virus clearance time, length of hospital stay, and duration of symptoms, by treatment type (including or not including corticosteroid therapy). RESULTS: Eleven of 31 patients with COVID‐19 received corticosteroid treatment. Cox proportional hazards regression analysis indicated no association between corticosteroid treatment and virus clearance time (hazard ratio [HR], 1.26; 95% CI, 0.58–2.74), hospital length of stay (HR, 0.77; 95% CI, 0.33–1.78), or duration of symptoms (HR, 0.86; 95% CI, 0.40–1.83). Univariate analysis indicated that virus clearance was slower in two patients with chronic hepatitis B infections (mean difference, 10.6 days; 95% CI, 6.2–15.1 days). CONCLUSIONS: Corticosteroids are widely used when treating patients with COVID‐19, but we found no association between therapy and outcomes in patients without acute respiratory distress syndrome. An existing HBV infection may delay SARS‐CoV‐2 clearance, and this association should be further investigated.

negative: A multicentre, randomised, double-blind, single-dose study assessing the efficacy of AMC/DCBA Warm lozenge or AMC/DCBA Cool lozenge in the relief of acute sore throat BACKGROUND: Clinically proven over-the-counter (OTC) treatment options are becoming increasingly important in the self-management of acute sore throat. The aim of this study was to determine the analgesic and sensorial benefits of two different amylmetacresol/2,4-dichlorobenzyl alcohol (AMC/DCBA) throat lozenge formulation variants, AMC/DCBA Warm lozenge and AMC/DCBA Cool lozenge, compared with an unflavoured, non-medicated placebo lozenge in the relief of acute sore throat due to upper respiratory tract infections. METHODS: In this multicentre, randomised, double-blind, single-dose study, 225 adult patients with acute sore throat were randomly assigned to receive either one AMC/DCBA Warm lozenge (n = 77), one AMC/DCBA Cool lozenge (n = 74) or one unflavoured, non-medicated lozenge (matched for size, shape and demulcency; n = 74). After baseline assessments, patients received their assigned lozenge and completed four rating assessments at 11 timepoints from 1 to 120 minutes post dose. Analgesic properties were assessed by comparing severity of throat soreness and sore throat relief ratings. Difficulty in swallowing, throat numbness, functional, sensorial and emotional benefits were also assessed. RESULTS: Both the AMC/DCBA Warm and AMC/DCBA Cool lozenge induced significant analgesic, functional, sensorial and emotional effects compared with the unflavoured, non-medicated lozenge. Sore throat relief, improvements in throat soreness and difficulty in swallowing, and throat numbness were observed as early as 1-5 minutes, and lasted up to 2 hours post dose. Sensorial benefits of warming and cooling associated with the AMC/DCBA Warm and AMC/DCBA Cool lozenge, respectively, were experienced soon after first dose, and in the case of the latter, it lasted long after the lozenge had dissolved. Emotional benefits of feeling better, happier, less distracted and less frustrated were reported in those taking either of the AMC/DCBA throat lozenge variants, with no differences in adverse events compared with the unflavoured, non-medicated lozenge. CONCLUSIONS: AMC/DCBA Warm and AMC/DCBA Cool lozenges are well-tolerated and effective OTC treatment options, offering functional, sensorial and emotional benefits to patients with acute sore throat, over and above that of the rapid efficacy effects provided. TRIAL REGISTRATION: ISRCTN: ISRCTN00003567

negative: The relation of innate and adaptive immunity with viral-induced acute asthma attacks: Focusing on IP-10 and cathelicidin BACKGROUND: Despite growing evidence suggesting potential association between innate and adaptive immunity in viral-induced acute asthma, there is paucity of data in this area. OBJECTIVE: This study aimed to investigate the association of innate and adaptive immunity with acute asthma attacks by analysing the role of IFN-γ-inducible protein 10 (IP-10), TLR2, cathelicidin, vitamin D and cytokines. MATERIAL AND METHODS: This prospective study included 33 patients with viral-induced acute asthma and 30 children with controlled asthma. Nasopharyngeal swab samples were collected for virus identification and asthma attack scores assessed in acute asthma group. Blood sampling for IP-10, TLR2, cathelicidin, vitamin D levels, and spirometric indices were employed. RESULTS: Serum IP-10 and cathelicidin levels of acute asthma group were significantly higher and vitamin D levels were lower than controlled asthma group (IP-10; p = 0.006, cathelicidin; p = 0.002, vitamin D; p < 0.001). Serum IP-10 levels showed a significant negative correlation with age (p = 0.009), TLR2 (p = 0.05) and spirometric indices (p = 0.002) in all asthmatics and a significant positive correlation with parameters of asthma attack severity (p = 0.03) in acute asthma group. Higher cathelicidin values showed significant positive relation to IP-10 (beta coefficient: 33, p = 0.02). Serum IP-10 levels higher than 38.9 pg/ml (sensitivity: 85%, specificity: 47%, p = 0.002) were predictive of virus-induced asthma. Serum IP-10 and vitamin D levels were found to be significantly related to viral-asthma attacks (IP-10; aOR: 8.93, p = 0.03 and vitamin D; aOR: 0.82, p = 0.001). CONCLUSIONS: Innate immunity biomarkers such as serum IP-10 and cathelicidin can be used to predict viral-induced acute asthma. These biomarkers may provide potential new treatment targets for acute asthma.

negative: Initial public health response and interim clinical guidance for the 2019 novel coronavirus outbreak — United States, December 31, 2019–February 4, 2020 This article summarizes what is currently known about the 2019 novel coronavirus and offers interim guidance.

negative: After the storm Discussion of the encephalitis problem has not lost its vigor, even after the passing of the great wave of epidemic encephalitis. The occurrence of encephalitic syndromes has repeatedly necessitated considering the relationships between the individual diseases. Such discussions were necessarily based largely upon comparative disease research, as the experimental–biological elucidation of epidemic encephalitis remains in the dark. Epidemiology, clinical manifestations, course, and anatomic substrate have nonetheless revealed quite specific characteristics that have enabled its differentiation from other frequently occurring encephalitic syndromes Gerhard Döring, 1941

negative: Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population-level observational study Summary Background As the outbreak of coronavirus disease 2019 (COVID-19) progresses, epidemiological data are needed to guide situational awareness and intervention strategies. Here we describe efforts to compile and disseminate epidemiological information on COVID-19 from news media and social networks. Methods In this population-level observational study, we searched DXY.cn, a health-care-oriented social network that is currently streaming news reports on COVID-19 from local and national Chinese health agencies. We compiled a list of individual patients with COVID-19 and daily province-level case counts between Jan 13 and Jan 31, 2020, in China. We also compiled a list of internationally exported cases of COVID-19 from global news media sources (Kyodo News, The Straits Times, and CNN), national governments, and health authorities. We assessed trends in the epidemiology of COVID-19 and studied the outbreak progression across China, assessing delays between symptom onset, seeking care at a hospital or clinic, and reporting, before and after Jan 18, 2020, as awareness of the outbreak increased. All data were made publicly available in real time. Findings We collected data for 507 patients with COVID-19 reported between Jan 13 and Jan 31, 2020, including 364 from mainland China and 143 from outside of China. 281 (55%) patients were male and the median age was 46 years (IQR 35–60). Few patients (13 [3%]) were younger than 15 years and the age profile of Chinese patients adjusted for baseline demographics confirmed a deficit of infections among children. Across the analysed period, delays between symptom onset and seeking care at a hospital or clinic were longer in Hubei province than in other provinces in mainland China and internationally. In mainland China, these delays decreased from 5 days before Jan 18, 2020, to 2 days thereafter until Jan 31, 2020 (p=0·0009). Although our sample captures only 507 (5·2%) of 9826 patients with COVID-19 reported by official sources during the analysed period, our data align with an official report published by Chinese authorities on Jan 28, 2020. Interpretation News reports and social media can help reconstruct the progression of an outbreak and provide detailed patient-level data in the context of a health emergency. The availability of a central physician-oriented social network facilitated the compilation of publicly available COVID-19 data in China. As the outbreak progresses, social media and news reports will probably capture a diminishing fraction of COVID-19 cases globally due to reporting fatigue and overwhelmed health-care systems. In the early stages of an outbreak, availability of public datasets is important to encourage analytical efforts by independent teams and provide robust evidence to guide interventions. Funding Fogarty International Center, US National Institutes of Health.

negative: Delivering urgent urological surgery during the COVID‐19 pandemic in the United Kingdom: Outcomes from our initial 52 patients. Since first reported in December 2019, the novel RNA betacoronavirus disease (COVID‐19) has spread rapidly across the world with, as of the 3rd May 2020, 3.3 million confirmed cases with more than 230,000 deaths worldwide and more than 200 countries affected. The most common symptoms reported include dry cough, fever and fatigue with ground‐glass opacification bilaterally in the lungs on imaging and lymphopenia on haematological analysis. In severe cases the patients can develop acute respiratory distress syndrome (ARDS) or multi organ failure which can lead to death. Transmission of the virus (SARS‐CoV‐2) is via direct contact or via droplets spread by a cough or sneeze from an infected individual. The difficulty in disease detection and containment has been the long course of COVID‐19. Current evidence shows an incubation period of up to 14 days post exposure to the virus, and on average most patients first display symptoms on day five after initial exposure. More importantly, carriers are contagious even during this preceding asymptomatic incubation phase of the disease.

negative: Comment on “Should COVID-19 Concern Nephrologists? Why and to What Extent? The Emerging Impasse of Angiotensin Blockade”

negative: Evidence Supporting Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 While Presymptomatic or Asymptomatic Recent epidemiologic, virologic, and modeling reports support the possibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission from persons who are presymptomatic (SARS-CoV-2 detected before symptom onset) or asymptomatic (SARS-CoV-2 detected but symptoms never develop). SARS-CoV-2 transmission in the absence of symptoms reinforces the value of measures that prevent the spread of SARS-CoV-2 by infected persons who may not exhibit illness despite being infectious. Critical knowledge gaps include the relative incidence of asymptomatic and symptomatic SARS-CoV-2 infection, the public health interventions that prevent asymptomatic transmission, and the question of whether asymptomatic SARS-CoV-2 infection confers protective immunity.

negative: SAA is a biomarker to distinguish the severity and prognosis of Coronavirus Disease 2019 (COVID-19) Abstract Background To explore the significance of SAA in evaluating the severity and prognosis of COVID-19. Methods A total of 132 patients with confirmed COVID-19 who were admitted to a designated COVID-19 hospital in Wuhan, China from January 18, 2020 to February 26, 2020 were collected. The dynamic changes of blood SAA, CRP, PCT, WBC, Lymphocyte (L), PLT, CT imaging, and disease progression were studied. All patients completed at least twice laboratory data collection and clinical condition assessment at three time points indicated for this study; The length of hospital stay was longer than 14 days prior to February 26, 2020. Results COVID-19 patients had significantly increased SAA and CRP levels, while L count decreased, and PCT, WBC, and PLT were in the normal range. As disease progressed from mild to critically severe, SAA and CRP gradually increased, while L decreased, and PLT, WBC, and PCT had no significant changes; ROC curve analysis suggests that SAA/L, CRP, SAA, and L count are valuable in evaluating the severity of COVID-19 and distinguishing critically ill patients from mild ones; Patients with SAA consistently trending down during the course of disease have better prognosis, compared with the patients with SAA continuously rising; The initial SAA level is positively correlated with the dynamic changes of the serial CT scans. Patient with higher initial SAA level are more likely to have poor CT imaging. Conclusions SAA and L are sensitive indicators in evaluating the severity and prognosis of COVID-19. Monitoring dynamic changes of SAA, combined with CT imaging could be valuable in diagnosis and treatment of COVID-19.

negative: CT screening for early diagnosis of SARS-CoV-2 infection

negative: COVID-19 early warning score: a multi-parameter screening tool to identify highly suspected patients BACKGROUND Corona Virus Disease 2019 (COVID-19) is spreading worldwide. Effective screening for patients is important to limit the epidemic. However, some defects make the currently applied diagnosis methods are still not very ideal for early warning of patients. We aimed to develop a diagnostic model that allows for the quick screening of highly suspected patients using easy-to-get variables. METHODS A total of 1,311 patients receiving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleicacid detection were included, whom with a positive result were classified into COVID-19 group. Multivariate logistic regression analyses were performed to construct the diagnostic model. Receiver operating characteristic (ROC) curve analysis were used for model validation. RESULTS After analysis, signs of pneumonia on CT, history of close contact, fever, neutrophil-to-lymphocyte ratio (NLR), Tmax and sex were included in the diagnostic model. Age and meaningful respiratory symptoms were enrolled into COVID-19 early warning score (COVID-19 EWS). The areas under the ROC curve (AUROC) indicated that both of the diagnostic model (training dataset 0.956 [95%CI 0.935-0.977, P < 0.001]; validation dataset 0.960 [95%CI 0.919-1.0, P < 0.001] ) and COVID-19 EWS (training dataset 0.956 [95%CI 0.934-0.978, P < 0.001] ; validate dataset 0.966 [95%CI 0.929-1, P < 0.001]) had good discrimination capacity. In addition, we also obtained the cut-off values of disease severity predictors, such as CT score, CD8+ T cell count, CD4+ T cell count, and so on. CONCLUSIONS The new developed COVID-19 EWS was a considerable tool for early and relatively accurately warning of SARS-CoV-2 infected patients.

negative: The aetiology, origins, and diagnosis of severe acute respiratory syndrome Summary Severe acute respiratory syndrome (SARS) is a new infectious disease that first emerged in Guangdong province, China, in November, 2002. A novel coronavirus was later identified in patients with SARS. The detection of the virus in these patients, its absence in healthy controls or other patients with atypical pneumonia, and the reproduction of a similar disease in a relevant animal model fulfilled Koch's postulates for implicating this coronavirus as the causal agent of SARS. The full genome sequence was determined within weeks of the virus's identification. The rapid progress in the aetiology, the development of laboratory diagnostic tests, and the defining of routes of viral transmission were facilitated through a unique WHO-coordinated virtual network of laboratories, which shared information on a real-time basis through daily teleconferences. Subsequent studies have indicated that the SARS coronavirus is of animal origin, that its precursor is still present in animal populations within the region, and that live-animal markets in southern China may have provided the animal-human interphase that allowed this precursor virus to adapt to human-human transmission. These findings underscore the potential for the re-emergence of SARS and the need for laboratory tests for early diagnosis. However, the low viral load in the respiratory tract makes early diagnosis of SARS a diagnostic challenge, although improvements in the sensitivity of molecular diagnostic methods continue to be made.

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

negative: A case of improved oxygenation in SARS-CoV-2 positive patient on nasal cannula undergoing prone positioning Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality worldwide. It has placed societal and financial burden on the globe. Its rapid progressions from mild URI symptoms to severe acute respiratory distress syndrome (ARDS) in a matter of days is the underlying reason as to why the world is struggling to keep up with ventilator production. In this case report, we went about proning a corona virus positive patient for 6-8hrs as a potential early intervention to prevent progression to ARDS. Our patient was initially in acute hypoxemic respiratory failure and placed on nasal cannula. He was started on hydroxychloroquine and azithromycin with no improvement of symptoms. However within the span of few hours of proning he experienced significant symptomatic relief with improvement of oxygenation. His oxygen saturation improved drastically and eventually was taken off of nasal cannula and discharged within span of one day of proning.

negative: Moderate mutation rate in the SARS coronavirus genome and its implications BACKGROUND: The outbreak of severe acute respiratory syndrome (SARS) caused a severe global epidemic in 2003 which led to hundreds of deaths and many thousands of hospitalizations. The virus causing SARS was identified as a novel coronavirus (SARS-CoV) and multiple genomic sequences have been revealed since mid-April, 2003. After a quiet summer and fall in 2003, the newly emerged SARS cases in Asia, particularly the latest cases in China, are reinforcing a wide-spread belief that the SARS epidemic would strike back. With the understanding that SARS-CoV might be with humans for years to come, knowledge of the evolutionary mechanism of the SARS-CoV, including its mutation rate and emergence time, is fundamental to battle this deadly pathogen. To date, the speed at which the deadly virus evolved in nature and the elapsed time before it was transmitted to humans remains poorly understood. RESULTS: Sixteen complete genomic sequences with available clinical histories during the SARS outbreak were analyzed. After careful examination of multiple-sequence alignment, 114 single nucleotide variations were identified. To minimize the effects of sequencing errors and additional mutations during the cell culture, three strategies were applied to estimate the mutation rate by 1) using the closely related sequences as background controls; 2) adjusting the divergence time for cell culture; or 3) using the common variants only. The mutation rate in the SARS-CoV genome was estimated to be 0.80 – 2.38 × 10(-3 )nucleotide substitution per site per year which is in the same order of magnitude as other RNA viruses. The non-synonymous and synonymous substitution rates were estimated to be 1.16 – 3.30 × 10(-3 )and 1.67 – 4.67 × 10(-3 )per site per year, respectively. The most recent common ancestor of the 16 sequences was inferred to be present as early as the spring of 2002. CONCLUSIONS: The estimated mutation rates in the SARS-CoV using multiple strategies were not unusual among coronaviruses and moderate compared to those in other RNA viruses. All estimates of mutation rates led to the inference that the SARS-CoV could have been with humans in the spring of 2002 without causing a severe epidemic.

negative: Imaging characteristics of initial chest computed tomography and clinical manifestations of patients with COVID-19 pneumonia PURPOSE: To investigate the chest CT imaging characteristics and clinical manifestations of patients with COVID-19 pneumonia. METHODS: This study included 150 patients with COVID-19 pneumonia diagnosed from January 10 to February 12, 2020 to analyze their clinical and CT imaging characteristics. RESULTS: The period between symptom onset and initial CT examination ranged from 1 to 8 days. There were 83 cases (55.33%) involving both lungs, 67 cases (44.67%) involving a single lung (left 25 cases and right 42 cases). There were 49 cases (32.67%) of single intrapulmonary lesion, 33 cases (22.00%) of multiple intrapulmonary lesions, 68 cases (44.00%) of diffused intrapulmonary lesions, 67 cases (44.67%) of subpleural lesions, 24 cases (16.00%) of lesions localizing along the bronchovascular bundles, and 59 cases (39.33%) with lesions in both locations. There were 18 cases (12.00%) exhibiting ground-glass nodules of < 10 mm, 124 cases (82.67%) of patchy ground-glass opacities with or without consolidation, 8 cases (5.33%) of cord-like lesions, 6 cases (4.00%) of pleural effusion, and 2 cases (1.33%) of enlarged lymph nodes. CONCLUSIONS: The main manifestations of initial chest CT in COVID-19 pneumonia patients was ground-glass opacities, commonly involving single site in patients < 35 years old and multiple sites and extensive area in patients > 60 years old. The common lesion sites were the subpleural region and the posterior basal segments of the lower lobes, mostly showing thickening of the interlobular septum and mixed with consolidation.

negative: Severe acute respiratory symptoms and suspected SARS again 2020.

negative: Epidemiology and Control: Principles, Practice and Programs Infectious disease epidemiology is concerned with the occurrence of both infection and disease in populations and the factors that determine their frequency, spread, expression and distribution. Viruses show characteristic infectivity, virulence and pathogenicity. The most well established host factors are age, sex and race, but other host biological and behavioral factors affect acquisition of viral infection and/or its course and manifestations. The physical, chemical and biological environment operates on the virus itself and may also alter the host biological or behavioral response. Viral infections have incubation periods lasting days or weeks, while their pathologic sequelae may not manifest for years or decades. Likewise the degree or intensity of host response and clinical expression may range from largely inapparent to highly lethal. The degree of cell, tissue and organ specificity is high. Common syndromes involve the respiratory, gastrointestinal, and central nervous systems, the liver, and mucocutaneous surfaces. Vertical transmission may produce a variety of congenital and perinatal conditions. Viruses spread by multiple modes, using nearly every bodily surface or fluid as a route of exit or entry, either by direct contact or indirectly through an animal vector or other inanimate vehicle. Different viral Infections occur nearly ubiquitously or sporadically; they may be present continuously throughout a population (endemic) or occur in seasonal rhythm or in unexpectedly explosive form (epidemic). Many viruses are refractory to all known therapeutic agents, while for a few, the increasing number of highly effective agents holds great promise. Vaccines have produced many historical successes including the ultimate goal of eradication, but many viral infections continue to elude effective vaccine development. Major government and private sector programs for treatment and prevention have raised expectations of successful control for certain widespread and serious viral diseases; however, in every case a unique set of scientific, socioeconomic, political and behavioral barriers remains to be overcome.

negative: Do chronic respiratory diseases or their treatment affect the risk of SARS-CoV-2 infection?

negative: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management and Infection Control in a Radiology Department Abstract Objective To describe the strategy and the emergency management and infection control procedure of our radiology department during the coronavirus disease 2019 (COVID-19) outbreak. Methods We set up emergency management and sensing control teams. The team formulated various measures: reconfiguration of the radiology department, personal protection and training of staff, examination procedures for patients suspected of or confirmed with COVID-19 as well as patients without an exposure history or symptoms. Those with suspected or confirmed COVID-19 infection were scanned in the designated fever-CT unit. Results From January 21, 2020, to March 9, 2020, 3,083 people suspected or confirmed to be infected with COVID-19 underwent fever-CT examinations. Including initial examinations and re-examinations, the total number of fever-CT examinations numbered 3,340. As a result of our precautions, none of the staff of the radiology department were infected with COVID-19. Conclusion Strategic planning and adequate protections can help protect patients and staff against a highly infectious disease while maintaining function at a high-volume capacity.

negative: Chapter 5 Virus Transmission and Epidemiology Abstract For transmission of a virus to occur, a virus must enter a host through a portal of entry, replicate or disseminate within the host, and be transmitted to a new host through a portal of exit. Unless delivered directly into bodily tissues through a bite or needle, most viruses interact with the epithelium at the site of entry. Localized infections replicate at the initial site of infection, while systemic infections spread to additional areas of the body. Viruses are shed into the environment most often through the same route they entered the body. The stability of virions within the environment is dependent upon virion and environmental factors. Epidemiology is the study of how diseases are transmitted through a population. Epidemiologists perform descriptive or analytic studies to characterize the chain of viral infection throughout a population and design control measures to interrupt it.

negative: [Which sampling method for the upper respiratory tract specimen should be taken to diagnose patient with COVID-19?] Coronavirus disease 2019 (COVID-19) is raging in China, especially in Hubei Province, which has resulted great dangers in people's life and national economy. According to the guidelines drafted by China's Center for Disease prevention and Control (CDC), the positive nucleic acid test is need to the diagnosis of patient with COVID-19. Upper respiratory tract specimens are the main sources for nucleic acid detection. However, based on international guidelines of COVID-19 , no recommended level of upper respiratory tract sampling method is proposed. Therefore, which kind of sampling methods should be chosen to help the COVID-19 diagnosis and which way is the most secure for doctors and nurses is our concern. In this review, we analyzed a total of 10 literatures on the sampling methods of upper respiratory tract related to infectious diseases such as severe acute respiratory syndrome coronavirus (SARS), middle east respiratory syndrome coronavirus (MERS), and influenza A (H1N1), which were spread worldwide in past years. Literatures were collected from the three dimensions of sampling method, sampling time, and sampling safety. It was found that among all the upper respiratory sampling methods, nasopharyngeal aspirate (NPA) had a higher positive rate within 2 weeks of symptom onset, while combined nasal and oropharyngeal swabs (NS + OPS) was the least harmful to medical staff during sampling. We wish this review is helpful for the prevention of COVID-19.

negative: WeChat, a Chinese social media, may early detect the SARS-CoV-2 outbreak in 2019 We plotted daily data on the frequencies of keywords related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from WeChat, a Chinese social media. Using 'Feidian', Chinese abbreviation for SARS, may detect the SARS-CoV-2 outbreak in 2019 two weeks earlier. WeChat offered a new approach to early detect disease outbreaks.

negative: Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely associated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patients Background: Although the SARS-CoV-2 viral load detection of respiratory specimen has been widely used for novel coronavirus disease (COVID-19) diagnosis, it is undeniable that serum SARS-CoV-2 nucleic acid (RNAaemia) could be detected in a fraction of the COVID-19 patients. However, it is not clear that if the incidence of RNAaemia could be correlated with the occurrence of cytokine storm or with the specific class of patients. Methods: This study enrolled 48 patients with COVID-19 admitted to the General Hospital of Central Theater Command, PLA, a designated hospital in Wuhan, China. The patients were divided into three groups according to the Diagnosis and Treatment of New Coronavirus Pneumonia (version 6) published by the National Health Commission of China. The clinical and laboratory data were collected. The serum viral load detection and serum IL-6 levels were determined. Except for routine statistical analysis, Generalized Linear Models (GLMs) analysis was used to establish a patient status prediction model based on real-time RT-PCR Ct value. Findings: The Result showed that cases with RNAaemia were exclusively confirmed in critically ill patients group and appeared to reflect the illness severity. Further more, the inflammatory cytokine IL-6 levels were significantly elevated in critically ill patients, which is almost 10-folds higher than those in other patients. More importantly, the extremely high IL-6 level was closely correlated with the incidence of RNAaemia (R=0.902) and the vital signs of COVID-19 patients (R= -0.682). Interpretation: Serum SARS-CoV-2 viral load (RNAaemia) is strongly associated with cytokine storm and can be used to predict the poor prognosis of COVID-19 patients. Moreover, our results strongly suggest that cytokine IL-6 should be considered as a therapeutic target in critically ill patients with excessive inflammatory response.

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

negative: Viral Shedding Prolongation in a Kidney Transplant Patient with COVID‐19 Pneumonia Coronavirus disease 2019 (COVID‐19) pandemic sweeps the globe. The information regarding the kinetic changes of SARS‐CoV‐2 in immunosuppressed patients is unclear. Herein, we present a case of prolonged viral shedding in a transplant patient with COVID‐19 pneumonia. A 49‐year‐old male kidney recipient was admitted to the hospital on February 7, 2020, for fever and fatigue. He was a permanent resident in Wuhan, China, and began having symptoms on January 29 (day 1 of illness). His maintenance immunosuppressive regime was consisted of tacrolimus (TAC, 1mg twice a day, orally), mycophenolate mofetil (MMF, 0.5g twice a day, orally) and prednisone (Pred, 5mg daily, orally) triple combination.

negative: Voice from China: nomenclature of the novel coronavirus and related diseases

negative: First statement on preparation for the COVID-19 pandemic in large German Speaking University-based radiation oncology departments The COVID-19 pandemic is challenging modern radiation oncology. At University Hospitals, we have a mandate to offer high-end treatments to all cancer patients. However, in times of crisis we must learn to prioritize resources, especially personnel. Compromising oncological outcome will blur all statistics, therefore all measures must be taken with great caution. Communication with our neighboring countries, within societies and between departments can help meet the challenge. Here, we report on our learning system and preparation measures to effectively tackle the COVID-19 challenge in University-Based Radiation Oncology Departments.

negative: The Molecular Biology of Coronaviruses Publisher Summary This chapter discusses the manipulation of clones of coronavirus and of complementary DNAs (cDNAs) of defective-interfering (DI) RNAs to study coronavirus RNA replication, transcription, recombination, processing and transport of proteins, virion assembly, identification of cell receptors for coronaviruses, and processing of the polymerase. The nature of the coronavirus genome is nonsegmented, single-stranded, and positive-sense RNA. Its size ranges from 27 to 32 kb, which is significantly larger when compared with other RNA viruses. The gene encoding the large surface glycoprotein is up to 4.4 kb, encoding an imposing trimeric, highly glycosylated protein. This soars some 20 nm above the virion envelope, giving the virus the appearance-with a little imagination-of a crown or coronet. Coronavirus research has contributed to the understanding of many aspects of molecular biology in general, such as the mechanism of RNA synthesis, translational control, and protein transport and processing. It remains a treasure capable of generating unexpected insights.

negative: What further should be done to control COVID-19 outbreaks in addition to cases isolation and contact tracing measures? Historically, these interventions have been successfully applied for controlling a variety of emerging infectious disease outbreaks, such as smallpox and SARS, but only partially effective for foot-and-mouth disease, and likely not effective for influenza [2,3,4] Currently, it is not yet clear whether case isolation and contact tracing measures are sufficient to contain a new outbreak from COVID-19 Recently, Hellewell and colleagues developed a stochastic transmission model to assess the potential effectiveness of case isolation and contact tracing in controlling COVID-19 outbreak [5] They suggested that in most modeled scenarios contact tracing and case isolation alone might be insufficient to control a new outbreak of COVID-19 within 3 months, especially when longer delays from symptom onset to isolation, fewer cases ascertained by contact tracing, and increased transmission before symptoms exist It is the first study using a stochastic model to evaluate the effects of isolation and contact tracing intervention for outbreak of COVID-19 In this study, the authors simplified the outputs of their model to the effects of contact tracing and isolation on the control of outbreaks under different scenarios of transmission, and included several parameters (e g , the basic reproduction number R0, the delay from symptom onset to isolation, and the probability contacts were traced) other than merely focusing on R0 This interesting study provides a timely evaluation strategy to quantify the potential effectiveness of case isolation and contact tracing measures and may bring insights for the control the COVID-19 outbreak in China and probably other areas of the world as wellDO - 10 1186/s12916-020-01551-8

negative: Functional Limitations of Plasmacytoid Dendritic Cells Limit Type I Interferon, T Cell Responses and Virus Control in Early Life Infant mortality from viral infection remains a major global health concern: viruses causing acute infections in immunologically mature hosts often follow a more severe course in early life, with prolonged or persistent viral replication. Similarly, the WE strain of lymphocytic choriomeningitis virus (LCMV-WE) causes acute self-limiting infection in adult mice but follows a protracted course in infant animals, in which LCMV-specific CD8(+) T cells fail to expand and control infection. By disrupting type I IFNs signaling in adult mice or providing IFN-α supplementation to infant mice, we show here that the impaired early life T cell responses and viral control result from limited early type I IFN responses. We postulated that plasmacytoid dendritic cells (pDC), which have been identified as one major source of immediate-early IFN-I, may not exert adult-like function in vivo in the early life microenvironment. We tested this hypothesis by studying pDC functions in vivo during LCMV infection and identified a coordinated downregulation of infant pDC maturation, activation and function: despite an adult-like in vitro activation capacity of infant pDCs, the expression of the E2-2 pDC master regulator (and of critical downstream antiviral genes such as MyD88, TLR7/TLR9, NF-κB, IRF7 and IRF8) is downregulated in vivo at baseline and during LCMV infection. A similar pattern was observed in response to ssRNA polyU, a model ligand of the TLR7 viral sensor. This suggests that the limited T cell-mediated defense against early life viral infections is largely attributable to / regulated by infant pDC responses and provides incentives for novel strategies to supplement or stimulate immediate-early IFN-α responses.

negative: C-reactive protein levels in the early stage of COVID-19 Abstract Background COVID-19 is a new infectious disease, for which there is currently no treatment. It is therefore necessary to explore biomarkers to determine the extent of lung lesions and disease severity. Objective We aimed to assess the usefulness of CRP levels in the early stage of COVID-19 and to correlate them with lung lesions and severe presentation. Methods Confirmed cases of COVID-19 were selected at the Fever Unit in two regions of Guizhou, China. On admission CRP levels were collected, and the diameter of the largest lung lesion was measured in the most severe lung lesion by lung CT scan. Differences in the diameter and CRP levels were compared in the following groups of patients: mild group, moderate group, severe group, and critical group. Result CRP levels and the diameter of the largest lung lesion in the moderate group were higher than those in the mild group (Mann-Whitney test=−2.647, −2.171, P ˂0.05), those in the severe group were higher than those in the moderate group (Mann-Whitney test=0.693, −2.177, P ˂0.05), and those in the critical group were higher than those in the severe group (Mann-Whitney test=−0.068, −1.549, P ˂0.05). The difference was statistically significant. CRP levels were positively correlated with the diameter of lung lesion and severe presentation (correlation coefficient=0.873, 0.734, P ˂0.001). Conclusion In the early stage of COVID-19 CRP levels were positively correlated with lung lesions and could reflect disease severity.

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: A retrospective analysis of the epidemiology, clinical manifestations, and imaging characteristics of familial cluster-onset COVID-19. Background The coronavirus disease 2019 (COVID-19) virus has a high incidence rate and strong infectivity. The diagnosis and evaluation of familial outbreaks requires a collective consideration of epidemiological history, molecular detection methods, chest computed tomography (CT), and clinical symptoms. Methods A group of family patients with COVID-19 diagnosed in Guizhou, China, in February 2020, was retrospectively analyzed. As of March 1, all patients in the group have been discharged from hospital. This study tracked all patients in the group. We report the epidemiology, radiological characteristics, treatment, and clinical outcomes of these patients. Results We collected a group of 8 clustered cases (3 men and 5 women) from a family with confirmed COVID-19 infection. In the first admission diagnosis, according to the degree of clinical symptoms, the 8 patients were defined as mild type (4/8) or moderate type (4/8). They were also divided according to the CT findings into early period (1/8), progressive period (3/8), and negative on CT scan (4/8); for the first 4 patients, the corresponding CT image scores were 1, 4, 5, and 5 respectively. In this group of COVID-19 patients, half of the patients showed occult clinical manifestations and negative CT performance. We defined these patients as COVID-19-infected patients, or asymptomatic carriers. Conclusions The family cluster analysis indicated that COVID-19-infected patients (asymptomatic carriers) and symptomatic COVID-19 patients are distinct but coexistent. This may indicate that the infectivity and virulence of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has decreased. In order to block the transmission pathway of this virus before it spreads, we need to identify the presence of asymptomatic carriers as early as possible.

negative: Potential effect of blood purification therapy in reducing cytokine storm as a late complication of critically ill COVID-19

negative: Being a front-line dentist during the Covid-19 pandemic: a literature review Coronavirus is an enveloped virus with positive-sense single-stranded RNA. Coronavirus infection in humans mainly affects the upper respiratory tract and to a lesser extent the gastrointestinal tract. Clinical symptoms of coronavirus infections can range from relatively mild (similar to the common cold) to severe (bronchitis, pneumonia, and renal involvement). The disease caused by the 2019 novel coronavirus (2019-nCoV) was called Covid-19 by the World Health Organization in February 2020. Face-to-face communication and consistent exposure to body fluids such as blood and saliva predispose dental care workers at serious risk for 2019-nCoV infection. As demonstrated by the recent coronavirus outbreak, information is not enough. During dental practice, blood and saliva can be scattered. Accordingly, dental practice can be a potential risk for dental staff, and there is a high risk of cross-infection. This article addresses all information collected to date on the virus, in accordance with the guidelines of international health care institutions, and provides a comprehensive protocol for managing possible exposure to patients or those suspected of having coronavirus.

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

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

negative: Community pharmacist in public health emergencies: Quick to action against the coronavirus 2019-nCoV outbreak The 2019-nCoV infection that is caused by a novel strain of coronavirus was first detected in China in the end of December 2019 and declared a public health emergency of international concern by the World Health Organization on January 30, 2020. Community pharmacists in one of the first areas that had confirmed cases of the viral infection, Macau, joined the collaborative force in supporting the local health emergency preparedness and response arrangements. This paper aimed to improve the understanding of community pharmacists’ role in case of 2019-CoV outbreak based on the practical experiences in consultation with the recommendations made by the International Pharmaceutical Federation on the Coronavirus 2019-nCoV outbreak.

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: Imaging Features of Coronavirus disease 2019 (COVID-19): Evaluation on Thin-Section CT Rationale and Objectives To retrospectively analyze the chest imaging findings in patients with coronavirus disease 2019 (COVID-19) on thin-section CT. Materials and Methods Fifty-three patients with confirmed COVID-19 infection underwent thin-section CT examination. Two chest radiologists independently evaluated the imaging in terms of distribution, ground-glass opacity (GGO), consolidation, air bronchogram, stripe, enlarged mediastinal lymph node, and pleural effusion. Results Fourty-seven cases (88.7%) had findings of COVID-19 infection, and the other six (11.3%) were normal. Among the 47 cases, 78.7% involved both lungs, and 93.6% had peripheral infiltrates distributed along the subpleural area. All cases showed GGO, 59.6% of which were round and 40.4% patchy. Other imaging features included “crazy-paving pattern” (89.4%), consolidation (63.8%), and air bronchogram (76.6%). Air bronchograms were observed within GGO (61.7%) and consolidation (70.3%). Neither enlarged mediastinal lymph nodes nor pleural effusion were present. Thirty-three patients (62.3%) were followed an average interval of 6.2 ± 2.9 days. The lesions increased in 75.8% and resorbed in 24.2% of patients. Conclusion COVID-19 showed the pulmonary lesions in patients infected with COVID-19 were predominantly distributed peripherally in the subpleural area.

negative: What further should be done to control COVID-19 outbreaks in addition to cases isolation and contact tracing measures?

negative: The early phase of the COVID-19 outbreak in Lombardy, Italy In the night of February 20, 2020, the first case of novel coronavirus disease (COVID-19) was confirmed in the Lombardy Region, Italy. In the week that followed, Lombardy experienced a very rapid increase in the number of cases. We analyzed the first 5,830 laboratory-confirmed cases to provide the first epidemiological characterization of a COVID-19 outbreak in a Western Country. Epidemiological data were collected through standardized interviews of confirmed cases and their close contacts. We collected demographic backgrounds, dates of symptom onset, clinical features, respiratory tract specimen results, hospitalization, contact tracing. We provide estimates of the reproduction number and serial interval. The epidemic in Italy started much earlier than February 20, 2020. At the time of detection of the first COVID-19 case, the epidemic had already spread in most municipalities of Southern-Lombardy. The median age for of cases is 69 years (range, 1 month to 101 years). 47% of positive subjects were hospitalized. Among these, 18% required intensive care. The mean serial interval is estimated to be 6.6 days (95% CI, 0.7 to 19). We estimate the basic reproduction number at 3.1 (95% CI, 2.9 to 3.2). We estimated a decreasing trend in the net reproduction number starting around February 20, 2020. We did not observe significantly different viral loads in nasal swabs between symptomatic and asymptomatic. The transmission potential of COVID-19 is very high and the number of critical cases may become largely unsustainable for the healthcare system in a very short-time horizon. We observed a slight decrease of the reproduction number, possibly connected with an increased population awareness and early effect of interventions. Aggressive containment strategies are required to control COVID-19 spread and catastrophic outcomes for the healthcare system.

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: Bioinformatics After reading this chapter, you should know the answers to these questions:

negative: The Diagnosis of Pandemic Coronavirus Pneumonia: A Review of Radiology Examination and Laboratory Test Abstract Since the outbreak of novel coronavirus disease 2019 (COVID-19), epidemic prevention strategies have been implemented worldwide. For the sake of controlling the infectious coronavirus pneumonia, early diagnosis and quarantine play an imperative role. Currently, the mainstream diagnostic methods are imaging and laboratory diagnosis, which differ in their efficacy of diagnosis. To compare the detection rate, we reviewed numerous literature on pneumonia caused by coronaviruses (SARS, MERS, and SARS-CoV-2) and analyzed two different ways of diagnosis. The results showed that the detection rate of computed tomography (CT) diagnosis was significantly higher than that of real-time quantitative polymerase chain reaction (qPCR) (P = 0.00697). Still, clinicians should combine radiology and laboratory methods to achieve a higher detection rate, so that instant isolation and treatment could be effectively conducted to curb the rampant spread of the epidemic.

negative: The Progression of Computed Tomographic (CT) Images in Patients with Coronavirus Disease (COVID-19) Pneumonia The CT progression of COVID-19 pneumonia • Of the 49 patients, 89.8% (44/49) patients had a typical transition from early stage to advanced stage, and then from advanced stage to dissipating stage. • With the evidence of fibrosis for progression of CT results, 42.9% (21/49) patients developed fibrosis whereas 57.1% (28/49) patients demonstrated no definite fibrosis. • Patients with fibrosis in follow CT were older (mean age, 45.4 vs. 33.8 years), with longer LOS (19.1 vs. 15.0 days), and higher rate of ICU admission (19.0% [4/21] vs. 3.6% [1/28]) than that of those without fibrosis.

negative: Two Critical Issues in Quantitative Modeling of Communicable Diseases: Inference of Unobservables and Dependent Happening In this chapter, we discuss two critical issues which must be remembered whenever we examine epidemiologic data of directly transmitted infectious diseases. Firstly, we would like the readers to recognize the difference between observable and unobservable events in infectious disease epidemiology. Since both infection event and acquisition of infectiousness are generally not directly observable, the total number of infected individuals could not be counted at a point of time, unless very rigorous contact tracing and microbiological examinations were performed. Directly observable intrinsic parameters, such as the incubation period and serial interval, play key roles in translating observable to unobservable information. Secondly, the concept of dependent happening must be remembered to identify a risk of an infectious disease or to assess vaccine efficacy. Observation of a single infected individual is not independent of observing other individuals. A simple solution for dependent happening is to employ the transmission probability which is conditioned on an exposure to infection.

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

negative: Organizing Pneumonias Organizing pneumonia is a particular type of inflammatory and reparative reaction of the lung parenchyma characterized by fibroblast proliferation in the distal airspaces with overall preservation of the lung architecture. When microscopic, it is an asymptomatic and nonspecific reaction of little clinical significance accompanying many pathological processes. When macroscopic and affecting large portions of the lung parenchyma, it manifests by restrictive ventilatory defect and gas exchange impairment leading to dyspnea, cough, hypoxemia, alveolar opacities at chest imaging, and symptoms of systemic inflammation such as fever, malaise, and weight loss. This picture constitutes the clinico-pathological syndrome of organizing pneumonia, which has been recognized and characterized as a distinct entity in the past 30 years. Although the classical features of organizing pneumonia are increasingly familiar to chest physicians, and the efficacy of corticosteroid treatment makes it appear at first sight as an easy problem to resolve, atypical clinical presentations, similarities with other diseases, severe forms, histological variants, side effects of therapy, and relapses can make the management more difficult than initially expected. This chapter will address the classical and less common features of organizing pneumonia, and will provide practical clues to the diagnosis and management of this disorder.

negative: A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version) In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named “2019 novel coronavirus (2019-nCoV)” by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world’s attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.

negative: Le nouveau Coronavirus Covid-19 : quels risques ophtalmiques ?

negative: Pulmonary Function and Clinical Manifestations of Patients Infected with Mild Influenza A Virus Subtype H1N1: A One-Year Follow-Up OBJECTIVE: To investigate the long-term effects of mild H1N1 influenza infection on the pulmonary function of a cohort of patients. METHODS: Forty-eight patients, all diagnosed with influenza A virus subtype H1N1 in 2009, were retrospectively included in this study. Each patient in the study was monitored for 11-13 months by standard pulmonary function examination. The examination included monitoring respiratory tract infection symptoms (cough, expectoration or gasping) and vital signs. Long-term changes in symptoms and changes in vital signs were correlated back to and compared with the severity of the initial H1N1 influenza infection. RESULTS: One year post discharge, mild to moderate pulmonary dysfunction was observed in the majority of patients. Further, 54.2% of patients had signs of severe abnormal pulmonary function, including diffusion disorder (33.3%) and small airway dysfunction (33.3%). Fourteen patients presented with respiratory tract infection symptoms; 12 with abnormal pulmonary function and two with normal pulmonary function. Our results indicated that the change in pulmonary function at one year post discharge was not significantly correlated with the severity of H1N1 influenza. CONCLUSION: Signs and symptoms of abnormal pulmonary function accompanied by respiratory tract infection symptoms remain for some patients after one year following discharge from the hospital for mild influenza A virus subtype H1N1 infection. These patients should continue to be monitored for any changes in condition and symptoms and rehabilitation treatment should be provided when necessary.

negative: Efficacy and safety of iota-carrageenan nasal spray versus placebo in early treatment of the common cold in adults: the ICICC trial ABSTRACT: Iota-carrageenan (I-C) is active against respiratory viruses in vitro and was effective as nasal spray in three previous clinical trials. The current trial served to further investigate I-C in patients with early common cold symptoms. METHODS: This randomized, placebo-controlled, double-blind phase IV trial was conducted in 200 adult patients with self-diagnosed colds of <48 h’ duration that were confirmed by baseline cold symptom scores. Patients were to self-administer 0.12 % I-C or placebo spray (NaCl 0.5 %) four times daily for four to ten days and record symptom information for ten days. Common respiratory viruses were quantified by RT-PCR during pretreatment and on Day 3 or 4. The primary endpoint was the mean total symptom score (TSS) of eight cold symptoms on Days 2–4 (TSS(2–4)). RESULTS: Patients in both treatment groups had similar baseline TSSs (mean TSS: 6.75 for I-C and 6.79 for placebo). Viruses were detected in baseline samples from 53 of 98 I-C patients (54.1 %) and 54 of 97 placebo patients (55.7 %). Mean ± SE for TSS(2–4) was 5.78 ± 0.25 for I-C patients and 6.39 ± 0.25 for placebo (p = 0.0895). Exploratory analyses after unblinding (TSS(2–4) excluding a patient with aberrantly high symptom scores [TSS(2–4, ex 1pt)]; mean of TSS over Days 1–4 [TSS(1–4)]; change in TSS(1–4) relative to baseline [TSS(1–4, rel)]) demonstrated treatment differences in favor of I-C (p = 0.0364, p = 0.0495 and p = 0.0421, respectively). For patients with quantifiable rhinovirus/enterovirus at baseline, there was a trend towards greater reduction of virus load at Day 3 or 4 (p = 0.0958; I-C: 90.2 % reduction in viral load; placebo: 72.0 %). Treatments were well tolerated with no differences in adverse event rates. CONCLUSIONS: The primary endpoint did not demonstrate a statistically significant difference between I-C and placebo but showed a trend towards I-C benefit. Exploratory analyses indicated significant reduction of cold symptoms in the I-C group relative to placebo during the first four days when symptoms were most severe, and also substantiated I-C’s activity against rhinovirus/enterovirus. TRIAL REGISTRATION: NCT01944631 (clinicaltrials.gov)

negative: Ventilation and laboratory confirmed acute respiratory infection (ARI) rates in college residence halls in College Park, Maryland Abstract Strategies to protect building occupants from the risk of acute respiratory infection (ARI) need to consider ventilation for its ability to dilute and remove indoor bioaerosols. Prior studies have described an association of increased self-reported colds and influenza-like symptoms with low ventilation but have not combined rigorous characterization of ventilation with assessment of laboratory confirmed infections. We report a study designed to fill this gap. We followed laboratory confirmed ARI rates and measured CO2 concentrations for four months during the winter-spring of 2018 in two campus residence halls: (1) a high ventilation building (HVB) with a dedicated outdoor air system that supplies 100% of outside air to each dormitory room, and (2) a low ventilation building (LVB) that relies on infiltration as ventilation. We enrolled 11 volunteers for a total of 522 person-days in the HVB and 109 volunteers for 6069 person-days in the LVB, and tested upper-respiratory swabs from symptomatic cases and their close contacts for the presence of 44 pathogens using a molecular assay. We observed one ARI case in the HVB (0.70/person-year) and 47 in the LVB (2.83/person-year). Simultaneously, 154 CO2 sensors distributed primarily in the dormitory rooms collected 668,390 useful data points from over 1 million recorded data points. Average and standard deviation of CO2 concentrations were 1230 ppm and 408 ppm in the HVB, and 1492 ppm and 837 ppm in the LVB, respectively. Importantly, this study developed and calibrated multi-zone models for the HVB with 229 zones and 983 airflow paths, and for the LVB with 529 zones and 1836 airflow paths by using a subset of CO2 data for model calibration. The models were used to calculate ventilation rates in the two buildings and potential for viral aerosol migration between rooms in the LVB. With doors and windows closed, the average ventilation rate was 12 L/s in the HVB dormitory rooms and 4 L/s in the LVB dormitory rooms. As a result, residents had on average 6.6 L/(s person) of outside air in the HVB and 2.3 L/(s person) in the LVB. LVB rooms located at the leeward side of the building had smaller average ventilation rates, as well as a somewhat higher ARI incidence rate and average CO2 concentrations when compared to those values in the rooms located at the windward side of the building. Average ventilation rates in twenty LVB dormitory rooms increased from 2.3 L/s to 7.5 L/s by opening windows, 3.6 L/s by opening doors, and 8.8 L/s by opening both windows and doors. Therefore, opening both windows and doors in the LVB dormitory rooms can increase ventilation rates to the levels comparable to those in the HVB. But it can also have a negative effect on thermal comfort due to low outdoor temperatures. Simulation results identified an aerobiologic pathway from a room occupied by an index case of influenza A to a room occupied by a possible secondary case.

negative: Estimating the reproductive number and the outbreak size of COVID-19 in Korea OBJECTIVES: Since the first novel coronavirus disease 2019 (COVID-19) patient in Korea was diagnosed on January 20, 2020, 30 patients were diagnosed until February 17, 2020. However, 5,298 additional patients were confirmed until March 4, 2020. Therefore, our objective was to estimate the reproduction number (R) and evaluate the effectiveness of preventive measures. METHODS: A COVID-19 transmission model (SEIHR) was established to suit the Korean outbreak. The number of daily confirmed cases in Daegu and North Gyeongsang Province (NGP), the main area of outbreak, was used. The first patient’ symptom onset date in the Daegu/NGP outbreak was assumed as January 22, 2020. The R according to the start date of the effect of preventive measures was estimated. RESULTS: The estimated R in Hubei Province, China, was 4.0281, whereas the estimated initial R in Korea was 0.555, but later in Daegu/NGP, the value was between 3.472 and 3.543. When the transmission period decreases from 4-day to 2-day, the outbreak ends early, but the peak of the epidemic increases, and the total number of patients does not change greatly. It was found that, if transmission rate decreases, the outbreak ends early, and the size of the peak and the total number of patients also decreases. CONCLUSIONS: To end the COVID-19 epidemic, efforts to reduce the spread of the virus, such as social distancing and wearing masks, are absolutely crucial with the participation of the public, along with the policy of reducing the transmission period by finding and isolating patients as quickly as possible through the efforts of the quarantine authorities.

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: The effect of disease life history on the evolutionary emergence of novel pathogens. We present a general analytical result for the probability that a newly introduced pathogen will evolve adaptations that allow it to maintain itself within any novel host population, as a function of disease life-history parameters. We demonstrate that this probability of "evolutionary emergence" depends on two key properties of the disease life history: (i) the basic reproduction number and (ii) the expected duration of an infection. These parameters encapsulate all of the relevant information and can be combined in a very simple expression, with estimates for the rates of adaptive mutation, to predict the probability of emergence for any novel pathogen. In general, diseases that initially have a large reproductive number and/or that cause relatively long infections are the most prone to evolutionary adaptation.

negative: Abstracts from the 11th International Congress of Behavioral Medicine

negative: Virus discovery: one step beyond Recent advances in the metagenomics field have had huge effects on the identification and characterization of newly emerging viral pathogens. To allow timely and efficient responses to future viral threats, an integrated multidisciplinary approach utilizing expertises in several areas, including clinical assessment, virus surveillance, virus discovery, pathogenesis, and the molecular basis of the host response to infection, is required. It requires the scientific community involved in virus discovery to go one step beyond.

negative: The profile of peripheral blood lymphocyte subsets and serum cytokines in children with 2019 novel coronavirus pneumonia Abstract Objectives The study was aimed at investigating the characteristics of peripheral blood lymphocyte subsets and serum cytokines in children with 2019 novel coronavirus (2019-nCoV) pneumonia. Methods Children with 2019-nCoV pneumonia or with respiratory syncytial virus (RSV) pneumonia were included. Data including lymphocyte subsets and serum cytokines were collected and analyzed. Results : 56 patients were included in the study, 40 children with 2019-nCoV pneumonia and 16 children with RSV pneumonia. Compared with children with RSV pneumonia, patients with 2019-nCoV pneumonia had higher count of CD3+8+ lymphocyte, higher percentages of CD3+, CD3+8+ lymphocytes and a lower percentage of CD19+ lymphocyte. The serum IL-10 level was significantly higher in children with RSV pneumonia. One 2019-nCoV pneumonia child who was with an obvious increase of IL-10 developed severe pneumonia. Conclusions Immune response played a very important role in the development of 2019-nCoV pneumonia. The effective CD8+ T cell response might influence the severity of 2019-nCoV pneumonia. The adaptable change in IL-10 level might contribute to the relatively mild pneumonia symptoms in children with 2019-nCoV pneumonia and bacterial co-infection might be a risk factor of severe 2019-nCoV pneumonia.

negative: The nonparametric maximum likelihood estimator for middle-censored data Abstract In this note, we consider data subjected to middle censoring where the variable of interest becomes unobservable when it falls within an interval of censorship. We demonstrate that the nonparametric maximum likelihood estimator (NPMLE) of distribution function can be obtained by using Turnbull's (1976) EM algorithm or self-consistent estimating equation (Jammalamadaka and Mangalam, 2003) with an initial estimator which puts mass only on the innermost intervals. The consistency of the NPMLE can be established based on the asymptotic properties of self-consistent estimators (SCE) with mixed interval-censored data (Yu et al., 2000, 2001).

negative: Literature-related discovery and innovation — update Abstract Literature-Related Discovery and Innovation (LRDI — formerly LRD — literature-related discovery) integrates 1) discovery generation from disparate literatures with 2) the wealth of knowledge contained in prior art to 3) potentially reverse chronic and infectious diseases and/or 4) potentially solve technical problems that appear intractable. This article describes the evolution of LRDI by the author and the insights gained/lessons learned over the past decade. To illustrate the potential power of LRDI, the article emphasizes the relationship between the results of our 2008 LRDI multiple sclerosis (MS) study and a recent demonstration of MS reversal. Lessons learned from the six LRDI medical studies done so far include: ⁎ The main operational problem in the author's LRDI approach is selecting the most important concepts from extremely large volumes of potential discovery retrieval. This is contrary to most published LRDI research, where the discovery focus is searching for rare events. ⁎ It is important to have topical specialist(s) working closely with information technologist(s); the topical specialist(s) applies judgment in selecting the most important concepts. ⁎ A functional form of the information retrieval query with proximity searching capability provides highly selective filtering for discovery retrieval and core prevention/treatment retrieval; the functional form of the query with proximity searching capability allows the use of full-text for discovery and core prevention/treatment. ⁎ Bibliographic coupling (identifying papers that share common references) combined with text-based relationships strengthens selection for potential discovery further. ⁎ Having ‘skin-in-the-game’ (being affected personally) relative to the medical outcome is a strong incentive to do whatever is necessary to solve the research problem. ⁎ Hormesis is critical to healing; relatively modest doses of stimuli tend to be beneficial, whereas relatively large doses may be harmful. The synergy of hormetic treatment doses produces effects larger than combinations of individual doses and requires smaller doses when combined; the synergy of hormetic doses allows conversion of megadoses of nutrients typically reported in lab/clinical studies to physiological (food-level) doses and associated increased safety. ⁎ Co-promoters (combinations of toxic stimuli required to produce disease symptoms) are extremely important for explaining seemingly conflicting results; if true co-promotion is present, elimination of one of the co-promoters may be adequate for removing symptoms, even though the overall problem persists. ⁎ Prior art (potential treatments already published in the literature but not pursued by mainline medicine) may have much to contribute to potentially solve many serious medical problems; much of prior art is overlooked, especially low-tech prior art (e.g., foods, food extracts, herbs, etc.). ⁎ Systemic and focused treatments are both necessary components of healing, but neither will be fully, or many times even partially, effective until the cause(s) is identified and removed. Any medical approach that involves administering treatments for chronic and infectious diseases without addressing the cause(s) results in a broad range of outcomes mainly involving substitution of one set of symptoms for another. ⁎ Past results of LRDI medical studies showed much overlap among preventatives/systemic treatments for different diseases. Differences will arise mainly in focused treatments, especially those involving high technology. ⁎ The central parameters to healing in much medical research are never identified nor reported. Many treatments require a combination of skilled practitioners, cause removal, and immune/neural/endocrine/circulatory systems to be healthy for full effectiveness, yet practitioner skill, degree of cause removal, and immune system et al. health are never reported. A lack of this information does not allow efficacy of different treatments to be compared. Reviews and meta-analyses that compare and draw conclusions about the effectiveness of these different treatments without the above critical information being reported are of extremely limited value and credibility. ⁎ Finally, the most important deficiency for fully reversing chronic and infectious diseases, as well as rapidly accelerating healing of injuries and wounds, is the credibility and integrity of the medical literature itself, especially in areas that concern commercial and government/political sensitivities. In the evaluation of many concepts that deviated from the norm, it was difficult to ascertain whether the difference was based on solid high-quality research, poor research, or deliberately skewed research.

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: Distinct early IgA profile may determine severity of COVID-19 symptoms: an immunological case series SARS-CoV-2 is the causative agent of COVID-19 and is a severe threat to global health. Patients infected with SARS-CoV-2 show a wide range of symptoms and disease severity, while limited data is available on its immunogenicity. Here, the kinetics of the development of SARS-CoV-2-specific antibody responses in relation to clinical features and dynamics of specific B-cell populations are reported. Immunophenotyping of B cells was performed by flow cytometry with longitudinally collected PBMCs. In parallel, serum samples were analyzed for the presence of SARS-CoV-2-specific IgA, IgG, and IgM antibodies using whole proteome peptide microarrays. Soon after disease onset in a mild case, we observed an increased frequency of plasmablasts concomitantly with a strong SARS-CoV-2-specific IgA response. In contrast, a case with more severe progression showed a delayed, but eventually very strong and broad SARS-CoV-2-specific IgA response. This case study shows that determining SARS-CoV-2-specific antibody epitopes can be valuable to monitor the specificity and magnitude of the early B-cell response, which could guide the development of vaccine candidates. Follow-up studies are required to evaluate whether the kinetics and strength of the SARS-CoV-2-specific IgA response could be potential prognostic markers of viral control.

negative: Infection-mediated asthma: etiology, mechanisms and treatment options, with focus on Chlamydia pneumoniae and macrolides Asthma is a chronic respiratory disease characterized by reversible airway obstruction and airway hyperresponsiveness to non-specific bronchoconstriction agonists as the primary underlying pathophysiology. The worldwide incidence of asthma has increased dramatically in the last 40 years. According to World Health Organization (WHO) estimates, over 300 million children and adults worldwide currently suffer from this incurable disease and 255,000 die from the disease each year. It is now well accepted that asthma is a heterogeneous syndrome and many clinical subtypes have been described. Viral infections such as respiratory syncytial virus (RSV) and human rhinovirus (hRV) have been implicated in asthma exacerbation in children because of their ability to cause severe airway inflammation and wheezing. Infections with atypical bacteria also appear to play a role in the induction and exacerbation of asthma in both children and adults. Recent studies confirm the existence of an infectious asthma etiology mediated by Chlamydia pneumoniae (CP) and possibly by other viral, bacterial and fungal microbes. It is also likely that early-life infections with microbes such as CP could lead to alterations in the lung microbiome that significantly affect asthma risk and treatment outcomes. These infectious microbes may exacerbate the symptoms of established chronic asthma and may even contribute to the initial development of the clinical onset of the disease. It is now becoming more widely accepted that patterns of airway inflammation differ based on the trigger responsible for asthma initiation and exacerbation. Therefore, a better understanding of asthma subtypes is now being explored more aggressively, not only to decipher pathophysiologic mechanisms but also to select treatment and guide prognoses. This review will explore infection-mediated asthma with special emphasis on the protean manifestations of CP lung infection, clinical characteristics of infection-mediated asthma, mechanisms involved and antibiotic treatment outcomes.

negative: Low serum 25-hydroxyvitamin D levels are associated with increased risk of viral coinfections in wheezing children

negative: COVID-19 convalescent plasma transfusion

negative: A Stable Calcium Alumanyl A seven‐membered N,N′‐heterocyclic potassium alumanyl nucleophile is introduced and utilised in the metathetical synthesis of Mg−Al and Ca−Al bonded derivatives. Both species have been characterised by experimental and theoretical means, allowing a rationalisation of the greater reactivity of the heavier group 2 species implied by an initial assay of their reactivity.

negative: Feline Infectious Peritonitis Virus Feline infectious peritonitis virus (FIP) is antigenically related with transmissible gastroenteritis (TGE) virus of swine, canine coronavirus, and human coronavirus 229E. The virus causes a variety of clinical manifestations from effusive peritonitis to noneffusive central nervous system (CNS) or visceral organ involvement. The hosts that are infected by feline infectious peritonitis virus include domestic cat (subfamily Felinae), lion, leopard, jaguar (subfamily Pantherinae), caracal, and lynx (subfamily Lyncinae); antibodies have also been found in cheetahs (subfamily Acinonychinae). The standard indirect fluorescent-antibody (IFA) technique of demonstrating antibodies against FIP virus uses either the cryostat sections of organ tissues from FIP affected cats or TGE virus-infected porcine cells as antigen preparations. High antibody titers in the sera/ascitic fluids of animals showing disease symptoms are taken as a confirmation of the clinical/pathological diagnosis.

negative: XXIV World Allergy Congress 2015: Seoul, Korea. 14-17 October 2015 A1 Pirfenidone inhibits TGF-b1-induced extracellular matrix production in nasal polyp-derived fibroblasts Jae-Min Shin, Heung-Man Lee, Il-Ho Park A2 The efficacy of a 2-week course of oral steroid in the treatment of chronic spontaneous urticaria refractory to antihistamines Hyun-Sun Yoon, Gyeong Yul Park A3 The altered distribution of follicular t helper cells may predict a more pronounced clinical course of primary sjögren’s syndrome Margit Zeher A4 Betamethasone suppresses Th2 cell development induced by langerhans cell like dendritic cells Katsuhiko Matsui, Saki Tamai, Reiko Ikeda A5 An evaluation of variousallergens in cases of allergic bronchial asthma at lucknow and neighbouring districts by intradermal skintest Drsushil Suri, Dranu Suri A6 Evaluation ferqency of ADHD in childhood asthma Marzieh Heidarzadeh Arani A7 Steven johnson syndrome caused by typhoid fever in a child Azwin Lubis, Anang Endaryanto A8 Chronic Bronchitis with Radio Contrast Media Hypersensitivity: A Case with Hypothesized GINA Step 1 Asthma Shinichiro Koga A9 The association between asthma and depression in Korean adult : An analysis of the fifth korea national health and nutrition examination survey (2010-2012) Lee Ju Suk A10 Management of allergic disease exacerbations in pregnancy Yasunobu Tsuzuki A11 Subcutaneous immunotherapy mouse model for atopic dermatitis Seo Hyeong Kim, Jung U Shin, Ji Yeon Noh, Shan Jin, Shan Jin, Hemin Lee, Jungsoo Lee, Chang Ook Park, Kwang Hoon Lee, Kwang Hoon Lee A12 Atopic disease and/or atopy are risk factors for local anesthetic allergy in patients with history of hypersensitivity reactions to drugs? Fatma Merve Tepetam A13 Food hypersensitivity in patients with atopic dermatitis in Korea Chun Wook Park, Jee Hee Son, Soo Ick Cho, Yong Se Cho, Yun Sun Byun, Yoon Seok Yang, Bo Young Chung, Hye One Kim, Hee Jin Cho A14 Anaphylaxis caused by an ant (Brachyponera chinensis) in Japan Yoshinori Katada, Toshio Tanaka, Akihiko Nakabayashi, Koji Nishida, Kenichi Aoyagi, Yuki Tsukamoto, Kazushi Konma, Motoo Matsuura, Jung-Won Park, Yoshinori Harada, Kyoung Yong Jeong, Akiko Yura, Maiko Yoshimura A15 Anti-allergic effect of anti-IL-33 by suppression of immunoglobulin light chain and inducible nitric oxide synthase Tae-Suk Kyung, Young Hyo Kim, Chang-Shin Park, Tae Young Jang, Min-Jeong Heo, Ah-Yeoun Jung, Seung-Chan Yang A16 Food hypersensitivity in patients with chronic urticaria in Korea Hye One Kim, Yong Se Cho, Yun Sun Byun, Yoon Seok Yang, Bo Young Chung, Jee Hee Son, Chun Wook Park, Hee Jin Cho A17 Dose optimizing study of a depigmented polymerized allergen extract of phleum pollen by means of conjunctival provocation test (CPT) Angelika Sager, Oliver Pfaar A18 Correlation of cutaneous sensitivity and cytokine response in children with asthma Amit Agarwal, Meenu Singh, Bishnupda Chatterjee, Anil Chauhan A19 Colabomycin E, a Streptomycete-Derived Secondary Metabolite, Inhibits Proinflammatory Cytokines in Human Monocytes/Macrophages Ilja Striz, Eva Cecrdlova, Katerina Petrickova, Libor Kolesar, Alena Sekerkova, Veronika Svachova, Miroslav Petricek A20 Intravenous immunoglobluin treatment in a child with resistant atopic dermatitis: A brief review on this therapeutic regimen Hyuck Hoon Kwon, Kyu Han Kim A21 Wheat allergy is difficult to diagnose then other food allergens Suman Kumar A22 The effects of spirulina (Arthrospira platensis) dietary supplement as an adjunct therapy for children aged 7 to 14 years old with asthma: A randomized - double blind placebo controlled clinical trial Lou Ver Leigh Arciaga Manzon, Pilar Agnes Gonzalez Andaya A23 The study about cause and clinicopathological findings of injection induced dermatitis Bark-Lynn Lew, Youngjun Oh, Dongwoo Suh, Woo-Young Sim A24 IgE reactivity of recombinant allergen pac c 3 of the Asian needle ant pachycondyla chinensis Kyoung Yong Jeong, Myung-Hee Yi, Mina Son, Dongpyo Lyu, Jae-Hyun Lee, Tai-Soon Yong, Chein-Soo Hong, Jung-Won Park A25 Characterization of specific IgE antibody related to antigen 5 of echinococcus granulosus Mohammadreza Siavashi A26 Development of binary forecast model of asthma exacerbation: Asthma index Hey Suk Yun, Ha-Na Kang, Jae-Won Oh, Young Jin Choi A27 Different levels in rantes, IL-5 and TNF-á between the nasal polyps of adolescents with allergic, local allergic and non-allergic rhinitis Ha-Na Kang, Jae-Won Oh, Young Jin Choi A28 Tgfβ1 level is associated with VDR gene polymorphism in children with allergy diseases Tatiana Sentsova, Ilya Vorozhko, Olga Chernyak, Vera Revyakina, Anna Timopheeva, Andrey Donnikov A29 Dynamics of immunological biomarkers in children with food allergy fed goat milk formula Tatiana Sentsova, Ilya Vorozhko, Olga Chernyak, Vera Revyakina, Anna Timopheeva A30 Association between obesity, abdominal obesity and adiposity and the prevalence of atopic dermatitis in young Korean adults: The korea national health and nutrition examination survey, 2008–2010 Ji Hyun Lee, Young Min Park, Sang Soo Choi, Kyung Do Han, Han Mi Jung, Young Hoon Youn, Jun Young Lee, Yong Gyu Park, Seung-Hwan Lee A31 Associations of natural history and environmental factors with asthma among children in rural and urban areas of guangdong, China Zhaowei Yang, Jing Li, Mulin Feng, Marjut Roponen, Bianca Schaub, Gary WK Wong A32 The effect of CO2-enriched atmospheres to producing of allergenic pollen by ragweed Young Jin Choi, Ha-Na Kang, Jae-Won Oh A33 Application evaluation of house dust mite and components specific-IgE and IgG4 in specific immunotherapy with allergic diseases Baoqing Sun, Peiyan Zheng A34 Effect of Asian dust events on asthma according to the socioeconomic status using claim data in KOREA Yoon-Sung Park A35 TSLP downregulates human â-defensin 2 through STAT3-dependent pathway in keratinocytes Sang Wook Son A36 Effects of anti-IgE on IL-4, IL-5, IL-17, and CD19,20,200 in a case of netherton syndrome (SPINK5 mutation) Arzu Didem Yalcin, Sukran Kose, Kemal Kiraz A37 Augmentation of arginase 1 expression exacerbates airway inflammation in murine asthma models Jin-Young Lee, Sehyo Yune, Jae-Won Paeng, Mi-Jung Oh, Byung-Jae Lee, Dong-Chull Choi, Young Hee Lim, Kyoung Won Ha A38 Caregivers of children with no food allergy – their experiences and perception of the condition Kiwako Yamamoto-Hanada, Masami Narita, Masaki Futamura, Yukihiro Ohya A39 Evaluation of Drug Provocation Tests in Korean Children: A Single Center Experience Jihyun Kim, Jinwha Choi, Kwanghoon Kim, Jaehee Choi, Kangmo Ahn A40 Danyoung classification 2015 update by digital HD endoscopic evaluation SUN-HO/Brian Chang A41 Effect on quality of life of the mixed house dust mite/weed pollen extract immunotherapy in polysensitized patients Lisha Li A42 Ambient desert dust and allergic symptoms: A time series analysis from a national birth cohort (JECS) Kumiko Tsuji Kanatani, Yu-Ichi Adachi A43 Individuals Allergic to Cow’s Milk Should be Vigilant When Consuming Beef Because It May be Injected Beef Shigeyuki Narabayashi, Ikuo Okafuji, Yuya Tanaka, Satoru Tsuruta, Nobue Takamatsu A44 Quality of life of chronic rhinosinusitis patients with or without nasal polyps in Korea Soo Whan Kim, Do Hyun Kim A45 House dust mite sensitization and exacerbation of asthma in the fall in children Jong-Seo Yoon, Jin Tack Kim, Hwan Soo Kim, Yoon Hong Chun, Hyun Hee Kim, Sul Mui Won A46 Evidence-based health advice for childhood eczema and household pets Kam Lun E. Hon, Chung Mo Chow, Ting Fan Leung A47 Relationship between allergic rhinitis and mental health in korea Do Hyun Kim, Soo Whan Kim A48 Oscillometric bronchodilator response in 3 to 5 years old healthy and asthmatic Filipino children Gemmalyn Esguerra, Emily Resurreccion, Kristine Elisa Kionisala, Jenni Rose Dela Cruz A49 The use of aeroallergen immunotherapy to treat eosinophilic esophagitis Muhammad Imran A50 A study of the eczema herpeticum in Korean Yun Seon Choe, Kyu Han Kim, Mira Choi A51 Specific sublingual immunotherapy in Korean patients with atopic dermatitis Byung Soo Kim, Hyun-Joo Lee, Jeong-Min Kim, Jeong-Min Kim, Gun-Wook Kim, Je-Ho Mun, Je-Ho Mun, Hoon-Soo Kim, Margaret Song, Hyun-Chang Ko, Hyun-Chang Ko, Moon-Bum Kim A52 Association between polymorphisms in bitter taste receptors genes and clinical features in Korean asthmatics Sun-Young Yoon A53 Effect of glycosides based standardized fenugreek seed extract in bleomycin-induced pulmonary fibrosis in rats Amit Kandhare A54 A kampo formula, ogi-kenchu-to, decreases side-effects of steroid ointment for infantile atopic dermatitis: Three cases report Noriko Yahiro A55 To test use of jet nebulizers NE-C802 as a drug delivery system in the children with asthma Amit Agarwal, Meenu Singh, Jasleen Kaur, Ruby Pawankar, Pankaj Pant, Sukhmanjeet Singh A56 Immunoglobulin e to allergen components of house dust mite in Korean children with allergic disease Hwan Soo Kim, Jong-Seo Yoon, Sul Mui Won, Yoon Hong Chun, Jin Tack Kim, Hyun Hee Kim A57 Effectiveness of premedication and rapid desensitization in hypersensitivity to l-asparaginase Hwan Soo Kim, Sul Mui Won, Yoon Hong Chun, Jong-Seo Yoon, Hyun Hee Kim, Jin Tack Kim A58 Angioedema with Eosinophilia: The First Report from Thailand Thatchai Kampitak A59 Evaluation of anti-pruritic and anti-inflammatory effects of Korean red ginseng extract on atopic dermatitis murine model So Min Kim, Hyun Joo Lee, Hei Sung Kim, Jeong Deuk Lee, Sang Hyun Cho A60 Subcutaneous autologous serum therapy in chronic urticaria Kiran Godse A61 Allergic bronchopulmonary aspergillosis in asthma and lung tuberculosis Juwita Soekarno, Sarie Ratnasari, E. Alwi Datau, Eko Surachmanto, JC Matheos A62 Infantile eczema is associated with campylobacter and roseburia subpopulations but not microbial diversity in stool samples of Chinese newborns Ting Fan Leung, Jamie Sui-Lam Kwok, Christine Kit-Ching Tung, Man Fung Tang, Stephen Kwok-Wing Tsui, Gary WK Wong, Kam Lun Ellis Hon, Wing Hung Tam, Hing Yee Sy A63 Association between serum chitinase level and toll-like receptor polymorphisms in bakery workers Sohee Lee A64 IFN-gamma contributes to nasal polypogenesis by inducing epithelial-to-mesenchymal transition via non-smad pathway Hyun-Woo Shin, Mingyu Lee, Dae Woo Kim, Roza Khalmuratova A65 Management and education status of anaphylaxis patients who visit our emergency room (ER) Mi Yeoung Kim, Jaewon Jeong, Chansun Park A66 Hypoallergen-Encoding DNA Plasmids As Immunoprophylactic Vaccines of Shrimp Tropomyosin Hypersensitivity Christine Yee Yan Wai, Patrick S.C. Leung, Nicki Y.H. Leung, Ka Hou Chu A67 The relationship between sputum pentraxin 3 levels and childhood asthma Hee Seon Lee, Kyung Eun Lee, Jung Yeon Hong, Mi Na Kim, Min Jung Kim, Yoon Hee Kim, In Suk Sol, Seo Hee Yoon, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim A68 The role of local antibody responses in the nasal inflammation of allergic rhinitis (AR) patients Ji Hye Kim, Hae-Sim Park, Yoo Seob Shin, Young Min Ye, Daehong Seo, Moon Gyeong Yoon, Young Mok Lee A69 A case of ofloxacin-induced anaphylaxis by non-IgE, but specific IgG4-mediated responses Daehong Seo, Ji Hye Kim, Young-Mok Lee, Young Min Ye, Hae-Sim Park A70 Serum LTE4 metabolite as a biomarker for aspirin exacerbated respiratory disease Ga Young Ban, Kumsun Cho, Seung-Hyun Kim, Yong Eun Kwon, Moon Gyeong Yoon, Ji Hye Kim, Yoo Seob Shin, Young Min Ye, Dong-Ho Nahm, Hae-Sim Park A71 Local and systemic reactions of dust mite subcutaneous immunotherapy (SCIT) among children in a tertiary care hospital Pilar Agnes Gonzalez Andaya A72 Effects of carboxymethyl glucan (CM-glucan) in children with allergic rhinitis and asthma: A randomized controlled trial Pilar Agnes Gonzalez Andaya A73 Autophagy mechanisms in patients with severe asthma: A new therapeutic target Ga Young Ban, Chang Gyu Jung, Seung-Ihm Lee, Duy Le Pham, Dong-Hyeon Suh, Eun-Mi Yang, Young Min Ye, Yoo Seob Shin, Hae-Sim Park A74 Aggravation of airway inflammation and hypperresponsiveness following nasal challenge with dermatophagoides pteronyssinus in perennial allergic rhinitis patients without symptoms of asthma Wan Jun Wang, MO Xian, Yan Qing Xie, Jing Ping Zheng, Jing Li A75 Serum 25-hydroxyvitamin d in early childhood is non-linearly associated with allergy Emma Merike Savilahti, Outi Mäkitie, Anna Kaarina Kukkonen, Sture Andersson, Heli Viljakainen, Erkki Savilahti, Mikael Kuitunen A76 Fric test in dermographism Kiran Godse A77 Neutrophil autophagy and extracellular trap could contribute to asthma severity Duy Le Pham, Ga Young Ban, Seung-Hyun Kim, Eun-Mi Yang, Hae-Sim Park, Ji-Ho Lee, Yong-Joon Chwae A78 Redox Modulation for the Treatment of Toluene Diisocyanates-Induced Lung Inflammation Li-Ming Chin, Chi-Chang Shieh A79 A case of occupational asthma and rhinitis with anaphylaxis to Korean ginseng and sanyak Ji Hye Kim, Hye-Soo Yoo, Moon Gyeong Yoon, Ga Young Ban, Ga Young Ban, Yoo Seob Shin, Young Min Ye, Hae-Sim Park A80 Factors of influencing epidermal permeability barrier defects in atopic dermatitis children Myong Soon Sung, Jin Uck Choi, Sung Won Kim, Yong Jin Hwang A81 Innate type 2 response to aspergillusfumigatus in a murine model of atopic dermatitis-like skin inflammation Arum Park, Eun Lee, Song-I Yang, Hyun-Ju Cho, Jinho Yu A82 Activin a receptor 1C may implicate in the development of sensitive skin Dong Hun Lee, Eun Ju Kim, Yeon Kyung Kim, Eun Jin Doh, Hee Chul Eun, Jin Ho Chung, Young Mee Lee, Seon Pil Jin A83 Genetic association and eQTL analyses of genes associated with allergy in atopic/non-atopic asthma Xingnan Li, Naftali Kaminski, Sally Wenzel, Eugene Bleecker, Deborah Meyers A84 Gastroscope feature and clinical characteristics in 172 cases of children with henoch-schonlein purpura Zeng Huasong A85 The role of TRPV1 in CD4+ t cell mediated inflammatory response of allergic rhinitis Ji-Hun Mo, Ramachandran Samivel, Eun-Hee Kim, Ji-Hye Kim, Jun-Sang Bae, Young-Jun Chung, Dae Woo Kim A86 A Phenotype of Rhinitis from School Children Is Associated with the Development of Bronchial Hyperresponsiveness Eun Lee, Si Hyeon Lee, Young-Ho Kim, Hyun-Ju Cho, Ho-Sung Yu, Mi-Jin Kang, Song-I Yang, Young-Ho Jung, Hyung Young Kim, Ju-Hee Seo, Byoung-Ju Kim, Hyo-Bin Kim, So-Yeon Lee, Ho-Jang Kwon, Soo-Jong Hong A87 Increased basal activation status was noted in adult anaphylaxis patients Sailesh Palikhe, Hae-Sim Park, Seung-Hyun Kim, Ji Hye Kim, Eun-Mi Yang A88 Clinical values of interferon-gamma enzyme-linked immunospot assays for management of antibiotic hypersensitivity in hospitalized patients Suda Sibunruang, Jettanong Klaewsongkram A89 VDR gene polymorphism and 25-hydroxy vitamin d levels in children with food allergy Tatiana Sentsova, Ilya Vorozhko, Anna Timopheeva, Olga Chernyak, Vera Revyakina, Andrey Sokolnikov A90 An analysis of 145 oral almond challenge tests Makoto Nisihino, Yu Okada, Noriyuki Yanagida, Motohiro Ebisawa, Sakura Sato, Kiyotake Ogura, Tomoyuki Asaumi, Kenichi Nagakura, Tetsuharu Manabe, Hirotoshi Unno A91 Effect of creatine supplementation in fish allergenic potential; A proteomics study Pedro M Rodrigues, Denise Schrama, Gadija Mohamed, Lizex Hüsselmann, Lizex Hüsselmann, Bongani Ndimba A92 Flagellin modulates the function of invariant NKT cells via dendritic cells in asthma patients Jae-Uoong Shim, Young Il Koh, Joon Haeng Rhee, Ji-Ung Jeong A93 Clinical and subclinical manifestations of allopurinol – induced severe cutaneous adverse reactions in Vietnam Dinh Van Nguyen, Hieu Chi Chu, Mui Thi Tran, Christopher Vidal, Suran Fernando, Sheryl Van Nunen, Sy Van Than A94 Time course of serum inhibitory activity for facilitated allergen-IgE binding during house dust mite immunotherapy Mulin Feng, Jing Li A95 Periostin is a novel biomarker in eosinophilic nasal polyps of chronic rhinosinusitis Dong-Kyu Kim, Seung-No Hong, Kyoung Mi Eun, Hong Ryul Jin, Dae Woo Kim A96 Dominance of Th1-response in children with refractory mycoplasma pneumoniae pneumonia Jun Bao, Yi-Xiao Bao A97 Studies on the role of CD14 polymorphism among pollen and mold induced asthmatics of kolkata, India Sanjoy Podder, Goutam Kumar, Shampa Dutta, Amlan Ghosh A98 House dust mite allergy – Indian perspective Goutam Kumar Saha, Sanjoy Podder, Salil Kumar Gupta A99 Increased expression of purinergic (P2Y12) receptor and cysteinyl leukotriene receptors in the lung tissue of a mouse model of allergic asthma Tu/Hoang Kim Trinh, Yoo Seob Shin, Hae-Sim Park, Jing-Nan Liu, Duy Le Pham A100 Autologous serum skin test in chronic idiopathic urticaria - relationship with autoimmune markers and disease severity Hyun-Chang Ko, Byung Soo Kim, Moon-Bum Kim A101 Anxiety and depression levels in severe asthma patients treated with omalizumab Ömer Özbudak, Fatih Üzer A102 Economic burden of refractory chronic spontaneous urticaria on Kuwait health system Mona Al-Ahmad, Maryam Alowayesh, Norman Carroll A103 IgE-mediated maize allergy in India: A 28 kd protein responsible for food-induced allergic reaction Anand Bahadur Singh A104 Liposomal encapsulation of house dust mite allergens and dexamethasone modulates allergic response in a murine model of asthma Yordanis Pérez-Llano, María Del Carmen Luzardo Lorenzo, Wendy Ramírez González, Carlos Calcines Cruz, Rady Laborde Quintana, Alain Morejón, Virgilio Bourg, Marilé Hechavarría Stoker A105 Immune Suppressive Effects of Tonsil-Derived Mesenchymal Stem Cells for Eosinophilic Rhinosinusitis with Nasal Polyps in a Mouse Model Jun-Sang Bae, Ramachandran Samivel, Eun-Hee Kim, Ji-Hye Kim, Ji-Hun Mo A106 Second line treatments of dermographic urticaria refractory to antihistamines Keiko Hanaoka, Michihiro Hide, Akio Tanaka, Makiko Hiragun, Mikio Kawai A107 Diagnostic Value of Specific IgE to Peanut and Ara h 2 in Korean Children with Peanut Allergy Kwanghoon Kim, Kwanghoon Kim, Hye-Young Kim, Jihyun Kim, Kangmo Ahn, Youngshin Han A108 Inappropriate amounts of topical tacrolimus applied on Korean patients with eczema Gun-Wook Kim, Hyun-Chang Ko, Byung Soo Kim, Moon-Bum Kim, Margaret Song A109 Identification of an IgG1-mediated anaphylaxis marker and its application in evaluating the antigenicity of infant formulas Takeshi Matsubara, Hiroshi Iwamoto, Yuki Nakazato, Kazuyoshi Namba, Yasuhiro Takeda A110 Nitric oxide as a screening tool for evaluation of postoperative state of chronic rhinosinusitis Jae Hoon Lee, Woo Yong Bae A111 Comparison of different medical treatment options for crswnp: Doxycycline, methylprednisolone, mepolizumab, omalizumab Els De Schryver, Lien Calus, Philippe Gevaert, Thibaut Van Zele, Claus Bachert A112 Successful treatment of steroid resistant asthma model by blocking CD28 signal Akio Mori, Satoshi Kouyama, Miyako Yamaguchi, Yo Iijima, Akemi Abe-Ohtomo, Hiroaki Hayashi, Kentaroh Watai, Chihiro Mitsui, Chiyako Oshikata, Kiyoshi Sekiya, Takahiro Tsuburai, Mamoru Ohtomo, Yuma Fukutomi, Masami Taniguchi A113 Serum periostin levels was not associated with allergic rhinitis and allergic sensitization in Korean children Ju Wan Kang, Jeong Hong Kim, Jeong Hong Kim, Keun-Hwa Lee, Hye-Sook Lee, Seong-Chul Hong, Jaechun Lee A114 Roles of ADAM10 and ADAM17 in allergic rhinitis Ji Won Seo, Jae Hoon Lee, Woo Yong Bae A115 Mechanism of oral and topical polyprenol action in atopic dermatitis Ivans Sergejs Kuznecovs, Galina Kuznecova A116 Technical and clinical validation of a mobile chamber for allergen exposure tests Karl-Christian Bergmann, Torsten Zuberbier, Joseph Salame, Torsten Sehlinger, Georg Bölke A117 The association between serum lead level and total immunoglobulin e according to allergic sensitization Yoo Suk Kim, Jung Hyun Chang, Jeong Hong Kim, Ju Wan Kang A118 Clinical and laboratory characteristics of nasal obstruction dominant allergic sensitization Seung-No Hong, Doo Hee Han, Chae-Seo Rhee A119 Nasal provocation test is useful for the diagnoses of allergic, non- allergic, and local allergic rhinitis Young-Joo Ko, Young Hyo Kim, Dae-Young Kim, Tae Young Jang A120 Aspirin facilitates the intestinal absorption and oral sensitization of food allergens in rats Tomoharu Yokooji, Taiki Hirano, Hiroaki Matsuo A121 Gestational Secondhand Smoke Exposure Could Affect Maternal n-Glycosylation and Cause Filaggrin Loss in Children with Atopic Dermatitis Galina Kuznecova, Ivans Sergejs Kuznecovs A122 Allergen specific immunotherapy in the treatment of allergic rhinitis and asthma--a randomized prospective study from kashmir valley-north of India Roohi Rasool Wani, Shafia Alam Syed, Ghulam Hassan, Ayaz Gul, Saniya Nissar, Zaffar Amin Shah A123 Sleep disorders in latin-American children with asthma and/or allergic rhinitis and normal controls Marilyn Urrutia Pereira, Carmen Fernandez, Dirceu Sole, Herberto Jose Chong Neto, Veronica Acosta, Alfonso Mario Cepeda, Mirta Alvarez Castello, Claudia Almendarez, Jose Santos Lozano Saenz, Juan C. Sisul, Nelson Rosario Filho, Antonio Castillo, Marylin Valentin Rostan, Jennifer Avila, Hector Badellino, Maria Carolina Manotas, Raúl Lázaro Castro Almarales, Mayda González León A124 Association between respiratory symptoms and exhaled nitric oxide in Afghanistan Woo Kyung Kim, Hae-Sun Yoon A125 ATP, a danger signal, activates human eosinophils via P2 purinergic receptors Takehito Kobayashi, Tooru Noguchi, Tomoyuki Soma, Kazuyuki Nakagome, Hidetomo Nakamoto, Hirohito Kita, Makoto Nagata A126 Atopic dermatitis and sleep disorders in latin American children Marilyn Urrutia Pereira, Dirceu Sole, Herberto Jose Chong Neto, Alfonso Mario Cepeda, Raúl Lázaro Castro Almarales, Juan C. Sisul, Marylin Valentin Rostan, Hector Badellino, Miguel Alejandro Medina Avalos, Antonio Castillo, Claudia Almendarez, Nelson Rosario Filho, Caridad Sanchez Silot, Jennifer Avila, Felicia Berroa Rodriguez, Jose Santos Lozano Saenz, Mirta Alvarez Castello, Carmen Fernandez A127 Der p 23: A Major House Dust Mite Allergen in Spite of Limited Release from Fecal Pellets and Prominent Protease Sensitivity Wai Tuck Soh, Alain Jacquet, Kiat Ruxrungtham, Emmanuel Nony, Maxime Le Mignon A128 Anaphylactic Reaction After Inhalation of Budesonide Mary Lee-Wong, Suzanne McClelland, Suzanne McClelland, Nanette B. Silverberg, Christian E. Song A129 Lipidomic analysis of mattress dust from urban and rural schoolchildren in China Zhaowei Yang, Jiukai Zhang, Wentao Zheng, Nanshan Zhong, Jing Li A130 Improvements in quality of life in children with allergic rhinitis after adenotonsillectomy Jung Ho Bae, Young Joo Cho, Joo Yeon Kim A131 The seasonal variation of asthma exacerbations in patients allergic to pollens in Greece Konstantinos Petalas, Dimitrios Vourdas, Christos Grigoreas A132 Whole-genome sequencing study in allergic rhinitis nuclear families Yuan Zhang A133 Effect of the production of extracellular matrix from nasal fibroblasts by eosinophils activated with airborne fungi Seung-Heon Shin, Mi-Kyung Ye, Jeong-Kyu Kim A134 The study of clinical characteristics, lung function and bronchodilator responsiveness in infants with RSV bronchiolitis Yong Feng, Yunxiao Shang A135 GIS-based association between PM10 and allergic diseases in seoul: Implication for health and environmental policy Sungchul Seo, Ji Tae Choung, Dohyeong Kim, Young Yoo, Hyunwook Lim A136 The relationship between rhinovirus and recurrent wheezing Wenjing Zhu, Chuanhe Liu, Li Sha, Li Chang, Min Zhao, Linqing Zhao, Yuan Qian, Yuzhi Chen A137 Dominancy of Staphylcoccus Aureus in the Skin of Atopic Dermatitis Patients Compared to Healthy Subjects through Metagenomic Analysis Min-Hye Kim, Young Joo Cho, Mina Rho, Jung-Won Kim, Yeon-Mi Kang, Kyung-Eun Yum, Hyeon-Il Choi, Jun-Pyo Choi, Han-Ki Park, Taek-Ki Min, Bok-Yang Pyun, Yoon-Keun Kim A138 Micronized Cellulose Powder Reduces the Dose of Locally Applied Glucocorticoids in Patients with Allergic Rhinitis Xueyan Wang A139 New strategy for atopic dermatitis therapy with modulation of calcium ion channels Woo Kyung Kim, Yu Ran Nam, Joo Hyun Nam A140 Difference in the Systemic Bacterial Composition of Atopic Dermatitis Patients Compared to Healthy Subjects through Metagenomic Analysis of Urine Jung-Won Kim, Min-Hye Kim, Mina Rho, Yeon-Mi Kang, Kyung-Eun Yum, Hyeon-Il Choi, Jun-Pyo Choi, Han-Ki Park, Taek-Ki Min, Young Joo Cho, Bok-Yang Pyun, Yoon-Keun Kim A141 Occurrence and physiological function of immune complexes of food proteins and IgA in human saliva Hiroshi Narita, Junko Hirose, Kumiko Kizu, Ayu Matsunaga A142 Association between DNA hypomethylation at IL13 gene and allergic rhinitis in house dust mite-sensitized subjects Jingyun Li, Yuan Zhang, Luo Zhang A143 Effect of dietary methyl donors on asthma and atopy is modified by MTHFR polymorphism Yean Jung Choi, Hye Lim Shin, Song-I Yang, So-Yeon Lee, Sung-Ok Kwon, Young-Ho Jung, Ji-Won Kwon, Hyung Young Kim, Ju-Hee Seo, Byoung-Ju Kim, Hyo-Bin Kim, Se-Young Oh, Ho-Jang Kwon, Eun Lee, Mi-Jin Kang, Soo-Jong Hong, Yun-Jeong Lee, Joonil Kim A144 The effect of TSLP in a murine model of allergic asthma Joon Young Choi, Ji Young Kang, Seok Chan Kim, Sei Won Kim, Seung Joon Kim, Young Kyoon Kim, Chin Kook Rhee, Hea Yon Lee, Hwa Young Lee, Sook Young Lee A145 Evaluation of Aspirin Hypersensitivity in Chronic Rhinosinusitis Patients Tae Kyung Koh, Sung Wan Kim, Kun Hee Lee, Chul Kwon, Joong-Saeng Jo, Sung-Hwa Dong, Young Seok Byun A146 Chronic cough without wheezing in young children as a manifestation of chronic sinusitis Charles Song A147 Expression of muscarinic receptors and effect of tiotropium bromide on chronic asthma according to age in a murine model Ji Young Kang, Hwa Young Lee, In Kyoung Kim, Sei Won Kim, Chin Kook Rhee, Seung Joon Kim, Seok Chan Kim, Sook Young Lee, Young Kyoon Kim, Soon Seog Kwon, Joon Young Choi A148 Discrimination between non-eosinophilic and eosinophilic chronic rhinosinusitis with nasal polyps Pona Park, Hong Ryul Jin, Dong-Kyu Kim, Dae Woo Kim A149 Significant reduction in allergic features in the offspring of mice supplemented with specific non-digestible oligosaccharides during lactation Astrid Hogenkamp A150 Allergenicity assessment of hydrolysed infant formula; A multicenter comparison of a mouse model and a Guinea pig model for cow’s milk allergy Leon Knippels, Betty C.a.m. Van Esch, Jolanda Van Bilsen, Prescilla V. Jeurink; Marjan Gros, Johan Garssen, Joost J Smit, Raymond H.H. Pieters A151 Clinical significance between the allergic test and serum eosinophil cationic protein Boo-Young Kim, Soo Whan Kim A152 Hydroclorothiazide-induced acute non-cardiogenic pulmonary edema Ramon Lleonart A153 A Synbiotic Mixture of Scgos/Lcfos and Bifidobacterium Breve M-16V Is Able to Restore the Delayed Colonization of Bifidobacterium Observed in C-Section Delivered Infants Christophe Lay, Kaouther Benamor, Chua Mei Chen, Jan Knol, Charmaine Chew, Voranush Chongsrisawat, Anne Goh, Wen Chin Chiang, Rajeshwar Rao, Surasith Chaithongwongwatthana, Nipon Khemapech A154 Atopic characteristics of patients with asthma-COPD overlap syndrome Ji Young Yhi, Sang-Heon Kim, Dong Won Park, Ji-Yong Moon, Tae Hyung Kim, Jang Won Sohn, Dong Ho Shin, Ho Joo Yoon, Seok Hyun Cho A155 Perceptions and practices of severe asthma and asthma-COPD overlap syndrome among specialists: A questionnaire survey Sang-Heon Kim, Ji-Yong Moon, Jae-Hyun Lee, Ga Young Ban, Sujeong Kim, Mi-Ae Kim, Joo-Hee Kim, Min-Hye Kim, Chan-Sun Park, Hyouk-Soo Kwon, Jae-Woo Kwon, Jae Woo Jung, Hye-Ryun Kang, Jong-Sook Park, Tae-Bum Kim, Heung Woo Park, You Sook Cho, Kwang-Ha Yoo, Yeon-Mok Oh A156 A case of surgical diagnosed eosinophilic enteritis with intussusception in adult patient Sang-Rok Lee A157 Reference values of total IgE in estonian children Kaja Julge, Maire Vasar, Tiia Voor, Tiina Rebane A158 A case of eosinophilic granulomatosis with polyangiitis accompanied by rapidly progressive glomerulonephritis Yu Jin Kim, Sang Min Lee, Shin Myung Kang, Sojeong Kim, Sun Young Kyung, Sung Hwan Jeong, Jeong-Woong Park, Hyunjung Hwang, Yong Han Seon, Sanghui Park, Sang Pyo Lee A159 Associations Between Infectious Diseases and Urticaria Marius Iordache A160 Sleep in infants in korea – finding of bisq survey Yeongsang Jeong, Sohee Eun, Byung Min Choi, Ji Tae Choung, Wonhee Seo A161 Increased Expression of Filaggrin, TSLP, Periostin, IL13 and IL-33 in Nasal Polyps Liang Zhang, Ruby Pawankar, Manabu Nonaka, Miyuki Hayashi, Shingo Yamanishi, Harumi Suzaki, Yasuhiko Itoh, So Watanabe, Hitome Kobayashi A162 Asymptomatic bacteruria increases the risk of edematous attacks in patients with hereditary angioedema due to C1 inhibitor deficency (C1-INH-HAE) Zsuzsanna Zotter, Henriette Farkas, Lilian Varga, Nora Veszeli, Eva Imreh, Gabor Kovacs, Marsel Nallbani A163 Gastric Erosions Cause Spontaneous Urticaria Independent of Helicobacter Pylori Semen Zheleznov, Galina Urzhumtseva, Natalia Petrova, Zhanna Sarsaniia, Nikolai Didkovskii, Torsten Zuberbier A164 The Effect of G2 Vaccine on the Gene Expression NKG2D and Receptor Presenting on the Surface of NK Cells in Peripheral Blood Nader Dashti Gerdabi, Ali Khodadadi, Zahra Abdoli, Mehri Ghafourian, Mohammad Ali Assarehzadegan, Khodayar Ghorban A165 Ethnic differences in lifetime prevalence and indoor environmental factors for childhood eczema Hyo-Bin Kim, Hui Zhou, Jeong Hee Kim, Rima Habre, Theresa Bastain, Frank Gilliland A166 A case of methazolamide-induced toxic epidermal necrolysis Jong-Wook Bae, Kyu-Hyung Han, Young-Koo Jee, Misoo Choi, Seung-Phil Hong, Seung-Hyun Kim A167 Inflammatory responses of human adipose-tissue derived stem cells to LPS and nanoparticles Hee-Kyoo Kim, Gil-Soon Choi, Jeonghoon Heo, Young-Ho Kim, Eun-Kee Park A168 Analysis of 71 Cashew Nut Oral Challenge Tests Takashi Inoue, Kiyotake Ogura, Noriyuki Yanagida, Hirotoshi Unno, Kenichi Nagakura, Tetsuharu Manabe, Tomoyuki Asaumi, Sakura Sato, Yu Okada, Motohiro Ebisawa A169 Fungal sensitization is associated with asthma exacerbation Min-Gu Kim, You Sook Cho, Tae-Bum Kim, Hee-Bom Moon, Jung-Hyun Kim, Hyo-Jung Kim, So-Young Park, Bomi Seo, Hyouk-Soo Kwon, Jaemoon Lee, Taehoon Lee A170 Individual therapeutic patient education and consultation in children with atopic dermatitis Hye-Soo Yoo, Jieun Kim, Inok Kim, Haejin Kim, Younhee Chang, Hae-Sim Park, Sooyoung Lee A171 Utility of Alpha-Lactalbumin Specific IgE Levels Using Immulite 2000 3gAllergy in Predicting Clinical Severity of Milk Allergy Kazuyo Kuzume, Munemitsu Koizumi, Koji Nishimura, Michiko Okamoto A172 Isoniazid/rifampicin-specific t-cell responses in patients with anti-tuberculosis –induced dress syndrome Seung-Hyun Kim, Young Min Ye, Gyu Young Hur, Hae-Sim Park, Sang-Heon Kim, Young-Koo Jee A173 Genetic biomarkers associated with aspirin-exacerbated respiratory disease (AERD) phenotype based on genome-wide association study Seung-Hyun Kim, Hyunna Choi, Young Min Ye, Hae-Sim Park A174 Assessment of ORAL drug provocation test in the diagnosis of NON-steroidal ANTI-inflammatory drugs hypersensitivity Bui VAN Khanh, Hieu Chi Chu, Nguyen Nhu Nguyet, Nguyen Hoang Phuong A175 Korean treatment guideline of atopic dermatitis Joo Young Roh, Hyun Jeong Kim, Jung Eun Kim, Bark-Lynn Lew, Kyung Ho Lee, Seung-Phil Hong, Yong Hyun Jang, Kui Young Park, Seong Jun Seo, Jung Min Bae, Eung Ho Choi, Ki Beom Suhr, Seung Chul Lee, Hyun-Chang Ko, Young Lip Park, Sang Wook Son, Young Jun Seo, Yang Won Lee, Sang Hyun Cho, Chun Wook Park A176 Systemic side reaction of subcutaneous immunotherapy(SCIT) for perennial allergic rhinitis Kun Hee Lee, Sung Wan Kim A177 Clinical baseline characteristics of Asian patients suffering from refractory chronic spontaneous urticaria (CSU) in three phase 3 omalizumab clinical trials Chia-Yu CHU, Derrick Aw, Young-Min Ye, Giovanni Bader, Fabrizio Dolfi, Nathalie Oliveira A178 A metagenomic approach through t-RFLP to the microbiome of asthma Jae Chol Choi, Jae Woo Jung, Hye-Ryun Kang, Kijeong Kim, Byoung Whui Choi A179 Clinical characteristics and ten-year trend of peripheral blood eosinophilia among health screening program recipients at a tertiary hospital of South Korea Jong Wook Shin, Jae Woo Jung, Jae Chol Choi, In Won Park, Byoung Whui Choi, Jae Yeol Kim A180 The prevalence of toxocariasis and diagnostic value of serologic tests in asymptomatic Korean adults Jin-Young Lee, Kyoung Won Ha, Yun-Jin Jeung, Sehyo Yune, Byung-Jae Lee, Dong-Chull Choi, Mi-Jung Oh, Young Hee Lim A181 Cutaneous Drug Hypersensitivity Reaction in Korean Children: An Analysis of KAERS Database on 2012-2013 Eui Jun Lee, Dongin Suh, Sung-Il Woo, Hwa Jin Cho, Eun Hee Chung, Soo Youn Chung A182 Comparison of clinical characteristics, quality of life and sleep in patients with allergic rhinitis when categorised as “sneezers and runners” and “blockers” Kamal Gera, Ashok Shah A183 Role of s-nitrosoglutathione reductase (GSNOR) in the murine strain differences of airway hyperresponsiveness Jin-Young Lee, Kyoung Won Ha, Mi-Jung Oh, Young Hee Lim, Sehyo Yune, Jae-Won Paeng, Mi-Jin Jang, Byung-Jae Lee, Dong-Chull Choi A184 Protection from airway bronchoconstriction by gsno Jin-Young Lee, Mi-Jin Jang, Jae-Won Paeng, Yun-Jin Jeung, Young Hee Lim, Mi-Jung Oh, Kyoung Won Ha, Byung-Jae Lee, Dong-Chull Choi, Sehyo Yune A185 Does EIA-targeted asthma treatment improve daily physical activity of children? Takahiro Ito A186 Wheezing as a clue to the diagnosis of cough variant asthma and nonasthmatic eosinophilic bronchitis Jihye Kim, Jin-Young Lee, Sehyo Yune, Byung-Jae Lee, Dong-Chull Choi, Mi-Jin Jang, Jae-Won Paeng, Young Eun Kim, Young Nam Kim, Yongseok Lee A187 Antagonism of microRNA-21 suppressed the airway inflammation in a mouse model of bronchial asthma Hwa Young Lee, Sook Young Lee, Soon Seog Kwon, Young Kyoon Kim, Chin Kook Rhee, Sei Won Kim, Hea Yon Lee, Joon Young Choi, In Kyoung Kim A188 Chlorhexidine anaphylaxis: A report of two cases Jose Antonio Navarro, Maria Ascension Aranzabal, Alejandro Joral, Susana Lizarza, Miguel Echenagusia, EVA Maria Lasa A189 Effects of Particulate Matter on Respiratory Allergic Diseases Considering Meteorological Factors in Busan, Korea Eun-Jung Jo, Sun-Mi Jang, Seung-Eon Song, Hae-Jung Na, Chang-Hoon Kim, Woo-Seop Lee, Hye-Kyung Park A190 Clinical characteristics of neutrophilic asthma Sachiko Miyauchi, Yoshitaka Uchida, Tomoyuki Soma, Susumu Yamazaki, Toru Noguchi, Takehito Kobayashi, Kazuyuki Nakagome, Makoto Nagata A191 Current Practice of Infants and Children with Acute Urticaria at a Single Wide Regional Emergency Medical Center Hea Lin Oh, Do Kyun Kim, Dongin Suh, Young Yull Koh A192 Discordance between sputum eosinophilia and exhaled nitric oxide Sehyo Yune, Jin-Young Lee, Byung-Jae Lee, Dong-Chull Choi, Jae-Won Paeng, Mi-Jin Jang, Jihye Kim, Young Nam Kim A193 Association between genetic polymorphisms of costimulatory molecules and antituberculosis drugs induced hepatitis Sang-Heon Kim, Sang-Hoon Kim, Jang Won Sohn, Ho Joo Yoon, Dong Ho Shin, Jae Hyung Lee, Byoung Hoon Lee, Youn-Seup Kim, Jae-Seuk Park, Young-Koo Jee A194 The prevalence of gastroesophageal reflux disease in chronic unexplained cough Sehyo Yune, Jin-Young Lee, Jae-Won Paeng, Mi-Jin Jang, Dong-Chull Choi, Byung-Jae Lee, Yongseok Lee, Young Eun Kim A195 Risk Factors of Allergic Rhinitis in Preschool Children and Clinical Utility of Feno Jisun Yoon A196 Relationship between serum 25-hydroxyvitamin d and asthma exacerbation severity in children Yong Feng, Li Zhang, Xuxu Cai A197 Usefulness of Specific IgE Antibody Levels to Wheat, Gluten and Ï-5 Gliadin for Wheat Allergy in Korean Children Jong-Seo Yoon, Kyunguk Jeong, Hye-Soo Yoo, Sooyoung Lee, Sooyoung Lee A198 Neutralization of stratum corneum accelerates the progress from atopic dermatitis to asthma-like lesion in flaky tail mice treated by house dust mite allergen Hae-Jin Lee, Noo Ri Lee, Bo-Kyung Kim, Minyoung Jung, Dong Hye Kim, Catharina S. Moniaga, Kenji Kabashima, Eung Ho Choi A199 Trends in oral food challenges in Japan: A six-year prospective study Noriyuki Yanagida, Sakura Sato, Chizuko Sugizaki, Motohiro Ebisawa A200 The Gut Microbiome in the Food Allergic Host Jamie Kiehm, Punita Ponda, Sherry Farzan, Jared Weiss, Claudia Elera, Catherine Destio, Cristina Sison, Annette Lee A201 Cord blood cytokines and maternal environmental exposure during pregnancy Soo Hyun Ri, Chang Hoon Lim A202 Rupatadine pharmacokinetics in Japanese healthy volunteers after single and repeated oral doses of 10, 20 and 40 mg Iñaki Izquierdo Pulido, Jorg Taubel, Georg Ferber, Eva Santamaria Masdeu A203 A safe and effective method to desensitize patients with wheat allergy Alireza Khayatzadeh, Masoud Movahedi, Motohiro Ebisawa, Mohammad Gharagozlou A204 RNA Binding Protein Hur Regulates CD4+ T Cell Differentiation and Is Required for Allergic Airway Inflammation and Normal IL-2 Homeostasis Ulus Atasoy, Patsharaporn Techasintana, Matt Gubin, Jacqueline Glascock, Suzanne Ridenhour, Joseph Magee A205 Time Trends in the Epidemiology of Recurrent Wheezing in Infants from South America Nelson Rosario Filho; Herberto Jose Chong Neto, Gustavo Falbo Wandalsen, Ana Caroline Dela Bianca, Carolina Aranda, Dirceu Sole, Javier Mallol, Luis Garcia-Marcos, Luis Garcia-Marcos A206 Successful Cyclophosphamide Desensitization in a Pediatric Patient with Systemic Lupus Erythematosus Jennifer Toh, Yoomie Lee, Joyce Huang, Elina Jerschow, Jenny Shliozberg A207 The Fatty Acid Binding Protein Der p 13 Is a Minor House Dust Mite Allergen Able to Activate Innate Immunity Pattraporn Satitsuksanoa, Narissara Suratannon, Jongkonnee Wongpiyabovorn, Pantipa Chatchatee, Kiat Ruxrungtham, Alain Jacquet A208 Epidemiology of Stevens-Johnson Syndrome and Toxic Epidemal Necrolysis: An Administrative Database Study Min Suk Yang; Jin Yong Lee, Ja Yeun Kim, Han-Ki Park, Ju-Young Kim, Woo-Jung Song, Hye-Ryun Kang, Heung Woo Park, Yoon-Seok Chang, Sang-Heon Cho, Kyung-up Min, Chang-Han Park, Suk-Il Chang, Sook-Hee Song A209 Regional Differences of Vitamin D and Food-Induced Anaphylaxis in Korea Si-Heon Kim, Gil-Soon Choi, Su-Chin Kim, Ji Hye Kim, Ga Young Ban, Yoo Seob Shin, Hae-Sim Park, Young Min Ye A210 Triggering Factors of Atopic Dermatitis By Severity Yoon Ha Hwang A211 Clinical Features of Adverse Drug Reactions of Monoclonal Antibodies in Korea Da Woon Sim, Kyung Hee Park, Kyung Hee Park, Hye Jung Park, Hye Jung Park, Jung-Won Park, Jung-Won Park, Jae-Hyun Lee, Jae-Hyun Lee A212 Food Allergy with Eczema Is Associated with Reduced Growth in the First Four Years of Life Katrina Allen, Cara Beck, Jennifer Koplin, Melanie Matheson, Mimi Tang, Anne-Louise Ponsonby, Lyle Gurrin, Shyamali Dharmage, Melissa Wake, Vicki Mcwilliam A213 The Preliminary Study on Clinical Efficacy and Impact Factors of One Year’s Dust Mite Specific Immunotherapy in Allergic Asthma and Rhinitis Children Sensitized to Dust Mite Xiaoying Liu, Jing Wang, Li Xiang, Qun Wang A214 Lipopolysaccharide Signaling through Toll- like Receptor 4 Could be Augmented By Dermatophagoides Farinae in the Human Middle Ear Epithelial Cell Ji-Eun Lee, Dong-Young Kim, Chae-Seo Rhee, Chae-Seo Rhee A215 Drug Allergy in Pregnant Adolescents: Relation with Familial and Personal Atopy, and Substances Use Francisco Vazquez-Nava A216 Patients and Physicians Concept of Well-Controlled Asthma: Findings from Realise Asia Sang-Heon Cho, Jaewon Jeong, Diahn-Warng Perng, David Price, Glenn Neira, Jiangtao Lin A217 The Role of Vasoactive Intestinal Peptide in the Pathophysiology of Acute Asthma Olga Semernik A218 Comparison of Serum Cytokine Levels According to the Severity in Atopic Dermatitis Ha-Su Kim, Jin-a Jung, Ji-in Jung A219 The Different Influence on the Regulatory T Cell Response Between Subcutanous Immnuotherapy(SCIT) and Sublingual Immunotherapy(SLIT) in Children with Asthma Qing Miao, Li Xiang A220 Asthma State of Affairs in Asia: Seeing through Physicians’ and Patients’ Lenses Sang-Heon Cho, Jaewon Jeong, Diahn-Warng Perng, Jiangtao Lin, David Price A221 Identification of Aspirin Exacerbated Respiratory Disease (AERD) Phenotypes Using Two Step Cluster Analysis Hyun Young Lee, Hae-Sim Park, Young Min Ye, Su Chin Kim A222 Dusty Air Pollution Are Associated with an Increase Risk of Allergic Diseases in General Population Shokrollah Farrokhi, Mohammadkazem Gheiby A223 A Genome-Wide Association Study of Antituberculosis Drugs-Induced Hepatitis Sang-Heon Kim; Heung Woo Park, Sang-Hoon Kim, Young-Koo Jee A224 The Role of peroxiredoxin6 of Bronchial Epithelial Cells in Regulating Mitochondrial Function Under Oxidative Stress By Translocation to Outside Mitochondrial Membrane Sunjoo Park, Keun Ai Moon, Hyouk-Soo Kwon, Tae-Bum Kim, You Sook Cho, Hee-Bom Moon, Kyoung Young Lee, Gyong Hwa Hong, Eun Hee Ha A225 Toxic and Adjuvant Effects of 3 Types of Silica Nanoparticles on Airway System Heejae Han, Hye Jung Park, Yoon Hee Park, Yoon-Jo Kim, Kangtaek Lee, Jung-Won Park, Jae-Hyun Lee A226 Procedure for Diagnostic and Selection of Immunotherapy Method for Children with Different Immunopathogenetic Phenotypes of Atopic Dermatitis Tatiana Slavyanskaya, Vladislava Derkach A227 Prediction of the Success of Our Desensitization Protocol with Symptoms and Results of a Skin Prick Test in Patients with Hypersensitivity to Platinum-Based Chemotherapy Hye Jung Park, Chein-Soo Hong, Jae-Hyun Lee, Jae-Hyun Lee, Sungryeol KIM, Sungryeol KIM, Kyung Hee Park, Kyung Hee Park, Choong-Kun Lee, Beodeul Kang, Seung-Hoon Beom, Sang Joon Shin, Minku Jung, Jung-Won Park, Jung-Won Park A228 Anti-Allergic Effect of Intralymphatic Injection of OVA-Flagelin Mixture in Mouse Model of Allergic Rhinitis Eun-Hee Kim, Ji-Hye Kim, Ji-Hun Mo, Young-Jun Chung A229 Serum Periostin Level Is Higher in Respiratory Type of NSAID Hypersensitivity Than Cutaneous Type Mi-Ae Kim, Hae-Sim Park, Moon Gyeong Yoon, Young-Soo Lee, Ji Hye Kim, Ga Young Ban, Hye-Soo Yoo, Yoo Seob Shin, Young Min Ye, Dong-Ho Nahm A230 A Retrospective Analysis of Allergy Blood Testing in Beijing Children’s Hospital in the Year of 2013: A Single-Center Research Qing Miao, Li Xiang A231 Role of Nrf2 in the Allergic Airway Inflammation Differ Between BALB/c and C57BL/6 Mice Ying-Ji Li, Takako Shimizu, Hirofumi Inagaki, Yukiyo Hirata, Hajime Takizawa, Arata Azuma, Masayuki Yamamoto, Tomoyuki Kawada A232 Effect of Human Mesenchymal Stem Cell on Neutrophilic Asthma Model Min-Gu Kim, Gyong Hwa Hong, Kyoung Young Lee, Eun Hee Ha, Keun Ai Moon, Sunjoo Park, Hyouk-Soo Kwon, Tae-Bum Kim, Hee-Bom Moon, You Sook Cho, Jung-Hyun Kim, Hyo-Jung Kim, So-Young Park, Bomi Seo A233 Immunomodulatory Effect of Tonsil Derived Mesenchymal Stem Cells in a Mouse Model of Allergic Rhinitis Ji-Hye Kim, Ramachandran Samivel, Eun-Hee Kim, Young-Jun Chung, Ji-Hun Mo A234 Alternative Therapy Such As Yoga May be a Low Cost Tool for Improving the Quality of Life of Patient’s with Allergic Rhinitis and Asthma Soumya M. S., G. Inbaraj, R. Chellaa, Ruby Pawankar A235 Substantial Impairment of the Quality of Life in Adult Patients with Chronic Urticaria Wonsun Choi, Hae-Sim Park, Young Min Ye, Ji Hye Kim, Ga Young Ban, Yoo-Seob Shin A236 Dietary Galacto-Oligosaccharides Reduce Airway Eosinophilia and Enhance the Th2 Suppressive Effect of Budesonide in House Dust Mite-Induced Asthma in Mice Saskia Braber, Kim Verheijden, Aletta Kraneveld, Johan Garssen, Linette Willemsen, Gert Folkerts A237 Production and Characterization of Recombinant Periplaneta americana Allergens for Component Resolved Diagnosis Stephanie Eichhorn, Fatima Ferreira, Isabel Pablos, Bianca Kastner, Bettina Schweidler, Sabrina Wildner, Peter Briza, Jung-Won Park, Naveen Arora, Stefan Vieths, Gabriele Gadermaier A238 Assessment of Characteristics of Itch in Patients with Hand Eczema Sung-Min Park, Won-Ku Lee, Jeong-Min Kim, Gun-Wook Kim, Je-Ho Mun, Hoon-Soo Kim, Margaret Song, Hyun-Chang Ko, Moon-Bum Kim, Byung Soo Kim A239 The Hidden Culprit: A Case of Repeated Anaphylaxis from Cremophor Hypersensitivity. Young Nam Kim, Sehyo Yune, Jin-Young Lee, Jihye Kim, Young Eun Kim, Jae-Won Paeng, Mi-Jin Jang, Dong-Chull Choi, Byung-Jae Lee, Yongseok Lee A240 Spectrum of Anaphylaxis in Children and Adults at Emergency Departments in Singapore Si Hui Goh, Bee Wah Lee, Jian Yi Soh A241 Improved Quality of Life through an Integrated Health Care Service for Children with Atopic Dermatitis Hyungoo Kang; Hyunhee Kim; Hye-Yung Yum A242 Criteria Combining Autologous Serum Skin Test and Clusterin for Predicting Antihistamine-Refractoriness in Patients with Chronic Spontaneous Urticaria Young Min Ye; Hae-Sim Park; Ga-Young Ban; Ji Hye Kim; Yoo Seob Shin A243 Urinary Leukotriene E4 Levels in Wheezing Infants Takumi Takizawa, Masahiko Tabata, Akira Aizawa, Hisako Yagi, Yutaka Nishida, Hirokazu Arakawa, Akihiro Morikawa, Solongo Orosoo A244 Allergic Sensitization to Whey in Mice Is Facilitated By the Mycotoxin Deoxynivalenol (DON) Saskia Braber, Marianne Bol-Schoenmakers, Peyman Akbari, Prescilla V. Jeurink, Prescilla V. Jeurink, Priscilla De Graaff, Joost J. Smit, Betty C. A. M. Van Esch, Johan Garssen, Johan Garssen, Johanna Fink-Gremmels, Raymond H. H. Pieters A245 How to Define Chronic Cough: Based on a Systematic Review of the Epidemiological Literature Gun-Woo Kim, Eun-Jung Jo, Sujeong Kim, Woo-Jung Song, Yoon-Seok Chang, Shoaib Faruqi, Ju-Young Kim, Mingyu Kang, Min-Hye Kim, Jana Plevkova, Heung Woo Park, Sang-Heon Cho, Alyn Morice, So-Hee Lee, Sun-Sin Kim, Seoung-Eun Lee A246 Asko Study: Comparison of Behavior and Habits in Diagnosis and Treatment of Adult Asthma and COPD Patients Bilun Gemicioglu, Zeynep Misirligil, Arif Hikmet Cimrin, Hakan Gunen, Tevfik Ozlu, Aykut Cilli, Levent Akyildiz, Hasan Bayram, Esra Uzaslan, Oznur Abadoglu, Mecit Suerdem A247 Changes in Pulmonary Function in the Treatment of Obesity in Children Keigo Kainuma A248 Changes of Feno and Nasal Feno Levels after Treatment in Pediatric Allergic Rhinitis Hyun-a Kim, Ha-Su Kim, Woo Yong Bae, Jin-a Jung A249 Prevalence of Vitamin D Deficiency in Exclusively Breastfed Infants in Kenya Rose Kamenwa, William Macharia, Nusrat Said A250 In-Vitro Screening of Atopy in the Indian Population: Are Current Methods Adequate, Keeping Local IgE Seroprevalence for Common Food & Inhalant Allergens in Mind? Vidya Nerurkar, Meenal Patel, Simi Bhatia A251 Usefulness of House Dust Mites Nasal Provocation Test in Asthma Inseon S Choi, Soo-Jeong Kim, Joo-Min Won, Myeong-Soo Park A252 Biomarker-Based Treatment Option for Preschool Children with Recurrent Wheeze Mizuho Nagao A253 Anti-Tuberculosis Drugs-Induced Liver Injury in Patients with Connective Tissue Diseases Dong Won Park, Jang Won Sohn, Ji Young Yhi, Ji-Yong Moon, Sang-Heon Kim, Tae Hyung Kim, Dong Ho Shin, Ho Joo Yoon A254 Ocular Symptoms of Cedar Pollinosis in Otolaryngology Patients Yukiyoshi Hyo A255 The Clinical Characteristics of Adverse Drug Reactions Reported in a Regional University Hospital for 6 Years and the Suggestions for the Reporting System Jaechun Lee, Su Hee Kim, Eunkyoung Lee A256 Changes in Skin Prick Test Results over 3 Years in School-Aged Children Hahn Jin Jung, Jaehyun Lim, Seung-No Hong, Doo Hee Han, Chae-Seo Rhee A257 The Analysis of Risk Factors and Features of Food Allergy in Korean Children: Nationwide Cross-Sectional Survey Kun Song Lee A258 A Sequential Indirect-Direct Bronchial Provocation Test for Diagnosis of Asthma: A Pilot Study Jaechun Lee, Sun Young Yang, Mi Young Ahn, Jong Hoo Lee, Jasmina Golez A259 Association of VDR and CYP2R1 Polymorphisms with Persistent Allergic Rhinitis in a Han Chinese Population Hui-Qin Tian, Lei Cheng, Xin-Yuan Chen A260 Associations of Metabolic Syndrome with Asthma and Atopy in Korean Adults Ji-Yong Moon, Sang-Heon Kim, Tae Hyung Kim, Ji Young Yhi, Ho Joo Yoon, Jang Won Sohn, Dong Ho Shin, Dong Won Park A261 Clinical Manifestation and Treatment Outcome of Eosinophilic Gastroenteritis in Korean Children Won Im Cho, Jong Sub Choi, Dongin Suh, Gyeong Hoon Kang, Jin Soo Moon, Jae Sung Ko, Kyung Jae Lee, Shin Jie Choi A262 The Sensitization Model and Correlation of Bermuda and Timothy Grass Pollen Allergen in Allergic Patients in Southern China Wenting Luo, Baoqing Sun A263 A Pilot Study on the Outcomes of Respiratory Allergic Diseases at Pre-School Age in Chinese Infants with Atopic Dermatitis Qi Gao, Li Xiang, Kunling Shen A264 Activation of Toll like Receptor 1 and 6 By House Dust Mite Enhances the Expression of Tight Junction Protein in Epidermal Keratinocytes Yong Hyun Jang A265 Pollen Exposure in a Mobile Exposure Chamber: Comparing Real-Life Symptoms with Exposure Symptoms Karl-Christian Bergmann, Torsten Sehlinger, Georg Bölke, Uwe Berger, Torsten Zuberbier A266 Retrospective Analysis of the Incidence of Allergy in Patients with Contact Eczema Joanna Kolodziejczyk, Milena Wojciechowska, Anna Hnatyszyn-Dzikowska, Micha Chojnacki, Zbigniew Bartuzi A267 Effect of Fungal Sensitization in Patients with Severe Asthma Katsunori Masaki, Koichi Fukunaga, Takashi Kamatani, Kengo Ohtsuka, Takae Tanosaki, Masako Matsusaka, Takao Mochimaru, Hiroki Kabata, Soichiro Ueda, Yusuke Suzuki, Katsuhiko Kamei, Koichiro Asano, Tomoko Betsuyaku A268 SCIg Patient Preference Pump Versus Push Karlee Trafford A269 Fixed Drug Eruption Induced By Ornidazole and Diclofenac Ismet Bulut, Zeynep Ferhan Ozseker A270 Transepidermal Water Loss Measurement during Infancy Can Predict the Subsequent Development of Atopic Dermatitis Kenta Horimukai, Hideaki Morita, Masami Narita, Hironori Niizeki, Kenji Matsumoto, Yukihiro Ohya, Hirohisa Saito, Shigenori Kabashima, Mai Kondo, Eisuke Inoue A271 Inhalant Allergens on Soft Toys: A Literature Review Robert Siebers, Francis FS Wu A272 Fractional Exhaled Nitric Oxide in Elderly Asthmatics Robert Siebers, Francis FS Wu, Ming-Hui Ting, Hung-En Laio, Tsung-Huai Kuo, Pei-Yuan Lee A273 Dye and Preservative Challenge in Meal-Associated Urticaria and Angioedema: A Low-Yield Diagnostic Maneuver Daniel Eugene Maddox A274 The Changes of Allergic Sensitization with Age in Children with Allergic Rhinitis Gwanghui RyuHyo Yeol Kim, Hun-Jong Dhong, Sang Duk Hong, Seung-Kyu Chung A275 Component-Specific IgE and IgG4 Levels in Milk Allergy Children Tolerated Baked Milk Products Osamu Higuchi, Yu-Ichi Adachi, Toshiko Itazawa, Yoko Adachi, Miki Hamamichi, Motokazu Nakabayashi, Yasunori Ito, Takuya Wada, Gyoukei Murakami, Miki Takao, Junko Yamamoto A276 Serum Surfactant Protein(SP)-D Level: A Potential Biomarker for Aspirin-Exacerbated Respiratory Disease Hyun Jung Jin, Moon Gyeong Yoon, Young Min Ye, Yoo-Seob Shin, Seung-Hyun Kim, Hae-Sim Park A277 Clinical Characteristics of Anaphylaxis in Korean Children Taek-Ki Min, Bok-Yang Pyun, So-Yeon Lee, Hyun Hee Kim, Gwang-Cheon Jang, Jinho Yu, Dongin Suh, Sooyoung Lee, Yong Mean Park, Jeong Hee Kim, Hye-Yung Yum, Kyung Won Kim, Hyeon-Jong Yang, Kangmo Ahn, Ji-Won Kwon, Myung Hyun Sohn, Hae Ran Lee, Jung Hyun Kwon, Kyu-Earn Kim, Soo-Jong Hong A278 Immunological Changes Induced By Intramuscular Injections of Autolologous Immunoglobulin in Patients with Severe Atopic Dermatitis Su-Mi Cho A279 Identification of Subtypes in Subjects with Mild to Moderate Airflow Limitation and Their Clinical and Socioeconomic Implications Jin Hwa Lee, Chin Kook Rhee, Hye Yun Park, Woo Jin Kim, Yong Bum Park, Kwang-Ha Yoo A280 Cephalosporin-Induced Dress (Drug Rash with Eosinophilia and Systemic Symptoms) Syndrome in a 7-Year-Old Boy Heejeong Kang, Hyeon-Jong Yang, Taek-Ki Min, Bok-Yang Pyun A281 Maternal Depression Is Associated with Children’s Asthma : An Analysis of the Fifth Korea National Health and Nutrition Examination Survey (2010-2012) Lee Ju Suk, Cheol Hong Kim A282 Increased Length of Hospitalization Associated with Infiltration on Chest Radiography in Pediatric Asthma Patients Jung Hyun Kwon, Sang Hyun Lee, Wonhee Seo A283 A Case of 16-Year-Old Boy with Smoking-Induced Acute Eosinophilic Pneumonia Kang-in Kim, Young Cheon Park, Hyeon-Jong Yang, Taek-Ki Min; Bok-Yang Pyun A284 A Case of Pranlukast Induced Anaphylactic Shock Sujeong Kim, Sun Jin, Jong-Myung Lee, Hye-Jin Jung, Jung-Wha Park A285 Comparison of Asthma-Related Outcomes Between Metabolically Healthy Obese and Metabolically Unhealthy Obese Asthma Patients Hyo-Jung Kim, Tae-Bum Kim, You Sook Cho, Hee-Bom Moon, Hyouk-Soo Kwon, So Young Park, So-Young Park, Jung-Hyun Kim, Bomi Seo, Min-Gu Kim, Youn Yee Kim A286 Rick Factors Associated with Longer Length of Stay in Infants Hospitalized with Respiratory Syncytial Virus Bronchiolitis Yena Lee, Taek-Ki Min, Hyeon-Jong Yang, Bok-Yang Pyun, Suk Hee Han, Suyeon Park, Jeongho Lee, Won-Ho Hahn A287 Urinary Excretion of 9Î±, 11Î(2)-Prostaglandin F(2) and Leukotriene E(4) in Patients with Exercise-Induced Bronchoconstriction Youhoon Jeon, Joo-Hee Kim, Tae-Rim Shin, Cheol-Hong Kim, In-Gyu Hyun, Jeong-Hee Choi A288 The Aeroallergen Sensitization Pattern and Effect on Airway Hyperresponsiveness in Busan, Korea Sun-Mi Jang, Hae-Jung Na, Seung-Eon Song, Hye-Kyung Park, Eun-Jung Jo A289 Multicenter Questionnaires on Current Management of Atopic Dermatitis Among Korean Patients and Caregivers Dong Hun Lee, Jin-Young Lee, Yang Park, Jae-Won Oh, Mi Hee Lee, Soo-Jong Hong, Soo-Jong Hong, So-Yeon Lee, Joon Soo Park, Dong-Ho Nahm, Hye-Yung Yum, Hye-Yung Yum A290 Der p 1, Der p 2 and Der p 10 IgE Reactivities in Allergic Rhinitis Patients in Korea Kyu Young, Dong-Young Kim A291 De-Labeling Beta-Lactam Hypersensitivity: An Experience from a Tertiary Care Hospital in Thailand Sirinoot Palapinyo; Jettanong Klaewsongkram A292 Sonic Hedgehog Signaling: Evidence for Its Protective Role in Endotoxin Induced Acute Lung Injury Mouse Model Xing Chen, Yuting Jin, Xiaoming Hou, Fengqin Liu, Chunyan Guo, Yulin Wang A293 Analyses of the Factors behind the Negative Attitudes Toward the Administration of Adrenaline Auto-Injectors in School Settings Ikuo Okafuji, Yuya Tanaka, Shegeyuki Narabayashi, Satoru Tsuruta A294 Low Vitamin D Levels Are Related to High House Dust Mite Sensitization in Patients with Severe Atopic Dermatitis Yong Hyun Jang A295 Appendicular Skeletal Muscle Mass Index: A Potential Predictor of Skeletal Muscle Abnormality According to the Severity Airflow Limitation of COPD Jun-Hong Ahn, Dong-Won Lee, Jin Hong Chung, Hyun Jung Jin, Min-Su Sohn A296 Etiology and Clinical Feature of Oral Allergy Syndrome in Children Young a Park, Kyunguk Jeong, Yoon Hee Kim, In Suk Sol, Seo Hee Yoon, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim, Sooyoung Lee A297 Traffic-Related Pollution Levels and Poorly Controlled Asthma in Adults Ho Kim, Ja Yeun Kim A298 Anaphylaxis in Korean Children, 2009-2013 : Triggers of Anaphylaxis By Age Groups So-Yeon Lee, Taek-Ki Min, Tae-Won Song, Kangmo Ahn, Jihyun Kim, Gwang-Cheon Jang, Hyeon-Jong Yang, Bok-Yang Pyun, Ji-Won Kwon, Myung Hyun Sohn, Kyu-Earn Kim, Jinho Yu, Soo-Jong Hong, Jung-Hyun Kwon, Sung-Won Kim, Sooyoung Lee, Woo Kyung Kim, Hyung Young Kim, Hye-Young Kim, Youhoon Jeon A299 Maternal Allergy Is Associated with Acute Bronchiolitis Severity in Infant Chang Hoon Lim, Yeongsang Jeong, Su Jung Kim A300 Evaluation of Inflammatory Mediator Profiles in Sputum of Asthmatics As an Endotype for Refractory Asthma Hun Soo Chang, Jeong-Seok Heo, Da-Jeong Bae, Jong-Uk Lee, Ji-Na Kim, Chang-Gi Min, Hyun Ji Song, Jong-Sook Park, Soo Hyun Kim, Choon-Sik Park A301 Autophagy Is Associated with the Severity of Asthma in an Ovalbumin-Specific Mouse Model of Allergic Asthma Jing-Nan Liu, Youngwoo Choi, Yoo Seob Shin, Hae-Sim Park A302 Interleukin-9 and Interleukin-33 Levels in Children with Asthma Nima Rezaei, Sedigheh Bahrami Mahneh, Arezou Rezaei, Maryam Sadr, Masoud Movahedi A303 Pediatric Anaphylaxis at a University Hospital in Cheonan, Korea, 2013~2014 Jun Seak Gang, Joon Soo Park, Seung Soo Kim, Hyun Ho Bang, Kyeong Bae Park, Hye Sun Kim, Tae Ho Kim, Young Hwangbo, Hyun Jung Lee, Gyeong Hee Yoo, Young Chang Kim A304 Initial Antigen-Specific IgE Levels Predict Clinical Outcome of Rush Oral Immunotherapy for Food Anaphylaxis Sakura Sato, Noriyuki Yanagida, Motohiro Ebisawa A305 ABCC4 gene Polymorphism Is Associated with High Periostin Levels in Asthmatic Patients Sailesh Palikhe, Hae-Sim Park, Seung-Hyun Kim, Ri-Yeon Kim, Eun-Mi Yang A306 The Role of Clinical Phenotype and Allergen Sensitization at 2 Years As Predictors of Atopic Disorders at 5 Years Li Yuan Gabriella Nadine Lee, Marion Aw, Marion Aw, Bee Wah Lee, Bee Wah Lee, Evelyn Xiu Ling Loo, Yiong Huak Chan, Lynette Shek, Lynette Shek, I-Chun Kuo, I-Chun Kuo, Phaik Ling Quah, Phaik Ling Quah, Genevieve Llanora, Gerez Irvin A307 The Effect of Korean Red Ginseng (KRG) on Rhinovirus Infection in Human Nasal Epithelial Cells Joo Hyun Jung, Il Gyu Kang, Seon Tae Kim, Hyoungmin Park A308 The Effect of Korean Red Ginseng on the Symptoms and Allergic Inflammation in Patients with Allergic Rhinitis Seon Tae Kim, Joo Hyun Jung, Il Gyu Kang, Hyoungmin Park, Kwang-Pil Ko A309 Validation of the Newly Developed Multiple Allergen Simultaneous Test in Korea Jungsoo Lee, Howard Chu, Hemin Lee, Jung U Shin, Chang Ook Park, Kwang Hoon Lee, Kwang Hoon Lee, Hong Kyu Kang A310 Assessment of Symptoms Severities of Allergic Rhinitis Patients Sensitive to Multiple Allergens in Skin Prick Test Dong Chang Lee, Geun Jeon Kim, Jae Hyung Hwang, Jin Bu Ha, Su Hee Jeong A311 Diurnal Temperature Range and Emergency Department Visits for Asthma in Korea 6 Cities Ho Kim, Shinha Hwang, Whahee Lee A312 Mannan-Binding Lectin Serum Levels in Atopic Mongolian Adults Enkhbayar Bazarsad, Logii Narantsetseg, Munkhbayarlakh Sonomjamts A313 Prevalence of Doctor Diagnosed Atopic Eczema, during 2003-2014 in KOREA ; Using Big Data of 48.1 Million South Korean Health-Care Records Gwang-Cheon Jang, Hyun-Hee Lee, Chang-Jong Lee, Huynsun Lim A314 Association of Recurrent Wheeze with Lung Function and Airway Inflammation in Preschool Children Ji-Eun Soh, Dae-Jin Song, Ji-Won Kwon, Hyung Young Kim, Ju-Hee Seo, Byoung-Ju Kim, Hyo-Bin Kim, So-Yeon Lee, Gwang-Cheon Jang, Woo Kyung Kim, Young-Ho Jung, Soo-Jong Hong, Jung Yeon Shim A315 Mannan-Binding Lectin Serum Levels in Healthy Mongolian Adults Enkhbayar Bazarsad, Logii Narantsetseg, Munkhbayarlakh Sonomjamts A316 Rotanebuliser Prabhakarrao Pv, Ranjitha Nadendla A317 The Level of Serum Interleukin 13 and Interleukin 17A and Its Effect Factors in Children with Asthma Juan Fang, Jing Zhao A318 Is Vitamin D Insufficiency Also Involved in Childhood Asthma in South Korea? Dae-Jin Song, Sungchul Seo, Young Yoo, Yu-Ri Kim, Ji Tae Choung, Jee Hoo Lee A319 Collection of Nasal Secretions for Measurement of Local IgE: A Quest for the Best Method Margot Berings, Natalie De Ruyck, Claus Bachert, Philippe Gevaert, Gabriële Holtappels A320 The Role of Claudin 5 in a Murine Model of Asthma Pureun-Haneul Lee, Byeong-Gon Kim, Choon-Sik Park, George D Leikauf, An-Soo Jang A321 Claudin-4 in a Murine Model of Asthma: Modulation By Acrolein, a Highly Reactive Unsaturated Aldehyde Byeong-Gon Kim, Pureun-Haneul Lee, Choon-Sik Park, An-Soo Jang A322 Efficacy and Safety of Sublingual Immunotherapy in House Dust Mite Sensitized Children with Allergic Rhinitis Yang Park A323 The Association of Vitamine D Deficiency and Skeletal Muscle Dysfunction in Chronic Airway Disease Min-Su Sohn, Hyun Jung Jin, Dong-Won Lee, Jun-Hong Ahn, Jin Hong Chung A324 Bacteria Derived Extracellular Vesicles in Indoor Dust Is Closely Associated with Airway Disease and Lung Cancer: Analysis of Indoor Dustâ€™s Microbiome and IgG Sensitization of Indoor Bacteria Derived Extracellular Vesicles Sae-in Kim, Han-Ki Park, Do-Yeon Kim, Mina Rho, Jun-Pyo Choi, Yoon-Keun Kim A325 Clinical Care Program for Childhood Asthma (CCP-Childhood Asthma); A Multidisciplinary Team Care at Samitivej International Children’s Hospital Wasu Kamchaisatian, Thitikul Hiranras, Surinda Wongpun, Phornthip Chiraphorn, Anupan Tantachun, Wannipa Wongrassamee, Planee Vatanasurkitt, Naratip Somboonkul, Nattipat Juthacharoenwong, Surangkana Techapaitoon, Montri Tuchinda A326 Continuous B Cell Stimulation with CD40 Ligand Induce IgE Isotype Switching Jae Ho Lee, Sejin An A327 Effects of Interleukin-9 on Allergen-Specific Immunotherapy in a Mouse Model of Allergic Rhinitis Ji-Hyeon Shin, Soo Whan Kim, Si Won Kim, Jun Myung Kang, Boo-Young Kim, Byung-Guk Kim A328 Usefulness of Exhaled Nitric Oxide for Evaluating Wheeze and Airway Hyperresponsiveness in Preschool Children Jung-Won Lee, Ji-Won Kwon, Woo Kyung Kim, Hyung Young Kim, Hyo-Bin Kim, Ju-Hee Seo, So-Yeon Lee, Gwang-Cheon Jang, Young-Ho Jung, Soo-Jong Hong, Byoung-Ju Kim, Dae-Jin Song, Jung Yeon Shim A329 Systemic Cyclosporine Treatment in Hand Eczema Patients Kyung Ho Kim A330 Lipid Profiles and Adipokines in Korean Children with Atopic Dermatitis Young Yoo, Won Suck Yoon, Sungchul Seo, In Soon Kang, Jae Won Choi, Hye-Young Lim, Ji Tae Choung A331 Validation of Montelukast and Levocetirizine Combination Tablet Versus Individual Tablets in the Treatment of Moderate to Severe Persistent Allergic Rhinitis Among Adult Filipinos Seen at the Philippine General Hospital-Outpatient Department Michelle Buela A332 Efficacy of Makyokansekito on Treatment of Wheezing Lower Respiratory Tract Infection in Children: A Retrospective Study of 68 Patients Koji Nishimura A333 Serum Eosinophilia and Total IgE Are Associated with the Risk of Allergic Sensitization and Allergic Symptoms in Two Years Follow-up, Respectively Sang Chul Park, Hyo Jin Chung, Chang-Hoon Kim, Ju Wan Kang, Seong-Chul Hong, Keun-Hwa Lee, Jaechun Lee, Hye-Sook Lee, Jeong Hong Kim A334 The Sensitization to Russian Thistle on Mongolian Patients Narantsetseg Logii A335 The Association Between Air Pollution, Allergic Sensitization to Inhalant Allergens and Airway Hyperresponsiveness in Ulaanbaatar, Mongolia Munkhbayarlakh Sonomjamts, Enkhbayar Bazarsad A336 Pre-Coseasonal Treatment with a 5-Grass Pollen Sublingual Tablet in Adults Demonstrated a Reduction on Asthma Symptoms in Réunion Island Bashir Omarjee A337 Peak Expiratory Flow Rate Reference Values for Children Aged 5-14 Years Old in Beijing Urban Area Shuo LI A338 Soybean Storage Proteins As the Main Allergen in a Patient with Food-Dependent Exercise-Induced Anaphylaxis Due to Tofu Miyuki Hayashi, Ruby Pawankar, Shingo Yamanishi, Toru Igarashi, Yasuhiko Itoh A339 A Study of Allergy Skin Prick Test with Weed Pollen Oyuntsatsral Batsaikhan, B. Gantulga, B. Enkhbayar, S. Munkhbayarlakh, L.Narantsetseg A340 The Role of Neurotrophin in a Murine Model of House Dust Mite Induced Allergic Rhinitis Pei-Chi Chen, Jiu-Yao Wang A341 Mimotopes of the Major Shellfish Allergen Tropomyosin Suppress Splenocyte Proliferation and Local Cytokine Expression in a Mouse Model of Shellfish Allergy Nicki Y. H. Leung, Christine Yee Yan Wai, Patrick S.C. Leung, Ka Hou Chu A342 A Questionnaire Survey on Understanding of Atopic Dermatitis Among Korean Patients and Caregivers Eun Jin Doh, Dong Hun Lee, Mira Choi, Hyun-Sun Yoon, Kyu Han Kim, Ji Soo Lim A343 Comparison of the Dosage of Bronchodilators in the Bronchodilator Response Test in Children Ji Hyeon Baek, Man Yong Han, Seung Jin Lee, Youhoon Jeon, Kyung Suk Lee, Young-Ho Jung, Hye Mi Jee, Youn Ho Shin A344 The Expression and Effect of Natural Killer T Lymphocytes in Chidren with Asthma Yi Jiang, Miao Liu A345 Oral Provocation Test in Non-Steroidal Anti-Inflammatory Drug Hypersensitive Patients Referred to Singapore General Hospital Chaw Su Naing, Tze Chin Tan, Yong Yeow Chong A346 Different Phenotypes of Bhr (bronchial hyperresponsiveness) By Natural Course in Children and It’s Characteristics Young-Ho Kim, Eun Lee, Song-I Yang, Hyun-Ju Cho, Hyung Young Kim, Ji-Won Kwon, Young-Ho Jung, Byoung-Ju Kim, Ju-Hee Seo, Ho-Jang Kwon, Hyo-Bin Kim, So-Yeon Lee, Soo-Jong Hong, Soo Hyun Kim A347 Spectrum of Allergens Causing Allergic Rhinitis and Asthma in Urban Bangalore, India − a Study of 120 Patients Jacqueline Elizabeth Joseph, Soumya M. S, Ruby Pawankar, Harshitha Kumar A348 High Prevalence of Wheezing Illness and Risk Factor of Atopic Asthma Progression in Korean Preschool Children Sohyoung Yang, Sung-Il Woo A349 Clinical and Laboratory Screening of Primary Immunodeficiency Diseases: International Effects Nima Rezaei A350 The Effect of Helicobacter Pylori Infection in Atopic Individuals Sukran Kose, Basak Gol Serin, Arzu Didem Yalcin, Süheyla Serin Senger, Mehmet Erden, Ertan Serin A351 Clinical Spectrum and Natural History of Chronic Urticaria in Hong Kong Children Agnes Sze-Yin Leung, Ting Fan Leung A352 Skin Prick Test Reactivity to Common Pollen Aeroallergens in Patients with Allergic Rhinitis − in Urban Bangalore, India Harshitha Kumar, Soumya M.S., Jacqueline Elizabeth Joseph, Ruby Pawankar A353 Seasonal Patterns of Asthma-Related ED Visits and Admissions in Children and Adolescents Who Visited Emergency Rooms of Korea in 2007-2012 Eun Hee Chung A354 Prevalence of Atopic Dermatitis and Its Associated Risk Factors in Elementary School Children: A Cross-Sectional Study in Gyeonggi-Do, South Korea Eunji Kim, Young Yoo, Ji Tae Choung, Sungchul Seo, In Soon Kang, Jue Seong Lee, Ji Hyen Hwang A355 Intralymphatic Immunotherapy for Dermatophagoides Farinae, Dermatophagoides Pteronyssinus, Cat, and/or Dog Allergy in Patients with Allergic Rhinitis: 1 Year Follow-up Sang Min Lee, Joo Hyun Jung, Seung Joon Choi, Eugene Joe, Hyunjung Hwang, Shin Myung Kang, Yu Jin Kim, Sun Young Kyung, Jeong-Woong Park, Sung Hwan Jeong, Sang Pyo Lee A356 Respiratory Syncytial Virus Regulates IL-33 Expression in Bronchoalveolar Cells and Lung Tissue in Vivo Alina Gaisina, Igor Shilovskiy, Aleksandra Nikonova, Oleg Kamyshnikov, Musa Khaitov, Alexander Mitin, Komogorova Viktoriya, Marina Litvina, Nina Sharova A357 The Prevalence of Parent-Perceived Food Hypersensitivity in Pre-School Children Attending a Tertiary Care Hospital in Malaysia Faizah Mohamed Jamli A358 Th2 Dominant Airway Inflammation Induced By House Dust Mite Chitin Is Dependent on TNF-a and NKT Cell Da-Il Yoon, Jun-Pyo Choi, Han-Byul Choi, Yoon-Keun Kim, Hyeon-Il Choi A359 Geographic Variations in the Patterns of Sensitization to Aeroallergens in Korean Adults: A Multi-Center Study Mingyu Kang, Mi Yeoung Kim, Sujeong Kim, Eun-Jung Jo, Seoung-Eun Lee, Woo-Jung Song, Sang Min Lee, Chansun Park, Yoon-Seok Chang, Jaechun Lee, Young-Koo Jee, Inseon S Choi, Kyung-up Min, Sang-Heon Cho A360 Experimental Mouse Model of Asthma Induced By Dust Mite Dermatophagoides Pteronyssinus allergenic Extract Anton Laskin, Oleg Kamyshnikov, Alexander Babakhin, Valentina Berzhets, Musa Khaitov A361 Severe Refractory Pulmonary Complications in Children with Mycoplasma Pneumoniae Pneumonia Sejin An, Jae Ho Lee A362 Usefulness of Interactive e-Learning Education Program for Asthma Guideline Sung-Yoon Kang, Yoon-Seok Chang, Kyung-up Min, Sang-Heon Cho, Sae-Hoon Kim, Yong Eun Kwon, Young-Koo Jee, Tae-Bum Kim, Hee-Bom Moon, Hye-Kyung Park A363 Airway Inflammation Induced By House Dust Mite Derived Vesicles Is Mainly Induced By LPS Derived from Gram Negative Bacteria in Dust Mite. Sang-Yoon Kim, Jun-Pyo Choi, Han-Ki Park, Ji-Hyun Lee, Yoon-Keun Kim A364 Changes in the Recognition of Causal Allergen, Its Avoidance, and Allergen Specific Immunotherapy after Skin Prick Test / Intradermal Test, Nasal Provocation Test, and Intralymphatic Immunotherapy in Patients with Allergic Rhinitis: 1 Year Follow-up Hyunjung Hwang, Eugene Joe, Sang Min Lee, Seung Joon Choi, Joo Hyun Jung, Yong Han Seon, Shin Myung Kang, Yu Jin Kim, Sun Young Kyung, Jeong-Woong Park, Sung Hwan Jeong, Sang Pyo Lee A365 Laboratory Diagnostic of Staphylococcal Sensitization Natalya Khramykhoverchenko A366 Th-17 Regulatory Cytokines Enhance Neutrophil Production of IL-17 during Asthma Saleh Al Muhsen, Asma Sultana, Rabih Halwani, Ahmed Bahammam A367 Diagnostic Value of Serum Total IgE and Prediction of Cut-Off Value to Recommend Mast in Allergic Rhinitis Hyung Chae Yang, Sun Kyung Kim, Kwang Il Nam A368 Diagnostic Value of an Increase in FEV1 and/or FVC >12% and >200 mL from Baseline after Bronchodilators for Diagnosis of Asthma Jeong-Eun Kim, Ju Suk Lee, Ji Hyun Lee, Kyung Woo Kang A369 Combined Use of Fractional Exhaled Nitric Oxide and Bronchodilator Response in Predicting Future Loss of Asthma Control Among Children with Atopic Asthma Je-Kyung Kim, Youn-Soo Hahn, Jae-Yub Jung A370 Antigen-Specific IgA Plays an Important Role in Mucosal Immune Response in Allergic Children : Measurement of Secretory IgA and Antigen-Specific IgA Yosuke Baba, Sususmu Yamazaki, Eisuke Inage, Mari Mori, Yoshikazu Ohtsuka, Masato Kantake, Toshiaki Shimizu, Asuka Honjoh, Tomoaki Yokokura A371 Why Teaching Pediatrics Trainees about Anaphylaxis and Its Acute Management Is Essential: Cross Sectional Survey. Mehdi Adeli, Shaza Ali Mohammed Elhassan, Caroline Beck A372 Prevalence and Clinical Characteristics of Local Allergic Rhinitis in Children Min Sun Na, Heysung Baek, Seung Jin Lee, Ji Hyeon Baek, Jungwon Yoon, Sun Hee Choi, Young-Ho Jung, Youn Ho Shin, Man Yong Han A373 House Dust Mites Sublingual Immunotherapy Can Influence the Long-Term Evolution of Severe Atopic Dermatitis and the Progression to Respiratory Allergy. Enrico Compalati, Maurizio Marogna A374 The Positive Distribution Characteristics of 90 Food Specific IgG in Patients with Allergic Diseases Huimin Huang, Baoqing Sun, Mingyu BAI, Yiting Huo, Peiyan Zheng, Nili Wei, Wenting Luo A375 Evaluation of Serum Levels of Osteopontin As a Potential Biomarker of Immune Activation in Patients with Allergic Diseases Elisa Villa, Anand Andiappan, Rosalba Minisini, Olaf Rötzschke, Elena Boggio, Luca Gigliotti, Nausicaa Clemente, Annalisa Chiocchetti, Umberto Dianzani, Mario Pirisi A376 Prevalence of Allergic Rhinitis in 3-6-Year-Old (preschool) Children in Chiba City (urban area), Japan Fumiya Yamaide, Syuji Yonekura, Naoki Shimojo, Yuzaburo Inoue, Yoshitaka Okamoto A377 Comparative Efficacy of Combination Nebulized Salbutamol and Fluticasone Propionate and Nebulized Salbutamol in Children with Mild Moderate Asthma Attack Retno Asih Setyoningrum, Landia Setiawati, Sri Sumei, Deddy Iskandar A378 Characteristics of Children Hospitalized with Asthma in West Nusa Tenggara General Hospital Mataram Indonesia Indriyani Sang Ayu Kompiyang A379 Identification of Phenotypes in Allergic Bronchopulmonary Aspergillosis Using Cluster Analysis Tsuyoshi Oguma, Jun Tanaka, Katsuyoshi Tomomatsu, Koichiro Asano A380 The Roles of Type 2 Innate Lymphoid Cells (ILC2) in Chronic Rhinosinusitis (CRS) Keisuke Uno, Yoshinori Matsuwaki, Kazuhiro Omura, Eika Hayashi, Norifumi Tatsumi, Hirohito Kita, Nobuyoshi Otori, Hiromi Kojima A381 Respiratory Symptoms, Signs and Spirometry Indexes Comparision in 7-12 Years Old Girls in Esfahan Metropolis and Its Far Suburb Mohammadreza Fatemi Khorasgani A382 Induction of Kruppel-like Transcription Factor (KLF4&5) By Baker’s Yeast Mannan in Human Bronchial Epithelial and Smooth Muscle Cells Dukhee/Betty Lew, Kim/S. Lemessurier, Joseph/a Moore, Jeoung-Eun Park, Ae-Kyung Yi, Chi/Young Song, Kafait/U Malik A383 Korean Profile in Childhood Asthma Severity Classification Dongin Suh, Ja Kyoung Kim, Hyeon-Jong Yang, Bong-Seong Kim, Youn Ho Shin, So-Yeon Lee, Geunhwa Park, Woo Kyung Kim, Hyo-Bin Kim, Heysung Baek, Dae Hyun Lim, Dae Hyun Lim, Jin Tack Kim A384 Prevalence of Food Sensitization, IgE-Mediated and Non-IgE-Mediated Food Allergy Among Pediatric Patients Diagnosed with Autism Spectrum Disorders Aimee Lou Manalo Nano A385 Component-Resolved Diagnostic Study of Dermatophagoides Pteronyssinus Major Allergen Molecules in a Southern China Wenting Luo, Baoqing Sun A386 Risk Factors for Systemic and Local Reactions to Subcutaneous Allergen Immunotherapy Hikmet Tekin Nacaroglu, Semiha Bahceci Erdem, Ozlem Sumer, Sait Karaman, Canan Sule Unsal Karkiner, Suna Asilsoy, Ilker Gunay, Demet Can A387 Literature Review and Current Treatment Options for Cyclical Anaphylaxis Danielle Kiers A388 The Effect of Surfactant Protein D in Acute Lung Injury and Pulmonary Fibrosis Induced By Bleomycin Hsu Han Yin, Jiu-Yao Wang A389 Activation of Endothelial Cells to Release Hsp90, an Activator of the Prekallikrein-High Molecular Weight Kininogen (HK) Complex Allen Kaplan, Kusumam Joseph, Baby G. Tholanikunnel A390 The Effect of Climatic Treatment in 51 Asthmatic Children from Areas Severely Polluted Environment of Northern Moravia, Czech Republic Radim Dudek A391 Comparison of Some Vitamin Groups in Asthmatic Patients Gulden Bilgin, Hatice Surer, Aytun Sadan Kilinc, Dogan Yucel A392 Sensitization in Children with Atopic Dermatitis: A Single Center Study Ji Young Lee, Jihyun Kim, Hea-Kyoung Yang, Minji Kim, Sang-Il Lee, Kangmo Ahn A393 Staphylococcal Enterotoxin IgE Sensitization: A Risk Factor for COPD Overlap in the Elderly Asthma? Sung Do Moon, Byung-Keun Kim, Sang-Heon Cho, Kyung-up Min, Yoon-Seok Chang, Heung Woo Park, Hye-Ryun Kang, Woo-Jung Song, Min-Koo Kang, Ju-Young Kim, Kyonghee Sohn, Ha Kyung Won, Seoung-Eun Lee, Kyung-Mook Kim, Claus Bachert A394 The Effects of Probiotics and PparÎ(3) on the Murine Model of Allergic Asthma Miao-Hsi Hsieh, Jiu-Yao Wang A395 Adult Patients’ Views on the Design of Adrenaline Autoinjectors Helen Smith, Clare Brown, Christina Jones, Mark Davies A396 CCL22 miRNA modulated Th1 responses and induced therapeutic effects on OVA-induced mouse model of asthma Won Suck Yoon A397 Clinical, Histological, and Skin Microbiome Characteristics of Head and Neck Dermatitis in Atopic Dermatitis Hemin Lee, Howard Chu, Jungsoo Lee, Jung U Shin, Chang Ook Park, Kwang Hoon Lee, Seo Hyeong Kim, Ji Yeon Noh, Ji Hye Kim A398 MicroRNA-432 modulates Th1 responses and induced therapeutic effects in atopic like murine model. Won Suck Yoon A399 Case Report of Near-Fatal Asthma Due to Snail Allergy in a House Dust Mite-Allergic Adult Jean-Pierre L’huillier, Jean-Eric Autegarden, Catherine Bertrand, Dominique Tardy A400 Relationship Between Gut Microbiota in the First 3 Months of Life and Infant Immune Function at Age 12 Months Intan Hakimah Ismail, Mimi Tang, Paul Licciardi, Frances Oppedisano, Robert Boyle, Roy Robins-Browne A401 A Pediatric Case of Food-Dependent Exercise-Induced Anaphylaxis Due to Spice Allergy Hisako Yagi, Harumi Koyama, Yutaka Nishida, Takumi Takizawa, Hirokazu Arakawa A402 Correlations Between Objective Severity Score and Each of the Subjective Severity Intensity in Atopic Dermatitis Hong Kyu Kang, Hemin Lee, Jungsoo Lee, Jung U Shin, Kwang Hoon Lee, Kwang Hoon Lee, Howard Chu, Chang Ook Park A403 Barrier Related Gene Mutations in Atopic Dermatitis Na Young Yoon, Hyeyoung Lee, Seong Jun Seo, Eunhee Choi, Hye-Young Wang, Minyoung Jung, Eung Ho Choi, Dong Hye Kim A404 Clinical Utility of Basophil Activation Test (BAT) in the Diagnosis of Drug Induced Anaphylaxis Joo-Hee KimYoung-Sook Jang, Jeong-Hee Choi, Sunghoon Park, Young Il Hwang, Seung Hun Jang, Ki-Suck Jung A405 Feeding Shapes the Colonization of Gut Microbiota and Associated with Total IgE in Infant Mi-Jin KangDongin Suh, Eun Lee, Kil Yong Choi, Young-Ho Jung, Song-I Yang, Bong-Soo Kim, Ha-Jung Kim, Juneyoung Koh, Hyun-Jin Kim, Kangmo Ahn, Youn Ho Shin, Hyun-Ju Cho, Byoung-Ju Kim, Young-Ho Kim, Yean Jung A406 CD8(+)T Cell-Intrinsic Smad4 Suppresses Th2 Responses in the Pathogenesis of Contact Hypersensitivity Mizuko Mamura, Jeong-Hwan Yoon, Susumu Nakae, Inkyu Lee, Isao Matsumoto, Takayuki Sumida, Jin Soo Han, Katsuko Sudo, Ji Hyeon Ju A407 Immune-Modulatory Genomic Properties Differentiate Gut Microbiotas of Infants with and without Eczema Gaik Chin Yap, Wen Tso Liu, Seungdae Oh, Pei Ying Hong, Chiung Hui Huang, Marion Aw, Lynette Shek, Bee Wah Lee A408 The Effect of Medication in OSA Patients with Allergic Rhinitis Young Seok Byun, Sung Wan Kim, Tae Kyung Koh, Joong-Saeng Jo, Kun Hee Lee, Chul Kwon, Sung-Hwa Dong A409 A Case of Generalized Pustular Psoriasis Mimicking Acute Generalized Exanthematous Pustulosis Myung Shin Kim, Chansun Park A410 Anaphylaxis Caused By Gummy Jelly Ingestion: A Case Report Han Seok Cho, Min-Ju Kim, Min Ji Kim, Young Ok Park, Hye Yeong Lee, Hee Seong Kim, Eun Lee, Hyun-Ju Cho, Jinho Yu, Soo-Jong Hong, Keum Hee Hwang A411 Serum Folliculin As a Novel Biomarker for Asthma Jung-Hyun Kim, You Sook Cho, Sae-Hoon Kim, Hyouk-Soo Kwon, Mira Yoo, Hyo-Jung Kim, So-Young Park, Bomi Shin, So Young Park, Bomi Seo, Min-Gu Kim, Hee-Bom Moon, Jin-Ah Park, Tae-Bum Kim, Jaemoon Lee A412 Corticosteroid Nasal Irrigations after Endoscopic Sinus Surgery in the Management of Chronic Rhinosinusitis with Asthma Jin Hyeok Jeong, Tae Wook Kang, Han Seok Yoo, Yong Hee Cho, Seok Hyun Cho, Kyung Rae Kim A413 Capsaicin Injection in Neonatal Period Potentiates Intensity and Duration of Atopic Dermatitis of Rats. Jue Seong Lee, Sun-Ho Kee, Sewon Kim, Young Yoo, Heung Sik Na, Seung Keun Back A414 Comparison Between the Impulse Oscillometry System, Spirometry, Feno, Lung Clearance Index and Asthma Control and Exacerbation Status. Seung Jin Lee, Bo Seon Seo, Ji Hyeon Baek, Kyung Suk Lee, Young-Ho Jung, Hye Mi Jee, Youn Ho Shin, Man Yong Han, Mi-Ae Kim A415 The Association of Exhaled Nitric Oxide and Airway Hyperresponsiveness in Patients with and without Asthma Young-Hee Nam, Dong Sub Jeon, Soo-Keol Lee A416 Effects of Air Pollution on Allergic Rhinitis in Korea Jisun Park A417 Exhaled Nitric Oxide in Korean Children with Allergic Rhinitis Seung Hyun Moon A418 A Questionnaire of Children with Asthma or Asthma and Allergic Rhinitis Rong Jun Lin, Ren Zheng Guan A419 A Case of Trimebutine-Induced Morbilliform Skin Eruption Gyeong Yul Park, Hyun-Sun Yoon A420 Comparison of Methacholine and Mannitol to Predict Exercise-Induced Bronchoconstriction in Children with Asthma Woo-Hyeok Choi, Heysung Baek A421 Different Inflammatory Mechanisms of Human Metapneumovirus and Respiratory Syncytial Virus Jin-Sung Park, Eunmi Kwon, Zac Callaway, Chang-Keun Kim, Takao Fujisawa A422 Sputum Microbiota in Chinese Adults with Eosinophilic Versus Non-Eosinophilic Asthma Qingling Zhang, Rihuang Qiu, Naijian Li, Zhaowei Yang, Jing Li, Kian Fan Chung, Nanshan Zhong A423 Which Clinical Features Are Useful in Predicting Presence of Staphylococcus Aureus colonization/Infection in Childhood Atopic Dermatitis? Kam Lun E. Hon, Yin Ching K. Tsang, Ting Fan Leung A424 Clinical Significance of Increased VEGF, TGF-Î(2)(1,) and YKL-40, a Chitinase like Protein, in Serum of the Children with Asthma Yoon Young Jang, Hai Lee Chung, Seung Gook Lee, Ji Hyun Na, Jong Hoon Lee A425 Analysis of Follow-up Results of Mannitol Challenge Test in Asthma Patients Young-Hee Nam, Dong Sub Jeon, Soo-Keol Lee A426 Analysis of 68 Oral Walnut Challenge Tests Mikita Yamamoto, Sakura Sato, Noriyuki Yanagida, Ayako Ogawa, Kanako Ogura, Kyohei Takahashi, Kenichi Nagakura, Shigehito Emura, Tomoyuki Asaumi, Katsuhito Iikura, Motohiro Ebisawa, Yu Okada A427 Effectiveness of Air Filters Intervention in Allergic Rhinitis Jiaying Luo, Xiao Lan, Baoqing Sun, Zhao Chen, Guiyuan Sun, Shimin Li, Jiaqing Hu A428 The Relationship Between Airway Hyperresponsiveness to Mannitol and Atopy in Asthmatic Children Woo-Hyeok Choi, Heysung Baek A429 Anaphylactoid Reactions to N-Acetylcysteine in the Treatment of Aacetaminophen Overdose Young-Hee Nam, Dong Sub Jeon, Hee-Joo Nam, Yeo Myeong Noh, Sang Hee Kim Kim, Ye Suel Park, Soo-Keol Lee A430 Effect of Prenatal Maternal Distress and GSDMB Polymorphism on the Development of Recurrent Wheezing in Early Childhood: COCOA Study Yean Jung Choi, Si Hyeon Lee, Young-Ho Kim, Mi-Jin Kang, Hyun-Ju Cho, Eun Lee, Song-I Yang, Youn Ho Shin, Kangmo Ahn, Kyung Won Kim, Yoon Hee Kim, So-Yeon Lee, Hyoung Yoon Chang, In Ae Choi, Kyung-Sook Lee, Yee-Jin Shin A431 Vitamin D Level in Allergic Rhinitis: A Systemic Review and Meta-Analysis Yoon Hee Kim, Min Jung Kim, In Suk Sol, Seo Hee Yoon, Young a Park, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim, Yong Ju Lee A432 Implication of Inspiratory and Expiratory Resistance and Reactance in Children with Asthma In Suk Sol, Kyu-Earn Kim, Yoon Hee Kim, Min Jung Kim, Seo Hee Yoon, Yong Ju Lee, Kyung Won Kim, Young a Park, Myung Hyun Sohn A433 The Association of Asthma Predictive Index with Asthma in Preschool Children with Recurrent Wheeze Sung Joo Park, Ji-Won Kwon, Woo Kyung Kim, Hyung Young Kim, Hyo-Bin Kim, Ju-Hee Seo, So-Yeon Lee, Gwang-Cheon Jang, Young-Ho Jung, Soo-Jong Hong, Byoung-Ju Kim, Dae-Jin Song, Yun Seok Yang, Jung Yeon Shim A434 Clinical Significance of Serum Total IgE Levels in Children with RSV-Associated Lower Respiratory Illness Yoon Young Jang, Hai Lee Chung, Ji Hye Kim, Hyun Seok Lee, Chang Ho Lee A435 Development of a Oak Pollen Emission and Transport Modeling Framework in South Korea Changbum Cho, Yun-Kyu Lim, Kyu Rang Kim, Mijin Kim, Baek-Jo Kim A436 Temperature, Humidity, and Air Pollution Affect Atopic Dermatitis Symptoms in Infants and Young Children Young-Min Kim, Youngshin Han, Jihyun Kim, Hae-Kwan Cheong, Byoung-Hak Jeon, Kangmo Ahn A437 Effects of Compound V on Pulmonary Fibrosis Model Chuang/Yao Ming, Jiu-Yao Wang, Ye/Yi Ling A438 Vitamin D Level and the Correlation with IgE in Children with Allergic Respiratory Diseases in Guangzhou China Huimin Huang, Baoqing Sun, Yun Chen, Peiyan Zheng, Nili Wei, Wenting Luo A439 Two Case Reports of Eosinophilic Gastroenteritis Associated with Allergic Disease Do Hyeong Lee, Gil-Soon Choi, Hee-Kyoo Kim, Han Su Park A440 Genome-Wide Association Study (GWAS) May Identify Common Genetic Variations Both in Immediate and Delayed Drug So-Young Park, Hyo-Jung Kim, Bomi Seo, Jung-Hyun Kim, Min-Gu Kim, Hyouk-Soo Kwon, You Sook Cho, Hee-Bom Moon, Tae-Bum Kim, Yoon Su Lee A441 Development of a Questionnaire for Secular Change of Atopic Dermatitis from Birth to 19-Year-Old. Akio Tanaka, Satoshi Morioke, Yukihiro Ohya, Naoki Shimojo, Akira Akasawa, Michihiro Hide, Hiroko Shizukawa A442 Evaluation of the Adherence Starts with Knowledge-20 (ASK-20) to Inhaled Drug in Patients with Bronchial Asthma Naoto Watanabe A443 The Epidemiology and Clinical Manifestation of Hmpv Infection in Children during Recent 4 Years: 2011-2014 Meeyong Shin, Myeong Sun Jang A444 Neutropenia Induced By Intravenous Immunoglobulin Young-Hee Nam, Yeo Myeong Noh, Dong Sub Jeon, Hee-Joo Nam, Sang Hee Kim Kim, Ye Suel Park, Soo-Keol Lee A445 A First Case of Lymphocytic Interstitial Pneumonitis in Healthy Child Ji-in Jung, Ha-Su Kim, Hyun-a Kim, Jin-a Jung A446 Cytokine Production upon House Dust Mite Stimulation of Cord Blood Mononuclear Cells from Caesarean Section-Delivered Singaporean Infants Anne Goh, Rajeshwar Rao, Bindu Nandanan, Ruurd Van Elburg, Chua Mei Chien, Juandy Jo, Johan Garssen, Johan Garssen, Leon Knippels, Elena Sandalova, Wen Chin Chiang A447 Dress Syndrome with Acute Interstitial Nephritis Caused By Quinolone and Nonsteroidal Anti-Inflammatory Drugs Young-Hee Nam, Ji Young Juong, Soo Jin Kim, Eun Young Kim, Su Mi Lee, Young Ki Son, Hee-Joo Nam, Ki-Ho Kim, Soo-Keol Lee A448 IL-23 Roles in the Development of House Dust Mite Allergic Sensitization and Asthma Da-Eun Park, Hye-Ryun Kang, Heung Woo Park, Hyun Seung Lee, Yoon-Seok Chang, Jung-Won Park, Sang-Heon Cho, Kyung-up Min, Woo-Jung Song A449 Exposure Profile of Indoor Risk Factors in Dwellings of Children with Atopic Dermatitis Hyunwook Lim, Sungchul Seo, Ji Tae Choung, Young Yoo, Jun-Sik Park, Byung Kwan Kim A450 Epidemiological Characterization of Blood Eosinophils in the Elderly Population Ha Kyeong Won, Hye-Ryun Kang, Byung-Keun Kim, Sung Do Moon, Ju-Young Kim, So-Hee Lee, Woo-Jung Song, Heung Woo Park, Min-Koo Kang, Sun-Sin Kim, Sang-Heon Cho, Kyung-up Min, Yoon-Seok Chang, Kyoung Hee Sohn, Kyung-Mook Kim, Ki-Woong Kim, Hak Chul Jang A451 Stevens-Johnson Syndrome Caused By Methotrexate in the Treatment of Psoriasis Young-Hee Nam, Dong Sub Jeon, Hee-Joo Nam, Yeo Myeong Noh, Sang Hee Kim Kim, Ye Suel Park, Soo-Keol Lee A452 Genetic Determinants for Lung Function Growth in Asthmatic Children Ting Fan Leung, Man Fung Tang, Hing Yee Sy, Wa Cheong Chan, Wilson Wai San Tam A453 The Power of Allergen Specific Ig E in the Classification of Rhinitis, Korean National Hanes 2010 Seung Kyu Chung, Sujin Kim, Sang Duk Hong, Hyo Yeol Kim Hyo Yeol Kim, Hun-Jong Dhong, Jong in Jeong A454 Analysis of Allergen Immunotherapy Practice and PatientsÃ¢â‚¬â„¢ Knowledge and Attitude about Allergen Immunotherapy in a Single Tertiary Hospital in Korea Young-Hee Nam, Dong Sub Jeon, Soo-Keol Lee A455 Roles of Staphylococcal Enterotoxin B in House Dust Mite-Induced Acute Asthma Models Ji Won Lee, Mingyu Kang, Soon-Hee Kim A456 A Clinical Comparison of Drug Reaction with Eosinophilia and Systemic Symptoms Syndrome in a Single Tertiary Hospital in Korea Young-Hee Nam, Dong Sub Jeon, Hee-Joo Nam, Yeo Myeong Noh, Sang Hee Kim Kim, Ye Suel Park, Soo-Keol Lee A457 The Beneficial Effect of Lactobacillus Gasseri PM-A0005 and Its Immunoregulatory Protein PMA5P40 on Milk-Induced Allergic Enteritis Yung-I Hou, Jiu-Yao Wang A458 Relationship Between Serum Folate Levels and Risks of Allergic and Respiratory Diseases in Early Childhood: The Mothers and Children’s Environmental Health Study Ja Hyeong Kim, Seol Jae Hee, Eun-Hee Ha, Hyesook Park, Mina Ha, Yun-Chul Hong, Yangho Kim, Namsoo Chang A459 Effects of Vitamin D in Patients with Chronic Rhinosinusitis Yuta Soma, So Watanabe, Ruby Pawankar, Ruby Pawankar, Harumi Suzaki, Harumi Suzaki, Hitome Kobayashi A460 Clinical Features of Systemic Contact Dermatitis from Ingestion of Rhus Young-Hee Nam, Chansun Park, Soo-Keol Lee A461 Sublingual Immunotherapy Efficacy in Patients with Atopic Dermatitis in Korea Jongrok Lee, Jooyoung Roh, Haryeong Ryu A462 Characteristics of Serious Adverse Drug Reactions in a Tertiary University Hospital Cheol-Woo Kim, Jae Hwa Cho, Mi Ra Eom, Ji Young Kang, Hye Gyeung Lee A463 Eyelid Dermatitis: Patch Test Results during a 15-Year Period in Korea and Evaluation of Metal Contents in Eye Shadows Hae Young Choi, Hye Jin Lee, Ju Yun Woo, Ji Yeon Byun, You Won Choi A464 Relationship Between Lipid Levels and Risks of Allergic and Respiratory Diseases in Early Childhood: The Mothers and Children’s Environmental Health Study Ja Hyeong Kim, Eun-Hee Ha, Hyesook Park, Mina Ha, Yun-Chul Hong, Yangho Kim, Namsoo Chang A465 IL-32 in the Induced Sputum of Patients with Asthma Jae-Woo Kwon, Hun Soo Chang, Jeong-Seok Heo, Jong-Uk Lee, Jong-Sook Park, Eusom Kim, Soo Hyun Kim, Choon-Sik Park A466 Clinical Characteristics of Patients with Chromium Allergy in a Single University Hospital in Korea Hae Young Choi, Ji Yeon Byun, Ju Yun Woo, You Won Choi A467 Efficacy and Safety of Oral Acitretin in Chronic Hand Eczema Hyun-Ju Jin, Jin-Hwa Son, Jeong-Min Kim, Gun-Wook Kim, Je-Ho Mun, Margaret Song, Hyun-Chang Ko, Moon-Bum Kim, Hoon-Soo Kim, Byung Soo Kim A468 Atypical Antipsychotics and Anticholinergic Agents Mimicking Anaphylaxis Sheryl Van Nunen, Dinh Van Nguyen, Anthony Elias, Susannah Olivia Lauer A469 Introducing Reach (Reliable Estimation of Atopic dermatitis in ChildHood): Novel, Questionnaire-Based Diagnostic Criteria for Childhood Atopic Dermatitis Seung-Chul Lee, Ho-June Lee, Jung Min Bae A470 Comprehensive Assessment to Identify the Causative Factors in Oral Allergy Syndrome Emi Ono A471 Comparison of Interpretation Methods in Allergic Skin Test Sung-Hwa Dong, Tae Kyung Koh, Young Seok Byun, Sung Wan Kim, Joong-Saeng Jo, Chul Kwon, Kun Hee Lee A472 Refraining Aminophylline Use Increases Hospitalization Among Children with Acute Asthma: A 10-Years Retrospective Cohort Study Li-Fan Liu A473 The Prevalence and Risk Factors of Atopic Dermatitis from Nationwide Study for Korean School Students Sunghee Lee A474 Probiotic Recombination Protein Effect on Atopic Dermatitis Wei-Leng Chen, Jiu-Yao Wang A475 Allergic Sensitization Status in Various Inflammatory Skin Diseases Youin Bae, Gyeong-Hun Park A476 Two Cases of Good’s Syndrome: A Rare Acquired Immunodeficiency Associated with Thymoma Suk Yeon Kim A477 IL-23 Has a Role to Play in the Development of Asthma in Short-Term Cigarette Smoke Exposure-Induced House-Dust Mite Allergic Model Hyun Seung Lee, Woo-Jung Song, Mingyu Kang, Han-Ki Park, Da-Eun Park, Hye-Ryun Kang, Heung Woo Park, Yoon-Seok Chang, Hye-Young Kim, Kyung-up Min, Sang-Heon Cho, Ji-Won Lee, Boram Bae, Jung-Won Park A478 The Relationship Between the Relevance of Allergic Disease and the Value of Non-Specific IgE Yasuhiro Suzuki A479 Two Caces of Prawn Allergy in Adult Patients Ismet Bulut, Zeynep Ferhan Ozseker A480 Early Gut Bifidobacterium Breve and B. Catenulatum Colonisation Differentially Modulate Eczema Risk in Children at High-Risk of Developing Allergic Disease Intan Hakimah Ismail, Robert Boyle, Paul Licciardi, Frances Oppedisano, Roy Robins-Browne, Mimi Tang A481 Effects of Chronic Repeated Exposure of Staphylococcal Enterotoxin B on Allergic Asthma Model in Mice Ji Won Lee, Hyun Seung Lee, Mingyu Kang, Da-Eun Park, Han-Ki Park, Soon-Hee Kim, Woo-Jung Song, Hye-Ryun Kang, Heung Woo Park, Yoon-Seok Chang, Chang-Han Park, Suk-Il Chang, Sook-Hee Song, Kyung-up Min, Sang-Heon Cho, Boram Bae A482 Skin Prick Test Result and Allergen Immunotherapy in Children with Allergic Rhinitis Grace Shieh A483 Role of Brp-39 in RSV-Induced Airway Inflammation in Mice Min Jung Kim, Jung Yeon Hong, Seo Hee Yoon, Doo Hee Shim, In Suk Sol, Yoon Hee Kim, Mi Na Kim, Kyung Eun Lee, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim, Jae Myun Lee A484 Long-Term Outcomes of Twenty-Four Adults with Primary Immunodeficiency from a Single Centre in Singapore Hiok Hee Chng A485 Breast Feeding Increases the Risk of Food Sensitization but Does Not Affect Food Allergy in Young Children with Atopic Dermatitis Dong Chan Kim, Song-I Yang, Hae Ran Lee, An Deok Seo, So Yeon Lee A486 IgE Immunoadsorption Knocks Down Anaphylaxis. Alessandro Fiocchi, Maria Cristina Artesani, Paola Francalanci, Lamia Dahdah, Thomas Schreiner A487 Burden and Correlates of Cigarette Smoking and Respiratory Airway Obstruction: An Observation in Urban Adult Population of West Bengal (India) Kaushik Chakraborty A488 Blood Eosinophils Could Predict Sputum Eosinophilia? : A Comparison Between Asthma and Non-Asthmatic Chronic Cough in the Elderly Ha Kyeong Won, Ju-Young Kim, Eun-Jung Jo, Kyoung Hee Sohn, Kyung-Mook Kim, Heung Woo Park, Yoon-Seok Chang, Sang-Heon Cho, Woo-Jung Song, Byung-Keun Kim A489 Complementary and Alternative Medicine for Allergic Rhinitis in Japan Syuji Yonekura, Yoshitaka Okamoto A490 Impact of Cognitive Impairment on Asthma Control Status in Elderly Asthmatics Gyu Young Hur, Young Min Ye, Joo-Hee Kim, Ki-Suck Jung, Junga Kim, Jae Jeong Shim, Hae-Sim Park A491 The Association Between Respiratory Tract Infection and Reactive Oxygen Stress Kazuhiro Sekimoto, Kazuko Sugai, Keiji Tsuchimoto, Hiromi Uehara, Masanori Ikeda A492 The Risk Factors and Lung Function of Current Allergic Rhinitis Due to Dust Mite Sensitization Euncho Chung, Kang Seo Park, Yean Jung Choi, Jeewon Park, Soo-Jong Hong, So Yeon Lee A493 Cloning and Expression of Recombinant Blomia Tropicalis Dust Mite Allergen Blo t 7 Alain Jacquet, Arun Buaklin, Nat Malainual A494 Seasonal Variations of Airborne Pollen in Bangalore, India Roopashree S A495 Pollen Observation and Use of Data Kyu Rang Kim, Mijin Kim, Changbum Cho, Baek-Jo Kim, Jae-Won Oh, Mae Ja Han A496 The Effect of Cord Serum 25-Hydroxyvitamin D (25(OH)D) on the Development of Atopic Dermatitis in First 3 Years of Life : Cocoa Study Hyun-Ju Cho, Youn Ho Shin, Eun Lee, Young-Ho Kim, Darae Lee, Mi-Jin Kang, Song-I Yang, Kangmo Ahn, Kyung Won Kim, Yoon Hee Kim, Hye-Sung Won, Soo Hyun Kim, Suk-Joo Choi, Young Han Kim, Jong Kwan Jun, Eun-Jin Kim, Jeom Gyu Lee, So-Yeon Lee, Soo-Jong Hong, Dongin Suh A497 Contribution of Stem Cell Factor Autocrine/Paracrine Mechanism to Aberrant Proliferation of Mast Cells Yosuke Amagai, Akane Tanaka, Hiroshi Matsuda A498 A Randomized Dbpc Dose-Finding Multicenter Trial of Sublingual Immunotherapy (SLIT) Allergoid Tablets in House Dust Mites (HDM) Allergic Patients Ralph Mösges, Pauline Dieterich, Anatoli Astvatsatourov, Christoph Hüser, Jaswinder Singh, Kija Shah-Hosseini, Silke Allekotte, Enrico Compalati A499 Depression and Allergy in the Elderly: A Community Population Analysis Kyoung Hee Sohn, Woo-Jung Song, Byung-Keun Kim, Ju-Young Kim, Min Suk Yang, So-Hee Lee, Sae-Hoon Kim, Hye-Ryun Kang, Heung Woo Park, Sun-Sin Kim, Kyung-up Min, Sang-Heon Cho, Yoon-Seok Chang A500 The Integrated Analysis of Correlation Between Total IgE and Other Immunological Factors in Allergic Diseases Woo-Sung Chang, Ji-Hye Do, Yeon-Seop Kim, Dankyu Yoon, Hye-Sun Lim, Jeom-Kyu Lee, Eun-Jin Kim A501 Pattern of Allergic Diseases Among Military Servicemen Referred to a Clinical Immunology/Allergy Service in Singapore Bernard Thong, Yew Kuang Cheng, Jinfeng Hou, Khai Pang Leong, Justina Tan, Faith Chia, Grace Chan, Sze-Chin Tan, Teck Choon Tan, Chwee Ying Tang, Hiok Hee Chng A502 A Case of Rifampicin-Induced Hypersensitivity Diagnosed By the Lymphocyte Activation Test with Successful Desensitization Chan-Sun Park, Mi Yeoung Kim, Eun-Young Kim, Jae-Gook Shin, Jae-Hyeog Choi, Saegwang Park, Yeonye Kim A503 Analysis of Individual Case Safety Reports of Drug-Induced Anaphylaxis Based on Korea Adverse Event Reporting System Database Kyung-Hwan Lim, Jae Woo Jung, Mingyu Kang, Ju-Young Kim, Ju-Young Kim, Hyun Jeong Kim, Yeon-Ju Woo, Soo-Youn Jung, Hye-Ryun Kang, Hye-Ryun Kang A504 Impact of Processes Certification on the Liability of Anti-Dust Mites Bed Covers Thierry Porée, Nabile Boukhettala, Emeline Furon A505 Localisation Kinetics of Aluminium after Subcutaneous Injection in a Rat Model Alan David Bullimore, Matthew Heath, Simon Hewings, Murray Skinner A506 Periostin Levels in Exhaled Breath Condensate of Competitive Athletes, Asthmatics and Healthy Subjects - Associations with Outdoor Ambient Conditions Marcin Kurowski, Hubert Krysztofiak, Aleksandra Wardzynska, Marzanna Jarzebska, Janusz Jurczyk, Marek L. Kowalski A507 The Role of PKR Pathway in Acute Exacerbation of Severe Bronchial Asthma So Ri Kim, Yong Chul Lee, Dong Im Kim, Yang Keun Rhee, Heung Bum Lee, Seoung Ju Park, Yeong Hun Choe Choe, Seung Yong Park A508 Diversity of Clinical Manifestations and Treatment Responses for Idiopathic Hypereosinophilic Syndrome Joo-Hee Kim, Sunghoon Park, Young Il Hwang, Seung Hun Jang, Ki-Suck Jung A509 Effect of Dexamethasone in Th17 Cell Mediating Neutrophilic Asthma Nong Guang-Min, Jiang Min A510 Allergen Profile for Asthma/Rhinitis and Eczema Among Patients in North India: An Immunocap Allergen Specific IgE Antibodies Assay Based Study Nalin Nag A511 Clinical Profile of Allergic Rhinitis in Children in Jakarta Wahyuni Indawati A512 Preclinical Study on the Use of Micro Crystalline Tyrosine (MCT) Adjuvants in Allergy Immunotherapy Alan David Bullimore, Matthew Heath, Murray Skinner A513 Genetic Diversity of Filaggrin Mutation and Its Clinical Implication in East Asian Atopic Dermatitis Patients Seong Jun Seo, Won Jong Oh A514 Protein and MPL Adsorption Capacities for MCT in Candidate Therapeutic Formulations for Use in Immunotherapy, Compared Against Existing Adjuvants Alan David Bullimore, Murray Skinner, Matthew Heath, Andrew Bell A515 Interleukin-22 Gene Variation in Inflammatory Bowel Disease Alireza Zarebidoki, Hournaz Hasanzadeh, Salman Sadeghzade, Nima Rezaei A516 Immunomodulatory Effects of Adipose-Derived Stem Cell Secretome in a Mouse Model of Asthma Kyu-Sup Cho A517 Diffuse Alveolar Hemorrhage with Positive Anti-Neutrophil Cytoplasmic Antibody in a Child : A Case Report Sung-Woo Kim, Moo-Young Oh A518 Clinical Analys the Serum TARC Levels As the Condition Index of Atopic Dermatitis in the Early Infancy Munemitsu Koizumi, Kazuyo Kuzume A519 An Analysis of the Filaggrin Gene Polymorphism in Korean Atopic Dermatitis Patients Kui Young Park, Won Jong Oh A520 A New Protocol for Wheat Oral Immunotherapy in Patients with Anaphylaxis Delara Babaie, Mohammad Nabavi, Fariborz Zandieh, Mehrdad Amir Moini, Zahra Chavoshzadeh, Hamideh Seifi, Mitra Sahragard, Mehrnaz Mesdaghi, Mohammad Hassan Bemanian A521 Clinical Characteristics of Filaggrin-Related Atopic Dermatitis Patients in Korea Sun Young Choi, Yeon a No A522 Early Allergy Diagnosis in Children - Self- Administered Questionnaire Vs Medical Verification Andrzej M. Fal, Dorota Kiedik, Agnieszka Muszynska, Iwona Pirogowicz A523 Asthma Impact on Children with Food Induced Anaphylaxis Chikako Motomura, Masatoshi Wakatsuki, Yuko Akamine, Mihoko Iwata, Hiroshi Matsuzaki, Naohiko Taba, Yoko Murakami, Hiroshi Odajima A524 Case Reports of Stevens-Johnson Syndrome and Stevens-Johnson Syndrome-Toxic Epidermal Necrolysis in Systemic Lupus Erythematosus Reni Ghrahani A525 The Effectiveness of Oral Tolerance Induction for Wheat Allergy Using Two Different Intake Levels Yuri Takaoka A526 Association of Plasma Interleukin-25 Levels with Development of Aspirin Induced Airway Spasm in Asthma Jong-Uk Lee, Jeong-Seok Heo, Da-Jeong Bae, Hyun Ji Song, Choon-Sik Park, Jong-Sook Park A527 Transition of Allergic and Nonallergic Rhinitis after 2 Years in Korean Children: Preliminary Study Jae Hoon Cho, Ji Ho Choi A528 Early Onset of Psoriasis Juvenile Idiopathic Arthritis Budi Setiabudiawan, Fiska Febriana, Reni Ghrahani, Gartika Sapartini A529 Clinical Features of Immediate Hypersensitivity to Histamine H2 Antagonists and Their Cross Reactivity Chan-Sun Park, Young-Hee Nam, Mi Yeoung Kim, Gil-Soon Choi A530 Detection of Galacto-Oligosaccharide Specific IgE in Vitro Chiung-Hui Huang, Chiung-Hui Huang, Jian Yi Soh, Lynette Shek, Lynette Shek, Dianne J. Delsing, Bee Wah Lee, Bee Wah Lee, Si Hui Goh, Wen Chin Chiang, Wenyin Loh A531 The Association Between Serum Vitamin D Levels and Allergic Diseases in Elementary Schoolchildren Hea-Kyoung Yang, Ji Young Lee, Minji Kim, Kangmo Ahn, Jihyun Kim, Young-Min Kim, Hye-Young Kim, Yong Mean Park, Woo Kyung KIM, So-Yeon Lee A532 Serum Levels Specific IgE to Toxic Shock Syndrome Toxin Type 1 in Eosinophilic Chronic Rhinosinusitis with Nasal Polyp in Korean Jongin Jeong, Sang Duk Hong, Seung Kyu Chung, Hun-Jong Dhong, Hyo Yeol Kim Hyo Yeol Kim, Sujin KIM A533 Impacts of Rhizosphere Cleaning Effects of Potted Indoor Plants on the Symptoms and Stress of Students with Allergic Rhinitis in Newly Built Schools Yong-Won Lee, Hana Bak, Hye-Rim Son, Si-Eun Lee, Kwang-Jin Kim, Young-Wook Lim, Ho-Hyun Kim A534 A Case of Multiple Food Allergies with Recurrent Anaphylaxis Successively Controlled By Omalizumab Mi-Ae Kim, Man Yong Han, Young-Ho Jung, Hye Mi Jee, Seung Jin Lee, Kyung Suk Lee A535 Bepotastine-Induced Urticaria, Cross-Reactive with Other Antihistamines Jasmina Golez, Jaechun Lee, Eunkyoung Lee A536 Role of SLC26a4 in Ozone - Induced Airway Reactivity and Inflammation Da-Jeong Bae, Chang-Gi Min, Jong-Uk Lee, Jong-Sook Park, Hun Soo Chang, Choon-Sik Park, An-Soo Jang A537 PAR2-Antagonist Suppresses Protease-Induced Allergic Inflammation Mediated By Degradation of Lung Epithelial Tight Junction and Generation of ROS Young-Joon Kim, Bok Kyoung Jung, Seung-Hwa Lee, Mi-Jin Kang, Sekyoo Jeong, Eun Lee, Hyun-Ju Cho, Young-Ho Kim, Song-I Yang, Seo Hee Kim, Soo-Jong Hong A538 Novel Anti-IL-4Ra Nanocarrier Approach for the Efficient Control of Lung Tissue Inflammation during Asthma Rabih Halwani, Saleh Al Muhsen, Asma Sultana, Achraf Al-Faraj, Rosan Kanana, Sibtain Afzal, Roaa Al Kufaidi A539 Clinical Factors for Improved Allergen Reactivities Induced By Subcutaneous Allergen Specific Immunotherapy with House Dust Mites during 1 Year Period Hee-Kyoo Kim, Chul-Ho Oak, Gil-Soon Choi, Ye-Jin Moon, Eun-Kee Park A540 Cytokine Gene Polymorphisms in Iranian Patients with Kidney Acute Rejection Alireza Zarebidoki, Mina Abrari, Ali Akbar Amirzargar A541 Phthalate Exposure and Obesity in Atopic Dermatitis of Korean Children and Adolescents Ju-Hee Seo, Mina Ha, Soo-Jong Hong A542 Which Drives Chronicity of Cough in Adults: Based on the Knhanes 2010-2012 Mingyu Kang, Byung-Ha Cho, Han-Ki Park, Han-Ki Park, Kyung-Mook Kim, Chang-Han Park, Heung Woo Park, Heung Woo Park, Yoon-Seok Chang, Yoon-Seok Chang, Yoon-Seok Chang, Sook-Hee Song, Mi-Kyeong Kim, Mi-Kyeong Kim, Sang-Heon Cho, Suk-Il Chang, Kyung-up Min, Kyung-up Min, Alyn Morice A543 Elevated Airway CD45RO Memory Cells in Wheezing Children with Lower Respiratory Infection Jungi Choi, Yusok Han, Jin-Sung Park, Eunmi Kwon, Chang-Keun Kim A544 Quality of Life in Obese Children with or without Atopic Disease Gartika Sapartini A545 Relation of Human microRNA in Sputum of Asthma with Influenza A Virus Infection-Induced Exacerbation Ji-Na Kim, Seungwoo Shin, Hun Soo Chang, Eun-Young Shim, Ji Ah Jun, Hyeonju Lee, Jong-Sook Park, Choon-Sik Park A546 Aeropolinologic Monitoring and Distribution of Allergoallergens in Western Georgia Revaz Sepiashvili, Darejan Khachapuridze, Sofio Gamkrelidze, Manana Chikhladze A547 Extracorporeal Membrane Oxygenation As Emergency Treatment for Patients with Near-Fatal Status Asthmaticus Seung-Eun Lee, Yun-Seong Kim, Doo-Soo Jeon, Woo-Hyun Cho, Hye-Ju Yeo, Seong-Hoon Yoon, Seung-Hyun Kim A548 Relationship of S100calcium Binding Protein A9 with Neutophilic Inflammation in Murine Asthma Model Taehyeong Lee, Hyun Ji Song, Choon-Sik Park, Ji Ah Jun, Jong-Sook Park A549 Whole-Exome Sequencing of Aatopic Dermatitis in Korean Childhood Dankyu Yoon, Yeon-Seop Kim, Woo-Sung Chang, Mi-Jin Kang, Soo-Jong Hong, Jeom-Kyu Lee, Eun-Jin Kim A550 A Case of Generalized Molluscum Contagiosum in an Adult Patient with Severe Atopic Dermatitis Minkee Park A551 Discovery of Putative Macadamia Nut Allergens By Patient IgE Binding and a Label-Free Shotgun Proteomics Approach Nanju Alice Lee, Johanna Rost, Sridevi Muralidharan, Dianne Campbell, Sam Mehr A552 Anti-FcÎμri Antibody Inhibits Allergic March in Mice By Suppressing Th17 Pathway Via Suppression of FcÎμri-Mediated Mast Cells Activation Seung-Hwa Lee, Seon-Joo Yoon, Ha-Jung Kim, Eun Lee, Song-I Yang, Young-Ho Jung, Ho-Sung Yu, Hee-Suk Kim, Yeon Hee Park, So-Yeon Lee, Jun-Sung Park A553 Clinical Characteristics and the Associated Factors of ATG Hypersensitivity Reaction Ha Kyeong Won, Min-Koo Kang, Sung Do Moon, Byung-Keun Kim, Ju-Young Kim, Sang-Heon Cho, Hye-Ryun Kang, Ji-Su Shim, Soo Jie Chung A554 Reference Value and Utility of Total Serum Immunoglobulin E in Korean Schoolchildren Jaehee Choi, Kangmo Ahn, Kwanghoon Kim, Jihyun Kim, Jiyoung Lee A555 Two-Step Prescreening Skin Testing May be Useful for Reducing Immediate Hypersensitivity Reaction to Nonionic Contrast Media: Results of 7-Year Period in a Secondary Hospital Bo Bae Park, In Young Nho, Chang-Han Park, Jang Min Kim, Suk-Il Chang A556 Prevalence of Allergic Sensitization in Patients with Allergy Rhinitis; Gwangju, Jeonnam State Study Sun Kyung Kim, Hyung Chae Yang, Kwang Il Nam A557 Analysis of IgE Binding Components of Walnut in Korean Children Effect of Cooking Methods on the Allergenicity of Walnut Proteins Jeongmin Lee, Jeongmin Lee, Sooyoung Lee, Kyunguk Jeong, Se-Ah Jeon A558 Assessment of Autonomic Nervous Function in Subjects with Cholinergic Urticaria Associated with Acquired Idiopathic Generalized Anhidrosis Midori Fujiwara, Shoko Shindo, Hiroyuki Murota, Mayuko Tahara, Aya Takahashi, Ichiro Katayama A559 Interleukin 1 Beta in Sputum of Patients with Asthma: Relation with Airway Obstruction and Neutrophilc Inflammation Jae Woo Jung, Hyun Ji Song, Taehyeong Lee, An-Soo Jang, Jong-Sook Park, Hun Soo Chang, Choon-Sik Park, Byoung Whui Choi A560 Interleukin 8 in Sputum of Patients with Asthma: Relation with Neutrophilc Inflammation and Exacerbation Min-Hye Kim, Da-Jeong Bae, Hyun Ji Song, Taehyeong Lee, Ji Ah Jun, Jong-Sook Park, An-Soo Jang, Hun Soo Chang, Young Joo Cho, Choon-Sik Park A561 Prostaglandin E2 and Transforming Growth Factor-Î(2) Play a Critical Role in Suppression of Allergic Airway Inflammation By Adipose-Derived Stem Cells Sue Jean Mun A562 Inhalation of Fine Particles Kill Alveolar Macrophages to Release IL-1alpha That Promote Inducible Bronchus-Associated Lymphoid Tissue (iBALT) Formation Etsushi Kuroda, Koji Ozasa, Ken Ishii A563 Association Between Smoking and Allergic Diseases in the Korean Adult General Population Sunmi Kim, Gyeong-Hun Park A564 Relationship of S100 Calcium Binding Protein A9 with Inflammasome Activation in Murine Asthma Model Hyun Ji Song, Taehyeong Lee, Ji Ah Jun, Hun Soo Chang, Jong-Sook Park, Choon-Sik Park A565 Cluster Analysis of Asthma Phenotypes to Predict Exacerbation in Korean Population Mi-Ae Kim, Seungwoo Shin, Jong-Sook Park, Hun Soo Chang, You Sook Cho, Hae-Sim Park, Choon-Sik Park A566 Effect of AG490 on the Expression of TH17 CELLS and Tregs in the MOUSE MODEL of Neutrophilic Asthma Zhang Min A567 Association Between the Clinical Characteristics and Disease Severity in Hospitalized Bronchiolitis Patients Younger Than Two Years Old Seo Hee Yoon, In Suk Sol, Young a Park, Yoon Hee Kim, Min Jung Kim, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim A568 Comparison Between House Dust Mite and Aspergillosis Sensitization in Patients with High Level of Tige Wu Shiquan A569 The Prevalence of Metal Allergy in the Patients with Orthodontic Appliance Yongwon Lee, Hana Bak A570 Component Resolved Diagnosis and Single Nucleotide Polymorphism Analyses: Towards the Development of Specific Immunotherapy for Allergy Maricar Wisco Ching, John Donnie Ramos A571 Clinical Features of Anaphylaxis Caused By Peanut, Tree Nuts and Seeds in Children and Adolescents: Multi-Center Study with 126 Patients Kyunguk Jeong, Sooyoung Lee, Kangmo Ahn, Myung Hyun Sohn, Kyung Won Kim, So-Yeon Lee, Tae Won Song, Youhoon Jeon, Jihyun Kim, Taek Ki Min, Kyu-Earn Kim, Bok-Yang Pyun, Hyeon-Jong Yang, Hae Ran Lee, Youngmin Ahn, Ji-Won Kwon, Dae Hyun Lim, Jeong Hee Kim, Dongin Suh, Hyung Young Ki A572 A Report of Two Cases of Anaphylaxis Caused By Perilla Seed in Children Kyunguk Jeong, Byeong Sub Park, Sooyoung Lee, Se-Ah Jeon, Kyu Jung Park A573 Prenatal Fine Particulate Matter Affects Wheezing in Children with TLR4 Polymorphism: Cocoa Study Song-I Yang, Eun Lee, Hyun-Ju Cho, Young-Ho Kim, Mi-Jin Kang, Yean Jung Choi, Kil Yong Choi, Youn Ho Shin, Kangmo Ahn, Kyung Won Kim, Byoung-Ju Kim, So-Yeon Lee, Eun-Jin K A574 Intensified B Lymphocyte Depletion (IBLD) without Immunosuppressive Maintenance Treatment As a Rescue Therapy in Refractory Lupus Nephritis (LN): a 4-Year Observation. Roccatello Dario A575 Relationship Between Th17 Cells and Neutrophilic Airway Inflammation in Childhood Neutrophilic Asthma Jing Liao A576 Clinical Applications of Impulse Oscillometry in Asthma Management after Exacerbation in Preschool Children Yong Feng, Yunxiao Shang A577 Contact Allergy to Sodium Sulfite and Its Relationship to Facial Cosmetic Contact Dermatitis Yongwon Lee, Hana Bak A578 Effect of Exposure to Air Pollution on Asthma and Lung Function Development Hyung Young Kim, Byoung-Ju Kim, Ji-Won Kwon, Ju-Hee Seo, Eun Lee, So-Yeon Lee, Song-I Yang, Young-Ho Jung, Hyo-Bin Kim, Ho-Jang Kwon, Hee Ju Park A579 Role and Relational Mechanism of AG490 in Airwayinflammation in the Mouse Model of Neutrophilic Asthma Zhang Min, Nong Guang-Min, Jiang Min A580 Incidence of Adverse Reaction to Radioconstrast Media in a Single Tertiary Hospital Gyu Young Hur, Eun Jung Sim, Sora Yoon, Juwhan Choi, Junga Kim, Jae Keom Sim, Jee Youn Oh A581 Cow’s Milk Oral Food Challenge: Clinical and Laboratory Features in Korean Children Kyunguk Jeong, Byeong Sub Park, Jeong-Min Lee, Sooyoung Lee, Eunjae Cheon, Youngjoo Na, Kyu Jung Park, Eunjoo Lee A582 Validation of the Red Maple Trials Allergen Challenge Theatre for Ragweed Pollen Challenge William Yang, Suzanne Kelly, Rob Perrins, Jimmy Yang A583 Preliminary Evaluation of the Red Maple Trials Allergen Challenge Theatre for Grass Pollen William Yang, Suzanne Kelly, Rob Perrins, Jacob Karsh, Jimmy Yang A584 The Association Between Tobacco and the Risk of Asthma in Urban and Rural Children in San Francisco, Argentina Hector Badellino, Alvaro Teijeiro, Mabel Cuello, Marilyn Urrutia Pereira, Gustavo Egues A585 The Prevalence of Allergic Rhinitis in University Students in Manisa Ayse Aktas A586 Allergen Sensitization in Zimbabwean Children with Atopic Dermatitis Jin-Kyong Chun, Hilda Angela Mujuru, Elopy N Sibanda A587 Vitamin D Insufficiency in Asthmatic Patients Andreea Ioana Popescu, Raluca Greblescu A588 The Prevalence of Hypersensitivity Reactions Against Drugs Among University Students. Suheyla Rahman, Ayse Aktas A589 Sublingual Immunotherapy Among Problematic Patients, Suffering from Allergic Rhinitis. Nataly Tataurshchikova A590 A Novel Biomarker for Wheezing and Atopy in Early Infancy Eishika Dissanayake, Yuzaburo Inoue, Naoki Shimojo, Taiji Nakano A591 Prognostic Factors for Atopic Dermatitis in Spontaneously Born Babies from Low Socioeconomic Background Conny Tanjung A592 Higher IgE Antibody Levels Mediate Anti-Cancer Immunity in Transgenic KN1 Hyper-IgE Mice Erika Jensen-Jarolim, Judit Fazekas, Josef Singer, Anna Lukschal, Reinhard Horvat, Gertrude Achatz-Straussberger, Gernot Achatz A593 Fructooligosaccharides Intake during Pregnancy and Lactation Increases Gut Bifidobacterium and IL-27 in Breast Milk Yuji Fujita, Shuji Ikegami, Yoshitaka Nakamura, Yuzaburo Inoue, Naoki Shimojo, Yoichi Kohno, Shuichi Suzuki, Naoko Ozawa, Takayuki Kubota, Ken Nonaka, Osamu Ohara, Kentaro Masuda A594 Effect of Nintedanib on Asthma in Mouse Model Chin Kook Rhee, Sook Young Lee, Hwa Young Lee, Hea Yon Lee, Ji Young Kang, Sei Won Kim, Soon Seog Kwon, Young Kyoon Kim A595 Delayed Contrast Media Hypersensitivity after Coronary Angiography Gun-Woo Kim, Ju-Young Kim, Sang-Heon Cho, Hye-Ryun Kang, Hyo-Soo Kim, Jung Gyu Han, Jin Lee, Ji Young Lee, Ji Young Go, So Jung Park A596 Gene Expression Profiling in Patients with Chronic Idiopathic Urticaria Reveals Unique Gene Signature Distinct from Healthy Controls Julie Kim-Chang, Cassandra Love, Patricia Lugar A597 Failure to Recognize Lymphopenia in Newborn Leads to Undetectable Primary Immunodeficiency Endah Citraresmi A598 The Concordance Between Lung Function Test and Indonesian Version of Childhood Asthma Control Test (CACT) Nastiti Kaswandani, Cynthia Utami, Mardjanis Said A599 Synergistic Interaction Between Bronchiolitis and PM(10) Is Modified By IL-13 Polymorphism on Asthma Development: Replication from Cheer Study Young-Ho Jung, Song-I Yang, Byoung-Ju Kim, Ji-Won Kwon, Hwan-Cheol Kim, Jong-Han Leem, Ju-Hee Seo, Hyung Young Kim, So-Yeon Lee, Ho-Jang Kwon, Hyo-Bin Kim, Hyun-Ju Cho A600 The Transcription Factor Ehf Is Involved in TGF-b-Induced Suppression of Fceri and c-Kit Expression and Fceri-Mediated Activation in Mast Cells Susumu Yamazaki, Nobuhiro Nakano, Asuka Honjoh, Eisuke Inage, Yosuke Baba, Yoshikazu Ohtsuka, Toshiaki Shimizu A601 The Follow up of the Potential Immunosuppressant Effects of Marijuana (MJA) Ishaq M, Sameera MI Khan, Imran Khan, Sabeen Khan A602 Risk Factors of Allergen Sensitization at 3 Years: Results from the Gusto Study Evelyn Xiu Ling Loo, Anne Goh, Oon Hoe Teoh, Yiong Huak Chan, Seang Mei Saw, Kenneth Kwek, Peter D Gluckman, Keith M Godfrey, Hugo Van Bever, Yap Seng Chong, Bee Wah Lee, Lynette Shek, Alison Joanne Lee A603 IL-6 Blockade As a Steroid-Sparing Treatment for Rhupus Patients Daniela Rossi A604 Examination of Late Pulmonary Toxicity in Children Treated for Malignancies Agnes Nemeth A605 Technical Validation of the Repurposing of a Personal Particle Sampler to Determine House Dust Mite Exposure in the Ambient Air Torsten Sehlinger, Karl-Christian Bergmann, Frank Goergen A606 Zinc Deficiency in Children with Severe Atopic Dermatitis: More Common Than Generally Thought Mohammad S. Ehlayel, Abdul Bari Bener A607 Strong Association Between HLA-B*5801 Allele and Allopurinol – Induced Severe Cutaneous Adverse Reactions in Vietnamese Hieu Chi Chu, Nga Thi Quynh Do, Dinh Van Nguyen, Ha Thi Thu Nguyen, Huong Thi Minh Le, Sheryl Van Nunen, Christopher Vidal, Suran Fernando A608 Successful Rapid Desensitization to Glatiramer Acetate: Report of 2 Cases Fotis Psarros, Ekaterini Syrigou, Ekaterini Politi, Spyridon Chrysoulakis A609 Asthma Exacerbations Seasonal Variation in Two Perennial Phenotypes during Twenty Years (1995-2014): House Dust Mite Monosensitized and Non Atopic Patients Dimitrios Vourdas, Konstantinos Petalas A610 Occupational Allergy to Fungal Spores Among the Farmers of Paddy Fields in West Bengal, India: An Aeromycological and Immunological Approach Mouli SAHA, Kashinath Bhattacharya A611 Study of Efficacy of Sublingual Immunotherapy (SLIT) in Cases of Severe Persistent Allergic Rhinitis Subir Jain A612 Mesenchymal Stem Cells Suppress Lung Inflammation and Airway Remodeling in Chronic Asthma Rat Model Via PI3K/Akt Signaling Pathway Mesenchymal Stem Cells Suppress Lung Inflammation and Airway Remodeling in Chronic Asthma Rat Model Via PI3K/Akt Signaling Xiaolian Song, Haiyan Lin A613 Development of Allergen ELISA Kits for Dust Mites, Pollen, and Pet Dander Kyohei Nishikawa, Takashi Shimada, Hiroshi Yasueda, Tadao Enomoto, Daisuke Aizawa, Takayoshi Kobayashi A614 Yoga As a Lifestyle Modification to Improve the Quality of Life in Smokers with Allergic Rhinitis Chellaa R A615 Study of Incidence of Severe Persistent Allergic Rhinitis in Different Age Groups,Sex Prevalance and Type of Allergen” Aeroallergen or Food Allergen” Responsible for Severe Persistent Allergic Rhinitis in Central India Subir Jain A616 Causative Allergens in Cases of Severe Persistent Allergic Rhinitis in Central India Subir Jain A617 Atopic Dermatitis: A New Data on the Mechanisms of Chronic Pruritus Marina Yudina A618 The Efficacy and Safety of Peanut Oral Immunotherapy in High-Dose with Predicting Factors Ishaq M, Sameera MI Khan, Imran Khan, Sabeen Khan A619 Evaluation of Long-Term Prognosis and Topical Corticosteroid Usage after One Year of Proactive Treatment for Children with Moderate-to-Severe Atopic Dermatitis Mayako Saito A620 Allergy Symptoms in the First Two Months of Life Nurul Iman Nilam Sari A621 Factors Related to the Seasonal Variation of Allergic Rhinitis Jae Young Kim, Jaechul Song, Inah Kim, Kyeong Joon Lee, Soo Jin Park, Soo Yong Roh A622 Allergic Risk Survey in Lao Children at out-Patient Department, Children’s Hospital, Vientiane Capital, Lao PDR Somxay Billamay A623 Correlation Between Food Allergy, Aeroinhalant Allergy, Allergic Rhinitis, Atopic Dermatitis, and Acute Upper Respiratory Tract Infections and Levels of Severity of Asthma in Pediatric Medicine Department Saiful Anwar Hospital Indonesia Muchammad Fahrul Udin A624 Comparative Study of Pine, Oak, and Ginkgo Pollen Counts in Korea during Last Four Years Mae Ja Han, Jae-Won Oh, Kyu Rang Kim, Baek-Jo Kim A625 Effectiveness of Allergy-Test Directed Elimination Diets in Eosinophilic Esophagitis Jorge A Mazza, Jason Kangeun Ko, David JT Huang A626 Comparison of Cut-Off Values and Probability Curves for Egg Specific IgE in Diagnosis of Egg Allergy in Young Children Kanae Furuya, Keigo Kainuma, Takahiro Ito, Mizuho Nagao, Takao Fujisawa, Junya Hirayama, Yu Kuwahara A627 A Case of Persistent Atopic Dermatitis Associated with Parasitic Infection Rosanna Qualizza, Cristoforo Incorvaia, Anna Maraschini A628 Aeroallergenic Profile of Indoor Allergens and Their Clinical Relevance in Allergy and Asthma Patients in Saudi Arabia Syed Mohammed Hasnain, Abdulrahman Al-Frayh A629 Oral Exposure to the Amino Acid Glycine Inhibits the Onset of Allergic Disorders Anita Hartog, Jacqueline Bastiaans, Reinilde Loonstra, Lieke Rutten, Lucien Harthoorn, Jeroen Van Bergenhenegouwen, Johan Garssen, Johan Garssen A630 Cough As a Key Symptom in Asthma, Allergic Rhinitis, COPD and Rhinosinusitis and Its Impact in Korea Kwang-Ha Yoo, Sang-Heon Cho, AG Ghoshal, Abdul Razak Bin Abdul Muttalif, Horng- Chyuan Lin, Sanguansak Thanaviratananich, Shalini Bagga, Rab Faruqi, Santwona Baidya, Colman Taylor, De Yun Wang, Hae-Ryun Ahn, Soon-Kwan Hong, Jong-Woong Kim, Gui-Hyun Nam, Mee-Ja Kim, Jae-Kyoung Park A631 Cysteine Protease Allergen Def f 1 Induces Th2 Cytokines in Mouse Bone Marrow Derived Basophils Via ERK and JNK Dependent Pathways Myung-Hee Yi, Kyoung Yong Jeong, Ju-Yeong Kim, Tai-Soon Yong A632 Novel Multiple Allergy Testing Kit Using Parallel Lines Array (PLA) Technology Bum Joon Kim, Hs Joo, Kj Lim, Jae-Hyun Lee, Jung-Won Park, Kh Yoon, DS Choi A633 Quantitative Rapid Kit for Human Immunoglobulin Hanseung Joo, Bum Joon Kim, Kj Lim, MJ KIM, DS Choi, Kh Yoon A634 Total IgE Measurement By Protia Allergy-Q: Comparison Study with Immunocap Bum Joon Kim, Hanseung Joo, Woo Sang Jung, Kj Lim, DS Choi A635 Prevalence and Risk Factors of Asthma Among Korean Farmers Ji-Hoon Lee, Soon-Chan Kwon, Soo-Jin Lee, Soo Yong Roh, Hogil Kim, Kyeong Joon Lee A636 Dietary Intake and Perceived Immune Status in Young Dutch Women Aurora Van De Loo, Amanda Fernstrand, Johan Garssen, Joris Verster A637 The Effects of Antihistamine Drugs on on-Road Driving Performance Aurora Van De Loo, Johan Garssen, Joris Verster A638 Grass Is Guilty: A Case of Anaphylactic Shock and Asthmatic Status in the Same Time in an Individual Jasmina Golez A639 Cyclic Gamp-AMP(cGAMP) Induces Allergic Inflammation Koji Ozasa, Etsushi Kuroda, Ken Ishii, Ken Ishii A640 Role of Omalizumab in the Setting of Recalcitrate Dermatitis with Extremely Elevated IgE Levels Muhammad Imran, Selina Gierer, John Martinez A641 Follow-up Study on the Natural History of Prawn Allergy Lydia Wong, Bee Wah Lee, Gaik Chin Yap, Genevieve Llanora, Bernard Thong, Lynette Shek A642 Protein-Losing Dermopathy Impairing Growth in Children with Severe Atopic Dermatitis Mohammad S. Ehlayel, Ashraf Soliman A643 Airways Assessment of Aged Nursing Homes Residents Pedro Martins, João Marques, Joana Gomes-Belo, Teresa Palmeiro, Iolanda Caires, Joana Belo, Maria Amália Botelho, Paula Leiria-Pinto, Nuno Neuparth A644 Use of Skin Prick Test, Specific IgE to Shrimp and Rpen a1 to Determine Clinical Reaction to Shrimp in Area with High Prevalence of House Dust Mite Sensitization Narissara Suratannon, Jaichat Mekaroonkamol, Jarungchit Ngamphaiboon, Piyawadee Lertchanaruengrith, Pantipa Chatchatee A645 Identification of Specific IgE-Binding Proteins in Tree of Heaven (Ailanthus altissima) Pollen Gholamali Kardar, Ahmad Majd, Youcef Shahali, Farrokh Ghahremaninejad, Zahra Pourpak, Fateme Mousavi A646 Allergy Immunotherapy Well Tolerated in Children Mahnaz Sadeghi-Shabestari A647 Steinert (DM1) Patients Have IgG1 Deficiency and Should be Screened for Immune Deficiency K. Van Bilsen, O. Manusama, W.a. Dik, M. Van Der Burg, V. H. J. Van Der Velden, V.a.S. H. Dalm, P. M. Van Hagen A648 The Change of Serous Sige and Three Evaluation before and after Sublingual Immunotherapy with Dermatophagoides Farinae for Persistent Allergic Rhinitis Yongping Liu A649 Garlic Extracts Reduce Histamine-Induced Proliferation and Migration of Human Asthmatic Bronchial Smooth Muscle Cells Yi Yeong Jeong A650 A Case of Occupational Contact Dermatitis Caused By N-Acetylcysteine Ji Hye Kim, Moon Gyeong Yoon, Young Min Ye, Yoo Seob Shin, Ga Young Ban, Hae-Sim Park, Hye Min Jung A651 The Association Between Pollen Change and Asthma Attacks Soo Yong Roh, Jaechul Song, Ji-Hoon Lee, Hogil Kim, Jae Young Kim, Kyeong Joon Lee A652 Incidence of Emergency Department Visits and Hospitalizations for Asthma Exacerbations during the Lunar Month in Singapore Lydia Wong, Mohana Rajakulendran, Haripriya Santhanam, Lynette Shek, Tow Keang Lim A653 The Prevalence of Positive Reaction for Skin Prick Test in Korean Farmers and Its Occupational Risk Factors Hogil Kim, Soo-Jin Lee, Ji-Hoon Lee, Soo Yong Roh, Soon-Chan Kwon A654 Drug Allergy in Children: A Three-Years Experience at Dr. Kariadi Hospital Semarang Indonesia Wistiani, Galuh H, Ani Wistiani A655 The Identification of Morphology, Structure and Study of Seasonal Variation of Airborne Fraxinus Excelsior Pollen Grains in the Tehran Gholam Ali Kardar, Maryam Sharifshoushtari, Ahmad Majd, Taher Nejadsattari, Zahra Pourpak, Mostafa Moin A656 Sublingual Immunotherapy in Elderly Rhinitis Patients Sensitized to House Dust Mites Ji Hye Kim, Daehong Seo, Young Min Ye, Hae-Sim Park, Jung-Won Park, Jae-Hyun Lee, Yoo Seob Shin A657 Healthy Ageing Research Center (HARC) As a Platform for Multidisciplinary Approaches to Respiratory Research in the Elderly Marek L. Kowalski, Aleksandra Wardzynska, Marcin Kurowski, Malgorzata / Ewa Pawelczyk, Adam Wysokinski, Iwona Kloszewska, Janina Grzegorczyk, Wojciech Piotrowski, Joanna Makowska A658 Estimation of Cases of Work-Related Asthma Using Capture-Recapture Methods Soon-Chan Kwon, Jaechul Song, Yong-Kyu Kim A659 Primary School Students’ Parents Reported ISAAC Questionnaire in a Low Income Area of Ankara Ilknur Bostanci, Zeynep Sengul Emeksiz, Aysegul Ertugrul, Serap Ozmen, Soner Sahin A660 Usefulness of PC20 Adenosine Monophosphate in Diagnosis and Treatment in Bronchial Asthma Sang-Ha Kim, Myoung Kyu Lee, Won Yeon Lee, Suk Joong Yong, Seok Jeong Lee, Ye-Ryung Jung A661 S100 Calcium Binding Protein A9 in Sputum of Patients with Steroid Naive Asthma: Relation with Airway Obstruction and Nneutrophilc Inflammation Myung Shin Kim, Jong-Sook Park, An-Soo Jang, Choon-Sik Park A662 Risk Factor Asthma in Pediatric Pneumonia Patients Diah Asri Wulandari, Cissy Kartasasmita A663 Prevalence and Risk Factors of Childhood Asthma and Allergic Disease at Exposed Area By Emission of Cement Padang Factory Finny Fitry Yani, Rizanda Machmud, Dhina Lydia Lestari A664 Association Between Serum Level of 25-Hydroxyvitamin D with Atopic Dermatitis Occurrence and Severity in Children Rusdi Rusdi, Yurmalina Yurmalina, Eryati Darwin A665 Thiol-Disulfide Balance in Children with Atopic Dermatitis Ilknur Bostanci, Gulin Karacan, Nazli Ercan, Asuman Colak, Murat Alisik, Gulay Basarir, Ozcan Erel A666 Recurrent Mouth Ulsers Caused By Braces after Developing a Nickel Allergy in Children Ilknur Bostanci, Yasemin Keskin A667 Anaphylactic Reaction to Famotidine with Pheniramine Hypersensitivity Ilkay Koca Kalkan A668 Novel Transcriptomic and Immunoproteotomic Approaches in Identifying Cross-Reactive Allergens Between Crustacean and Molluscs Andreas/Ludwig Lopata, Kyall Zenger, Roni Nugraha, Sandip Kamath A669 Pollen Season and Climate Change in the Continental United States (CONUS) Leonard Bielory, Panos Georgopoulos, Yong Zhang, Wheat Mi, Ting Cai A670 Differences of Change in Der p IgG4 and CD4+CD25+FoxP3+ Treg Cells Between Sublingual and Subcutaneous Immunotherapy with House Dust Mite in Chinese Patients with Allergic Rhinitis MO Xian, Jing Li, Mulin Feng

negative: Surveillance of Acute Respiratory Infections Using Community-Submitted Symptoms and Specimens for Molecular Diagnostic Testing Participatory systems for surveillance of acute respiratory infection give real-time information about infections circulating in the community, yet to-date are limited to self-reported syndromic information only and lacking methods of linking symptom reports to infection types. We developed the GoViral platform to evaluate whether a cohort of lay volunteers could, and would find it useful to, contribute self-reported symptoms online and to compare specimen types for self-collected diagnostic information of sufficient quality for respiratory infection surveillance. Volunteers were recruited, given a kit (collection materials and customized instructions), instructed to report their symptoms weekly, and when sick with cold or flu-like symptoms, requested to collect specimens (saliva and nasal swab). We compared specimen types for respiratory virus detection sensitivity (via polymerase-chain-reaction) and ease of collection. Participants were surveyed to determine receptivity to participating when sick, to receiving information on the type of pathogen causing their infection and types circulating near them. Between December 1 2013 and March 1 2014, 295 participants enrolled in the study and received a kit. Of those who reported symptoms, half (71) collected and sent specimens for analysis. Participants submitted kits on average 2.30 days (95 CI: 1.65 to 2.96) after symptoms began. We found good concordance between nasal and saliva specimens for multiple pathogens, with few discrepancies. Individuals report that saliva collection is easiest and report that receiving information about what pathogen they, and those near them, have is valued and can shape public health behaviors. Community-submitted specimens can be used for the detection of acute respiratory infection with individuals showing receptivity for participating and interest in a real-time picture of respiratory pathogens near them.

negative: Respiratory virus infection after allogeneic hematopoietic stem cell transplant in a tropical center: Predictive value of the immunodeficiency scoring index BACKGROUND: Respiratory virus infection (RVI) is a prevalent infection in patients after allogeneic hematopoietic stem cell transplant (allo‐HSCT) and can result in significant morbidity and mortality. Ability to assess the potential severity of RVI is important in the management of such patients. METHODS: We reviewed the cases of RVI in allo‐HSCT recipients and explored the predictive value of the immunodeficiency scoring index (ISI) established for respiratory syncytial virus (RSV) and its applicability for RVI caused by other respiratory viruses. RESULTS: RVI occurred year‐round in our tropical transplant center, with peaks in the middle and end of the year. Ninety‐five of the 195 recipients developed a total of 191 episodes of RVI, giving a cumulative incidence of 28% by 6 months and 52% by 24 months for the first episode of RVI. RSV, influenza, rhinovirus, and parainfluenza were the most common viruses. Pneumonia occurred in 63.64%, 42.31%, and 32.42% of adenovirus, influenza, and RSV RVI episodes, respectively, but was also non‐negligible in the more benign viruses, such as coronavirus (31.58%) and rhinovirus (23.68%). Nineteen of the 63 episodes of viral pneumonia required mechanical ventilation and 14 deaths occurred within 6 weeks of the RVI. Receiver operating characteristic analysis showed that an ISI of ≥8 predicted pneumonia with a positive predictive value of >80% for RVI caused by RSV, influenza, adenovirus, and parainfluenza, while it was not predictive for coronavirus and rhinovirus. CONCLUSIONS: The ISI is a useful aid for decision‐making during clinic consultation for patients presenting with symptoms suggestive of an RVI.

negative: Laboratory diagnosis of emerging human coronavirus infections – the state of the art The three unprecedented outbreaks of emerging human coronavirus (HCoV) infections at the beginning of the twenty-first century have highlighted the necessity for readily available, accurate and fast diagnostic testing methods. The laboratory diagnostic methods for human coronavirus infections have evolved substantially, with the development of novel assays as well as the availability of updated tests for emerging ones. Newer laboratory methods are fast, highly sensitive and specific, and are gradually replacing the conventional gold standards. This presentation reviews the current laboratory methods available for testing coronaviruses by focusing on the coronavirus disease 2019 (COVID-19) outbreak going on in Wuhan. Viral pneumonias typically do not result in the production of purulent sputum. Thus, a nasopharyngeal swab is usually the collection method used to obtain a specimen for testing. Nasopharyngeal specimens may miss some infections; a deeper specimen may need to be obtained by bronchoscopy. Alternatively, repeated testing can be used because over time, the likelihood of the SARS-CoV-2 being present in the nasopharynx increases. Several integrated, random-access, point-of-care molecular devices are currently under development for fast and accurate diagnosis of SARS-CoV-2 infections. These assays are simple, fast and safe and can be used in the local hospitals and clinics bearing the burden of identifying and treating patients.

negative: Efficacy of a Carrageenan nasal spray in patients with common cold: a randomized controlled trial BACKGROUND: The common cold is the most widespread viral infection in humans. Iota-carrageenan has previously shown antiviral effectiveness against cold viruses in clinical trials. This study investigated the efficacy of a carrageenan-containing nasal spray on the duration of the common cold and nasal fluid viral load in adult patients. METHODS: In a randomized, double-blind, placebo-controlled trial, 211 patients suffering from early symptoms of the common cold were treated for seven days. Application was performed three times daily with either a carrageenan-supplemented nasal spray or saline solution as placebo with an overall observation period of 21 days. The primary endpoint was the duration of disease defined as the time until the last day with symptoms followed by all other days in the study period without symptoms. During the study, but prior unblinding, the definition of disease duration was adapted from the original protocol that defines disease duration as the time period of symptoms followed by 48 hours without symptoms. RESULTS: In patients showing a laboratory-confirmed cold virus infection and adherence to the protocol, alleviation of symptoms was 2.1 days faster in the carrageenan group in comparison to placebo (p = 0.037). The primary endpoint that had been prespecified but was changed before unblinding was not met. Viral titers in nasal fluids showed a significantly greater decrease in carrageenan patients in the intention-to-treat population (p = 0.024) and in the per protocol population (p = 0.018) between days 1 and 3/4. CONCLUSIONS: In adults with common cold virus infections, direct local administration of carrageenan with nasal sprays reduced the duration of cold symptoms. A significant reduction of viral load in the nasal wash fluids of patients confirmed similar findings from earlier trials in children and adults. TRIAL REGISTRATION: Current Controlled Trials ISRCTN80148028

negative: Early chest CT features of patients with 2019 novel coronavirus (COVID-19) pneumonia: relationship to diagnosis and prognosis OBJECTIVE: To determine the consistency between CT findings and real-time reverse transcription-polymerase chain reaction (RT-PCR) and to investigate the relationship between CT features and clinical prognosis in COVID-19. METHODS: The clinical manifestations, laboratory parameters, and CT imaging findings were analyzed in 34 COVID-19 patients, confirmed by RT-PCR from January 20 to February 4 in Hainan Province. CT scores were compared between the discharged patients and the ICU patients. RESULTS: Fever (85%) and cough (79%) were most commonly seen. Ten (29%) patients demonstrated negative results on their first RT-PCR. Of the 34 (65%) patients, 22 showed pure ground-glass opacity. Of the 34 (50%) patients, 17 had five lobes of lung involvement, while the 23 (68%) patients had lower lobe involvement. The lesions of 24 (71%) patients were distributed mainly in the subpleural area. The initial CT lesions of ICU patients were distributed in both the subpleural area and centro-parenchyma (80%), and the lesions were scattered. Sixty percent of ICU patients had five lobes involved, while this was seen in only 25% of the discharged patients. The lesions of discharged patients were mainly in the subpleural area (75%). Of the discharged patients, 62.5% showed pure ground-glass opacities; 80% of the ICU patients were in the progressive stage, and 75% of the discharged patients were at an early stage. CT scores of the ICU patients were significantly higher than those of the discharged patients. CONCLUSION: Chest CT plays a crucial role in the early diagnosis of COVID-19, particularly for those patients with a negative RT-PCR. The initial features in CT may be associated with prognosis. KEY POINTS: â¢ Chest CT is valuable for the early diagnosis of COVID-19, particularly for those patients with a negative RT-PCR. â¢ The early CT findings of COVID-19 in ICU patients differed from those of discharged patients.

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: 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: COVID-19 Outbreak in Oman: Model-Driven Impact Analysis and Challenges Motivated by the rapid spread of COVID-19 all across the globe, we have performed simulations of a system dynamic epidemic spread model in different possible situations. The simulation, not only captures the model dynamic of the spread of the virus, but also, takes care of population and mobility data. The model is calibrated based on epidemic data and events specifically of Sultanate of Oman, which can easily be generalized. The simulation results are quite disturbing, indicating that, during a process of stringent social distancing and testing strategies, a small perturbation can lead to quite undesirable outcomes. The simulation results, although consistent in expected outcomes across changing parameters' values, also indicate a substantial mismatch with real numbers. An analysis of what can be the reason of this mismatch is also performed. Within these contradictions, for Oman, regarding the eradication of epidemic, the future is not extremely alarming.

negative: Harmonizing the COVID-19 cacophony: People need guidance

negative: 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.

negative: Global Consortium Study of Neurological Dysfunction in COVID-19 (GCS-NeuroCOVID): Study Design and Rationale BACKGROUND: As the COVID-19 pandemic developed, reports of neurological dysfunctions spanning the central and peripheral nervous systems have emerged. The spectrum of acute neurological dysfunctions may implicate direct viral invasion, para-infectious complications, neurological manifestations of systemic diseases, or co-incident neurological dysfunction in the context of high SARS-CoV-2 prevalence. A rapid and pragmatic approach to understanding the prevalence, phenotypes, pathophysiology and prognostic implications of COVID-19 neurological syndromes is urgently needed. METHODS: The Global Consortium to Study Neurological dysfunction in COVID-19 (GCS-NeuroCOVID), endorsed by the Neurocritical Care Society (NCS), was rapidly established to address this need in a tiered approach. Tier-1 consists of focused, pragmatic, low-cost, observational common data element (CDE) collection, which can be launched immediately at many sites in the first phase of this pandemic and is designed for expedited ethical board review with waiver-of-consent. Tier 2 consists of prospective functional and cognitive outcomes assessments with more detailed clinical, laboratory and radiographic data collection that would require informed consent. Tier 3 overlays Tiers 1 and 2 with experimental molecular, electrophysiology, pathology and imaging studies with longitudinal outcomes assessment and would require centers with specific resources. A multicenter pediatrics core has developed and launched a parallel study focusing on patients ages <18 years. Study sites are eligible for participation if they provide clinical care to COVID-19 patients and are able to conduct patient-oriented research under approval of an internal or global ethics committee. Hospitalized pediatric and adult patients with SARS-CoV-2 and with acute neurological signs or symptoms are eligible to participate. The primary study outcome is the overall prevalence of neurological complications among hospitalized COVID-19 patients, which will be calculated by pooled estimates of each neurological finding divided by the average census of COVID-19 positive patients over the study period. Secondary outcomes include: in-hospital, 30 and 90-day morality, discharge modified Rankin score, ventilator-free survival, ventilator days, discharge disposition, and hospital length of stay. RESULTS: In a one-month period (3/27/20–4/27/20) the GCS-NeuroCOVID consortium was able to recruit 71 adult study sites, representing 17 countries and 5 continents and 34 pediatrics study sites. CONCLUSIONS: This is one of the first large-scale global research collaboratives urgently assembled to evaluate acute neurological events in the context of a pandemic. The innovative and pragmatic tiered study approach has allowed for rapid recruitment and activation of numerous sites across the world—an approach essential to capture real-time critical neurological data to inform treatment strategies in this pandemic crisis.

negative: Treatment Considerations for COVID-19: A Critical Review of the Evidence (or Lack Thereof) Abstract The novel severe acute respiratory syndrome coronavirus 2 is causing a worldwide pandemic that may lead to a highly morbid and potentially fatal coronavirus disease-19 (COVID-19). There is currently no drug that has been proven as an effective therapy for COVID-19. Several candidate drugs are being considered and evaluated for treatment. This includes clinically-available drugs, such as chloroquine, hydroxychloroquine, and lopinavir/ritonavir, which are being repurposed for the treatment of COVID-19. Novel experimental therapies, such as remdesivir and favipiravir, are also actively being investigated for antiviral efficacy. Clinically-available and investigational immunomodulators, such as the IL-6 inhibitors tocilizumab and sarilumab and the anti-GMCSF lenzilumab, are being tested for their anticipated effect in counteracting the pro-inflammatory cytokine environment that characterizes severe and critical COVID-19. This review article examines the evidence behind the potential use of these leading drug candidates for the treatment of COVID-19. The authors conclude, based on this review, that there is still no high-quality evidence to support any of these proposed drug therapies. The authors, therefore, encourage the enrollment of eligible patients to multiple ongoing clinical trials that assess the efficacy and safety of these candidate therapies. Until the results of controlled trials are available, none of the suggested therapeutics is clinically proven as an effective therapy for COVID-19.

negative: Anesthetic Management of Patients with COVID 19 Infections during Emergency Procedures Objectives The aim of the present study was to prevent cross-infection in the operating room during emergency procedures for patients with confirmed or suspected 2019 novel coronavirus (2019-nCoV) by following anesthesia management protocols, and to document clinical- and anesthesia-related characteristics of these patients. Design This was a retrospective, multicenter clinical study. Setting This study used a multicenter dataset from 4 hospitals in Wuhan, China. Participants Patients and health care providers with confirmed or suspected 2019-nCoV from January 23 to 31, 2020, at the Wuhan Union Hospital, the Wuhan Children's Hospital, The Central Hospital of Wuhan, and the Wuhan Fourth Hospital in Wuhan, China. Interventions Anesthetic management and infection control guidelines for emergency procedures for patients with suspected 2019-nCoV were drafted and applied in 4 hospitals in Wuhan. Measurements and Main Results Cross-infection in the operating rooms of the 4 hospitals was effectively reduced by implementing the new measures and procedures. The majority of patients with laboratory-confirmed 2019-nCoV infection or suspected infection were female (23 [62%] of 37), and the mean age was 41.0 years old (standard deviation 19.6; range 4-78). 10 (27%) patients had chronic medical illnesses, including 4 (11%) with diabetes, 8 (22%) with hypertension, and 8 (22%) with digestive system disease. Twenty-five (68%) patients presented with lymphopenia, and 23 (62%) patients exhibited multiple mottling and ground-glass opacity on computed tomography scanning. Conclusions The present study indicates that COVID 19–specific guidelines for emergency procedures for patients with confirmed or suspected 2019-nCoV may effectively prevent cross-infection in the operating room. Most patients with confirmed or suspected COVID 19 presented with fever and dry cough and demonstrated bilateral multiple mottling and ground-glass opacity on chest computed tomography scans.

negative: A Case of Pseudoaneurysm of the Internal Carotid Artery Following Endoscopic Endonasal Pituitary Surgery: Endovascular Treatment with Flow-Diverting Stent Implantation. Internal carotid artery (ICA) pseudoaneurysm is a rare complication of endoscopic endonasal surgery occurring in 0.4-1.1% of cases. Pseudoaneurysms can subsequently result in other complications, such as subarachnoid hemorrhage, epistaxis, and caroticocavernous fistula with resultant death or permanent neurologic deficit. In this case, we illustrate endovascular treatment with a flow-diverting stent for an ICA pseudoaneurysm after endoscopic endonasal surgery for a pituitary adenoma in a 56-year-old male. Surgery was complicated by excessive intraoperative bleeding and emergent CT angiography confirmed an iatrogenic pseudoaneurysm on the anteromedial surface of the ICA. The pseudoaneurysm was treated endovascularly with flow-diverting stent implantation only. Follow-up CT angiography after three months demonstrated occlusion of the pseudoaneurysm.

negative: Pharyngitis and Epiglottitis Acute pharyngitis is one of the most common illnesses for which patients visit primary care physicians. Most cases are of viral origin, and with few exceptions these illnesses are both benign and self-limited. The most important bacterial cause is the beta-hemolytic group A streptococcus. There are other uncommon or rare types of pharyngitis. For some of these treatment is required or available, and some may be life threatening. Among those discussed in this article are diphtheria, gonorrhea, HIV infection, peritonsillar abscess, and epiglottitis.

negative: Preliminary epidemiological analysis on children and adolescents with novel coronavirus disease 2019 outside Hubei Province, China: an observational study utilizing crowdsourced data Background: The outbreak of coronavirus disease 2019 (COVID-19) continues to expand across the world. Though both the number of cases and mortality rate in children and adolescents is reported to be low in comparison to adults, limited data has been reported on the outbreak with respect to pediatric patients. To elucidate information, we utilized crowdsourced data to perform a preliminary epidemiologic analysis of pediatric patients with COVID-19 Methods: In this observational study, data was collected from two open-access, line list crowdsourced online databases. Pediatric cases of COVID-19 were defined as patients ≤19 years of age with a laboratory confirmed diagnosis. The primary outcomes were case counts and cumulative case counts. Secondary outcomes included days between symptoms onset and first medical care and days between first medical care and reporting. Tertiary outcomes were rate of travel to Wuhan, rate of infected family members and rates of symptoms. Results: A total of 82 patients were included. The median age was 10 [IQR: 5-15] years. Patients from mainland China (outside Hubei) accounted for 46.3% of cases, while the remaining 53.7% of cases were international. Males and females accounted for 52.4% and 32.9% of cases, respectively, with the remaining 14.6% being designated as unknown. A male skew persisted across subgroup analyses by age group (p=1.0) and location (inside/outside China) (p=0.22). While the number of reported international cases has been steadily increasing over the study period, the number of reported cases in China rapidly decreased from the start point. The median reporting delay was 3 [IQR: 2-4.8] days. The median delay between symptom onset and first seeking medical care was 1 [IQR: 0-3.25] day. In international cases, time to first seeking medical care was a median of 2.5 days longer than in China (p=0.04). When clinical features were reported, fever was the most common presentation (68.0%), followed by cough (36.0%). Conclusions: The number of reported international pediatric COVID-19 cases is rapidly increasing. COVID-19 infections are, to-date, more common in males than females in both the children and adolescent age groups. Additionally, this male predominance remains the case both inside and outside of China. Crowdsourced data enabled early analysis of epidemiologic variables in pediatric patients with COVID-19. Further data sharing is required to enable analyses that are required to understand the course of this infection in children.

negative: A Longitudinal Study on the Mental Health of General Population during the COVID-19 Epidemic in China Abstract In addition to being a public physical health emergency, Coronavirus disease 2019 (COVID-19) affected global mental health, as evidenced by panic-buying worldwide as cases soared. Little is known about changes in levels of psychological impact, stress, anxiety and depression during this pandemic. This longitudinal study surveyed the general population twice - during the initial outbreak, and the epidemic's peak four weeks later, surveying demographics, symptoms, knowledge, concerns, and precautionary measures against COVID-19. There were 1738 respondents from 190 Chinese cities (1210 first-survey respondents, 861 second-survey respondents; 333 respondents participated in both). Psychological impact and mental health status were assessed by the Impact of Event Scale-Revised (IES-R) and the Depression, Anxiety and Stress Scale (DASS-21), respectively. IES-R measures PTSD symptoms in survivorship after an event. DASS -21 is based on tripartite model of psychopathology that comprise a general distress construct with distinct characteristics. This study found that there was a statistically significant longitudinal reduction in mean IES-R scores (from 32.98 to 30.76, p<0.01) after 4 weeks. Nevertheless, the mean IES-R score of the first- and second-survey respondents were above the cut-off scores (>24) for PTSD symptoms, suggesting that the reduction in scores was not clinically significant. During the initial evaluation, moderate-to-severe stress, anxiety and depression were noted in 8.1%, 28.8% and 16.5%, respectively and there were no significant longitudinal changes in stress, anxiety and depression levels (p>0.05). Protective factors included high level of confidence in doctors, perceived survival likelihood and low risk of contracting COVID-19, satisfaction with health information, personal precautionary measures. As countries around the world brace for an escalation in cases, Governments should focus on effective methods of disseminating unbiased COVID-19 knowledge, teaching correct containment methods, ensuring availability of essential services/commodities, and providing sufficient financial support.

negative: Knowledge synthesis from 100 million biomedical documents augments the deep expression profiling of coronavirus receptors The COVID-19 pandemic demands assimilation of all available biomedical knowledge to decode its mechanisms of pathogenicity and transmission. Despite the recent renaissance in unsupervised neural networks for decoding unstructured natural languages, a platform for the real-time synthesis of the exponentially growing biomedical literature and its comprehensive triangulation with deep omic insights is not available. Here, we present the nferX platform for dynamic inference from over 45 quadrillion possible conceptual associations extracted from unstructured biomedical text, and their triangulation with Single Cell RNA-sequencing based insights from over 25 tissues. Using this platform, we identify intersections between the pathologic manifestations of COVID-19 and the comprehensive expression profile of the SARS-CoV-2 receptor ACE2. We find that tongue keratinocytes, airway club cells, and ciliated cells are likely underappreciated targets of SARS-CoV-2 infection, in addition to type II pneumocytes and olfactory epithelial cells. We further identify mature small intestinal enterocytes as a possible hotspot of COVID-19 fecal-oral transmission, where an intriguing maturation-correlated transcriptional signature is shared between ACE2 and the other coronavirus receptors DPP4 (MERS-CoV) and ANPEP (α-coronavirus). This study demonstrates how a holistic data science platform can leverage unprecedented quantities of structured and unstructured publicly available data to accelerate the generation of impactful biological insights and hypotheses. The nferX Platform Single-cell resource - https://academia.nferx.com/

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: On the origin and continuing evolution of SARS-CoV-2 The SARS-CoV-2 epidemic started in late December 2019 in Wuhan, China, and has since impacted a large portion of China and raised major global concern. Herein, we investigated the extent of molecular divergence between SARS-CoV-2 and other related coronaviruses. Although we found only 4% variability in genomic nucleotides between SARS-CoV-2 and a bat SARS-related coronavirus (SARSr-CoV; RaTG13), the difference at neutral sites was 17%, suggesting the divergence between the two viruses is much larger than previously estimated. Our results suggest that the development of new variations in functional sites in the receptor-binding domain (RBD) of the spike seen in SARS-CoV-2 and viruses from pangolin SARSr-CoVs are likely caused by mutations and natural selection besides recombination. Population genetic analyses of 103 SARS-CoV-2 genomes indicated that these viruses evolved into two major types (designated L and S), that are well defined by two different SNPs that show nearly complete linkage across the viral strains sequenced to date. Although the L type (∼70%) is more prevalent than the S type (∼30%), the S type was found to be the ancestral version. Whereas the L type was more prevalent in the early stages of the outbreak in Wuhan, the frequency of the L type decreased after early January 2020. Human intervention may have placed more severe selective pressure on the L type, which might be more aggressive and spread more quickly. On the other hand, the S type, which is evolutionarily older and less aggressive, might have increased in relative frequency due to relatively weaker selective pressure. These findings strongly support an urgent need for further immediate, comprehensive studies that combine genomic data, epidemiological data, and chart records of the clinical symptoms of patients with coronavirus disease 2019 (COVID-19).

negative: The sequence of human ACE2 is suboptimal for binding the S spike protein of SARS coronavirus 2 The rapid and escalating spread of SARS coronavirus 2 (SARS-CoV-2) poses an immediate public health emergency. The viral spike protein S binds ACE2 on host cells to initiate molecular events that release the viral genome intracellularly. Soluble ACE2 inhibits entry of both SARS and SARS-2 coronaviruses by acting as a decoy for S binding sites, and is a candidate for therapeutic, prophylactic and diagnostic development. Using deep mutagenesis, variants of ACE2 are identified with increased binding to the receptor binding domain of S. Mutations are found across the interface, in the N90-glycosylation motif, and at buried sites where they are predicted to enhance local folding and presentation of the interaction epitope. When single substitutions are combined, large increases in binding can be achieved. The mutational landscape offers a blueprint for engineering high affinity proteins and peptides that block receptor binding sites on S to meet this unprecedented challenge.

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: Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20–28 January 2020 A novel coronavirus (2019-nCoV) is causing an outbreak of viral pneumonia that started in Wuhan, China. Using the travel history and symptom onset of 88 confirmed cases that were detected outside Wuhan in the early outbreak phase, we estimate the mean incubation period to be 6.4 days (95% credible interval: 5.6–7.7), ranging from 2.1 to 11.1 days (2.5th to 97.5th percentile). These values should help inform 2019-nCoV case definitions and appropriate quarantine durations.

negative: Experimental Piscine orthoreovirus infection mediates protection against pancreas disease in Atlantic salmon (Salmo salar) Viral diseases are among the main challenges in farming of Atlantic salmon (Salmo salar). The most prevalent viral diseases in Norwegian salmon aquaculture are heart and skeletal muscle inflammation (HSMI) caused by Piscine orthoreovirus (PRV), and pancreas disease (PD) caused by Salmonid alphavirus (SAV). Both PRV and SAV target heart and skeletal muscles, but SAV additionally targets exocrine pancreas. PRV and SAV are often present in the same locations and co-infections occur, but the effect of this crosstalk on disease development has not been investigated. In the present experiment, the effect of a primary PRV infection on subsequent SAV infection was studied. Atlantic salmon were infected with PRV by cohabitation, followed by addition of SAV shedder fish 4 or 10 weeks after the initial PRV infection. Histopathological evaluation, monitoring of viral RNA levels and host gene expression analysis were used to assess disease development. Significant reduction of SAV RNA levels and of PD specific histopathological changes were observed in the co-infected groups compared to fish infected by SAV only. A strong correlation was found between histopathological development and expression of disease related genes in heart. In conclusion, experimentally PRV infected salmon are less susceptible to secondary SAV infection and development of PD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-016-0389-y) contains supplementary material, which is available to authorized users.

negative: Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain Coronaviruses have developed various measures to evade innate immunity. We have previously shown that severe acute respiratory syndrome (SARS) coronavirus M protein suppresses type I interferon (IFN) production by impeding the formation of functional TRAF3-containing complex. In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain (TM1) located at the N terminus. M protein from human coronavirus HKU1 does not inhibit IFN production. Whereas N-linked glycosylation of SARS coronavirus M protein has no influence on IFN antagonism, TM1 is indispensable for the suppression of IFN production. TM1 targets SARS coronavirus M protein and heterologous proteins to the Golgi apparatus, yet Golgi localization is required but not sufficient for IFN antagonism. Mechanistically, TM1 is capable of binding with RIG-I, TRAF3, TBK1 and IKKε, and preventing the interaction of TRAF3 with its downstream effectors. Our work defines the molecular architecture of SARS coronavirus M protein required for suppression of innate antiviral response.

negative: Clinical characteristics of COVID-19 infection in pregnant women: a systematic review and meta-analysis Background: On December 2019, Novel coronavirus disease (COVID-19) was detected in Wuhan, China, and then spread around the world. There is little information about effects of COVID-19 on Pregnant women and newborns as a sensitive population. The current study is a systemic review and Meta-analysis to measure the risks and determine the presentations of COVID-19 in pregnant women and newborn. Methods: online data bases were searched on march 20. Heterogeneity of the included studies was assessed using the Cochran Q test and Higgins I2 statistic and expressed as percentage. All data were analyzed with 95% confidence intervals. Results: A total of 7 studies involving 50 participants with Positive test of COVID-19 were enrolled. Mean age of pregnant women was 30.57 years old and the Mean Gestational age was 36.9 weeks. Other variables such as Apgar score, birth weight, Sign and symptoms, Complications and Laboratory data were Analyzed. Conclusion: Our findings showed same clinical characteristics in pregnant women as in non-pregnant adults, with the main symptoms being cough and fever. No vertical transmission was seen and all patients delivered healthy neonates. Our findings would be of great help to the decision making process, regarding the management of pregnant women diagnosed with COVID-19.

negative: Clinical features and outcomes of 221 patients with COVID-19 in Wuhan, China Rationale: In late December 2019, an outbreak of acute respiratory illness, now officially named as COVID-19, or coronavirus disease 2019, emerged in Wuhan, China, now spreading across the whole country and world. More data were needed to understand the clinical characteristics of the disease. Objectives: To study the epidemiology, clinical features and outcomes of patients with COVID-19. Methods: we performed a single center, retrospective case series study in 221 patients with laboratory confirmed SARS-CoV-2 pneumonia at a university hospital. Measurements and Main Results: The median age was 55.0 years and 48.9% were male and only 8 (3.6%) patients had a history of exposure to the Huanan Seafood Market. Compared to the non-severe pneumonia patients, the median age of the severe patients was significantly older, and they were more likely to have chronic comorbidities. Most common symptoms in severe patients were high fever, anorexia and dyspnea. On admission, 33.0% patients showed leukopenia and 73.8% showed lymphopenia. In addition, the severe patients suffered a higher rate of co-infections with bacteria or fungus and they were more likely to developing complications. As of February 15, 2020, 19.0% patients had been discharged and 5.4% patients died. 80% of severe cases received ICU care, and 52.3% of them transferred to the general wards due to relieved symptoms, and the mortality rate of severe patients in ICU was 20.5%. Conclusions: The COVID-19 epidemic spreads rapidly by human-to-human transmission. Patients with elder age, chronic comorbidities, blood leukocyte/lymphocyte count, procalcitonin level, co-infection and severe complications might increase the risk of poor clinical outcomes. Keywords: coronavirus disease 2019; clinical features; outcomes; severe patients

negative: Effect of early pregnancy diagnosis by per rectum amniotic sac palpation on pregnancy loss, calving rates, and abnormalities in newborn dairy calves The objectives of the present study were to evaluate the effect of per rectal amniotic sac palpation (ASP) for pregnancy diagnosis during the late embryonic period on pregnancy loss, calving rates, and abnormalities in newborn calves. A controlled, randomized, blocked, blind experiment containing 680 lactating pregnant dairy cows with a viable embryo diagnosed by transrectal ultrasonography was performed. Two dairy operation sites (farm A and farm B) were selected. At each farm, the cows were randomly divided into control (CON) and ASP groups. The CON group was not subjected to pregnancy diagnosis via per rectum palpation. The ASP examinations were performed by one experienced veterinarian between Days 34 and 45 after breeding. All cows were reevaluated by transrectal ultrasonography only between 2 and 4 weeks later. Two calving rates were calculated: calving rate 1 (cows that calved from the initial number of pregnant cows) and calving rate 2 (cows that calved from cows pregnant at reexamination). In farm A, the percentages of early pregnancy loss were 11.5% (19 of 165) and 13.2% (24 of 182) for the CON and the ASP groups, respectively (P = 0.64). In farm B, the percentage of early pregnancy loss was 11.2% (19 of 170) for the CON group and 8.8% (14 of 159; P = 0.48) for the ASP group. In farm A, the percentage of late pregnancy loss was 7.6% (11 of 145) for the CON group and 5.5% (8 of 155; P = 0.39) for the ASP group. In farm B, the percentage of late pregnancy loss was 3.7% (5 of 137) for the CON group and 6.3% (8 of 127; P = 0.32) for the ASP group. In farm A, early pregnancy loss was higher than late pregnancy loss (12.4% vs. 6.3%; P = 0.01), and in farm B, the same tendency was detected (10.0% vs. 4.9%, for early and late pregnancy loss, respectively; P = 0.02). In farm A, calving rate 1 was 81.2% (134 of 165) for the CON group and 80.8% (147 of 182; P = 0.92) for the ASP group. Calving rate 2 for the same groups was 92.4% (134 of 145) and 94.8% (147 of 155), respectively (P = 0.68). In farm B, calving rate 1 was 77.7% (132 of 170) for the CON group and 74.8% (119 of 159; P = 0.55) for the ASP group. Calving rates 2 for the same groups were 87.4% (132 of 151) and 82.1% (119 of 145), respectively (P = 0.20). Two female calves with atresia coli were diagnosed only in the CON group. It was concluded that ASP during the late embryonic period for pregnancy diagnosis did not increase the pregnancy loss, affect calving rates, or produce abnormalities in calves.

negative: Spread of SARS-CoV-2 Coronavirus likely to be constrained by climate As new cases of COVID-19 are being confirmed pressure is mounting to increase understanding of the factors underlying the spread the disease. Using data on local transmissions until the 23rd of March 2020, we develop an ensemble of 200 ecological niche models to project monthly variation in climate suitability for spread of SARS-CoV-2 throughout a typical climatological year. Although cases of COVID-19 are reported all over the world, most outbreaks display a pattern of clustering in relatively cool and dry areas. The predecessor SARS-CoV-1 was linked to similar climate conditions. Should the spread of SARS CoV-2 continue to follow current trends, asynchronous seasonal global outbreaks could be expected. According to the models, temperate warm and cold climates are more favorable to spread of the virus, whereas arid and tropical climates are less favorable. However, model uncertainties are still high across much of sub- Saharan Africa, Latin America and South East Asia. While models of epidemic spread utilize human demography and mobility as predictors, climate can also help constrain the virus. This is because the environment can mediate human-to-human transmission of SARS-CoV-2, and unsuitable climates can cause the virus to destabilize quickly, hence reducing its capacity to become epidemic.

negative: Detection of the New Human Coronavirus HKU1: A Report of 6 Cases Background. Human coronavirus HKU1 (HCoV-HKU1), a new group 2 coronavirus, was first characterized in 2005 from 2 adults with pneumonia in Hong Kong, China. To the best of our knowledge, there is no other report to date about the detection of this new virus. We report a molecular method allowing for the detection of HCoV-HKU1 and also report the clinical presentation of 6 infected patients. Methods. We screened 141 specimens (135 nasal samples and 6 stool samples) received in February and March 2005 in our laboratory and obtained from 135 hospitalized patients (61.5% of whom were <5 years old and 34.1% of whom were >20 years old) for HCoV-HKU1. Results. HCoV-HKU1 was detected in 6 (4.4%) of the 135 nasal specimens and in 2 (33.3%) of the 6 stool samples; the positive samples were obtained from 6 patients (5 children and 1 adult). The clinical presentation of these 6 patients was as follows: 3 were admitted to the hospital for acute enteric disease resulting in severe dehydration associated with upper respiratory symptoms; 1 had fever, otitis, and febrile seizure; 1 had a sample obtained to investigate failure to thrive; and 1 had a sample obtained for exploration of X-linked agammaglobulinemia and hyperleucocytosis. Conclusion. HCoV-HKU1 can be detected in respiratory and stool samples from children and adults in a part of the world other than Hong Kong. Our results suggest that HCoV-HKU1 could be associated with respiratory and enteric diseases, and its detection can be related to a persistent asymptomatic infection in patients with poor underlying conditions.

negative: Coronavirus infections and type 2 diabetes-shared pathways with therapeutic implications Individuals with diabetes are at increased risk for bacterial, mycotic, parasitic and viral infections. The severe acute respiratory syndrome (SARS)-CoV2 (also referred to as COVID-19) coronavirus pandemic highlights the importance of understanding shared disease pathophysiology potentially informing therapeutic choices in individuals with Type 2 diabetes (T2D). Two coronavirus receptor proteins, Angiotensin Converting Enzyme 2 (ACE2) and Dipeptidyl Peptidase-4 (DPP4) are also established transducers of metabolic signals and pathways regulating inflammation, renal and cardiovascular physiology, and glucose homeostasis. Moreover, glucose-lowering agents such as the DPP4 inhibitors, widely used in subjects with T2D, are known to modify the biological activities of multiple immunomodulatory substrates. Here we review the basic and clinical science spanning the intersections of diabetes, coronavirus infections, ACE2, and DPP4 biology, highlighting clinical relevance and evolving areas of uncertainty underlying the pathophysiology and treatment of T2D in the context of coronavirus infection

negative: Development and Initial Validation of the COVID Stress Scales Abstract Research and clinical observations suggest that during times of pandemic many people exhibit stress- or anxiety-related psychopathology that include fear of becoming infected, fear of coming into contact with possibly contaminated objects or surfaces, fear of foreigners who might be carrying infection (i.e., disease-related xenophobia), fear of the socio-economic consequences of the pandemic, compulsive checking and reassurance-seeking regarding possible pandemic-related threats, and traumatic stress symptoms about the pandemic (e.g., nightmares, intrusive thoughts). We developed the 36-item COVID Stress Scales (CSS) to measure these features, as they pertain to COVID-19. The CSS were developed to better understand and assess COVID-19-related psychopathology. The scales were intentionally designed so they could be readily adapted for future pandemics. The CSS were developed and initially validated in population-representative samples from Canada (N = 3,479) and the United States (N = 3,375). A stable 5-factor solution was identified, corresponding to scales assessing COVID-related stress and anxiety symptoms: (1) Danger and contamination fears, (2) fears about economic consequences, (3) xenophobia, (4) compulsive checking, and (5) traumatic stress symptoms about COVID-19. The scales performed well on various indices of reliability and validity. The scales were intercorrelated, providing evidence of a COVID Stress Syndrome. The scales offer promise as tools for better understanding the psychopathology associated with COVID-19 and for identifying people in need of mental health services.

negative: A Rare Case of Human Coronavirus 229E Associated with Acute Respiratory Distress Syndrome in a Healthy Adult Human coronavirus 229E (HCoV-229E) is one of the first coronavirus strains being described. It is linked to common cold symptoms in healthy adults. Younger children and the elderly are considered vulnerable to developing lower respiratory tract infections (LRTIs). In particular, immunocompromised patients have been reported with severe and life-threatening LRTIs attributed to HCoV-229E. We report for the first time a case of LRTI and acute respiratory distress syndrome developed in a healthy adult with no comorbidities and HCoV-229E strain identified as the only causative agent. A 45-year-old female with a clear medical history presented with fever, cough, and headache. Respiratory tract infection was diagnosed, and empirical antibiotics were started. Within two days, she developed bilateral pleural effusions, diffuse consolidations, and ground glass opacities involving all lung fields. She needed immediate oxygen supply, while ABGs deteriorated and chest imaging and PaO(2)/FiO(2) indicated ARDS. Early administration of systemic corticosteroids led to gradual clinical improvement. Multiplex PCR from nasal secretions was positive only for HCoV-229E and negative for multiple other pathogens. It remains to be elucidated how an immunocompetent adult developed a life-threatening LRTI caused by a “benign considered” coronavirus strain, the HCoV-229E.

negative: Que doivent savoir les chirurgiens à propos des troubles digestifs et des anomalies paracliniques induits par le COVID 19?/ [What do surgeons need to know about the digestive disorders and paraclinical abnormalities induced by COVID-19?] The symptoms associated with COVID-19 are mainly characterized by a triad composed of fever, dry cough and dyspnea. However, digestive symptoms have also been reported; at first considered as infrequent, they in fact seem to affect (to some extent) more than half of patients. The symptoms are mainly manifested by anorexia, diarrhea, nausea and/or vomiting and abdominal pain. Even though prognosis is associated with lung injury, digestive symptoms seem significantly more frequent in patients presenting with severe COVID-19 infection. Digestive forms, which may be isolated or which can precede pulmonary symptoms, have indeed been reported, with diarrhea as a leading clinical sign. The main biological abnormalities that can suggest COVID-19 infection at an early stage are lymphopenia, elevated CRP and heightened ASAT transaminases. Thoraco-abdominal scan seems useful as a means of on the one hand ruling out digestive pathology not connected with coronavirus and on the other hand searching for pulmonary images compatible with COVID-19 infection. No data exist on the interest of digestive endoscopy in cases of persistent digestive symptoms. Moreover, the endoscopic surgeons may themselves be at significant risk of contamination. Fecal-oral transmission of the infection is possible, especially insofar as viral shedding in stools seems frequent and of longer duration than at the ENT level, including in patients with negative throat swab and without digestive symptoms. In some doubtful cases, virologic assessment of stool samples can yield definitive diagnosis. In the event of prolonged viral shedding in stools, a patient's persistent contagiousness is conceivable but not conclusively established. Upcoming serology should enable identification of the patients having been infected by the COVID-19 epidemic, particularly among previously undetected pauci-symptomatic members of a health care staff. Resumption of medico-surgical activity should be the object of a dedicated strategy preceding deconfinement.

negative: Steroid‐responsive encephalitis in Covid‐19 disease Covid‐19 infection has the potential for targeting the central nervous system and several neurological symptoms have been described in patients with severe respiratory distress. Here we described the case of a 60‐year old subject with SARS‐CoV‐2 infection but only mild respiratory abnormalities who developed an akinetic mutism due to encephalitis. MRI was negative whereas EEG showed generalized theta slowing. CSF analyses during the acute stage were negative for SARS‐CoV‐2, positive for pleocytosis and hyperproteinorrachia, and showed increased IL‐8 and TNF‐α concentrations while other infectious or autoimmune disorders were excluded. A progressive clinical improvement along with a reduction of CSF parameters was observed after high‐dose steroid treatment, thus arguing for an inflammatory‐mediated brain involvement related to Covid‐19. This article is protected by copyright. All rights reserved.

negative: Infection Community-Acquired Pneumonia (CAP) is the first leading cause of death due to infection worldwide.Many gram-positive, gram-negative bacteria, funguses and viruses can cause the infectious pulmonary disease, and the severity of pneumonia depends on the balance between the microorganism charge, the body immunity defenses and the quality of the underlying pulmonary tissue. The microorganisms may reach the lower respiratory tract from inhaled air or from infected oropharyngeal secretions. The same organism may produce several different patterns that depend on the balance between the microorganism charge and the body immunity defenses.CAP is classified into three main groups: lobar pneumonia, bronchopneumonia and interstitial pneumonia.Lobar pneumonia is characterized by the filling of alveolar spaces by edema full of white and inflammatory cells. Necrotizing pneumonia consists of a fulminant process associated with focal areas of necrosis that results in abscesses. Bronchopneumonia or lobular pneumonia, is characterized by a peribronchiolar inflammation with thickening of peripheral bronchial wall, the diffusion of inflammation to the centrilobular alveolar spaces and development of nodules.The interstitial pneumonia represents with the destruction and esfoliation of the respiratory ciliated and mucous cells. The interstitial septa, the bronchial and bronchiolar walls become thickened for the inflammation process and lymphocytes interstitial infiltrates.Chest radiography represents an important initial examination in all patients suspected of having pulmonary infection and for monitoring response to therapy.Its role is to identify the pulmonary opacities, their internal characteristics and distribution, pleural effusion and presence of other complications as abscesses and pneumothorax.High spatial CT resolution allows accurate assessment of air space inflammation.The CT findings include nodules, interlobular septal thickening, intralobular reticular opacities, ground-glass opacities, tree-in-bud pattern, lobar-segmental consolidation, lobular consolidation, abscesses, pneumatocele, pleural effusion, pericardial effusion, mediastinal and hilar lymphoadenopaties, airway dilatation and emphysema.

negative: Efficacy and Safety of Antibiotic Agents in Children with COVID-19: A Rapid Review Background: The aim of this review was to evaluate the efficacy and safety of antibiotic agents in children with COVID-19, as well as to introduce the present situation of antibiotics use and bacterial coinfections in COVID-19 patients. Methods: We searched Cochrane library, Medline, Embase, Web of Science, CBM, Wanfang Data and CNKI from their inception to March 31, 2020. In addition, we searched related studies on COVID-19 published before March 31, 2020 through Google Scholar. We evaluated the risk of bias of included studies, and synthesized the results using a qualitative synthesis. Results: Six studies met our inclusion criteria. Five studies on SARS showed an overall risk of death of 7.2% to 20.0%. One study of SARS patients who used macrolides, quinolones or beta lactamases showed that the mean duration of hospital stay was 14.2, 13.8 and 16.2 days, respectively, and their average duration of fever was 14.3, 14.0 and 16.2 days, respectively. One cohort study on MERS indicated that macrolide therapy was not associated with a significant reduction in 90-day mortality (adjusted odds ratio [OR] 0.84, 95% confidence interval [CI] 0.47-1.51, P = 0.56) and improvement in MERS-CoV RNA clearance (adjusted hazard ratio [HR] 0.88, 95% CI 0.47, -1.64], P = 0.68). According to the findings of 33 studies, the proportion of antibiotics use ranged from 19.4% to 100.0% in children and 13.2% to 100.0% in adults, despite the lack of etiological evidence. The most commonly used antibiotics in adults were quinolones, cephalosporins and macrolides and in children meropenem and linezolid. Conclusions: The benefits of antibiotic agents for adults with SARS or MERS were questionable in the absence of bacterial coinfections. There is no evidence to support the use of antibiotic agents for children with COVID-19 in the absence of bacterial coinfection.

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: Loss and Grief amidst COVID-19: A Path to Adaptation and Resilience Abstract The COVID-19 pandemic has posed an extreme threat to global health and become a leading cause of death worldwide. Loss, as a more encompassing theme, interweaves many aspects of people’s life in this challenging time. Failure to address the pressing needs of those experiencing loss and grief may result in poor mental and physical health. Recognizing the uniqueness of each individual and their loss and grief will provide opportunities to develop tailored strategies that facilitate functional adaptation to loss and promote mental health and wellbeing in this crisis.

negative: Characteristics of registered clinical trials assessing treatments for COVID-19: a cross-sectional analysis OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has prompted many initiatives to identify safe and efficacious treatments, yet little is known regarding where early efforts have focused. We aimed to characterise registered clinical trials assessing drugs or plasma treatments for COVID-19. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional analysis of clinical trials for the treatment of COVID-19 that were registered in the USA or in countries contributing to the WHO's International Clinical Trials Registry Platform. Relevant trial entries of drugs or plasma were downloaded on 26 March 2020, deduplicated, verified with reviews of major medical journals and WHO websites and independently analysed by two reviewers. MAIN OUTCOMES: Trial intervention, sponsorship, critical design elements and specified outcomes RESULTS: Overall, 201 clinical trials were registered for testing the therapeutic benefits of 92 drugs or plasma, including 64 in monotherapy and 28 different combinations. Only eight (8.7%) products or combinations involved new molecular entities. The other test therapies had a wide range of prior medical uses, including as antivirals, antimalarials, immunosuppressants and oncology treatments. In 152 trials (75.7%), patients were randomised to treatment or comparator, including 55 trials with some form of blinding and 97 open-label studies. The 49 (24.4%) of trials without a randomised design included 29 single armed studies and 20 trials with some comparison group. Most trial designs featured multiple endpoints. Clinical endpoints were identified in 134 (66.7%) of trials and included COVID-19 symptoms, death, recovery, required intensive care and hospital discharge. Clinical scales were being used in 33 (16.4%) trials, most often measures of oxygenation and critical illness. Surrogate endpoints or biomarkers were studied in 88 (42.3%) of trials, primarily assays of viral load. Although the trials were initiated in more than 17 countries or regions, 100 (49.8%) were registered in China and 78 (37.8%) in the USA. Registered trials increased rapidly, with the number of registered trials doubling from 1 March to 26 March 2020. CONCLUSIONS: While accelerating morbidity and mortality from the COVID-19 pandemic has been paralleled by early and rapid clinical investigation, many trials lack features to optimise their scientific value. Global coordination and increased funding of high-quality research may help to maximise scientific progress in rapidly discovering safe and effective treatments.

negative: Implications of COVID-19 for the management of patients with inflammatory rheumatic diseases

negative: Knowledge and practice of preventive measures against COVID-19 infection among pregnant women in a low-resource African setting Background: Coronavirus disease pandemic has resulted in death of thousands of people across several countries. Several preventive measures have been recommended to halt the spread of the disease and its associated mortality. However, the level knowledge and practice of these preventive measures against COVID-19 infection among pregnant women, which constitute vulnerable groups, are yet to be evaluated. Aim: To determine the knowledge and practice of preventive measures against COVID-19 infection among pregnant women in Abakaliki. Materials and Methods: This was a self-administered questionnaire-based cross-sectional study conducted from February 1, 2020 to March 31, 2020 among 284 antenatal clinic attendees at Alex Ekwueme Federal University Teaching Hospital, Abakaliki, Ebonyi State. A pretested and validated questionnaire was used to collect the data. Data analysis was done using SPSS version 22. Results: Of 284 participants, 60.9% (n=173) had adequate knowledge of the preventive measures against COVID-19 infection. However, the overall practice of these preventive measures among the participants were poor as 69.7% of the participants were not practicing the preventive measures against the coronavirus. The determinants of poor practice of the preventive measures among the participants were being in age group 31-40 years (AOR=2.04, 95%CI: 1.26 - 5.37, p=0.022), married (AOR=2.99, 95%CI: 1.40 - 6.33, p=0.035) grandmultiparous (AOR=3.11, 95%CI: 1.32 - 6.56, p=0.021), residing in rural area (AOR=2.08, 95%CI: 1.32 - 4.05, p=0.031), and having no formal education (AOR=6.73, 95%CI: 2.66 - 18.34, p=0.002). Conclusion: The study showed that most of the participants had adequate knowledge of preventive measures against COVID-19 infection but the practice of these preventive measures were poor among the participants.

negative: Avian Influenza: a global threat needing a global solution There have been three influenza pandemics since the 1900s, of which the 1919–1919 flu pandemic had the highest mortality rates. The influenza virus infects both humans and birds, and mutates using two mechanisms: antigenic drift and antigenic shift. Currently, the H5N1 avian flu virus is limited to outbreaks among poultry and persons in direct contact to infected poultry, but the mortality rate among infected humans is high. Avian influenza (AI) is endemic in Asia as a result of unregulated poultry rearing in rural areas. Such birds often live in close proximity to humans and this increases the chance of genetic re-assortment between avian and human influenza viruses which may produce a mutant strain that is easily transmitted between humans. Once this happens, a global pandemic is likely. Unlike SARS, a person with influenza infection is contagious before the onset of case-defining symptoms which limits the effectiveness of case isolation as a control strategy. Researchers have shown that carefully orchestrated of public health measures could potentially limit the spread of an AI pandemic if implemented soon after the first cases appear. To successfully contain and control an AI pandemic, both national and global strategies are needed. National strategies include source surveillance and control, adequate stockpiles of anti-viral agents, timely production of flu vaccines and healthcare system readiness. Global strategies such as early integrated response, curbing the disease outbreak at source, utilization of global resources, continuing research and open communication are also critical.

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: Compassionate use of hydroxychloroquine in clinical practice for patients with mild to severe Covid-19 in a French university hospital BACKGROUND: Data from non-randomized studies have suggested that hydroxychloroquine could be an effective therapeutic agent against Covid-19. METHODS: We conducted an observational, retrospective cohort study involving hospitalized adult patients with confirmed, mild to severe Covid-19 in a French university hospital. Patients who received hydroxychloroquine (200mg tid dosage for 10 days) on a compassionate basis in addition to SOCwere compared to patients without contraindications to hydroxychloroquine who received SOCalone. A propensity score-weighted analysis was performed to control for confounders: age, sex, time between symptom onset and admission ≤ 7 days, Charlson comorbidity index, medical history of arterial hypertension, and obesity, NEWS2 score at admission, and pneumonia severity. The primary endpoint was time to unfavorable outcome, defined as: death, admission to an intensive care unit, or decision to withdraw or withhold life-sustaining treatments, whichever came first. RESULTS: Data from 89 patients with laboratory-confirmed Covid-19 were analyzed, 84 of whom were considered in the primary analysis; 38 patients treated with hydroxychloroquine and 46 patients treated with SOCalone. At admission, the mean age of patients was 66 years, the median Charlson comorbidity index was 3, and the median NEWS2 severity score was 3. After propensity score weighting, treatment with hydroxycholoroquine was not associated with a significantly reduced risk of unfavorable outcome (HR 0.90 [0.38; 2.1], p = 0.81). Overall survival was not significantly different between the two groups (HR 0.89 [0.23; 3.47], p = 1) CONCLUSION: In hospitalized adults with Covid-19, no significant reduction of the risk of unfavorable outcomes was observed with hydroxychloroquine in comparison to standard of care. Unmeasured confounders may however have persisted despite careful propensity-weighted analysis and the study might be underpowered. Ongoing controlled trials in patients with varying degrees of initial severity on a larger scale will help determine whether there is a place for hydroxychloroquine in the treatment of Covid-19.

negative: Extracting Possibly Representative COVID-19 Biomarkers from X-ray Images with Deep Learning Approach and Image Data Related to Pulmonary Diseases PURPOSE: While the spread of COVID-19 is increased, new, automatic, and reliable methods for accurate detection are essential to reduce the exposure of the medical experts to the outbreak. X-ray imaging, although limited to specific visualizations, may be helpful for the diagnosis. In this study, the problem of automatic classification of pulmonary diseases, including the recently emerged COVID-19, from X-ray images, is considered. METHODS: Deep Learning has proven to be a remarkable method to extract massive high-dimensional features from medical images. Specifically, in this paper, the state-of-the-art Convolutional Neural Network called Mobile Net is employed and trained from scratch to investigate the importance of the extracted features for the classification task. A large-scale dataset of 3905 X-ray images, corresponding to 6 diseases, is utilized for training MobileNet v2, which has been proven to achieve excellent results in related tasks. RESULTS: Training the CNNs from scratch outperforms the other transfer learning techniques, both in distinguishing the X-rays between the seven classes and between Covid-19 and non-Covid-19. A classification accuracy between the seven classes of 87.66% is achieved. Besides, this method achieves 99.18% accuracy, 97.36% Sensitivity, and 99.42% Specificity in the detection of COVID-19. CONCLUSION: The results suggest that training CNNs from scratch may reveal vital biomarkers related but not limited to the COVID-19 disease, while the top classification accuracy suggests further examination of the X-ray imaging potential.

negative: The Clinical Presentation and Immunology of Viral Pneumonia and Implications for Management of Coronavirus Disease 2019 This review will briefly examine the clinical presentation and important immunology of viral pneumonia with a focus on severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019). DATA SOURCES, STUDY SELECTION, DATA EXTRACTION, AND DATA SYNTHESIS: The most relevant, original and review literature were assessed for inclusion in this review. Sources included the Centers for Disease Control and Prevention, World Health Organization, and PubMed. CONCLUSIONS: Pneumonia is a leading cause of hospitalization and death worldwide, with viral etiologies being very common. Given the rapidly emerging pandemic associated with the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019, it is important to review the clinical presentation and immunologic changes associated with viral pneumonia. Symptoms of viral pneumonia include common respiratory tract infection symptoms of cough, fever, and shortness of breath. Immunologic changes include up-regulation of airway pro-inflammatory cytokines and pathogen- and damage-associated molecular patterns contributing to cytokine and genomic changes. Coronavirus disease 2019 clinical presentation is typical of viral pneumonia with an increased prevalence of early pulmonary infiltrates and lymphopenia. Principles of early coronavirus disease 2019 management and isolation as well as potential therapeutic approaches to the emerging pandemic are discussed.

negative: Recognition of potential Covid-19 drug treatments through the study of existing protein-drug and protein-protein structures: an analysis of kinetically active residues We report results of our study of approved drugs as potential treatments for COVID 19, based on the application of various bioinformatics predictive methods. The drugs studied include Chloroquine, Ivermectin, Remdesivir and alpha-difluoromethylornithine (DMFO). Our results indicate that these small drug molecules selectively bind to stable, kinetically active residues and residues adjoining them on the surface of proteins and inside protein pockets, and that some prefer hydrophobic over other active sites. Our approach is not restricted to viruses and can facilitate rational drug design, as well as improve our understanding of molecular interactions, in general.

negative: The response of Milan's Emergency Medical System to the COVID-19 outbreak in Italy

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: Computed tomography manifestations in super early stage 2019 novel coronavirus pneumonia BACKGROUND: The recent outbreak of pneumonia cases in Wuhan, PR China, was caused by a novel beta coronavirus, the 2019 novel coronavirus (COVID-19). PURPOSE: To summarize chest computed tomography (CT) manifestations of the early stage of COVID-19 infection and provide a piece of reliable imaging evidence for initial screening and diagnosis. MATERIAL AND METHODS: From 10 January 2020 to 10 February 2020, we continuously observed chest CT imaging of 14 patients with clinically suspected new coronavirus infection in the two weeks after onset of symptoms. Ground-glass opacity (GGO), consolidation, reticular pattern, and ground-glass mimic nodules in each patient's chest CT image were recorded. RESULTS: We enrolled 14 patients, of which nine patients had the infection confirmed by reverse transcription polymerase chain reaction (RT-PCR). Five patients were highly suspected of infection. All cases had epidemiological evidence. GGO was a dominant imaging manifestation in the initial days of infection. GGO performance accounts for 40% in 1- 2 days, 90% in 3- 6 days, and 85% in 7- 10 days. With disease progression, consolidation appeared on follow-up CT. Consolidation performance accounts for 0% in 1- 2 days, 40% in 3- 6 days, and 71% in 7- 10 days. The lesions are mostly near the pleura. The number of lesions and the extent of the lesions increased as the disease progressed. CONCLUSION: Patients with novel coronavirus pneumonia have characteristic CT features in the initial stage of infection, which can be used as an essential supplement for nucleic acid examination.

negative: Modelling the Epidemiology of Infectious Diseases for Decision Analysis: A Primer The number of economic evaluations related to infectious disease topics has increased over the last 2 decades. However, many such evaluations rely on models that do not take into account unique features of infectious diseases that can affect the estimated value of interventions against them. These include their transmissibility from infected to susceptible individuals, the possibility of acquiring natural immunity following recovery from infection and the uncertainties that arise as a result of their complex natural history and epidemiology. Modellers conducting economic evaluations of infectious disease interventions need to know the main features of different types of infectious disease models, the situations in which they should be applied and the effects of model choices on the cost effectiveness of interventions.

negative: Evaluation of a COVID-19 IgM and IgG rapid test; an efficient tool for assessment of past exposure to SARS-CoV-2 COVID-19 is the most rapidly growing pandemic in modern time, and the need for serological testing is most urgent. Although the diagnostics of acute patients by RT-PCR is both efficient and specific, we are also crucially in need of serological tools for investigating antibody responses and assessing individual and potential herd immunity. We evaluated a commercially available test developed for rapid (within 15 minutes) detection of SARS-CoV-2-specific IgM and IgG by 29 PCR-confirmed COVID-19 cases and 124 negative controls. The results revealed a sensitivity of 69% and 93.1% for IgM and IgG, respectively, based solely on PCR-positivity due to the absence of a serological gold standard. The assay specificities were shown to be 100% for IgM and 99.2% for IgG. This indicates that the test is suitable for assessing previous virus exposure, although negative results may be unreliable during the first weeks after infection. More detailed studies on antibody responses during and post infection are urgently needed.

negative: Viral Pneumonia in Older Adults Viruses account for a substantial portion of respiratory illnesses, including pneumonia, in the elderly population. Presently, influenza virus A H3N2 and respiratory syncytial virus are the most commonly identified viral pathogens in older adults with viral pneumonia. As diagnostic tests such as reverse-transcription polymerase chain reaction become more widely used, the relative importance of additional viruses (such as parainfluenza, rhinoviruses, coronaviruses, and human metapneumovirus) will likely increase. Influenza virus should be considered as a cause of pneumonia during the winter months, especially during periods of peak activity. Patients with high-grade fever, myalgias, and cough should arouse the highest suspicion. Respiratory syncytial virus pneumonia should also be suspected during the winter in patients with coryza, wheezing, low-grade fever, and patchy infiltrates, especially if negative for influenza on rapid testing. Because clinical features and periods of activity for many viruses overlap, laboratory confirmation of influenza is recommended for cases involving seriously ill or institutionalized patients.

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: Animal viruses of economic importance: Genetic variation, persistence, and prospects for their control

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: Crisis Symptom Management and Patient Communication Protocols Are Important Tools for All Clinicians Responding to COVID-19 Symptom management and skilled communication with patients and families are essential clinical services in the midst of the coronavirus disease 2019 pandemic. Although palliative care specialists have training in these skills, many frontline clinicians from other specialties do not. It is imperative that all clinicians responding to the coronavirus disease 2019 crisis have access to clinical tools to support symptom management and difficult patient and family communication.

negative: Effect of oral care gel on the quality of life for oral lichen planus in patients with chronic HCV infection BACKGROUND: Oral lichen planus (OLP) decreases the quality of life because it can cause spontaneous pain during eating and tooth-brushing and an uncomfortable feeling in the mouth. In addition, OLP may be associated with HCV-related liver disease. We investigated the visual analogue scale (VAS) and effects of oral care gel, REFRECARE-H(®), on patients with OLP associated with HCV infection. RESULTS: Nine OLP patients (mean age 67.9 ± 7.6 years) with HCV-related liver diseases were recruited and their VAS score determined along with a biochemical examination of the blood. Types of OLP included erosive (6 patients) and reticular (3). REFRECARE-H(®), an oral care gel (therapeutic dentifrice) containing hinokitiol, was applied by each patient as a thin layer on the oral membrane, after each meal and at bedtime for 30 days. Application of REFRECARE-H(® )improved the quality of life in all terms of dry mouth, breath odor, oral freshness, oral pain during rest, oral pain at a mealtimes, taste disorder, loss of appetite, sleep disorder, depressive mood and jitteriness. VAS scores of dry mouth, breath odor, oral freshness, and sleep disorder were significantly increased 30 days after application of REFRECARE-H(® )(P = 0.01, P = 0.05, P = 0.03, P = 0.04). VAS scores of oral pain at a mealtimes and taste disorder were increased 30 days after application of REFRECARE-H(® )(P = 0.06). There was an absence of side effects. CONCLUSIONS: REFRECARE-H(® )improved the quality of life for OLP. It is necessary for the hepatologist to educate patients regarding oral hygiene, as well as provide treatment of liver disease.

negative: Decoding the enigma of antiviral crisis: Does one target molecule regulate all? Abstract Disease fatality associated with Ebola, SARS-CoV and dengue infections in humans is attributed to a cytokine storm that is triggered by excessive pro-inflammatory responses. Interleukin (IL)-6 acts as a mediator between pro- and anti-inflammatory reactivity by initiating trans- and classical-signaling, respectively. Hence, IL-6 is assumed to provide a target for a broad range of antiviral agents. Available immunosuppressive antivirals are directed to control an often exaggerated pro-inflammatory response that gives rise to complex clinical conditions such as lymphocytopenia. It is known that IL-6, via its soluble receptor (sIL-6R), initiates a pro-inflammatory response while an anti-inflammatory response is triggered by the membrane-bound IL-6 receptor (IL-6R). Future antivirals should thus aim to target the mechanism that regulates switching between IL-6 trans- and classical-signaling. In this review, we propose that the tumour necrosis factor-α converting enzyme ADAM-17 could be the master molecule involved in regulating IL-6 class switching and through this in controlling pro- and anti-inflammatory responses to viral antigenic stimuli. Therefore, ADAM-17 should be considered as a potential target molecule for novel antiviral drug discovery that would regulate host reactivity to infection and thereby limit or prevent fatal outcomes.

negative: COVID-19 pneumonia manifestations at the admission on chest ultrasound, radiographs, and CT: single-center study and comprehensive radiologic literature review PURPOSE: To investigate the imaging features of emerging COVID-19 pneumonia on chest ultrasound (US), radiographs (CXR) and computed tomography (CT) examinations performed at admission and to provide a comprehensive radiological literature review on ongoing radiological data from recent publications. MATERIALS AND METHODS: In this retrospective single-center study, we enrolled consecutive patients from February 15, 2020, to March 15, 2020, with laboratory-confirmed SARS-CoV-2 hospitalized in Valduce Hospital (Como, Italy). Multi-modality imaging findings were evaluated and compared. Literature research was conducted through a methodical search on Pubmed and Embase databases. RESULTS: Fifty-eight patients (36 men, 22 women; age range, 18–98 years) were included in the study. Among these, chest US, CXR, and CT were performed respectively in twenty-two, thirty-two and forty-two patients. Lung US findings were consistent with diffuse B lines (100%) and subpleural consolidations (27.3%). CXR showed prevalent manifestations of consolidations (46.9%) and hazy increased opacities (37.5%). Typical CT features included bilateral and multilobar ground-glass opacities (GGO) with (59.5%) and without (35.7%) consolidations having a predominantly peripheral distribution (64.3%). Other imaging features included crazy paving pattern (57.1%), fibrous stripes (50%), subpleural lines (35.7%), architectural distortion (28.6%), air bronchogram sign (26.2%), vascular thickening (23.8%) and nodules (2.4%). Also, enlarged lymph nodes (14.3 %) and pleural effusion (7.1%) were observed. The literature review identified twenty-six original studies supporting our imaging chest findings. CONCLUSION: The spectrum of chest imaging manifestations of COVID-19 pneumonia upon admission includes B-lines and consolidations on US, consolidations and hazy increased opacities on CXR, and multifocal GGO with consolidations on CT.

negative: Guidelines for preventing respiratory illness in older adults aged 60 years and above living in long-term care: A rapid review of clinical practice guidelines Background: The overall objective of this rapid review was to identify infection protection and control recommendations from published clinical practice guidelines (CPGs) for adults aged 60 years and older in long-term care settings Methods: Comprehensive searches in MEDLINE, EMBASE, the Cochrane Library, and relevant CPG publishers/repositories were carried out in early March 2020. Title/abstract and full-text screening, data abstraction, and quality appraisal (AGREE-II) were carried out by single reviewers. Results: A total of 17 relevant CPGs were identified, published in the USA (n=8), Canada (n=6), Australia (n=2), and the United Kingdom (n=1). All of the CPGs dealt with infection control in long-term care facilities (LTCF) and addressed various types of viral respiratory infections (e.g., influenza, COVID-19, severe acute respiratory syndrome). Ten or more CPGs recommended the following infection control measures in LTCF: hand hygiene (n=13), wearing personal protective equipment (n=13), social distancing or isolation (n=13), disinfecting surfaces (n=12), droplet precautions (n=12), surveillance and evaluation (n=11), and using diagnostic testing to confirm illness (n=10). While only two or more CPGs recommended these infection control measures: policies and procedures for visitors, staff and/or residents (n=9), respiratory hygiene/cough etiquette (n=9), providing supplies (n=9), staff and/or residents education (n=8), increasing communication (n=6), consulting or notifying health professionals (n=6), appropriate ventilation practices (n=2), and cohorting equipment (n=2). Ten CPGs also addressed management of viral respiratory infections in LTCF and recommended antiviral chemoprophylaxis (n=10) and one CPG recommended early mobilization of residents. Conclusion: The recommendations from current guidelines overall seem to support environmental measures for infection prevention and antiviral chemoprophylaxis for infection management as the most appropriate first-line response to viral respiratory illness in long-term care.

negative: Sleep quality and mood symptoms in conscripted frontline nurse in Wuhan, China during COVID-19 outbreak: A cross-sectional study The aim of this study was to investigate the prevalence of sleep problems, depression and anxiety symptoms among conscripted frontline nurses fighting coronavirus disease 2019 (COVID-19) in Wuhan. This study was a cross-sectional study conducted with 100 frontline nurses. Sleep quality, depression, and anxiety symptoms were measured using the Pittsburgh sleep quality index (PSQI), the Generalized Anxiety Disorder 7-Item Scale (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9), respectively. Mean sleep duration was 5.71 hours (SD = 1.09) and mean sleep latency was 33.49 minutes (SD = 28.87). A total of 76%, 81%, 45%, and 19% reported difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS) or early morning awakening (EMA), nightmares and using hypnotics respectively. Among 100 participants in this study, 60 (60%) had poor sleep quality, 46 (46%) suffered depression symptoms and 40 (40%) reported anxiety symptoms. Sleep quality (OR = 3.16, 95% CI: 1.17–8.52) and anxiety symptoms (OR = 8.07, 95% CI: 2.92–22.33) were significantly associated with depression symptoms. Depression symptoms (OR = 7.92, 95% CI: 2.89–21.73) were related to anxiety symptoms. Similarly, depression symptoms (OR = 3.24, 95% CI: 1.19–8.79) were associated with poor sleep quality. Sleep disturbance, depression, and anxiety symptoms are very common among frontline nurses who treating patients with COVID-19 in Wuhan, China. Comprehensive measures that involve psychosocial and personal behaviors should be implemented to improve sleep quality and prevent depression and anxiety symptoms.

negative: SARS-CoV-2 causing pneumonia-associated respiratory disorder (COVID-19): diagnostic and proposed therapeutic options. SARS-CoV-2 is responsible for the outbreak of severe respiratory illness (COVID-19) in Wuhan City, China and is now spreading rapidly throughout the world. The prompt outbreak of COVID-19 and its quick spread without any controllable measure defines the severity of the situation. In this crisis, a collective pool of knowledge about the advancement of clinical diagnostic and management for COVID-19 is a prerequisite. Here, we summarize all the available updates on the multidisciplinary approaches for the advancement of diagnosis and proposed therapeutic strategies for COVID-19. Moreover, the review discusses different aspects of the COVID-19, including its epidemiology; incubation period; the general clinical features of patients; the clinical features of intensive care unit (ICU) patients; SARS-CoV-2 infection in the presence of co-morbid diseases and the clinical features of pediatric patients infected with the SARS-CoV-2. Advances in various diagnostic approaches, such as the use of real-time polymerase chain reaction (RT-PCR), chest radiography, and computed tomography (CT) imaging; and other modern diagnostic methods, for this infection have been highlighted. However, due to the unavailability of adequate evidence, presently there are no officially approved drugs or vaccines available against SARS-CoV-2. Additionally, we have discussed various therapeutic strategies for COVID-19 under different categories, like the possible treatment plans with drug (antiviral drugs and anti-cytokines) therapy for disease prevention. Lastly, potentials candidates for the vaccines against SARS-CoV-2 infection have been described. Collectively, the review provides an overview of the SARS-CoV-2 infection outbreak along with the recent advancements and strategies for diagnosis and therapy of COVID-19.

negative: Should we mind for late neurologic manifestations from novel coronavirus?

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: 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.

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: Abstracts from the 36th Annual Meeting of the Society of General Internal Medicine

negative: A Nanoparticle Pseudo Pathogen for Rapid Detection and Diagnosis of Virus Infection Abstract We herein report a new rapid blood test for virus infection detection and diagnosis. A citrate gold nanoparticle is first coated with a virus lysate to form a gold nanoparticle pseudo pathogen. The gold nanoparticle pseudo virus is then mixed with a blood plasma or serum samples. If the blood sample is from a positive patient, the activated immune molecules in the blood such as antibodies, complement proteins and others will react with the nanoparticle pseudo virus, leading to nanoparticle aggregate formation. The nanoparticle aggregate formation is detected and measured using a particle sizing technique called dynamic light scattering. In this study, we applied this test for Zika virus infection detection. We tested blood plasma samples from 85 Zika positive patients, 40 Dengue positive patients, 10 Chikungunya positive patients, and 78 non-patient control samples collected from both endemic and non-endemic locations. The study shows that the new test has a higher sensitivity compared to some existing commercial tests in the market, while maintaining a similar specificity. Within 7 days from the symptom onset, the new test can detect 43% of the infected patients while a commercial anti-Zika IgM test detects only 26% of the infected patients. Within 14 days from the symptom onset, our new test detects 73% of the infected patients while the same commercial anti-Zika IgM test detects 53% of the infected patients. The test is extremely simple, easy to develop, with test results obtained within minutes. This new test platform may be potentially adapted for the detection and diagnosis of a wide range of viral infectious diseases, for example, the currently ongoing COVID-19.

negative: How will country-based mitigation measures influence the course of the COVID-19 epidemic?

negative: Covid-19 and Children with Immune Thrombocytopenia: Emerging Issues

negative: Emerging infectious diseases: Focus on infection control issues for novel coronaviruses (Severe Acute Respiratory Syndrome-CoV and Middle East Respiratory Syndrome-CoV), hemorrhagic fever viruses (Lassa and Ebola), and highly pathogenic avian influenza viruses, A(H5N1) and A(H7N9) Over the past several decades, we have witnessed the emergence of many new infectious agents, some of which are major public threats. New and emerging infectious diseases which are both transmissible from patient-to-patient and virulent with a high mortality include novel coronaviruses (SARS-CoV, MERS-CV), hemorrhagic fever viruses (Lassa, Ebola), and highly pathogenic avian influenza A viruses, A(H5N1) and A(H7N9). All healthcare facilities need to have policies and plans in place for early identification of patients with a highly communicable diseases which are highly virulent, ability to immediately isolate such patients, and provide proper management (e.g., training and availability of personal protective equipment) to prevent transmission to healthcare personnel, other patients and visitors to the healthcare facility.

negative: Analysis of factors associated early diagnosis in coronavirus disease 2019 (COVID-19) Background The pandemic of coronavirus disease 2019 (COVID-19) has become the first concern in international affairs as the novel coronavirus (SARS-CoV-2) is spreading all over the world at a terrific speed. The accuracy of early diagnosis is critical in the control of the spread of the virus. Although the real-time RT-PCR detection of the virus nucleic acid is the current golden diagnostic standard, it has high false negative rate when only apply single test. Objective Summarize the baseline characteristics and laboratory examination results of hospitalized COVID-19 patients. Analyze the factors that could interfere with the early diagnosis quantitatively to support the timely confirmation of the disease. Methods All suspected patients with COVID-19 were included in our study until Feb 9th, 2020. The last day of follow-up was Mar 20th, 2020. Throat swab real-time RT-PCR test was used to confirm SARS-CoV-2 infection. The difference between the epidemiological profile and first laboratory examination results of COVID-19 patients and non-COVID-19 patients were compared and analyzed by multiple logistic regression. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to assess the potential diagnostic value in factors, which had statistical differences in regression analysis. Results In total, 315 hospitalized patients were included. Among them, 108 were confirmed as COVID-19 patients and 207 were non-COVID-19 patients. Two groups of patients have significance in comparing age, contact history, leukocyte count, lymphocyte count, C-reactive protein, erythrocyte sedimentation rate (p<0.10). Multiple logistic regression analysis showed age, contact history and decreasing lymphocyte count could be used as individual factor that has diagnostic value (p<0.05). The AUC of first RT-PCR test was 0.84 (95% CI 0.73-0.89), AUC of cumulative two times of RT-PCR tests was 0.92 (95% CI 0.88-0.96) and 0.96 (95% CI 0.93-0.99) for cumulative three times of RT-PCR tests. Ninety-six patients showed typical pneumonia radiological features in first CT scan, AUC was 0.74 (95% CI 0.60-0.73). The AUC of patients age, contact history with confirmed people and the decreased lymphocytes were 0.66 (95% CI 0.60-0.73), 0.67 (95% CI 0.61-0.73), 0.62 (95% CI 0.56-0.69), respectively. Taking chest CT scan diagnosis together with patients age and decreasing lymphocytes, AUC would be 0.86 (95% CI 0.82-0.90). The age threshold to predict COVID-19 was 41.5 years, with a diagnostic sensitivity of 0.70 (95% CI 0.61-0.79) and a specificity of 0.59 (95% CI 0.52-0.66). Positive and negative likelihood ratios were 1.71 and 0.50, respectively. Threshold of lymphocyte count to diagnose COVID-19 was 1.53x109/L, with a diagnostic sensitivity of 0.82 (95% CI 0.73-0.88) and a specificity of 0.50 (95% CI 0.43-0.57). Positive and negative likelihood ratios were 1.64 and 0.37, respectively. Conclusion Single RT-PCR test has relatively high false negative rate. When first RT-PCR test show negative result in suspected patients, the chest CT scan, contact history, age and lymphocyte count should be used combinedly to assess the possibility of SARS-CoV-2 infection.

negative: A model of bi-mode transmission dynamics of hepatitis C with optimal control In this paper, we present a rigorous mathematical analysis of a deterministic model for the transmission dynamics of hepatitis C. The model is suitable for populations where two frequent modes of transmission of hepatitis C virus, namely unsafe blood transfusions and intravenous drug use, are dominant. The susceptible population is divided into two distinct compartments, the intravenous drug users and individuals undergoing unsafe blood transfusions. Individuals belonging to each compartment may develop acute and then possibly chronic infections. Chronically infected individuals may be quarantined. The analysis indicates that the eradication and persistence of the disease is completely determined by the magnitude of basic reproduction number R (c). It is shown that for the basic reproduction number R (c) < 1, the disease-free equilibrium is locally and globally asymptotically stable. For R (c) > 1, an endemic equilibrium exists and the disease is uniformly persistent. In addition, we present the uncertainty and sensitivity analyses to investigate the influence of different important model parameters on the disease prevalence. When the infected population persists, we have designed a time-dependent optimal quarantine strategy to minimize it. The Pontryagin’s Maximum Principle is used to characterize the optimal control in terms of an optimality system which is solved numerically. Numerical results for the optimal control are compared against the constant controls and their efficiency is discussed.

negative: Adult-Onset Still’s Disease Adult-onset Still’s disease (AOSD) is a rare systemic, autoinflammatory disorder that often presents in adolescence and early adulthood with fever, rash, and polyarthritis. There are significant genetic and clinical similarities with systemic juvenile idiopathic arthritis (sJIA) with a different chronological disease onset. The disease can have many protean characteristics leading to delays in diagnosis. Treatment includes corticosteroids; traditional immunomodulators, such as methotrexate; and targeted biologic treatments that include IL-1 and IL-6 inhibitors.

negative: Virological assessment of hospitalized patients with COVID-2019 Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 20191,2. Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses3. This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung2,4; the same receptor tropism is thought to have determined the pathogenicity-but also aided in the control-of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission6-8. There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 108 RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples-in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19.

negative: First documentation of persistent SARS-CoV-2 infection presenting with late acute severe myocarditis A 64 year-old man presented with severe myocarditis 6 weeks after an initial almost asymptomatic SARS-CoV2 infection. He was found to have a persistent positive swab. Mechanisms explaining myocardial injury in patients with COVID-19 remains unclear, but this case suggests that severe acute myocarditis can develop in the late phase of COVID-19 infection, even after a symptom-free interval.

negative: Emergency Responses to Covid-19 Outbreak: Experiences and Lessons from a General Hospital in Nanjing, China BACKGROUND: The novel coronavirus 2019 (SARS-CoV-2) has caused wide dissemination across the world. Global health systems are facing the unprecedented challenges. Here we shared the experiences and lessons in emergency responses and management from our hospital, a government-assigned regional anti-Covid-19 general hospital in Nanjing, Jiangsu Province, China. METHODS: Our periodic strategies in dealing with Covid-19 were described in detail. An administrative response including the establishment of Emergency Leadership Committee that was in full charge of management was established. Modifications of infrastructure including the Fever Clinic, inpatient ward, outpatient clinic and operation room were carried out. Special arrangements for outpatient services, hospitalization and surgeries were introduced. Medical personnel training and patient educations were performed. Initiations of Covid-19 researches and application of information technology were introduced. FINDINGS: Since January 16, three cases have been confirmed in our hospital and no healthcare-associated infection was found. During the epidemics, 6.46% staffs suffered depression, 9.87% had anxiety, and 98% were satisfied with the infection control policy. Shortages in staffs and medical consumables, and limitation in space were the obstacles we encountered. INTERPRETATION: As the cost of in-hospital transmission is unbearable, our experiences and lessons suggested that prompt actions should be taken immediately to decrease or eliminate potential in-hospital transmission. Experience shared herein may be useful for those facilities that are and may encounter Covid-19.

negative: Understanding the symptoms of the common cold and influenza Summary The common cold and influenza (flu) are the most common syndromes of infection in human beings. These diseases are diagnosed on symptomatology, and treatments are mainly symptomatic, yet our understanding of the mechanisms that generate the familiar symptoms is poor compared with the amount of knowledge available on the molecular biology of the viruses involved. New knowledge of the effects of cytokines in human beings now helps to explain some of the symptoms of colds and flu that were previously in the realm of folklore rather than medicine—eg, fever, anorexia, malaise, chilliness, headache, and muscle aches and pains. The mechanisms of symptoms of sore throat, rhinorrhoea, sneezing, nasal congestion, cough, watery eyes, and sinus pain are discussed, since these mechanisms are not dealt with in any detail in standard medical textbooks.

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: Repurposing Therapeutics for COVID-19: Rapid Prediction of Commercially available drugs through Machine Learning and Docking Background The outbreak of the novel coronavirus disease COVID 19, caused by the SARS-CoV-2 virus has spread rapidly around the globe during the past 3 months. As the virus infected cases and mortality rate of this disease is increasing exponentially, scientists and researchers all over the world are relentlessly working to understand this new virus along with possible treatment regimens by discovering active therapeutic agents and vaccines. So, there is an urgent requirement of new and effective medications that can treat the disease caused by SARS CoV 2. Methods and findings We perform the study of drugs that are already available in the market and being used for other diseases to accelerate clinical recovery, in other words repurposing of existing drugs. The vast complexity in drug design and protocols regarding clinical trials often prohibit developing various new drug combinations for this epidemic disease in a limited time. Recently, remarkable improvements in computational power coupled with advancements in Machine Learning (ML) technology have been utilized to revolutionize the drug development process. Consequently, a detailed study using ML for the repurposing of therapeutic agents is urgently required. Here, we report the ML model based on the Naive Bayes algorithm, which has an accuracy of around 73% to predict the drugs that could be used for the treatment of COVID-19. Our study predicts around ten FDA approved commercial drugs that can be used for repurposing. Among all, we suggest that the antiretroviral drug Atazanavir (DrugBank ID DB01072) would probably be one of the most effective drugs based on the selected criterions. Conclusions Our study can help clinical scientists in being more selective in identifying and testing the therapeutic agents for COVID 19 treatment. The ML based approach for drug discovery as reported here can be a futuristic smart drug designing strategy for community applications.

negative: COVID-19: lessons from the Italian reproductive medical experience

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: Environmental and non-infectious factors in the aetiology of pharyngitis (sore throat) OBJECTIVES: The aim of this review is to examine the causes, pathophysiology and experimental models of non-infectious pharyngitis (sore throat). INTRODUCTION: The causes of sore throat can be infectious (viruses, bacteria, and fungi) or non-infectious, although the relative proportion of each is not well documented. METHODS: A PubMed database search was performed for studies of non-infectious sore throat. RESULTS AND CONCLUSIONS: Non-infectious causes of sore throat include: physico-chemical factors, such as smoking, snoring, shouting, tracheal intubation, medications, or concomitant illness; and environmental factors including indoor and outdoor air pollutants, temperature and humidity, and hazardous or occupational irritants. The pathophysiology underlying non-infectious sore throat is largely uncharacterised, although neurogenic inflammation looks to be a promising candidate. It is likely that there will be individual disposition factors or the coincidence of more than one irritant with possible—up to now unknown—interactions between them. Therefore, experimental models with defined conditions and objective endpoints are needed. A new model using cold dry air to directly induce pharyngeal irritation in humans, with pharyngeal lavage to measure biomarkers, may provide a useful tool for the study of mechanisms and treatment of non-infectious sore throat.

negative: Middle East Respiratory Syndrome Coronavirus and Pulmonary Tuberculosis Coinfection: Implications for Infection Control Coinfection of Middle East respiratory syndrome coronavirus (MERS-CoV) with tuberculosis (TB) has not been previously reported. Here, we present 2 cases with both MERS-CoV and pulmonary TB. The first case was a 13-year-old patient who was admitted with a 2-month history of fever, weight loss, night sweats, and cough. The second patient was a 30-year-old female who had a 4-week history of cough associated with shortness of breath and weight loss of 2 kg. The 2 patients were diagnosed with pulmonary TB and had positive MERS-CoV. Both patients were discharged to complete their therapy for TB at home. It is likely that both patients had pulmonary TB initially as they had prolonged symptoms and they subsequently developed MERS-CoV infection. It is important to carefully evaluate suspected MERS-CoV patients for the presence of other infectious diseases, such as TB, especially if cohorting is done for suspected MERS-CoV to avoid nosocomial transmission.

negative: Human cytomegalovirus-inhibitory flavonoids: Studies on antiviral activity and mechanism of action Abstract We report antiviral activity against human cytomegalovirus for certain dietary flavonoids and their likely biochemical mechanisms of action. Nine out of ten evaluated flavonoids blocked HCMV replication at concentrations that were significantly lower than those producing cytotoxicity against growing or stationary phase host cells. Baicalein was the most potent inhibitor in this series (IC50 =0.4–1.2μM), including positive control ganciclovir. Baicalein and genistein were chosen as model compounds to study the antiviral mechanism(s) of action for this series. Both flavonoids significantly reduced the levels of HCMV early and late proteins, as well as viral DNA synthesis. Baicalein reduced the levels of HCMV immediate-early proteins to nearly background levels while genistein did not. The antiviral effects of genistein, but not baicalein, were fully reversible in cell culture. Pre-incubation of concentrated virus stocks with either flavonoid did not inhibit HCMV replication, suggesting that baicalein did not directly inactivate virus particles. Baicalein functionally blocked epidermal growth factor receptor tyrosine kinase activity and HCMV nuclear translocation, while genistein did not. At 24h post infection HCMV-infected cells treated with genistein continued to express immediate-early proteins and efficiently phosphorylate IE1-72. However, HCMV induction of NF-κB and increases in the levels of cell cycle regulatory proteins—events that are associated with immediate-early protein functioning – were absent. The data suggested that the primary mechanism of action for baicalein may be to block HCMV infection at entry while the primary mechanism of action for genistein may be to block HCMV immediate-early protein functioning.

negative: The value of mitigating epidemic peaks of COVID-19 for more effective public health responses

negative: The Novel Coronavirus Disease (COVID-19): A PRISMA Systematic Review and Meta-analysis of Clinical and Paraclinical characteristics An outbreak of pneumonia, caused by a novel coronavirus (COVID-19) was Identified in China in Dec 2019. This virus expanded worldwide, causing global concern. Clinical, laboratory and imaging features of this infection are characterized in some observational studies. We undertook a systematic review and meta-analysis to assess the frequency of clinical, laboratory, and CT features in COVID-19 patients. We did a systematic review and meta-analysis using three databases to identify clinical, laboratory, and CT features of rRT-PCR confirmed cases of COVID-19. Data for 3420 patients from 30 observational studies were included. Overall, the results showed that fever (84.2%, 95%CI 82.6-85.7), cough (62%, 95%CI 60-64), and fatigue (39.4%, 95%CI 37.2-41.6%) were the most prevalent symptoms in COVID-19 patients. Increased CRP level, decreased lymphocyte count, and increased D-dimer level were the most common laboratory findings. Among COVID-19 patients, 92% had a positive CT finding, most prevalently GGO (60%, 95%CI 58-62) and peripheral distribution (64%, 95%CI 60-69). These results demonstrate the clinical, paraclinical, and imaging features of COIVD-19.

negative: Emergent Strategies for the Next Phase of COVID-19

negative: Incidental diagnosis of Covid-19 pneumonia on chest computed tomography Abstract Purpose: The purpose of this study was to determine the prevalence and imaging characteristics of incidentally diagnosed COVID-19 pneumonia on computed tomography (CT). Materials and methods: This retrospective study was conducted between March 20th and March 31st, 2020 at Cochin hospital, Paris France. Thoracic CT examinations of all patients referred for another reason than a suspicion of SARS-CoV-2 infection were reviewed. CT images were analyzed by a chest radiologist to confirm the presence of findings consistent with COVID-19 pneumonia and quantify disease extent. Clinical and biological data (C-reactive protein serum level [CRP] and white blood cell count) of patients with CT findings suggestive for COVID-19 pneumonia were retrieved from the electronic medical chart. Results: During the study period, among 205 diagnostic CT examinations, six examinations (6/205, 3%) in 6 different patients (4 men, 2 women; median age, 57 years) revealed images highly suggestive of COVID-19 pneumonia. The final diagnosis was confirmed by RT-PCR. Three inpatients were suspected of extra thoracic infection whereas three outpatients were either fully asymptomatic or presented with fatigue only. All had increased CRP serum level and lymphopenia. Disease extent on CT was mild to moderate in 5/6 patients (83%) and severe in 1/6 patient (17%). Conclusion: umulative incidence of fortuitous diagnosis if COVID-19 pneumonia did not exceed 3% during the highest pandemic phase and was predominantly associated with limited lung involvement.

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: Dynamic profile for the detection of anti-SARS-CoV-2 antibodies using four immunochromatographic assays Abstract In order to fight the SARS-CoV-2 pandemic infection, there is a growing need and demand for diagnostic tools that are complementary and different from the RT-PCR currently in use. Multiple serological tests are or will be very soon available but need to be evaluated and validated. We have thus tested 4 immunochromatographic tests for the detection of antibodies to SARS-CoV-2. In addition, we assessed the kinetics of antibody appearance using these assays in 22 patients after they were tested positive by RT-PCR. We observed great heterogeneity in antiboy detection post-symptom onset. The median antibody detection time was between 8 and 10 days according to the manufacturers. All the tests showed a sensitivity of 60 to 80% on day 10 and 100% on day 15. In addition, a single cross-reaction was observed with other human coronavirus infections. Thus, immunochromatographic tests for the detection of anti-SARS-CoV-2 antibodies may have their place for the diagnostic panel of COVID-19.

negative: Estimation of the asymptomatic ratio of novel coronavirus infections (COVID-19)

negative: COVID-19 randomised trial protocols: rapid publication without barriers

negative: Obesity is the comorbidity more strongly associated for Covid-19 in Mexico. A case-control study Some comorbidities are associated with severe coronavirus disease (Covid-19) but it is unclear whether some increase susceptibility to Covid-19. In this case-control Mexican study we found that obesity represents the strongest predictor for Covid-19 followed by diabetes and hypertension in both sexes and chronic renal failure in females only. Active smoking was associated with decreased odds of Covid-19. These findings indicate that these comorbidities are not only associated with severity of disease but also predispose for getting Covid-19. Future research is needed to establish the mechanisms involved in each comorbidity and the apparent “protective” effect of cigarette smoking.

negative: Clinical analysis and early differential diagnosis of suspected pediatric patients with 2019 novel coronavirus infection Abstract Background: Early differential diagnosis of suspected pediatric patients is difficult during the 2019-nCoV epidemic. Objective: To identify clinical characteristics and key points of early differential diagnosis. Methods: A retrospective analysis was performed on suspected pediatric cases. Results:A total of 77 suspected cases were admitted from Jan 22nd to Mar 1st. Compared with non-2019-nCoV group (n=33),2019-nCoV confirmed group (n=35) had fewer fever (OR[95% CI] 0.39[0.242 to 0.628];P<.001) and symptoms of ARI (0.454[0.287 to 0.719];P<.001),more asymptomatic (15.086[2.117 to 107.475];P<.001), and more family cluster infections (5.469[2.405 to 12.433]; P<.001),while chest CT had more positive findings of viral pneumonia (1.813[1.131 to 2.908];P=.014).There were significant statistical differences between the two groups in age (7.2[3.9 to 11.4] vs 5[2.1 to 7.8];P=.031),body temperature (36.7[36.2 to 36.9] vs 37[36.7 to 37.9];P=.001), heart rate ([97.1 and 16.8] vs [109.7 and 15.6];P=.002),percentage ([39.4 and 14.9] vs [52.5 and 17.5]; P=.001) and count (2.25[1.43 to 3.53] vs 3.33[2.8 to 5.18];P=.007) of neutrophil, percentage (45.3[39.2 to 56.6] vs 33.2[22.7 to 42.5];P=.001) of lymphocyte,hs-CRP (5.52[1.1 to 9.04] vs 9.04[7.35 to 9.54];P=.002) and PCT (0.05[0.03 to 0.08] vs 0.1[0.05 to 0.21];P<.001),while gender (42.9% vs 57.6%;P=.332),respiratory rate (22[20 to 22] vs 22[20 to 24];P=.092),WBC (5.37[4.67 to 8.08] vs 6.94[5.72 to 8.87];P=.198), lymphocyte count (2.68[1.99 to 4.01] vs 2.26[1.66 to 2.92];P=.096),Hb (128[124 to 142] vs 130[119 to 137];P=.572) and PLT ([279.1 and 77.5] vs [263.4 and 65.1];P=.37) were statistically insignificant. Conclusions: Asymptoms or mild symptoms,positive CT findings and family cluster infection are the main clinical characteristics of infected pediatric patients. The CBC, hs-CRP and PCT can provide an important basis for early differential diagnosis. Compared with other non-bacterial infections,hs-CRP and PCT in 2019-nCoV infection are reduced,but further evidence is needed to support whether their reduction is specific. Keywords: 2019 novel coronavirus;acute respiratory infection; pediatric;differential diagnosis;suspected infection. Abbreviations:2019-nCoV,2019 novel coronavirus;CT,computed tomography; RT-PCR,real-time reverse transcriptase polymerase chain reaction;IQR,interquartile range;OR,odds ratio;CI,confidence interval;SD,standard deviation;ARI,acute respiratory infection; CAP,community-acquired pneumonia;RSV, respiratory syncytial virus; MP, mycoplasma pneumoniae; INF A,B,influenza A,B;CBC,complete blood count;WBC,white blood cell;N%, percentage of neutrophil; L%, percentage of lymphocyte; Hb, Hemoglobin;PLT, platelet; hs-CRP,high sensitivity C-reactive protein; PCT, procalcitonin.

negative: Occupational risks for COVID-19 infection

negative: One Academic Health System’s Early (and Ongoing) Experience Responding to COVID-19: Recommendations From the Initial Epicenter of the Pandemic in the United States On January 19, 2020, the first case of a patient with coronavirus disease 2019 (COVID-19) in the United States was reported in Washington State. On February 29, 2020, a patient infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) passed away in a hospital in Seattle-King County, the first reported COVID-19-related death in the United States. That same day, a skilled nursing and rehabilitation facility in the county reported that several of its residents tested positive for SARS-CoV-2 and that many staff had symptoms compatible with COVID-19. The University of Washington Medicine health system (UW Medicine), which is based in Seattle-King County and provides quaternary care for the region, was one of several health care organizations called upon to address this growing crisis. What ensued was a series of swiftly enacted decisions and activities at UW Medicine, in partnership with local, state, and national public health agencies, to respond to the COVID-19 pandemic. Tapping into the multipronged mission areas of academic medicine, UW Medicine worked to support the community, innovate in science and clinical practice; lead policy and practice guideline development; and adopt changes as the crisis unfolded. In doing so, health system leaders had to balance their commitments to students, residents and fellows, researchers, faculty, staff, and hospital and health center entities, while ensuring that patients continued to receive cutting-edge, high-quality, safe care. In this Invited Commentary, the authors highlight the work and challenges UW Medicine has faced in responding to the global COVID-19 pandemic.

negative: Épidémiologie et impact clinique des nouveaux virus respiratoires

negative: Viral Infections of the Central Nervous System Viral-mediated central nervous system (CNS) disease is a complex spectrum of clinical syndromes that result from viral tropism and individual immune responses and genetic susceptibility of patients. The epidemiology of the pathogens is constantly influenced by the availability, or non-availability, of health care services; preventative strategies; and the process of globalization, with rapid movement of people, animals and products. It is further complicated by natural disasters, wars and changes in lifestyle. The effects of the neurotropic viruses are discussed against the background of the epidemiology. The pathogenesis is a chain of events with the point of departure when the virus enters the body to spread and reach the different sites of the CNS. The blood-brain barrier and blood-cerebrospinal fluid barrier are then overcome by captivating mechanisms. Once the different viruses have settled at the preferred site or sites, and have sidestepped the initial immune surveillance, the phases of injury commence. The cytopathic effect of the viruses elicits a para- and post-infectious inflammatory response and a vicious circle of continued damage, viral entry and inflammation results in a process not merely of inflammation, but of intense inflammation. The different clinical syndromes are then identifiable and should be interpreted against their own specific and appropriate epidemiological backgrounds. Clinicians face the challenge of problematic management decisions while awaiting results on gravely ill patients and differential diagnostic considerations have to be taken into account. Establishing a diagnosis is a two-tier process: first it requires the integration of cerebrospinal fluid findings, imaging results, electrophysiological studies, serology and ancillary blood tests, for example full blood count, liver function tests and other appropriate microbiological investigations, and then these should be correlated with the clinical condition of the patient. Treatment should be initiated as soon as possible. General treatment principles for stabilizing and maintaining vital functions are crucial and empiric treatment should be initiated as soon as possible. This usually includes a broad-spectrum antibiotic, such as third-generation cephalosporin and acyclovir. As soon as specific etiologies have been excluded antibiotics can be stopped. The use of acyclovir is discussed. In the last section of the chapter specific characteristics of the neurotropic viral families are summarized.

negative: Rapid implementation of mobile technology for real-time epidemiology of COVID-19 The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic (COVID-19) presents challenges to the robust collection of population-scale data to address this global health crisis. We established the COronavirus Pandemic Epidemiology (COPE) consortium to bring together scientists with expertise in big data research and epidemiology to develop a COVID-19 Symptom Tracker mobile application that we launched in the UK on March 24, 2020 and the US on March 29, 2020 garnering more than 2.25 million users to date. This mobile application offers data on risk factors, herald symptoms, clinical outcomes, and geographical hot spots. This initiative offers critical proof-of-concept for the repurposing of existing approaches to enable rapidly scalable epidemiologic data collection and analysis which is critical for a data-driven response to this public health challenge.

negative: Lung Ultrasound Findings in Patients Hospitalized with Covid-19 Introduction: Point-of-care ultrasound (POCUS) has the potential to transform healthcare delivery in the era of COVID-19 with its diagnostic and therapeutic expediency. It can be performed by clinicians already at the bedside, which permits an immediate and augmented assessment of a patient. Although lung ultrasound can be used to accurately diagnose a variety of disease states such as pneumothorax, pleural effusions, pneumonia and interstitial lung disease2, there are limited reports on the sonographic manifestations of COVID-19. There is an urgent need to identify alternative diagnostic modalities that can be immediately employed at the bedside of COVID-19 patients. Methods: This study was conducted at two medical centers in the United States from 3/21/2020-6/01/2020. Any adult who was hospitalized with COVID-19 (based on symptomatology and a confirmatory RT-PCR for SARS-CoV-2) and received a pulmonary POCUS examination was included. Providers were instructed to use a 12-zone scanning protocol for pulmonary views and save 6 second clips of each lung zone. This study utilized several POCUS devices, including Butterfly IQ, Vave, Lumify, and Sonosite. The collected images were interpreted by the study researchers based on a consensus document developed by the study authors and previously accepted definitions of lung POCUS findings. Results: A total of 22 eligible patients who received 36 lung scans were included in our study. Eleven (50%) patients experienced clinical deterioration (defined as either ICU admission, invasive mechanical ventilation, or death within 28 days from the initial symptom onset). Among the 36 lung scans collected, only 3 (8%) were classified as normal. The remaining scans had the following abnormalities: presence of B-lines (n=32, 89%), consolidations (n=20, 56%), pleural thickening (n=17, 47%), and pleural effusion (n=4, 11%). Out of 20 scans with consolidations, 14 (70%) were subpleural and 5 (25%) were translobar. A-lines were present in 26 (72%) of patients, although they were only observed in the majority of the collected lung zones in 5 (14%) of patients. Ultrasound findings were stratified by time from symptom onset to the scan based on the following time periods: early (0-6 days), middle (7-13 days), and late (14-28 days). B-lines appeared early after symptom onset and persisted well into the late disease course. In contrast, pleural thickening increased in frequency over time (early: 25%, middle: 47%, late: 67%). Subpleural consolidations also appeared in higher frequency later in the disease course (early: 13%, middle 42%, late: 56%). Discussion: certain lung ultrasound findings may be common in Covid-19, while others may appear later in the disease course or only occur in patients who experience clinical deterioration. Future efforts should investigate the predictive utility of consolidations, pleural thickening and B-lines for clinical deterioration and compare them to traditional radiological studies such as X-rays or CTs.

negative: Sustained Egr-1 Response via p38 MAP Kinase Signaling Modulates Early Immune Responses of Dendritic Cells Parasitized by Toxoplasma gondii As a response to a diverse array of external stimuli, early growth response protein 1 (Egr-1) plays important roles in the transcriptional regulation of inflammation and the cellular immune response. However, a number of intracellular pathogens colonize immune cells and the implication of Egr-1 in the host-pathogen interplay has remained elusive. Here, we have characterized the Egr-1 responses of primary murine and human dendritic cells (DCs) upon challenge with the obligate intracellular parasite Toxoplasma gondii. We report that live intracellular parasites induce a sustained high expression of Egr-1 in DCs, different from the immediate-early Egr-1 response to parasite lysates, inactivated parasites or LPS. Moreover, a distinct nuclear localization of elevated amounts of Egr-1 protein was detected in infected DCs, but not in by-stander DCs. The ERK1/2 MAPK signaling pathway mediated the canonical immediate-early Egr-1 response to soluble antigens in a MyD88/TLR-dependent fashion. In contrast, a non-canonical extended Egr-1 response that relied primarily on p38 MAPK signaling was induced by intracellular parasites and was exhibited similarly by MyD88-deficient and wildtype DCs. The extended phase Egr-1 response was dramatically reduced upon challenge of DCs with T. gondii parasites deficient in GRA24, a secreted p38-interacting protein. Further, Egr-1-silenced primary DCs maintained their migratory responses upon T. gondii challenge. Importantly, Egr-1 silencing led to elevated expression of co-stimulatory molecules (CD40, CD80) in Toxoplasma-infected DCs and in LPS-challenged immature DCs, indicating that Egr-1 responses suppressed maturation of DCs. Moreover, the IL-12 and IL-2 responses of Toxoplasma-challenged DCs were modulated in a GRA24-dependent fashion. Jointly, the data show that the Egr-1 responses of DCs to microbial external stimuli and intracellular stimuli can be selectively mediated by ERK1/2 or p38 MAPK signaling, and that Egr-1 can act as an intrinsic negative modulator of maturation in primary DCs.

negative: Clinical Pathway for Early Diagnosis of COVID-19: Updates from Experience to Evidence-Based Practice The COVID-19 pandemic is a significant global event in the history of infectious diseases. The SARS-CoV-2 appears to have originated from bats but is now easily transmissible among humans, primarily through droplet or direct contact. Clinical features of COVID-19 include high fever, cough, and fatigue which may progress to ARDS. Respiratory failure can occur rapidly after this. The primary laboratory findings include lymphopenia and eosinopenia. Elevated D-dimer, procalcitonin, and CRP levels may correlate with disease severity. Imaging findings include ground-glass opacities and patchy consolidation on CT scan. Mortality is higher in patients with hypertension, cardiac disease, diabetes mellitus, cancer, and COPD. Elderly patients are more susceptible to severe disease and death, while children seem to have lower rates of infection and lower mortality. Diagnostic criteria and the identification of persons under investigation have evolved as more data has emerged. However, the approach to diagnosis is still very variable from region to region, country to country, and even among different hospitals in the same city. The importance of a clinical pathway to implement the most effective and relevant diagnostic strategy is of critical importance to establish the control of this virus that is responsible for more and more deaths each day.

negative: Characterization of Rift Valley Fever Virus MP-12 Strain Encoding NSs of Punta Toro Virus or Sandfly Fever Sicilian Virus Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) is a mosquito-borne zoonotic pathogen which can cause hemorrhagic fever, neurological disorders or blindness in humans, and a high rate of abortion in ruminants. MP-12 strain, a live-attenuated candidate vaccine, is attenuated in the M- and L-segments, but the S-segment retains the virulent phenotype. MP-12 was manufactured as an Investigational New Drug vaccine by using MRC-5 cells and encodes a functional NSs gene, the major virulence factor of RVFV which 1) induces a shutoff of the host transcription, 2) inhibits interferon (IFN)-β promoter activation, and 3) promotes the degradation of dsRNA-dependent protein kinase (PKR). MP-12 lacks a marker for differentiation of infected from vaccinated animals (DIVA). Although MP-12 lacking NSs works for DIVA, it does not replicate efficiently in type-I IFN-competent MRC-5 cells, while the use of type-I IFN-incompetent cells may negatively affect its genetic stability. To generate modified MP-12 vaccine candidates encoding a DIVA marker, while still replicating efficiently in MRC-5 cells, we generated recombinant MP-12 encoding Punta Toro virus Adames strain NSs (rMP12-PTNSs) or Sandfly fever Sicilian virus NSs (rMP12-SFSNSs) in place of MP-12 NSs. We have demonstrated that those recombinant MP-12 viruses inhibit IFN-β mRNA synthesis, yet do not promote the degradation of PKR. The rMP12-PTNSs, but not rMP12-SFSNSs, replicated more efficiently than recombinant MP-12 lacking NSs in MRC-5 cells. Mice vaccinated with rMP12-PTNSs or rMP12-SFSNSs induced neutralizing antibodies at a level equivalent to those vaccinated with MP-12, and were efficiently protected from wild-type RVFV challenge. The rMP12-PTNSs and rMP12-SFSNSs did not induce antibodies cross-reactive to anti-RVFV NSs antibody and are therefore applicable to DIVA. Thus, rMP12-PTNSs is highly efficacious, replicates efficiently in MRC-5 cells, and encodes a DIVA marker, all of which are important for vaccine development for Rift Valley fever.

negative: Coronavirus-induced ER stress response and its involvement in regulation of coronavirus–host interactions Abstract Coronavirus replication is structurally and functionally associated with the endoplasmic reticulum (ER), a major site of protein synthesis, folding, modification and sorting in the eukaryotic cells. Disturbance of ER homeostasis may occur under various physiological or pathological conditions. In response to the ER stress, signaling pathways of the unfolded protein response (UPR) are activated. UPR is mediated by three ER transmembrane sensors, namely the PKR-like ER protein kinase (PERK), the inositol-requiring protein 1 (IRE1) and the activating transcriptional factor 6 (ATF6). UPR facilitates adaptation to ER stress by reversible translation attenuation, enhancement of ER protein folding capacity and activation of ER-associated degradation (ERAD). In cells under prolonged and irremediable ER stress, UPR can also trigger apoptotic cell death. Accumulating evidence has shown that coronavirus infection causes ER stress and induces UPR in the infected cells. UPR is closely associated with a number of major signaling pathways, including autophagy, apoptosis, the mitogen-activated protein (MAP) kinase pathways, innate immunity and pro-inflammatory response. Therefore, studies on the UPR are pivotal in elucidating the complicated issue of coronavirus-host interaction. In this paper, we present the up-to-date knowledge on coronavirus-induced UPR and discuss its potential involvement in regulation of innate immunity and apoptosis.

negative: A study of non-prescription usage of antibiotics in the upper respiratory tract infections in the urban population

negative: Severe respiratory illness associated with a nationwide outbreak of enterovirus D68 in the USA (2014): a descriptive epidemiological investigation BACKGROUND: Enterovirus D68 (EV-D68) has been infrequently reported historically, and is typically associated with isolated cases or small clusters of respiratory illness. Beginning in August, 2014, increases in severe respiratory illness associated with EV-D68 were reported across the USA. We aimed to describe the clinical, epidemiological, and laboratory features of this outbreak, and to better understand the role of EV-D68 in severe respiratory illness. METHODS: We collected regional syndromic surveillance data for epidemiological weeks 23 to 44, 2014, (June 1 to Nov 1, 2014) and hospital admissions data for epidemiological weeks 27 to 44, 2014, (June 29 to Nov 1, 2014) from three states: Missouri, Illinois and Colorado. Data were also collected for the same time period of 2013 and 2012. Respiratory specimens from severely ill patients nationwide, who were rhinovirus-positive or enterovirus-positive in hospital testing, were submitted between Aug 1, and Oct 31, 2014, and typed by molecular sequencing. We collected basic clinical and epidemiological characteristics of EV-D68 cases with a standard data collection form submitted with each specimen. We compared patients requiring intensive care with those who did not, and patients requiring ventilator support with those who did not. Mantel-Haenszel χ(2) tests were used to test for statistical significance. FINDINGS: Regional and hospital-level data from Missouri, Illinois, and Colorado showed increases in respiratory illness between August and September, 2014, compared with in 2013 and 2012. Nationwide, 699 (46%) of 1529 patients tested were confirmed as EV-D68. Among the 614 EV-D68-positive patients admitted to hospital, age ranged from 3 days to 92 years (median 5 years). Common symptoms included dyspnoea (n=513 [84%]), cough (n=500 [81%]), and wheezing (n=427 [70%]); 294 (48%) patients had fever. 338 [59%] of 574 were admitted to intensive care units, and 145 (28%) of 511 received ventilator support; 322 (52%) of 614 had a history of asthma or reactive airway disease; 200 (66%) of 304 patients with a history of asthma or reactive airway disease required intensive care compared with 138 (51%) of 270 with no history of asthma or reactive airway disease (p=0·0004). Similarly, 89 (32%) of 276 patients with a history of asthma or reactive airway disease required ventilator support compared with 56 (24%) of 235 patients with no history of asthma or reactive airway disease (p=0·039). INTERPRETATION: In 2014, EV-D68 caused widespread severe respiratory illness across the USA, disproportionately affecting those with asthma. This unexpected event underscores the need for robust surveillance of enterovirus types, enabling improved understanding of virus circulation and disease burden. FUNDING: None.

negative: COVID-19 target: A specific target for novel coronavirus detection An ongoing outbreak of pneumonia associated with a novel coronavirus has been reported worldwide and become a global health problem; hence, the diagnosis and differentiation of this virus from other types of coronavirus is essential to control of the disease. To this end, the analysis of genomics data plays a vital role in introducing a stronger target and consequently provides better results in laboratory examinations. The modified comparative genomics approach helps us to find novel specific targets by comparing two or more sequences on the nucleotide collection database. We, for the first time, detected ORF8 gene as a potential target for the detection of the novel coronavirus. Unlike previous reported genes (RdRP, E and N genes), ORF8 is entirely specific to the novel coronavirus (COVID-19) and has no cross-reactivity with other kinds of coronavirus. Accordingly, ORF8 gene can be used as an additional confirmatory assay.

negative: Role of viruses in asthma Respiratory viral infections are the most important triggers of asthma exacerbations. Rhinovirus (RV), the common cold virus, is clearly the most prevalent pathogen constantly circulating in the community. This virus also stands out from other viral factors due to its large diversity (about 170 genotypes), very effective replication, a tendency to create Th2-biased inflammatory environment and association with specific risk genes in people predisposed to asthma development (CDHR3). Decreased interferon responses, disrupted airway epithelial barrier, environmental exposures (including biased airway microbiome), and nutritional deficiencies (low in vitamin D and fish oil) increase risk to RV and other virus infections. It is intensively debated whether viral illnesses actually cause asthma. Respiratory syncytial virus (RSV) is the leading causative agent of bronchiolitis, whereas RV starts to dominate after 1 year of age. Breathing difficulty induced by either of these viruses is associated with later asthma, but the risk is higher for those who suffer from severe RV-induced wheezing. The asthma development associated with these viruses has unique mechanisms, but in general, RV is a risk factor for later atopic asthma, whereas RSV is more likely associated with later non-atopic asthma. Treatments that inhibit inflammation (corticosteroids, omalizumab) effectively decrease RV-induced wheezing and asthma exacerbations. The anti-RSV monoclonal antibody, palivizumab, decreases the risk of severe RSV illness and subsequent recurrent wheeze. A better understanding of personal and environmental risk factors and inflammatory mechanisms leading to asthma is crucial in developing new strategies for the prevention and treatment of asthma.

negative: Ocular manifestations of coronavirus disease 2019 PURPOSE: Coronavirus disease 2019 (COVID-19) is an ongoing global public health problem, and most of the COVID-19 research is focused mainly on the respiratory system because of life-threatening results. However, manifestations in other organs should not be ignored since they can also be a mode of transmission. We sought to describe the ocular manifestations of COVID-19 and investigate the association between ocular involvement and clinical presentation and laboratory outcomes. METHODS: This cross-sectional study was conducted between March 1, 2020, and April 30, 2020. Ninety-three sequentially hospitalized and clinically confirmed COVID-19 patients were included in the study. The systemic and ocular symptoms, clinical findings, and laboratory outcomes were recorded. RESULTS: Of the 93 COVID-19 patients, 54 (58.1%) were male, and 39 (41.9%) were female. Mean age of the patients was 39.4 ± 21.9 (min 7, max 88) years. Twenty patients (n 21.5%) had at least one ocular abnormality. Most common findings included hyperemia (n = 20), epiphora (n = 9), increased secretion (n = 6), chemosis (n = 3), follicular conjunctivitis (n = 2), and episcleritis (n = 2). The most common symptom was photophobia (n 15). Patients with ocular involvement were more likely to have higher neutrophil counts (p = 0.001), and increased CRP (p < 0.001), PCT (p = 0.001), and ESR levels (p < 0.001). Mean lymphocyte count was statistically lower in patients with ocular manifestations (p = 0.001). Mean age and number of patients with fever over 37.3 °C in the ocular involvement group was found to be higher (p < 0.001, p = 0.006, respectively). CONCLUSION: Older age, high fever, increased neutrophil/lymphocyte ratio, and high levels of acute phase reactants seemed to be risk factors for ocular involvement.

negative: Case Report: Human Bocavirus Associated Pneumonia as Cause of Acute Injury, Cologne, Germany Although the human bocavirus (HBoV) is known since a decade, limited information about its pathogenesis is available due to the lack of an animal model. Thus, clinical cases and studies are the major source of novel information about the course of infection and the related pathophysiology. In this context, a clinical case of an adult patient suffering from severe HBoV-pneumonia is described that was associated with loss of consciousness followed by acute rib fracture and subsequent neurological disorder. Following initial global respiratory dysfunction the clinical respiratory symptoms recovered but the neurological symptoms maintained after weaning and intensive care in the stroke unit. During the initial phase, an acute active HBoV infection was confirmed by positive polymerase chain reactions from bronchoalveolar lavage fluid and serum. The case further demonstrates that HBoV can cause severe pneumonia, induce secondary disease also in adults, and may be associated with neurological symptoms as previously assumed.

negative: Clinical course of coronavirus disease 2019 in 11 patients after thoracic surgery and challenges in diagnosis OBJECTIVES: To illustrate the clinical course and difficulties in early diagnosis of coronavirus disease 2019 (COVID-19) in patients after thoracic surgery. METHODS: We retrospectively analyzed the clinical course of the first 11 patients diagnosed with COVID-19 after thoracic surgery in early January 2020. Postoperative clinical, laboratory, and radiologic records and the time line of clinical course were summarized. Potential prognostic factors were evaluated. RESULTS: In the 11 confirmed cases (3 female, 8 male), median days from symptom onset to case detection was 8. Insidious symptom onset and misinterpreted postoperative changes on chest computed tomography (CT) resulted in delay in diagnosis. There were 3 fatalities due to respiratory failure, whereas 4 severe and 4 mild cases recovered and were discharged. All patients had once experienced leukocytosis and eosinopenia. Remittent fever and resected lung segments ≥5 were associated with fatality. CONCLUSIONS: The case fatality rate of postsurgical patients subsequently diagnosed with COVID-19 was 27.3%. Insidious symptom onset, postoperative leukocytosis with lymphopenia, and postsurgical CT changes overshadowed the early signs of viral pneumonia. Dynamic symptom monitoring, serial chest CTs, and tests for viral RNA and serum antibody improve the chance for prompt detection of COVID-19. Consideration should be given to preadmission and preoperative screening and strict contact isolation during the postoperative period.

negative: Access to Care for Dementia patients suffering from COVID-19

negative: COVID-19 diagnostics in context. The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for different types of diagnostics, comparative validation of new tests, faster approval by federal agencies, and rapid production of test kits to meet global demands. In this Perspective, we discuss the utility and challenges of current diagnostics for COVID-19.

negative: There are asymptomatic and pre-symptomatic patients infected with COVID-19. So what? Pandemic response implications Abstract Asymptomatic but infectious people have been reported in many infectious diseases. Asymptomatic and pre-symptomatic carriers would be a hidden reservoir of COVID-19. Aim This review identifies primary empirical evidence about the ability of asymptomatic carriers to infect others with COVID-19 pandemic and reflects on the implications for control measures. Methods A systematic review is followed by a narrative report and commentary inclusion criteria were: studies reporting primary data on asymptomatic or pre-symptomatic patients, who were considered to have passed on COVID-19 infection; and published in indexed journals or in peer review between January 1 and March 31, 2020. Results Nine articles reported on 83 asymptomatic or pre-symptomatic persons. Conclusions The evidence confirms COVID-19 transmission from people who were asymptomatic at the time. A series of implications for health service response are laid out. Keywords: Covid-19, Asymptomatic, Pre-symptomatic, Public Health

negative: Immunoreactivity characterisation of the three structural regions of the human coronavirus OC43 nucleocapsid protein by Western blot: Implications for the diagnosis of coronavirus infection Abstract Previous studies have reported that a prokaryotic-expressed recombinant nucleocapsid protein (NP) is a suitable reagent for the epidemiological screening of coronavirus infection. In this study, soluble recombinant human coronavirus OC43 (HCoV-OC43) NP was produced to examine the antigenicity of the HCoV-OC43 NP of betacoronavirus. Using the purified recombinant NP as an antigen, a polyclonal antibody from rabbit serum with specificity for HCoV-OC43 NP was generated; this antibody reacts specifically with HCoV-OC43 NP and does not cross-react with other human CoV NPs (including those of SARS-CoV and HCoV-229E) by Western blot. Sera from 26 young adults, 17 middle-aged and elderly patients with respiratory infection, and 15 cord blood samples were also tested. Strong reactivity to the NPs of HCoV-OC43 was observed in 96%, 82%, and 93% of the serum samples from the young adults, respiratory patients, and cord blood samples, respectively. To identify the immunoreactivities of the three structural regions of the NP that are recognised by the rabbit polyclonal antibody and human serum, the antigenicities of three protein fragments, including the N-terminal domain (aa 1-173), the central-linker region (aa 174-300), and the C-terminal domain (aa 301-448), were evaluated by Western blot. The rabbit polyclonal antibody demonstrated greater immunoreactivity to the central-linker region and the C-terminal domain than to the N-terminal domain. Three different patterns for the immunoreactivities of the three structural regions of HCoV-OC43 NP were observed in human serum, suggesting variability in the immune responses that occur during HCoV-OC43 infection in humans. The central-linker region of the NP appeared to be the most highly immunoreactive region for all three patterns observed. The goal of this study was to offer insight into the design of diagnostic tools for HCoV infection.

negative: Saliva: potential diagnostic value and transmission of 2019-nCoV 2019-nCoV epidemic was firstly reported at late December of 2019 and has caused a global outbreak of COVID-19 now. Saliva, a biofluid largely generated from salivary glands in oral cavity, has been reported 2019-nCoV nucleic acid positive. Besides lungs, salivary glands and tongue are possibly another hosts of 2019-nCoV due to expression of ACE2. Close contact or short-range transmission of infectious saliva droplets is a primary mode for 2019-nCoV to disseminate as claimed by WHO, while long-distance saliva aerosol transmission is highly environment dependent within indoor space with aerosol-generating procedures such as dental practice. So far, no direct evidence has been found that 2019-nCoV is vital in air flow for long time. Therefore, to prevent formation of infectious saliva droplets, to thoroughly disinfect indoor air and to block acquisition of saliva droplets could slow down 2019-nCoV dissemination. This review summarizes diagnostic value of saliva for 2019-nCoV, possibly direct invasion into oral tissues, and close contact transmission of 2019-nCoV by saliva droplets, expecting to contribute to 2019-nCoV epidemic control.

negative: Protease inhibitors broadly effective against feline, ferret and mink coronaviruses Abstract Ferret and mink coronaviruses typically cause catarrhal diarrhea in ferrets and minks, respectively. In recent years, however, systemic fatal coronavirus infection has emerged in ferrets, which resembles feline infectious peritonitis (FIP) in cats. FIP is a highly fatal systemic disease caused by a virulent feline coronavirus infection in cats. Despite the importance of coronavirus infections in these animals, there are no effective commercial vaccines or antiviral drugs available for these infections. We have previously reported the efficacy of a protease inhibitor in cats with FIP, demonstrating that a virally encoded 3C-like protease (3CLpro) is a valid target for antiviral drug development for coronavirus infections. In this study, we extended our previous work on coronavirus inhibitors and investigated the structure-activity relationships of a focused library of protease inhibitors for ferret and mink 3CLpro. Using the fluorescence resonance energy transfer assay, we identified potent inhibitors broadly effective against feline, ferret and mink coronavirus 3CLpro. Multiple amino acid sequence analysis and modelling of 3CLpro of ferret and mink coronaviruses were conducted to probe the structural basis for these findings. The results of this study provide support for further research to develop broad-spectrum antiviral agents for multiple coronavirus infections. To the best of our knowledge, this is the first report on small molecule inhibitors of ferret and mink coronaviruses.

negative: Membrane ectopeptidases targeted by human coronaviruses Six coronaviruses, including the recently identified Middle East respiratory syndrome coronavirus, are known to target the human respiratory tract causing mild to severe disease. Their interaction with receptors expressed on cells located in the respiratory tract is an essential first step in the infection. Thus far three membrane ectopeptidases, dipeptidyl peptidase 4 (DPP4), angiotensin-converting enzyme 2 (ACE2) and aminopeptidase N (APN), have been identified as entry receptors for four human-infecting coronaviruses. Although the catalytic activity of the ACE2, APN, and DPP4 peptidases is not required for virus entry, co-expression of other host proteases allows efficient viral entry. In addition, evolutionary conservation of these receptors may permit interspecies transmissions. Because of the physiological function of these peptidase systems, pathogenic host responses may be potentially amplified and cause acute respiratory distress.

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: 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: Liver Disease Associated with Viral Infections

negative: Collaborated effort against SARS‐CoV‐2 outbreak in China A previously unknown beta coronavirus, SARS‐CoV‐2, was discovered from a cluster of patients with pneumonia of unknown cause in Wuhan since the end of 2019. Ever since the start of COVID‐19, government administrations, academic institutions, and technology enterprises are under unprecedented cooperation in controlling this outbreak from pathogen identification, epidemic situation assessment, to outbreak containment. Timely identification, isolation, and whole‐genome sequencing of SARS‐CoV‐2 have laid the foundation for effective control of this novel infection. With the increasing case numbers worldwide, more real‐time information is emerging, changing our understandings to SARS‐CoV‐2 outbreak, and nonetheless refining the outbreak control responses. The efficient management of COVID‐19 requires global collaboration and an efficient share of information.

negative: [Correlation between clinical classification of COVID-19 and imaging characteristics of MSCT volume scanning of the lungs]. OBJECTIVE To investigate the correlation between the clinical classification of coronavirus disease 2019 (COVID-19) and the imaging characteristics of multislice spiral computed tomography (MSCT) volume scanning of the lungs. METHODS The clinical data and thoracic MSCT volume scanning data were analyzed retrospectively for 102 patients with COVID-19 diagnosed and hospitalized in the First Affiliated Hospital of Bengbu Medical College between January 18 and February 26, 2020. According to the Fifth Edition of the Diagnosis and Treatment Guidelines by the National Health Commission, the patients were divided into common type, severe type and critical type. The imaging characteristics including the lung sides of the lesions, lung segment involved, lesion distribution, and lesion number and density were compared among the patients with different clinical types of COVID-19. RESULTS Seventy-seven of the patients had common type, 18 had severe type and 7 had critical type of COVID-19. The main clinical manifestations included fever, cough and fatigue. Severe and critical types were more frequently seen in elderly patients, who were more prone to show such symptoms as asthenia, breathing difficulty and dyspnea. Two patients presented with no obvious abnormality in the first CT examinations; in the remaining 100 patients, 89.0% had bilateral lung lesions, 16.0% had diffuse lesions, involving a mean of 6.56±4.22 lung segments. Compared with the patients with the common type, the severe and critical patients had a significantly greater number of lung segments involved (P < 0.05), and were also more likely to show diffuse lesions (P < 0.05). The lesion side, lesion number or lesion density did not differ significantly among the patients with different clinical types of COVID-19 (P > 0.05). CONCLUSIONS MSCT volume scanning not only allows early diagnosis of COVID-19 but also provides evidence for evaluating the severity of COVID-19 to assist in the clinical treatment of the patients.

negative: [Clinical consideration and management of coronavirus disease 2019] Coronavirus disease 2019 (COVID-19) outbreak in Wuhan city, Hubei province in December 2019 and the epidemic so rapidly happened within the whole country and abroad, raising serious problems and urgent concerns, such as: how to control most effectively human-to-human transmission? When does 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 use the existing drugs to achieve the best effect? Can available drugs effectively improve the survival rate of critical patients? In view of the above questions, this article now puts forwards the corresponding suggestions and considerations from the perspective of clinical infectious diseases physician.

negative: Potential drugs for the treatment of the novel coronavirus pneumonia (COVID-19) in China The fight against the novel coronavirus pneumonia (namely COVID-19) that seriously harms human health is a common task for all mankind. Currently, development of drugs against the novel coronavirus (namely SARS-CoV-2) is quite urgent. Chinese medical workers and scientific researchers have found some drugs to play potential therapeutic effects on COVID-19 at the cellular level or in preliminary clinical trials. However, more fundamental studies and large sample clinical trials need to be done to ensure the efficacy and safety of these drugs. The adoption of these drugs without further testing must be careful. The relevant articles, news, and government reports published on the official and Preprint websites, PubMed and China National Knowledge Infrastructure (CNKI) databases from December 2019 to April 2020 were searched and manually filtered. The general pharmacological characteristics, indications, adverse reactions, general usage, and especially current status of the treatment of COVID-19 of those potentially effective drugs, including chemical drugs, traditional Chinese medicines (TCMs), and biological products in China were summarized in this review to guide reasonable medication and the development of specific drugs for the treatment of COVID-19.

negative: Private collection: high correlation of sample collection and patient admission date in clinical microbiological testing complicates sharing of phylodynamic metadata Infectious pathogens are known for their rapid evolutionary rates with new mutations arising over days to weeks. The ability to rapidly recover whole genome sequences and analyze the spread and evolution of pathogens using genetic information and pathogen collection dates has lead to interest in real-time tracking of infectious transmission and outbreaks. However, the level of temporal resolution afforded by these analyses may conflict with definitions of what constitutes protected health information (PHI) and privacy requirements for de-identification for publication and public sharing of research data and metadata. In the United States, dates and locations associated with patient care that provide greater resolution than year or the first three digits of the zip code are generally considered patient identifiers. Admission and discharge dates are specifically named as identifiers in Department of Health and Human Services guidance. To understand the degree to which one can impute admission dates from specimen collection dates, we examined sample collection dates and patient admission dates associated with more than 270,000 unique microbiological results from the University of Washington Laboratory Medicine Department between 2010 and 2017. Across all positive microbiological tests, the sample collection date exactly matched the patient admission date in 68.8% of tests. Collection dates and admission dates were identical from emergency department and outpatient testing 86.7% and 96.5% of the time, respectively, with >99% of tests collected within 1 day from the patient admission date. Samples from female patients were significantly more likely to be collected closer to admission date that those from male patients. We show that PHI-associated dates such as admission date can confidently be imputed from deposited collection date. We suggest that publicly depositing microbiological collection dates at greater resolution than the year may not meet routine Safe Harbor-based requirements for patient de-identification. We recommend the use of Expert Determination to determine PHI for a given study and/or direct patient consent if clinical laboratories or phylodynamic practitioners desire to make these data available.

negative: [The differential diagnosis for novel coronavirus pneumonia and similar lung diseases in general hospitals]. Novel coronavirus pneumonia was novel coronavirus infection that has dominated pulmonary infection since December 2019. The main manifestations were fever, dry cough, shortness of breath, normal or leukopenia in peripheral blood and changes in chest CT and in severe cases, multiple organ failure might occur. The National Health Commission, PRC has revised the consensus on diagnosis and treatment seven times in a short period of time, indicating the growing understanding of the disease. Patients with novel coronavirus pneumonia usually had history of travelling or living in the epidemic area including Wuhan within 14 days before onset, or have been exposed to patients who had fever or respiratory symptoms from the epidemic area, or had clustering diseases. However, novel coronavirus pneumonia was becoming more and more blurred after vanishing epidemic. The diagnosis and differential diagnosis of novel coronavirus pneumonia was facing challenges not only because of large number of tourists increasing dramatically after the relieving of epidemic, but also patients with other diseases return from different areas to search for medical care. In this article, the clinical and chest imaging features of the novel coronavirus pneumonia were reviewed and compared with other infections and non-infectious diffuse pulmonary diseases. We were trying to find the similarities and differences among them, and to identify clues to the diagnosis of novel coronavirus pneumonia, so as to ensure accurate diagnosis and treatment.

negative: High mortality rate in cancer patients with symptoms of COVID-19 with or without detectable SARS-COV-2 on RT-PCR BACKGROUND: Cancer patients presenting with COVID-19 have a high risk of death. In this work, predictive factors for survival in cancer patients with suspected SARS-COV-2 infection were investigated. METHODS: PRE-COVID-19 is a retrospective study of all 302 cancer patients presenting to this institute with a suspicion of COVID-19 from March 1st to April 25th 2020. Data were collected using a web-based tool within electronic patient record approved by the Institutional Review Board. Patient characteristics symptoms and survival were collected and compared in SARS-COV-2 RT-PCR positive and negative patients. RESULTS: 55 of the 302 (18.2%) patients with suspected COVID-19 had detectable SARS-COV-2 with RT-PCR in nasopharyngeal samples. RT-PCR+ patients were older, had more frequently haematological malignancies, respiratory symptoms and suspected COVID-19 pneumonia of CTscan. However, respectively 38% and 20% of SARS-COV-2 RT-PCR negative patients presented similar respiratory symptoms and CT scan images. Thirty of the 302 (9.9%) patients died during the observation period, including 24 (80%) with advanced disease. At the median follow-up of 25 days after first symptoms, the death rate in RT-PCR+ and RT-PCR-patients were 21% and 10% respectively. In both groups, independent risk factors for death were male gender, KPS<60, cancer in relapse, and respiratory symptoms. Detection of SARS-COV-2 on RT-PCR was not associated with an increased death rate (p=0.10). None of the treatment given in the previous month (including cytotoxics, PD1 Ab, anti-CD20, VEGFR2…) correlated with survival. The survival of RT-PCR positive and negative patients with respiratory symptoms and/or COVID-19 type pneumonia on CTscan was similar with a 18.4% and 19.7% death-rate at day-25. Most (22/30, 73%) cancer patients dying during this period were RT-PCR negative. CONCLUSION: The 30-day death rate of cancer patients with or without documented SARS-COV-2 infection is poor, but the majority of deaths occur in RT-PCR negative patients.

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: The Waiting Time for Inter-Country Spread of Pandemic Influenza BACKGROUND: The time delay between the start of an influenza pandemic and its subsequent initiation in other countries is highly relevant to preparedness planning. We quantify the distribution of this random time in terms of the separate components of this delay, and assess how the delay may be extended by non-pharmaceutical interventions. METHODS AND FINDINGS: The model constructed for this time delay accounts for: (i) epidemic growth in the source region, (ii) the delay until an infected individual from the source region seeks to travel to an at-risk country, (iii) the chance that infected travelers are detected by screening at exit and entry borders, (iv) the possibility of in-flight transmission, (v) the chance that an infected arrival might not initiate an epidemic, and (vi) the delay until infection in the at-risk country gathers momentum. Efforts that reduce the disease reproduction number in the source region below two and severe travel restrictions are most effective for delaying a local epidemic, and under favourable circumstances, could add several months to the delay. On the other hand, the model predicts that border screening for symptomatic infection, wearing a protective mask during travel, promoting early presentation of cases arising among arriving passengers and moderate reduction in travel volumes increase the delay only by a matter of days or weeks. Elevated in-flight transmission reduces the delay only minimally. CONCLUSIONS: The delay until an epidemic of pandemic strain influenza is imported into an at-risk country is largely determined by the course of the epidemic in the source region and the number of travelers attempting to enter the at-risk country, and is little affected by non-pharmaceutical interventions targeting these travelers. Short of preventing international travel altogether, eradicating a nascent pandemic in the source region appears to be the only reliable method of preventing country-to-country spread of a pandemic strain of influenza.

negative: Co-circulation of human metapneumovirus and SARS-associated coronavirus during a major nosocomial SARS outbreak in Hong Kong Abstract Background The clinico-epidemiological significance of human metapneumovirus (hMPV) detected during the SARS outbreak is unknown. Objectives To characterize a nosocomial hMPV outbreak during the 2003 SARS epidemic. Study design and methods All available nasopharyngeal aspirate (NPA) collected from confirmed patients during the first 8 weeks of the SARS outbreak in 2003 were tested for hMPV by a nested RT-PCR assay targeting the F-gene. Clinico-epidemiological information was used to analyze the relationship of hMPV co-infection to specific risk factors (demographics/symptoms/outcomes; status as health-care workers (HCWs)/patients; history of exposure/contact; ward location). Multivariate logistic regression analysis was performed to determine independent risk factors. Results An hMPV outbreak occurred during 6–16 March 2003 (first week of the Hong Kong SARS epidemic). hMPV RNA was detected in 31 of 155 (20%) NPAs from SARS patients. HCW status (OR 2.72, 95% CI 1.11–6.68; p =0.029) or epidemiological linkage to the SARS outbreak ward (OR 3.59, 95% CI 1.42–9.05; p =0.007) were independent factors associated with hMPV infection. Symptoms of cough and coryza were more common in co-infected individuals (22.6% vs. 15.9%) but this was not statistically significant. Other clinical manifestations and outcomes were not different in co-infected patients. Conclusions A major nosocomial hMPV outbreak involving HCWs occurred during the early SARS epidemic. Patients with dual hMPV and SARS infection were not sicker than those with SARS infection only.

negative: The Role of Repeat Chest CT Scan in the COVID-19 Pandemic

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: Early Detection Of COVID-19 Using A Smartwatch Wearable devices digitally measuring vital signs have been used for monitoring health and illness onset and have high potential for real-time monitoring and disease detection. As such they are potentially useful during public health crises, such as the current COVID-19 global pandemic. Using smartwatch data from 31 infected individuals identified from a cohort of over 5000 participants, we investigated the use of wearables for early, presymptomatic detection of COVID-19. From physiological and activity data, we first demonstrate that COVID-19 infections are associated with alterations in heart rate, steps and sleep in 80% of COVID-19 infection cases. Failure to detect these changes in the remaining patients often occurred in those with chronic respiratory/lung disease. Importantly the physiological alterations were detected prior to, or at, symptom onset in over 85% of the positive cases (21/24), in some cases nine or more days before symptoms. Through daily surveys we can track physiological changes with symptom onset and severity. Finally, we develop a method to detect onset of COVID-19 infection in real-time which detects 67% of infection cases at or before symptom onset. Our study provides a roadmap to a rapid and universal diagnostic method for the large-scale detection of respiratory viral infections in advance of symptoms, highlighting a useful approach for managing epidemics using digital tracking and health monitoring.

negative: Severe acute respiratory syndrome—a global concern—influenza virus isolated from suspected cases in Brazil from April to June 2003 Abstract Severe acute respiratory syndrome (SARS) is a condition associated with substantial morbidity and mortality. Coronavirus has been associated with this severe emerging disease, with a pattern suggesting droplet or contact transmission. From April to June 2003, Institute Adolfo Lutz received 16 respiratory secretions from hospitalized patients with recent history of travel to an area with local transmission of SARS. Rapid antigen detection for influenza A and B, parainfluenza types 1, 2 and 3, respiratory syncytial virus and adenovirus; electron microscopy, polymerase chain reaction (PCR), reverse transcription PCR (RT–PCR) and serologic assay were performed. Virus isolation attempts were performed in Hep-2, Vero, MDCK, NCI-H292, MRC-5, LLC-MK2 and FRhK-4. Influenza virus of type A/Panama/2007/99 (H3N2) and A/New Caledonia/20/99 (H1N2) were identified.

negative: Feasibility of controlling COVID-19 outbreaks by isolation of cases and contacts BACKGROUND: Isolation of cases and contact tracing is used to control outbreaks of infectious diseases, and has been used for coronavirus disease 2019 (COVID-19). Whether this strategy will achieve control depends on characteristics of both the pathogen and the response. Here we use a mathematical model to assess if isolation and contact tracing are able to control onwards transmission from imported cases of COVID-19. METHODS: We developed a stochastic transmission model, parameterised to the COVID-19 outbreak. We used the model to quantify the potential effectiveness of contact tracing and isolation of cases at controlling a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-like pathogen. We considered scenarios that varied in the number of initial cases, the basic reproduction number (R0), the delay from symptom onset to isolation, the probability that contacts were traced, the proportion of transmission that occurred before symptom onset, and the proportion of subclinical infections. We assumed isolation prevented all further transmission in the model. Outbreaks were deemed controlled if transmission ended within 12 weeks or before 5000 cases in total. We measured the success of controlling outbreaks using isolation and contact tracing, and quantified the weekly maximum number of cases traced to measure feasibility of public health effort. FINDINGS: Simulated outbreaks starting with five initial cases, an R0 of 1·5, and 0% transmission before symptom onset could be controlled even with low contact tracing probability; however, the probability of controlling an outbreak decreased with the number of initial cases, when R0 was 2·5 or 3·5 and with more transmission before symptom onset. Across different initial numbers of cases, the majority of scenarios with an R0 of 1·5 were controllable with less than 50% of contacts successfully traced. To control the majority of outbreaks, for R0 of 2·5 more than 70% of contacts had to be traced, and for an R0 of 3·5 more than 90% of contacts had to be traced. The delay between symptom onset and isolation had the largest role in determining whether an outbreak was controllable when R0 was 1·5. For R0 values of 2·5 or 3·5, if there were 40 initial cases, contact tracing and isolation were only potentially feasible when less than 1% of transmission occurred before symptom onset. INTERPRETATION: In most scenarios, highly effective contact tracing and case isolation is enough to control a new outbreak of COVID-19 within 3 months. The probability of control decreases with long delays from symptom onset to isolation, fewer cases ascertained by contact tracing, and increasing transmission before symptoms. This model can be modified to reflect updated transmission characteristics and more specific definitions of outbreak control to assess the potential success of local response efforts. FUNDING: Wellcome Trust, Global Challenges Research Fund, and Health Data Research UK.

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: Estimating survival rates in MERS-CoV patients 14 and 45 days after experiencing symptoms and determining the differences in survival rates by demographic data, disease characteristics and regions: a worldwide study Although Middle East respiratory syndrome coronavirus (MERS-CoV) has a recorded 5 years of circulation in 27 countries worldwide, there is no international study to assess whether there is variation in mortality by region. Neither has there been a comprehensive study detailing how the disease characteristics of MERS-CoV influence mortality in patients presenting symptoms. This study aimed to assess how region, patient and disease characteristics influence 14- and 45-day mortality in MERS patients. The author utilised publically available data on MERS-CoV. The study included 883 MERS patients reported between 5 January 2015 and 10 March 2017. Data on patient and disease characteristics were collected. The mean age at MERS-CoV diagnosis was 54.3 years: 69.1% were male, and 86.7% of the cases were reported from Saudi Arabia. About 40% of MERS patients studied were over the age of 60. The study estimated 14- and 45-day survival rates after initial onset of symptoms: 83.67% and 65.9%, respectively. Saudi Arabian MERS patients exhibited 4.1 and 5.0 times higher 14-day (adjusted hazard risk (aHR) = 4.1; 95% confidence interval (CI) 1.012–16.921) and 45-day (aHR = 5.0; 95% CI 1.856–13.581) mortality risk compared with MERS patients in the Republic of Korea or other countries. Similarly, Middle Eastern MERS patients showed 5.3 and 4.1 times higher 14-day (aHR = 5.3; 95% CI 1.070–25.902) and 45-day (aHR = 4.1; 95% CI 1.288–113.076) mortality risk compared with MERS patients in the Republic of Korea or other countries. The results demonstrated a link between mortality and geography, disease and patient factors such as regions, symptoms, source of infections, underlying medical conditions, modes of transmission, non-healthcare workers and those of older age. Educational programmes, access to healthcare and early diagnosis could be implemented as modifiable factors to reduce the higher mortality rates in MERS patients.

negative: Longitudinal Change of SARS-Cov2 Antibodies in Patients with COVID-19 BACKGROUND: A novel coronavirus, SARS-CoV-2, has recently emerged and caused the rapid spread of COVID-19 worldwide. METHODS: We did a retrospective study and included COVID-19 patients admitted to Renmin Hospital of Wuhan University between February 1 and February 29, 2020. Antibody assay was conducted to detect COVID-19 envelope protein E and nucleocapsid protein N antigen. RESULTS: 112 patients were recruited with symptoms of fever, cough, fatigue, myalgia, and diarrhoea. All patients underwent antibody tests. Fifty-eight (51.79%) were positive for both IgM and IgG, 7 (6.25%) were negative for both antibodies, 1 (0.89%) was positive for only IgM, and 46 (41.07%) were positive for only IgG. IgM antibody appeared within a week post disease onset, and lasted for one month and gradually decreased, while IgG antibody was produced 10 days after infection, and lasted for a longer time. However, no significant difference in level of IgM and IgG antibody between positive and negative patients of nucleic acid test after treatment was found. CONCLUSIONS: Our results indicate that serological tests could be powerful approach for the early diagnosis of COVID-19.

negative: Severe acute respiratory syndrome (sars) in children

negative: Characteristics and outcomes of a cohort of SARS-CoV-2 patients in the Province of Reggio Emilia, Italy Objectives. To describe the age- and sex-specific prevalence of SARS-CoV-2 disease (COVID-19) and its prognostic factors. Design. Population-based prospective cohort study on archive data. Setting. Preventive services and hospital care in the province of Reggio Emilia, Northern Italy. Participants. All 2653 symptomatic patients who tested positive for SARS-CoV-2 from February 27 to April 2, 2020 in the province of Reggio Emilia. Main outcome measures. Hospitalization and death up to April 2, 2020. Results. Females had higher prevalence of infection than males below age 50 (2.61 vs. 1.84 per 1000), but lower in older ages (16.49 vs. 20.86 per 1000 over age 80). Case fatality rate reached 20.7% (22/106) in cases with more than 4 weeks follow up. After adjusting for age and comorbidities, men had a higher risk of hospitalization (hazard ratio (HR) 1.4 95% confidence interval (95% CI) 1.2 to 1.6) and of death (HR 1.6, 95% CI 1.2 to 2.1). Patients over age 80 compared to < age 50 had HR 7.1 (95% CI 5.4 to 9.3) and HR 27.8 (95% CI 12.5 to 61.7) for hospitalization and death, respectively. Immigrants had a higher risk of hospitalization (HR 1.3, 95% CI 0.99 to 1.81) than Italians and a similar risk of death. Risk of hospitalization and of death were higher in patients with heart failure (HR 1.6, 95% CI 1.2 to 2.1and HR 2.3, 95% CI 1.6 to 3.2, respectively), arrhythmia (HR 1.5, 95% CI 1.2 to 1.9 and HR 1.8, 95% CI 1.3 to 2.5, respectively), dementia (HR 1.2, 95% CI 0.9 to 1.8 and HR 1.8, 95% CI 1.1 to 2.8, respectively), ischemic heart disease (HR 1.3, 95% CI 1.0 to 1.7 and HR 1.7, 95% CI 1.2 to 2.5, respectively), diabetes (HR 1.5, 95% CI 1.3 to 1.9 and HR 1.6, 95% CI 1.1 to 2.2, respectively), and hypertensions(HR 1.4, 95% CI 1.2 to 2.6 and HR 1.6, 95% CI 1.2 to 2.1, respectively), while COPD increased the risk of hospitalization (HR 1.9, 95% CI 1.4 to 2.5) but not of death (HR 1.1, 95% CI 0.7 to 1.7). Previous use of ACE inhibitors has no effect on risk of death (HR 0.97, 95% CI 0.69 to 1.34) Conclusions. The mechanisms underlying these associations are mostly unknown. A deeper understanding of the causal chain from infection, disease onset, and immune response to outcomes may explain how these prognostic factors act.

negative: Infections Lower respiratory tract infection is a very common illness in children and is a significant cause of morbidity and mortality. Clinical signs and symptoms are nonspecific especially in infants and younger children and some even present with nonrespiratory complaints. Infectious agents causing pneumonia is not limited to viruses and bacteria, but it could also be due to Mycoplasma, Mycobacteria, fungi, protozoa, and parasites. Coinfection with two or more microbial agents can also occur. The etiologic agent of lower respiratory infection in a child is often difficult to obtain, but the patient’s age can help narrow the possible cause. Microbiological tests are important but could be difficult to obtain especially in younger children. Various medical imaging modalities not only play an important role as an aid in diagnosis but can also help during and after therapy. Imaging can also help evaluate complications to pneumonia and exclude other causes of respiratory distress including underlying developmental anomalies, foreign body, gastroesophageal reflux disease, and aspiration. In this chapter, the imaging modalities utilized in the detection of pulmonary infections will be discussed. The spectrum of typical imaging findings for various etiologic agents in both immunocompetent and immunocompromised children will be presented.

negative: Human coronavirus NL63: a clinically important virus? Respiratory tract infection is a leading cause of morbidity and mortality worldwide, especially among young children. Human coronaviruses (HCoVs) have only recently been shown to cause both lower and upper respiratory tract infections. To date, five coronaviruses (HCoV-229E, HCoV-OC43, SARS-CoV, HCoV-NL63 and HCoV HKU-1) that infect humans have been identified, four of which (HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU-1) circulate continuously in the human population. Human coronavirus NL63 (HCoV-NL63) was first isolated from the aspirate from a 7-month-old baby in early 2004. Infection with HCoV-NL63 has since been shown to be a common worldwide occurrence and has been associated with many clinical symptoms and diagnoses, including severe lower respiratory tract infection, croup and bronchiolitis. HCoV-NL63 causes disease in children, the elderly and the immunocompromised, and has been detected in 1.0–9.3% of respiratory tract infections in children. In this article, the current knowledge of human coronavirus HCoV-NL63, with special reference to the clinical features, prevalence and seasonal incidence, and coinfection with other respiratory viruses, will be discussed.

negative: Correction: Coronavirus Cell Entry Occurs through the Endo-/Lysosomal Pathway in a Proteolysis-Dependent Manner [This corrects the article DOI: 10.1371/journal.ppat.1004502.].

negative: CT Features of Coronavirus Disease 2019 (COVID-19) Pneumonia in 62 Patients in Wuhan, China OBJECTIVE. The purpose of this study was to investigate 62 subjects in Wuhan, China, with laboratory-confirmed coronavirus disease (COVID-19) pneumonia and describe the CT features of this epidemic disease. MATERIALS AND METHODS. A retrospective study of 62 consecutive patients with laboratory-confirmed COVID-19 pneumonia was performed. CT images and clinical data were reviewed. Two thoracic radiologists evaluated the distribution and CT signs of the lesions and also scored the extent of involvement of the CT signs. The Mann-Whitney U test was used to compare lesion distribution and CT scores. The chi-square test was used to compare the CT signs of early-phase versus advanced-phase COVID-19 pneumonia. RESULTS. A total of 62 patients (39 men and 23 women; mean [± SD] age, 52.8 ± 12.2 years; range, 30-77 years) with COVID-19 pneumonia were evaluated. Twenty-four of 30 patients who underwent routine blood tests (80.0%) had a decreased lymphocyte count. Of 27 patients who had their erythrocyte sedimentation rate and high-sensitivity C-reactive protein level assessed, 18 (66.7%) had an increased erythrocyte sedimentation rate, and all 27 (100.0%) had an elevated high-sensitivity C-reactive protein level. Multiple lesions were seen on the initial CT scan of 52 of 62 patients (83.9%). Forty-eight of 62 patients (77.4%) had predominantly peripheral distribution of lesions. The mean CT score for the upper zone (3.0 ± 3.4) was significantly lower than that for the middle (4.5 ± 3.8) and lower (4.5 ± 3.7) zones (p = 0.022 and p = 0.020, respectively), and there was no significant difference in the mean CT score of the middle and lower zones (p = 1.00). The mean CT score for the anterior area (4.4 ± 4.1) was significantly lower than that for the posterior area (7.7 ± 6.3) (p = 0.003). CT findings for the patients were as follows: 25 patients (40.3%) had ground-glass opacities (GGO), 21 (33.9%), consolidation; 39 (62.9%), GGO plus a reticular pattern; 34 (54.8%), vacuolar sign; 28 (45.2%), microvascular dilation sign; 35 (56.5%), fibrotic streaks; 21 (33.9%), a subpleural line; and 33 (53.2%), a subpleural transparent line. With regard to bronchial changes seen on CT, 45 patients (72.6%) had air bronchogram, and 11 (17.7%) had bronchus distortion. In terms of pleural changes, CT showed that 30 patients (48.4%) had pleural thickening, 35 (56.5%) had pleural retraction sign, and six (9.7%) had pleural effusion. Compared with early-phase disease (≤ 7 days after the onset of symptoms), advanced-phase disease (8-14 days after the onset of symptoms) was characterized by significantly increased frequencies of GGO plus a reticular pattern, vacuolar sign, fibrotic streaks, a subpleural line, a subpleural transparent line, air bronchogram, bronchus distortion, and pleural effusion; however, GGO significantly decreased in advanced-phase disease. CONCLUSION. CT examination of patients with COVID-19 pneumonia showed a mixed and diverse pattern with both lung parenchyma and the interstitium involved. Identification of GGO and a single lesion on the initial CT scan suggested early-phase disease. CT signs of aggravation and repair coexisted in advanced-phase disease. Lesions presented with a characteristic multifocal distribution in the middle and lower lung regions and in the posterior lung area. A decreased lymphocyte count and an increased high-sensitivity C-reactive protein level were the most common laboratory findings.

negative: Case of the Index Patient Who Caused Tertiary Transmission of COVID-19 Infection in Korea: the Application of Lopinavir/Ritonavir for the Treatment of COVID-19 Infected Pneumonia Monitored by Quantitative RT-PCR Since mid-December of 2019, coronavirus disease 2019 (COVID-19) infection has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 infection in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, ß-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.

negative: Hemorrhagic shock and encephalopathy syndrome – the markers for an early HSES diagnosis BACKGROUND: The hemorrhagic shock and encephalopathy syndrome (HSES) is a devastating disease that affects young children. The outcomes of HSES patients are often fatal or manifesting severe neurological sequelae. We reviewed the markers for an early diagnosis of HSES. METHODS: We examined the clinical, biological and radiological findings of 8 patients (4 months to 9 years old) who met the HSES criteria. RESULTS: Although cerebral edema, disseminated intravascular coagulopathy (DIC), and multiple organ failure were seen in all 8 cases during their clinical courses, brain computed tomography (CT) scans showed normal or only slight edema in 5 patients upon admission. All 8 patients had normal platelet counts, and none were in shock. However, they all had severe metabolic acidosis, which persisted even after 3 hours (median base excess (BE), -7.6 mmol/L). And at 6 hours after admission (BE, -5.7 mmol/L) they required mechanical ventilation. Within 12 hours after admission, fluid resuscitation and vasopressor infusion for hypotension was required. Seven of the patients had elevated liver enzymes and creatine kinase (CK) upon admission. Twenty-four hours after admission, all 8 patients needed vasopressor infusion to maintain blood pressure. CONCLUSION: CT scan, platelet count, hemoglobin level and renal function upon admission are not useful for an early diagnosis of HSES. However, the elevated liver enzymes and CK upon admission, hypotension in the early stage after admission with refractory acid-base disturbance to fluid resuscitation and vasopressor infusion are useful markers for an early HSES diagnosis and helpful to indicate starting intensive neurological treatment.

negative: Clinical and Laboratory Features of Severe Acute Respiratory Syndrome Vis-À-Vis Onset of Fever Study objectives: Severe acute respiratory syndrome (SARS) is a rapidly progressive disease caused by a novel coronavirus (CoV) infection. However, the disease presentation is nonspecific. The aim of this study was to define clearly the presentation, clinical progression, and laboratory data in a group of patients who had SARS. Design: Retrospective observational study. Setting: A tertiary care medical center with 51 negative-pressure isolation rooms in Taipei, Taiwan. Patients: Fifty-three patients with SARS seen between April 27 and June 16, 2003. Results: Fever (ie, temperature > 38°C) was the most common symptom (98%) and the earliest. When admitted to the isolation unit of the hospital for observation, most patients reported nonspecific symptoms associated with their fever. Only two patients with preexisting illnesses had cough on the same day the fever began. Eventually, 39 patients (74%) developed cough, beginning at a mean (± SD) time of 4.5 ± 1.9 days after fever onset, and 35 patients (66%) had diarrhea beginning at a mean time of 6.0 ± 3.3 days after fever onset. Thirty-one patients (59%) had abnormal findings on chest radiographs on hospital admission, and all but 1 patient (98%) eventually developed lung infiltrates that were consistent with pneumonia. The majority of patients (63%) first developed unifocal infiltrates at a mean time of 4.5 ± 2.1 days after fever onset, while in 37% of patients the initial infiltrates were multifocal, appearing at a mean time of 5.8 ± 1.3 days after fever onset. Common laboratory findings included lymphopenia (on hospital admission, 70%; during hospitalization, 95%), thrombocytopenia (on hospital admission, 28%; during hospitalization, 40%), elevated lactate dehydrogenase (on hospital admission, 58%; during hospitalization, 88%), creatine kinase (on hospital admission, 18%; during hospitalization, 32%), and aspartate aminotransferase or alanine aminotransferase levels (on hospital admission, 27%; during hospitalization, 62%). Throat or nasopharyngeal swab for SARS-CoV by reverse transcriptase polymerase chain reaction (PCR) and real-time PCR was positive in 40 of the 47 patients (85%) in whom the test was performed. Conclusions: None of the presenting symptoms or laboratory findings are pathognomonic for SARS. Even though cough developed in a majority of patients, it did not occur until later in the disease course, suggesting that a cough preceding or concurrent with the onset of fever is less likely to indicate SARS. While PCR for SARS-CoV appears to be the best early diagnostic test currently available, it is clear that better methods are needed to differentiate between SARS and non-SARS illness on initial presentation.

negative: A Two-Tube Multiplex Reverse Transcription PCR Assay for Simultaneous Detection of Sixteen Human Respiratory Virus Types/Subtypes There is a need for the development of a rapid and sensitive diagnosis of respiratory viral pathogens. With an intended application in provincial Centers for Diseases Control and Prevention, in this study, we present a two-tube multiplex RT-PCR assay (two-tube assay) using automatic electrophoresis to simultaneously detect sixteen common respiratory viruses. The specificity and the sensitivity of the assay were tested. The assay could detect 20–200 copies per reaction when each viral type was assayed individually, 2000 copies with 9 premixed viral targets in the multiplexed assay in tube 1, and 200 copies with 8 premixed templates in tube 2. A total of 247 specimens were used to evaluate the two-tube assay, and the results were compared with those obtained from the Luminex xTAG RVP Fast assay. The discordant results were confirmed by sequencing or by the Seeplex RV15 ACE detection kit. There were no false positives, but six false negatives occurred with the two-tube assay. In conclusion, the two-tube assay is demonstrated to have great potential for routine surveillance of respiratory virus infection in China.

negative: Smell and taste disorders Disorders of taste and smell can present a challenge to the facial plastic surgeon. Obtaining a detailed history and examination is the key to the diagnosis and work-up of olfactory and gustatory dysfunction. Easy-to-administer tests are available for olfactory evaluation (University of Pennsylvania Smell Identification Test) and gustatory evaluation (taste sticks, tasting tablets). The prognosis and management of olfactory and gustatory disease depend on its causes. Despite ongoing research, the treatment of the disorders of smell and taste is limited.

negative: SARS Epidemic: SARS Outbreaks in Inner-land of China Severe Acute Respiratory Syndrome (SARS), also known in China as Infectious Atypical Pneumonia (IAP), is the 21st century’s first infectious disease to severely threaten the public health of the human population (WHO, 2003a). A respiratory transmitted disease caused by a virus, SARS is highly infectious and is rapidly transmitted, inflicting severe complications and a high case fatality rate. The first round of the SARS pandemic led to global panic and billions of dollars economic losses, for due to lack of effective SARS drugs, governments throughout the world had to take rigid steps toward prevention and treatment of the disease. The SARS epidemic began with the first reported case in Guangzhou, China (Wang et al., 2004), on 16 November 2002. Eight months later, the disease had spread to 26 countries in Asia, America, and Europe, resulting in a reported 8,096 cases and 774 deaths (WHO, 2004). In this global epidemic, China, with 7,429 cases and 685 deaths, accounted for 91.8% of the world’s reported cases and 88.5% of the deaths (5,327 SARS cases and 349 deaths were reported in 24 provinces in the inner-land of China – mostly in Beijing and Guangzhou, which, with a combined 4,033 cases, accounted for 75.7% of the total number in the inner-land of China; Hong Kong had 1,755 cases, 299 deaths; Taiwan: 346 cases, 37 deaths; Macao: 1 case, 0 deaths) (He et al., 2003; Peng et al., 2003; Yang et al., 2003; Leadership Group of SARS Prevention and Control in Beijing, 2003; Chinese Center for Disease Control and Prevention, 2003).

negative: Vaccines and Drug Therapeutics to Lock Down Novel Coronavirus Disease 2019 (COVID-19): A Systematic Review of Clinical Trials The ongoing novel coronavirus disease 2019 (COVID-19) pandemic has been responsible for millions of infections and hundreds of thousands of deaths. To date, there is no approved targeted treatment, and many investigational therapeutic agents and vaccine candidates are being considered for the treatment of COVID-19. To extract and summarize information on potential vaccines and therapeutic agents against COVID-19 at different stages of clinical trials from January to March 2020, we reviewed major clinical trial databases such as ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP), and other primary registries between January and March 15, 2020. Interventional studies at different phases under the COVID-19 pipeline were included. A total of 249 clinical trials were identified between January to March 15, 2020. After filtering observational studies (194 studies), a total of 56 interventional trials were considered. The majority of clinical trials have been conducted on chloroquine (n=10) and traditional Chinese medications (TCMs; n=10), followed by antivirals (n=8), anti-inflammatory/immunosuppressants (n=9), cellular therapies (n=4), combinations of different antivirals therapies (n=3), antibacterial (n=1), and other therapies (n=5). Five vaccines are under phase I, and there are a couple of phase III trials on the Bacillus Calmette-Guérin (BCG) vaccine under investigation among healthcare workers. Many novel compounds and vaccines against COVID-19 are currently under investigation. Some candidates have been tested for other viral infections and are listed for clinical trials against the COVID-19 pipeline. Currently, there are no effective specific antivirals or drug combinations available for the treatment of COVID-19.

negative: COVID‐19 diagnosis and management: a comprehensive review Severe acute respiratory syndrome coronavirus (SARS‐CoV)‐2, a novel coronavirus from the same family as SARS‐CoV and Middle East respiratory syndrome coronavirus, has spread worldwide leading the World Health Organization to declare a pandemic. The disease caused by SARS‐CoV‐2, coronavirus disease 2019 (COVID‐19), presents flu‐like symptoms which can become serious in high‐risk individuals. Here, we provide an overview of the known clinical features and treatment options for COVID‐19. We carried out a systematic literature search using the main online databases (PubMed, Google Scholar, MEDLINE, UpToDate, Embase and Web of Science) with the following keywords: ‘COVID‐19’, ‘2019‐nCoV’, ‘coronavirus’ and ‘SARS‐CoV‐2’. We included publications from 1 January 2019 to 3 April 2020 which focused on clinical features and treatments. We found that infection is transmitted from human to human and through contact with contaminated environmental surfaces. Hand hygiene is fundamental to prevent contamination. Wearing personal protective equipment is recommended in specific environments. The main symptoms of COVID‐19 are fever, cough, fatigue, slight dyspnoea, sore throat, headache, conjunctivitis and gastrointestinal issues. Real‐time PCR is used as a diagnostic tool using nasal swab, tracheal aspirate or bronchoalveolar lavage samples. Computed tomography findings are important for both diagnosis and follow‐up. To date, there is no evidence of any effective treatment for COVID‐19. The main therapies being used to treat the disease are antiviral drugs, chloroquine/hydroxychloroquine and respiratory therapy. In conclusion, although many therapies have been proposed, quarantine is the only intervention that appears to be effective in decreasing the contagion rate. Specifically designed randomized clinical trials are needed to determine the most appropriate evidence‐based treatment modality.

negative: COVID-19: ICU delirium management during SARS-CoV-2 pandemic The novel coronavirus, SARS-CoV-2-causing Coronavirus Disease 19 (COVID-19), emerged as a public health threat in December 2019 and was declared a pandemic by the World Health Organization in March 2020. Delirium, a dangerous untoward prognostic development, serves as a barometer of systemic injury in critical illness. The early reports of 25% encephalopathy from China are likely a gross underestimation, which we know occurs whenever delirium is not monitored with a valid tool. Indeed, patients with COVID-19 are at accelerated risk for delirium due to at least seven factors including (1) direct central nervous system (CNS) invasion, (2) induction of CNS inflammatory mediators, (3) secondary effect of other organ system failure, (4) effect of sedative strategies, (5) prolonged mechanical ventilation time, (6) immobilization, and (7) other needed but unfortunate environmental factors including social isolation and quarantine without family. Given early insights into the pathobiology of the virus, as well as the emerging interventions utilized to treat the critically ill patients, delirium prevention and management will prove exceedingly challenging, especially in the intensive care unit (ICU). The main focus during the COVID-19 pandemic lies within organizational issues, i.e., lack of ventilators, shortage of personal protection equipment, resource allocation, prioritization of limited mechanical ventilation options, and end-of-life care. However, the standard of care for ICU patients, including delirium management, must remain the highest quality possible with an eye towards long-term survival and minimization of issues related to post-intensive care syndrome (PICS). This article discusses how ICU professionals (e.g., physicians, nurses, physiotherapists, pharmacologists) can use our knowledge and resources to limit the burden of delirium on patients by reducing modifiable risk factors despite the imposed heavy workload and difficult clinical challenges posed by the pandemic.

negative: 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: Central Nervous System Infections Central nervous system (CNS) infections—i.e., infections involving the brain (cerebrum and cerebellum), spinal cord, optic nerves, and their covering membranes—are medical emergencies that are associated with substantial morbidity, mortality, or long-term sequelae that may have catastrophic implications for the quality of life of affected individuals. Acute CNS infections that warrant neurointensive care (ICU) admission fall broadly into three categories—meningitis, encephalitis, and abscesses—and generally result from blood-borne spread of the respective microorganisms. Other causes of CNS infections include head trauma resulting in fractures at the base of the skull or the cribriform plate that can lead to an opening between the CNS and the sinuses, mastoid, the middle ear, or the nasopharynx. Extrinsic contamination of the CNS can occur intraoperatively during neurosurgical procedures. Also, implanted medical devices or adjunct hardware (e.g., shunts, ventriculostomies, or external drainage tubes) and congenital malformations (e.g., spina bifida or sinus tracts) can become colonized and serve as sources or foci of infection. Viruses, such as rabies, herpes simplex virus, or polioviruses, can spread to the CNS via intraneural pathways resulting in encephalitis. If infection occurs at sites (e.g., middle ear or mastoid) contiguous with the CNS, infection may spread directly into the CNS causing brain abscesses; alternatively, the organism may reach the CNS indirectly via venous drainage or the sheaths of cranial and spinal nerves. Abscesses also may become localized in the subdural or epidural spaces. Meningitis results if bacteria spread directly from an abscess to the subarachnoid space. CNS abscesses may be a result of pyogenic meningitis or from septic emboli associated with endocarditis, lung abscess, or other serious purulent infections. Breaches of the blood–brain barrier (BBB) can result in CNS infections. Causes of such breaches include damage (e.g., microhemorrhage or necrosis of surrounding tissue) to the BBB; mechanical obstruction of microvessels by parasitized red blood cells, leukocytes, or platelets; overproduction of cytokines that degrade tight junction proteins; or microbe-specific interactions with the BBB that facilitate transcellular passage of the microorganism. The microorganisms that cause CNS infections include a wide range of bacteria, mycobacteria, yeasts, fungi, viruses, spirochaetes (e.g., neurosyphilis), and parasites (e.g., cerebral malaria and strongyloidiasis). The clinical picture of the various infections can be nonspecific or characterized by distinct, recognizable clinical syndromes. At some juncture, individuals with severe acute CNS infections require critical care management that warrants neuro-ICU admission. The implications for CNS infections are serious and complex and include the increased human and material resources necessary to manage very sick patients, the difficulties in triaging patients with vague or mild symptoms, and ascertaining the precise cause and degree of CNS involvement at the time of admission to the neuro-ICU. This chapter addresses a wide range of severe CNS infections that are better managed in the neuro-ICU. Topics covered include the medical epidemiology of the respective CNS infection; discussions of the relevant neuroanatomy and blood supply (essential for understanding the pathogenesis of CNS infections) and pathophysiology; symptoms and signs; diagnostic procedures, including essential neuroimaging studies; therapeutic options, including empirical therapy where indicated; and the perennial issue of the utility and effectiveness of steroid therapy for certain CNS infections. Finally, therapeutic options and alternatives are discussed, including the choices of antimicrobial agents best able to cross the BBB, supportive therapy, and prognosis.

negative: [Clinical features of 2019 novel coronavirus pneumonia in the early stage from a fever clinic in Beijing]. Objective: To summarize and analyze the clinical and imaging characteristics of patients with 2019 novel coronavirus pneumonia in the early stage in Beijing. Methods: A retrospective analysis of clinical and imaging data of 9 patients with 2019 novel coronavirus infection diagnosed in one fever clinicic in Beijing from January 18, 2020 to February 3, 2020. Results: 5 male and 4 female was included in those 9 patients, whose median age was 36 years, and the age range from 15 to 49 years. 8 of these patients had no underlying disease and one suffered from diabetes. 7 patients had a history of travel to Wuhan City or Hubei Province, and one patient was a medical staff. Two family clustered was found. The incubation period was 1 to 6 days. The clinical manifestations were fever in 8 cases (8/9) , dry cough in 5 cases (5/9) , pharyngalgia in 4 cases (4/9) , fatigue in 4 cases (4/9) , body soreness in 4 cases (4/9) , and blocked or watery nose in 1 case (1/9) . Six patients (6/9) had abnormal cell peripheral blood, of which 3 (3/9) had an increased monocyte count, 2 (2/9) had a reduced lymphocyte , and 1 (1/9) had an increased leukocyte count, while the 3 patients had normal cell blood routines. The median of CRP was 16.3 mg/L, including 5 patients with slightly elevated (5/9) , 4 patients with normal values (4/9) . the results of procalcitonin test were negative in5 patients. Three patients were examined by chest X-ray examination, one of which was normal, one case showed infiltrates of right upper lung, and another showed in right lower lung. All patients underwent chest HRCT. And 7 cases (7/9) showed multiple ground glass exudation, including 5 cases (5/7) involved bilateral lungs, 2 cases (2/7) involved unilateral lung, 3 cases (3/7) with patchy consolidation, and 2 cases (2/9) showed no abnormality. Conclusions: The patents with 2019 novel coronavirus pneumonia in this study generally have an epidemiological history. The clinical manifestations are fever and cough. Peripheral white blood cell counts were most normal And PCT were all negative. Chest HRCT manifested as multiple ground-glass opacities with partly consolidation. Some patients had normal chest radiographs but HRCT showed pneumonia. Some patients had no pneumonia on chest HRCT.

negative: Rapid asymptomatic transmission of COVID-19 during the incubation period demonstrating strong infectivity in a cluster of youngsters aged 16-23 years outside Wuhan and characteristics of young patients with COVID-19: A prospective contact-tracing study BACKGROUND: The outbreak of coronavirus-disease-2019 (COVID-19) has rapidly spread to many places outside Wuhan. Previous studies on COVID-19 mostly included older hospitalized-adults. Little information on infectivity among and characteristics of youngsters with COVID-19 is available. METHODS: A cluster of 22 close-contacts of a 22-year-old male (Patient-Index) including youngsters with laboratory-confirmed COVID-19 and hospitalized close-contacts testing negative for severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) in Anhui Province, China was prospectively-traced. RESULTS: Since January 23, 2020, we enrolled a cluster of eight youngsters with COVID-19 (median age [range], 22 [16-23] years; six males) originating from Patient-Index returning from Wuhan to Hefei on January 19. Patient-Index visited his 16-year-old female cousin in the evening on his return, and met 15 previous classmates in a get-together on January 21. He reported being totally asymptomatic and were described by all his contacts as healthy on January 19-21. His very first symptoms were itchy eyes and fever developed at noon and in the afternoon on January 22, respectively. Seven youngsters (his cousin and six classmates) became infected with COVID-19 after a-few-hour-contact with Patient-Index. None of the patients and contacts had visited Wuhan (except Patient-Index), or had any exposure to wet-markets, wild-animals, or medical-institutes within three months. For affected youngsters, the median incubation-period was 2 days (range, 1-4). The median serial-interval was 1 day (range, 0-4). Half or more of the eight COVID-19-infected youngsters had fever, cough, sputum production, nasal congestion, and fatigue on admission. All patients had mild conditions. Six patients developed pneumonia (all mild; one bilateral) on admission. As of February 20, four patients were discharged. CONCLUSIONS: SARS-CoV-2-infection presented strong infectivity during the incubation-period with rapid transmission in this cluster of youngsters outside Wuhan. COVID-19 developed in these youngsters had fast onset and various nonspecific atypical manifestations, and were much milder than in older patients as previously reported.

negative: Infectious Diseases: The Role of the Healthcare Professional For the healthcare professional dealing with infections presents two main problems. First, managing detainees or police personnel who have contracted a disease and may be infectious or unwell, and second, handling complainants of assault, including police officers, who have potentially been exposed to an infectious disease. This chapter addresses some general principles of infection control and safety in the working environment and then goes on to discuss some infections that may be encountered in police custody and how they can best be managed.

negative: Neutrophil-to-Lymphocyte Ratio Predicts Severe Illness Patients with 2019 Novel Coronavirus in the Early Stage Background: Severe ill patients with 2019 novel coronavirus (2019-nCoV) infection progressed rapidly to acute respiratory failure. We aimed to select the most useful prognostic factor for severe illness incidence. Methods: The study prospectively included 61 patients with 2019-nCoV infection treated at Beijing Ditan Hospital from January 13, 2020 to January 31, 2020. Prognostic factor of severe illness was selected by the LASSO COX regression analyses, to predict the severe illness probability of 2019-CoV pneumonia. The predictive accuracy was evaluated by concordance index, calibration curve, decision curve and clinical impact curve. Results: The neutrophil-to-lymphocyte ratio (NLR) was identified as the independent risk factor for severe illness in patients with 2019-nCoV infection. The NLR had a c-index of 0.807 (95% confidence interval, 0.676-0.38), the calibration curves fitted well, and the decision curve and clinical impact curve showed that the NLR had superior standardized net benefit. In addition, the incidence of severe illness was 9.1% in age ≥ 50 and NLR < 3.13 patients, and half of patients with age ≥ 50 and NLR ≥ 3.13 would develop severe illness. Based on the risk stratification of NLR with age, the study developed a 2019-nCoV pneumonia management process. Conclusions: The NLR was the early identification of risk factors for 2019-nCoV severe illness. Patients with age ≥ 50 and NLR ≥ 3.13 facilitated severe illness, and they should rapidly access to intensive care unit if necessary.

negative: Significance of serology testing to assist timely diagnosis of SARS-CoV-2 infections: implication from a family cluster Confirmative diagnosis of SARS-CoV-2 infections has been challenged due to unsatisfactory positive rate of molecular assays. Here we identified a family cluster of SARS-CoV-2 infections, with five of six family members were SARS-CoV-2-specific immunoglobin serology testing positive, while molecular assays only detected two of this five patients even repeated twice. We comprehensively analyzed this familial cluster of cases based on the clinical characteristics, chest CT images, SARS-CoV-2 molecular detection results, and serology testing results. At last, two patients were diagnosed with COVID-19, two were suspected of COVID-19, and two were considered close contacts. Our results emphasized the significance of serology testing to assist timely diagnosis of SARS-CoV-2 infections, especially for COVID-19 close contacts screening.

negative: Clinical characteristics and outcomes of hospitalised patients with COVID-19 treated in Hubei (epicentre) and outside Hubei (non-epicentre): a nationwide analysis of China BACKGROUND: During the outbreak of coronavirus disease 2019 (COVID-19), consistent and considerable differences in disease severity and mortality rate of patients treated in Hubei province compared to those in other parts of China have been observed. We sought to compare the clinical characteristics and outcomes of patients being treated inside and outside Hubei province, and explore the factors underlying these differences. METHODS: Collaborating with the National Health Commission, we established a retrospective cohort to study hospitalised COVID-19 cases in China. Clinical characteristics, the rate of severe events and deaths, and the time to critical illness (invasive ventilation or intensive care unit admission or death) were compared between patients within and outside Hubei. The impact of Wuhan-related exposure (a presumed key factor that drove the severe situation in Hubei, as Wuhan is the epicentre as well the administrative centre of Hubei province) and the duration between symptom onset and admission on prognosis were also determined. RESULTS: At the data cut-off (31 January 2020), 1590 cases from 575 hospitals in 31 provincial administrative regions were collected (core cohort). The overall rate of severe cases and mortality was 16.0% and 3.2%, respectively. Patients in Hubei (predominantly with Wuhan-related exposure, 597 (92.3%) out of 647) were older (mean age 49.7 versus 44.9â years), had more cases with comorbidity (32.9% versus 19.7%), higher symptomatic burden, abnormal radiologic manifestations and, especially, a longer waiting time between symptom onset and admission (5.7 versus 4.5â days) compared with patients outside Hubei. Patients in Hubei (severe event rate 23.0% versus 11.1%, death rate 7.3% versus 0.3%, HR (95% CI) for critical illness 1.59 (1.05-2.41)) have a poorer prognosis compared with patients outside Hubei after adjusting for age and comorbidity. However, among patients outside Hubei, the duration from symptom onset to hospitalisation (mean 4.4 versus 4.7â days) and prognosis (HR (95%) 0.84 (0.40-1.80)) were similar between patients with or without Wuhan-related exposure. In the overall population, the waiting time, but neither treated in Hubei nor Wuhan-related exposure, remained an independent prognostic factor (HR (95%) 1.05 (1.01-1.08)). CONCLUSION: There were more severe cases and poorer outcomes for COVID-19 patients treated in Hubei, which might be attributed to the prolonged duration of symptom onset to hospitalisation in the epicentre. Future studies to determine the reason for delaying hospitalisation are warranted.

negative: Hypertransaminasemia in the course of infection with SARS-CoV-2: Incidence and pathogenetic hypothesis In patients infected with severe acute respiratory syndrome coronavirus 2, the respiratory symptoms, such as fever, cough and dyspnea, are the most frequent clinical manifestations. These patients may also present with less well-defined symptoms like diarrhea, nausea, vomiting and/or abdominal discomfort both at the time of diagnosis and during the clinical course. In a few cases, these symptoms may also present before the appearance of respiratory symptoms. To penetrate the body, Severe acute respiratory syndrome coronavirus 2 uses ACE2 receptors, which are present not only in respiratory epithelium but also in gastrointestinal mucosa and liver cholangiocytes. In several cases, viral RNA is detectable in the stool of patients with coronavirus disease 2019 (COVID-19). The liver damage seems to show a multifactorial origin. About 2%-11% of patients with COVID-19 have known underlying hepatic pathologies. In 14%-53% of COVID-19 cases, there is an alteration of the indices of liver cytolysis and is more frequently observed in severe forms of COVID-19, especially during hospitalization.

negative: Patients with RT-PCR-confirmed COVID-19 and Normal Chest CT

negative: Distribution of a novel binding site for angiotensins II and III in mouse tissues Abstract A novel binding site for angiotensins II and III that is unmasked by parachloromercuribenzoate has been reported in rat, mouse and human brains. Initial studies of this binding site indicate that it is not expressed in the adrenal, liver or kidney of the rat and mouse. To determine if this binding site occurs in other mouse tissues, 8 tissues were assayed for expression of this binding site by radioligand binding assay and compared with the expression of this binding site in the forebrain. Particulate fractions of homogenates of testis, epididymis, seminal vesicles, heart, spleen, pancreas, lung, skeletal muscle, and forebrain were incubated with 125I-sarcosine1, isoleucine8 angiotensin II in the presence or absence of 0.3mM parachloromercuribenzoate plus 10µM losartan and 10µM PD123319 (to saturate AT1 and AT2 receptors). Specific (3µM angiotensin II displaceable) high affinity binding occurred in the testis>forebrain>epididymis>spleen>pancreas>lung when parachloromercuribenzoate was present. Binding could not be reliably observed in heart, skeletal muscle and seminal vesicles. High affinity binding of 125I-sarcosine1, isoleucine8 angiotensin II was observed in the absence of parachloromercuribenzoate in the pancreas on occasion. This suggests that this novel angiotensin binding site may have a functional role in these tissues.

negative: Specific ACE2 expression in small intestinal enterocytes may cause gastrointestinal symptoms and injury after 2019-nCoV infection 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: Challenges in lung cancer therapy during the COVID-19 pandemic

negative: Early Insights into Immune Responses during COVID-19 Coronavirus disease-2019 (COVID-19) is caused by the newly emerged virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was recently declared as a pandemic by the World Health Organization. In its severe form, the disease is characterized by acute respiratory distress syndrome, and there are no targeted intervention strategies to treat or prevent it. The immune response is thought to both contribute to the pathogenesis of disease and provide protection during its resolution. Thus, understanding the immune response to SARS-CoV-2 is of the utmost importance for developing and testing vaccines and therapeutics. In this review, we discuss the earliest knowledge and hypotheses of the mechanisms of immune pathology in the lung during acute infection as well at the later stages of disease resolution, recovery, and immune memory formation.

negative: ELM—the database of eukaryotic linear motifs Linear motifs are short, evolutionarily plastic components of regulatory proteins and provide low-affinity interaction interfaces. These compact modules play central roles in mediating every aspect of the regulatory functionality of the cell. They are particularly prominent in mediating cell signaling, controlling protein turnover and directing protein localization. Given their importance, our understanding of motifs is surprisingly limited, largely as a result of the difficulty of discovery, both experimentally and computationally. The Eukaryotic Linear Motif (ELM) resource at http://elm.eu.org provides the biological community with a comprehensive database of known experimentally validated motifs, and an exploratory tool to discover putative linear motifs in user-submitted protein sequences. The current update of the ELM database comprises 1800 annotated motif instances representing 170 distinct functional classes, including approximately 500 novel instances and 24 novel classes. Several older motif class entries have been also revisited, improving annotation and adding novel instances. Furthermore, addition of full-text search capabilities, an enhanced interface and simplified batch download has improved the overall accessibility of the ELM data. The motif discovery portion of the ELM resource has added conservation, and structural attributes have been incorporated to aid users to discriminate biologically relevant motifs from stochastically occurring non-functional instances.

negative: Early occurrence of influenza A epidemics coincided with changes in occurrence of other respiratory virus infections BACKGROUND: Viral interaction in which outbreaks of influenza and other common respiratory viruses might affect each other has been postulated by several short studies. Regarding longer time periods, influenza epidemics occasionally occur very early in the season, as during the 2009 pandemic. Whether early occurrence of influenza epidemics impacts outbreaks of other common seasonal viruses is not clear. OBJECTIVES: We investigated whether early occurrence of influenza outbreaks coincides with shifts in the occurrence of other common viruses, including both respiratory and non‐respiratory viruses. METHODS: We investigated time trends of and the correlation between positive laboratory diagnoses of eight common viruses in the Netherlands over a 10‐year time period (2003–2012): influenza viruses types A and B, respiratory syncytial virus (RSV), rhinovirus, coronavirus, norovirus, enterovirus, and rotavirus. We compared trends in viruses between early and late influenza seasons. RESULTS: Between 2003 and 2012, influenza B, RSV, and coronavirus showed shifts in their occurrence when influenza A epidemics occurred earlier than usual (before week 1). Although shifts were not always consistently of the same type, when influenza type A hit early, RSV outbreaks tended to be delayed, coronavirus outbreaks tended to be intensified, and influenza virus type B tended not to occur at all. Occurrence of rhinovirus, norovirus, rotavirus, and enterovirus did not change. CONCLUSION: When influenza A epidemics occured early, timing of the epidemics of several respiratory winter viruses usually occurring close in time to influenza A was affected, while trends in rhinoviruses (occurring in autumn) and trends in enteral viruses were not.

negative: The Panhandle Formed by Influenza A and C Virus NS Non-Coding Regions Determines NS Segment Expression Exchange of the extremities of the NS segment of type A and C influenza viruses in reverse genetics systems was used to assess their putative role in type specificity. Restoration of each specific proximal panhandle was mandatory to allow the rescue of viruses with heterotypic extremities. Moreover, the transcription level of the modified segment seemed to be directly affected by the distal panhandle strength.

negative: Cutaneous manifestations of the Coronavirus Disease 2019 (COVID‐19): A brief review COVID‐19, first appeared in December 2019 in Wuhan, China, has been spreading quickly throughout the world. We reviewed the evidence on cutaneous manifestations of COVID‐19 based on PubMed database. The searching strategy was (COVID* or coronavirus*) and (dermatol* or skin* or cutaneous*). The publication time was limited to 2019 onward. After independent review by two authors, 14 studies with 228 confirmed cases were included in the analysis. A total of 60 patients developed skin rashes, and the age ranged from 8 to 84. Exanthematous eruptions potentially related to COVID‐19 infection were highly variable and heterogeneous. Skin lesions mainly appeared erythematous, urticarial, and vesicular (chicken pox‐like or varicelliform). Petechiae rash, livedo reticularis, and reactivation of oral HSV‐1 were also observed in single cases. Newly reported eruptions like vascular lesions and peculiar (perniosis‐like) skin lesions caused concern among dermatologists. Exanthems were widely distributed and were primarily located on the trunk. Associated symptoms, latency time, treatment, and prognosis were also carefully summarized. This study reviewed the recently published COVID‐19 studies with skin manifestations, which may pave the way for further research.

negative: Preliminary estimation of the basic reproduction number of novel coronavirus (2019-nCoV) in China, from 2019 to 2020: A data-driven analysis in the early phase of the outbreak Backgrounds An ongoing outbreak of a novel coronavirus (2019-nCoV) pneumonia hit a major city of China, Wuhan, December 2019 and subsequently reached other provinces/regions of China and countries. We present estimates of the basic reproduction number, R0, of 2019-nCoV in the early phase of the outbreak. Methods Accounting for the impact of the variations in disease reporting rate, we modelled the epidemic curve of 2019-nCoV cases time series, in mainland China from January 10 to January 24, 2020, through the exponential growth. With the estimated intrinsic growth rate (γ), we estimated R0 by using the serial intervals (SI) of two other well-known coronavirus diseases, MERS and SARS, as approximations for the true unknown SI. Findings The early outbreak data largely follows the exponential growth. We estimated that the mean R0 ranges from 2.24 (95%CI: 1.96-2.55) to 3.58 (95%CI: 2.89-4.39) associated with 8-fold to 2-fold increase in the reporting rate. We demonstrated that changes in reporting rate substantially affect estimates of R0. Conclusion The mean estimate of R0 for the 2019-nCoV ranges from 2.24 to 3.58, and significantly larger than 1. Our findings indicate the potential of 2019-nCoV to cause outbreaks.

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: Enteric Viruses Many viruses use the enteric tract as a route of entry to the human, animal, or avian host. The onset of acute enteritis is associated with infection by viruses that replicate at or near the site of entry into the intestinal mucosa, including caliciviruses, rotaviruses, adenoviruses, astroviruses, and coronaviruses. These ‘enteric’ viruses occur globally and share similar features. Most are RNA viruses that replicate in the cytoplasm of mature absorptive epithelial cells lining the villi of the small intestine, leading to inflammation and villus atrophy. Vomiting and diarrhea can result in dehydration and death if untreated. Despite abundant growth in vivo, they initially proved difficult or impossible to grow in vitro. Most are genetically diverse, species specific, highly infectious within species and transmitted by the fecal–oral route. Severe symptoms are most commonly associated with primary infections of young animals, and are followed by short-lived immunity. Reinfections are common throughout life, but are often only mildly symptomatic. Safe and effective vaccines have been developed to prevent severe rotavirus disease in young children. In addition to these enterotropic viruses, enteric disease can also result from spread to the intestine of HIV or cytomegaloviruses during the later stages of systemic disease in immunocompromised hosts.

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: The reproductive number R0 of COVID-19 based on estimate of a statistical time delay dynamical system In this paper, we estimate the reproductive number R0 of COVID-19 based on Wallinga and Lipsitch framework {11} and a novel statistical time delay dynamic system. We use the observed data reported in CCDC's paper to estimate distribution of the generation interval of the infection and apply the simulation results from the time delay dynamic system as well as released data from CCDC to fit the growth rate. The conclusion is: Based our Fudan-CCDC model, the growth rate r of COVID-19 is almost in [0.30, 0.32] which is larger than the growth rate 0.1 estimated by CCDC {9}, and the reproductive number R0 of COVID-19 is estimated by 3.25≤ R0 ≤3.4 if we simply use R=1+r*Tc with Tc=7.5, which is bigger than that of SARS. Some evolutions and predictions are listed.

negative: Middle East respiratory syndrome coronavirus in pediatrics: a report of seven cases from Saudi Arabia Infection with Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 as an important respiratory disease with high fatality rates of 40%–60%. Despite the increased number of cases over subsequent years, the number of pediatric cases remained low. A review of studies conducted from June 2012 to April 19, 2016 reported 31 pediatric MERS-CoV cases. In this paper, we present the clinical and laboratory features of seven patients with pediatric MERS. Five patients had no underlying medical illnesses, and three patients were asymptomatic. Of the seven cases, four (57%) patients sought medical advice within 1–7 days from the onset of symptoms. The three other patients (43%) were asymptomatic and were in contact with patients with confirmed diagnosis of MERS-CoV. The most common presenting symptoms were fever (57%), cough (14%), shortness of breath (14%), vomiting (28%), and diarrhea (28%). Two (28.6%) patients had platelet counts of < 150 × 10(9)/L, and one patient had an underlying end-stage renal disease. The remaining patients presented with normal blood count, liver function, and urea and creatinine levels. The documented MERS-CoV Ct values were 32–38 for four of the seven cases. Two patients (28.6%) had abnormal chest radiographic findings of bilateral infiltration. One patient (14.3%) required ventilator support, and two patients (28.6%) required oxygen supplementation. All the seven patients were discharged without complications.

negative: CT manifestations of lung changes and complications in patients with severe acute respiratory syndrome Objective: To investigate the role of CT scanning in diagnosing severe acute respiratory syndrome (SARS).Methods: One hundred and twelve times of spiral CT scanning, 106 times on the chest with standard pulmonary and mediastinal window, 5 on the brain and once on the abdomen, were performed in 82 patients (37 males and 45 females) of SARS.Results: Bilateral shadows showed in 66 patients (80.48%) and unilateral shadow in 16 (19.52%). The lung CT findings were sub-pleural focal consolidation in 26 patients (31.70%), flaky cloudy opacity in 53 (64.63%), large area consolidation in 9 (10.97%), ground-glass blurry shadow in 31 (37.80%), alveolar substantive shadow in 14 (17.07%) and interstitial changes in 16 (19.51%). The pulmonary CT signs of SARS were relatively characterized by: (1) The lesions tending to multiply occur, mostly to be bilaterally distributed and commonly involved in the lower lung field. (2) The lung shadows mostly showed as sub-pleural focal consolidation, flaky cloudy shadow, large area consolidation, ground-glass blurry shadow, and often accompanied with signs of broncho-inflation. (3) Having opacified nodular shadows in the alveolar cavities. (4) Rapid progressions or changes on the size, amount, and distribution of the lesions likely to be found in dynamic observation of chest X-ray and CT scanning, i.e., markedly dynamic changes found within 24 to 48 hrs. Lesions with these characteristics may be recognized as pulmonary changes possibly induced by SARS. Complications were found in 6 patients (7.31%), including tuberculosis of lung and brain accompanied with pneumomediastinum in one patient, secondary infection of lung in 2, pneumothorax in 1, pulmonary fungus in 1, and pyothorax in 1.Conclusion: CT scanning is a sensitive method for diagnosis of SARS, by which more accurate assessment of the abnormal changes of lung and occurrence of complications in SARS patients can be made.

negative: Unrevealing sequence and structural features of novel coronavirus using in silico approaches: The main protease as molecular target Direct-acting antivirals are effective tools to control viral infections. SARS-CoV-2 is a coronavirus associated with the epidemiological outbreak in late 2019. Previous reports showed that HIV-1 protease inhibitors could block SARS-CoV main protease. Based on that and using an in silico approach, we evaluated SARS-CoV-2 main protease as a target for HIV-1 protease inhibitors to reveal the structural features related to their antiviral effect. Our results showed that several HIV inhibitors such as lopinavir, ritonavir, and saquinavir produce strong interaction with the active site of SARS-CoV-2 main protease. Furthermore, broad library protease inhibitors obtained from PubChem and ZINC (www.zinc.docking.org) were evaluated. Our analysis revealed 20 compounds that could be clustered into three groups based on their chemical features. Then, these structures could serve as leading compounds to develop a series of derivatives optimizing their activity against SARS-CoV-2 and other coronaviruses. Altogether, the results presented in this work contribute to gain a deep understanding of the molecular pharmacology of SARS-CoV-2 treatment and validate the use of protease inhibitors against SARS-CoV-2.

negative: COVID-19 diagnostics in context The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for different types of diagnostics, comparative validation of new tests, faster approval by federal agencies, and rapid production of test kits to meet global demands. In this Perspective, we discuss the utility and challenges of current diagnostics for COVID-19.

negative: A preliminary study on serological assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 238 admitted hospital patients Background The outbreak of the recently emerged novel corona virus disease 2019 (COVID-19) poses a challenge for public health laboratories. We aimed to evaluate the diagnostic value of serological assay for SARS-CoV-2. Methods A newly-developed ELISA assay for IgM and IgG antibodies against N protein of SARS-CoV-2 were used to screen the serums of 238 admitted hospital patients with confirmed or suspected SARS-CoV-2 infection from February 6 to February 14, 2020. SARS-CoV-2 RNA was detected by real time RT-PCR on pharyngeal swab specimens. Findings Of the 238 patients, 194 (81.5%) were detected to be antibody (IgM and/or IgG) positive, which was significantly higher than the positive rate of viral RNA (64.3%). There was no difference in the positive rate of antibody between the confirmed patients (83.0%, 127/153) and the suspected patients (78.8%, 67/85) whose nucleic acid tests were negative. After the patients were defined to the different stages of disease based on the day when the test samples were collected, the analysis results showed that the antibody positive rates were very low in the first five days after initial onset of symptoms, and then rapidly increased as the disease progressed. After 10 days, the antibody positive rates jumped to above 80% from less than 50%. On the contrary, the positive rates of viral RNA kept above 60% in the first 11 days after initial onset of symptoms, and then rapidly decreased. In addition, half of the suspected patients with symptoms for 6-10 days were detected to be antibody positive. Interpretation The suspected patients were most likely infected by SARS-CoV-2. Before the 11th day after initial onset of symptoms, nucleic acid test is important for confirmation of viral infection. The combination of serological assay can greatly improve the diagnostic efficacy. After that, the diagnosis for viral infection should be majorly dependent on serological assay. Keywords. SARS-CoV-2; diagnosis; serological assay; nucleic acid test

negative: Clinical Performance of SARS-CoV-2 Molecular Testing Molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the gold standard for diagnosis of coronavirus disease 2019 (COVID-19), but the test clinical performance is poorly understood. From 3/10/2020-5/1/2020 NewYork-Presbyterian laboratories performed 27,377 SARS-CoV-2 molecular assays from 22,338 patients. Repeat testing was performed in 3,432 patients, of which 2,413 had negative and 1,019 had positive first day results. Repeat-tested patients were more likely to be older, male, African-American or Hispanic, and to have severe disease. Among the patients with initially negative results, 18.6% became positive upon repeat-testing. Only 58.1% of any-time positive patients had a result of "detected" on the first test. The clinical sensitivity of COVID-19 molecular assays is estimated between 66.2% and 95.6%, depending on the unknown number of false negative results in single-tested patients. Conversion to a negative result is unlikely to occur before 15 to 20 days after initial testing or 20-30 days after the onset of symptoms, with 50% conversion occurring at 28 days after initial testing. Forty-nine initially-positive patients converted to negative and then back to positive in subsequent days. Conversion from first day negative to positive results increased linearly with each day of testing, reaching 25% probability in 20 days. In summary, our study provides estimates of the clinical performance of SARS-CoV-2 molecular assays and suggests time frames for appropriate repeat testing, namely 15 to 20 days after a positive test and the same or next 2 days after a negative test in a patient with high suspicion for COVID-19.

negative: Viral Innate Immune Evasion and the Pathogenesis of Emerging RNA Virus Infections Positive-sense single-stranded RNA (+ssRNA) viruses comprise many (re-)emerging human pathogens that pose a public health problem. Our innate immune system and, in particular, the interferon response form the important first line of defence against these viruses. Given their genetic flexibility, these viruses have therefore developed multiple strategies to evade the innate immune response in order to optimize their replication capacity. Already many molecular mechanisms of innate immune evasion by +ssRNA viruses have been identified. However, research addressing the effect of host innate immune evasion on the pathology caused by viral infections is less prevalent in the literature, though very relevant and interesting. Since interferons have been implicated in inflammatory diseases and immunopathology in addition to their protective role in infection, antagonizing the immune response may have an ambiguous effect on the clinical outcome of the viral disease. Therefore, this review discusses what is currently known about the role of interferons and host immune evasion in the pathogenesis of emerging coronaviruses, alphaviruses and flaviviruses.

negative: Viral Diseases of the Liver Viruses other than the classic hepatotropic viruses, hepatitis A through E, may cause hepatic injury [1]. Among these are Epstein–Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus (HSV), varicella zoster virus (VZV), human herpes viruses (HHV) 6, 7, and 8, human parvovirus B19, and adenoviruses (Table 11.1). The clinical presentation of infections with these viruses may be indistinguishable from that associated with infection with classic hepatotropic viruses. The presentation ranges from mild and transient elevation of aminotransferases to acute hepatitis and can also lead to acute liver failure [1]. These viruses should be considered as possible etiologic agents in patients who have acute liver injury and whose serologic markers for the classic hepatotropic viruses are not indicative of an active infection [1]. In the present chapter, we review the clinical manifestations and the potential for immune-mediated liver injury associated with several of these viruses (see summary Table 11.2).

negative: Clinical time course of COVID-19, its neurological manifestation and some thoughts on its management Coronavirus disease-2019 (COVID-19) has become a global pandemic. COVID-19 runs its course in two phases, the initial incubation phase and later clinical symptomatic phase. Patients in the initial incubation phase often have insidious clinical symptoms, but they are still highly contagious. At the later clinical symptomatic phase, the immune system is fully activated and the disease may enter the severe infection stage in this phase. Although many patients are known for their respiratory symptoms, they had neurological symptoms in their first 1-2 days of clinical symptomatic phase, and ischaemic stroke occurred 2 weeks after the onset of the clinical symptomatic phase. The key is to prevent a patient from progressing to this severe infection from mild infection. We are sharing our experience on prevention and management of COVID-19.

negative: Actualización de la situación epidemiológica de la infección por SARS-CoV-2 en España. Comentarios a las recomendaciones de manejo de la infección en pediatría

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

negative: Predicting the number of reported and unreported cases for the COVID-19 epidemics in China, South Korea, Italy, France, Germany and United Kingdom The novel coronavirus (SARS-CoV-2) is currently causing concern in the medical, epidemiological and mathematical communities as the virus is rapidly spreading around the world. Internationally, there are more than 1,200,000 cases detected and confirmed in the world on April 6. The asymptomatic and mild symptomatic cases are just going to be really crucial for us to understand what is driving this epidemic to transmit rapidly. Combining a mathematical model of severe (SARS-CoV-2) transmission with data from China, South Korea, Italy, France, Germany and United Kingdom, we provide the epidemic predictions of the number of reported and unreported cases for the SARS-CoV-2 epidemics and evaluate the effectiveness of control measures for each country.

negative: Seroprevalence of SARS-CoV-2 IgG Specific Antibodies among Healthcare Workers in the Northern Metropolitan Area of Barcelona, Spain, after the first pandemic wave Background: The rapid spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) around the world has caused a global pandemic, infecting millions of individuals worldwide, with an unprecedented impact in health care systems worldwide. Healthcare workers are one of the risk groups that need to be well characterized due to their strategic role in the management of patients, presently and in prevention of healthcare needs for future outbreaks. This study presents the results of the first SARS-CoV-2 seroprevalence study in the Northern Metropolitan Area of Barcelona, Spain. Methods: IgG SARS-CoV2 antibodies were analyzed in serum samples from 7563 healthcare workers of the Northern Metropolitan Area of Barcelona taken during the pandemia (from May 4th to May 22nd, 2020) by chemiluminescence assays. Results: A total of 779 of 7563 (10.3%) healthcare workers had detectable anti-SARS-CoV-2 IgG (specific for either S1/S2 or N antigens). No significant differences were observed between those working at primary care or at the reference hospital. Interestingly, in 29 (8.53%) of the previously confirmed positive reverse-transcriptase polymerase chain reaction (rRT-PCR) patients SARS-CoV-2 IgG (S1/S2 or recombinant N antigen) were negative. Conclusion: Seroprevalence of anti-SARS-CoV-2 IgG in the healthcare workers of the Nord Metropolitan Area of Barcelona was significantly increased in comparison with the general population in the same geographical area. These results give us an important insight for a better understanding of SARS-CoV-2 epidemiology, in a collective that is essential for the response against this pandemic.

negative: Impact of severe acute respiratory syndrome on the status of lung cancer chemotherapy patients and a correlation of the signs and symptoms Abstract Our aim was to describe the impact of severe acute respiratory syndrome (SARS) on the status and chemotherapy of non-small-cell lung cancer (NSCLC) patients who had entered clinical trials, and to review how to differentiate the signs and symptoms of SARS from lung cancer and its treatment-related toxicities. A prospective case series involving 79 NSCLC patients who were enrolled in clinical trials undergoing chemotherapy at Taipei Veterans General Hospital, between April 1 and July 15, 2003, was studied. Whether or not there existed a delay, omission, or refusal of scheduled chemotherapy, was recorded. Whether or not our patients had been suspected of or treated as having SARS, was recorded. The patients filled out questionnaires regarding lung cancer treatment and the risk of getting SARS from the hospital. Among these patients, five were placed in an isolation unit to rule out SARS infection during this period of time, and no patient was documented to have suffered from a SARS infection after examinations. Of 373 scheduled chemotherapy injections in 79 patients, a delay in treatment occurred only 10 times. Three patients refused further chemotherapy because of a fear of getting SARS if they visited the hospital. Fifty-eight patients responded to our questionnaires. Thirty-seven patients (63.8%) were afraid of visiting hospital during this SARS infection period. Twenty-one patients (36.2%) felt that a SARS infection was more severe and fatal than their lung cancer. In conclusion, SARS is a new disease entity that is highly contagious. Its clinical manifestations overlap with the signs and symptoms of lung cancer. Thus, a clear differentiation between the two conditions is needed, especially for those patients who are under active anti-cancer treatment.

negative: Association of "initial CT" findings with mortality in older patients with coronavirus disease 2019 (COVID-19) OBJECTIVES: To investigate the association of chest CT findings with mortality in clinical management of older patients. METHODS: From January 21 to February 14, 2020, 98 older patients (≥ 60 years) who had undergone chest CT scans ("initial CT") on admission were enrolled. Manifestation and CT score were compared between the death group and the survival group. In each group, patients were sub-grouped based on the time interval between symptom onset and the "initial CT" scan: subgroup1 (interval ≤ 5 days), subgroup2 (interval between 6 and 10 days), and subgroup3 (interval > 10 days). Adjusted ROC curve after adjustment for age and gender was applied. RESULTS: Consolidations on CT images were more common in the death group (n = 46) than in the survival group (n = 52) (53.2% vs 32.0%, p < 0.001). For subgroup1 and subgroup2, a higher mean CT score was found for the death group (33.0 ± 17.1 vs 12.9 ± 8.7, p < 0.001; 38.8 ± 12.3 vs 24.3 ± 11.9, p = 0.002, respectively) and no significant difference of CT score was identified with respect to subgroup3 (p = 0.144). In subgroup1, CT score of 14.5 with a sensitivity of 83.3% and a specificity of 77.3% for the prediction of mortality was an optimal cutoff value, with an adjusted AUC of 0.881. In subgroup2, CT score of 27.5 with a sensitivity of 87.5% and a specificity of 70.6% for the prediction of mortality was an optimal cutoff value, with an adjusted AUC of 0.895. CONCLUSIONS: "Initial CT" scores may be useful to speculate prognosis and stratify patients. Severe manifestation on CT at an early stage may indicate poor prognosis for older patients with COVID-19. KEY POINTS: â¢ Severe manifestation on CT at an early stage may indicate poor prognosis for older patients with COVID-19. â¢ Radiologists should pay attention to the time interval between symptom onsets and CT scans of patients with COVID-19. â¢ Consolidations on CT images were more common in death patients than in survival patients.

negative: Viral Kinetics and Antibody Responses in Patients with COVID-19 Background A pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading over the world. However, the viral dynamics, host serologic responses, and their associations with clinical manifestations, have not been well described in prospective cohort. Methods We conducted a prospective cohort and enrolled 67 COVID-19 patients admitting between Jan 26 and Feb 5, 2020. Clinical specimens including nasopharyngeal swab, sputum, blood, urine and stool were tested periodically according to standardized case report form with final follow-up on February 27. The routes and duration of viral shedding, antibody response, and their associations with disease severity and clinical manifestations were systematically evaluated. Coronaviral particles in clinical specimens were observed by transmission electron microscopy (TEM). Results The median duration of SARS-CoV-2 RNA shedding were 12 (3-38), 19 (5-37), and 18 (7-26) days in nasopharyngeal swabs, sputum and stools, respectively. Only 13 urines (5.6%) and 12 plasmas (5.7%) were viral positive. Prolonged viral shedding was observed in severe patients than that of non-severe patients. Cough but not fever, aligned with viral shedding in clinical respiratory specimens, meanwhile the positive stool-RNA appeared to align with the proportion who concurrently had cough and sputum production, but not diarrhea. Typical coronaviral particles could be found directly in sputum by TEM. The anti-nucleocapsid-protein IgM started on day 7 and positive rate peaked on day 28, while that of IgG was on day 10 and day 49 after illness onset. IgM and IgG appear earlier, and their titers are significantly higher in severe patients than non-severe patients (p<0.05). The weak responders for IgG had a significantly higher viral clearance rate than that of strong responders (p= 0.011). Conclusions Nasopharyngeal, sputum and stools rather than blood and urine, were the major shedding routes for SARS-CoV-2, and meanwhile sputum had a prolonged viral shedding. Symptom cough seems to be aligned with viral shedding in clinical respiratory and fecal specimens. Stronger antibody response was associated with delayed viral clearance and disease severity.

negative: A family cluster of Middle East Respiratory Syndrome Coronavirus infections related to a likely unrecognized asymptomatic or mild case Abstract Background Ninety confirmed cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) have been reported to the World Health Organization. We report the details of a second family cluster of MERS-CoV infections from Riyadh, Saudi Arabia. Methods We present the clinical, laboratory and epidemiological details of 3 patients from a family cluster of MERS-CoV infections. Results The first patient developed respiratory symptoms and fever 14 days after admission to hospital for an unrelated reason. He died 11 days later with multi-organ failure. Two of his brothers presented later to another hospital with respiratory symptoms and fever. MERS-CoV infection in the latter 2 patients was confirmed by reverse transcriptase polymerase chain reaction testing. All 3 patients had fever, cough, shortness of breath, bilateral infiltrates on chest x-ray, thrombocytopenia, lymphopenia and rises in serum creatinine kinase and alanine transaminase. No hospital or other social contacts are known to have acquired the infection. It appears that the index patient in this cluster acquired MERS-CoV infection whilst in hospital from an unrecognized mild or asymptomatic case. Conclusion MERS-CoV acquisition from unrecognized mild or asymptomatic cases may be a more important contributor to ongoing transmission than previously appreciated.

negative: Evolving epidemiology of novel coronavirus diseases 2019 and possible interruption of local transmission outside Hubei Province in China: a descriptive and modeling study Background The COVID-19 epidemic originated in Wuhan City of Hubei Province in December 2019 and has spread throughout China. Understanding the fast evolving epidemiology and transmission dynamics of the outbreak beyond Hubei would provide timely information to guide intervention policy. Methods We collected individual information on 8,579 laboratory-confirmed cases from official publically sources reported outside Hubei in mainland China, as of February 17, 2020. We estimated the temporal variation of the demographic characteristics of cases and key time-to-event intervals. We used a Bayesian approach to estimate the dynamics of the net reproduction number (Rt) at the provincial level. Results The median age of the cases was 44 years, with an increasing of cases in younger age groups and the elderly as the epidemic progressed. The delay from symptom onset to hospital admission decreased from 4.4 days (95%CI: 0.0-14.0) until January 27 to 2.6 days (0.0-9.0) from January 28 to February 17. The mean incubation period was estimated at 5.2 days (1.8-12.4) and the mean serial interval at 5.1 days (1.3-11.6). The epidemic dynamics in provinces outside Hubei was highly variable, but consistently included a mix of case importations and local transmission. We estimate that the epidemic was self-sustained for less than three weeks with Rt reaching peaks between 1.40 (1.04-1.85) in Shenzhen City of Guangdong Province and 2.17 (1.69-2.76) in Shandong Province. In all the analyzed locations (n=10) Rt was estimated to be below the epidemic threshold since the end of January. Conclusion Our findings suggest that the strict containment measures and movement restrictions in place may contribute to the interruption of local COVID-19 transmission outside Hubei Province. The shorter serial interval estimated here implies that transmissibility is not as high as initial estimates suggested.

negative: Imaging features of the initial chest thin-section CT scans from 110 patients after admission with suspected or confirmed diagnosis of COVID-19 BACKGROUND: In December 2019, an outbreak of a novel coronavirus pneumonia, now called COVID-19, occurred in Wuhan, Hubei Province, China. COVID-19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread quickly across China and the rest of the world. This study aims to evaluate initial chest thin-section CT findings of COVID-19 patients after their admission at our hospital. METHODS: Retrospective study in a tertiary referral hospital in Anhui, China. From January 22, 2020 to February 16, 2020, 110 suspected or confirmed COVID-19 patients were examined using chest thin-section CT. Patients in group 1 (n = 51) presented with symptoms of COVID-19 according to the diagnostic criteria. Group 2 (n = 29) patients were identified as a high degree of clinical suspicion. Patients in group 3 (n = 30) presented with mild symptoms and normal chest radiographs. The characteristics, positions, and distribution of intrapulmonary lesions were analyzed. Moreover, interstitial lesions, pleural thickening and effusion, lymph node enlargement, and other CT abnormalities were reviewed. RESULTS: CT abnormalities were found only in groups 1 and 2. The segments involved were mainly distributed in the lower lobes (58.3%) and the peripheral zone (73.8%). The peripheral lesions, adjacent subpleural lesions, accounted for 51.8%. Commonly observed CT patterns were ground-glass opacification (GGO) (with or without consolidation), interlobular septal thickening, and intralobular interstitial thickening. Compared with group 1, patients in group 2 presented with smaller lesions, and all lesions were distributed in fewer lung segments. Localized pleural thickening was observed in 51.0% of group 1 patients and 48.2% of group 2 patients. The prevalence of lymph node enlargement in groups 1 and 2 combined was extremely low (1 of 80 patients), and no significant pleural effusion or pneumothorax was observed (0 of 80 patients). CONCLUSION: The common features of chest thin-section CT of COVID-19 are multiple areas of GGO, sometimes accompanied by consolidation. The lesions are mainly distributed in the lower lobes and peripheral zone, and a large proportion of peripheral lesions are accompanied by localized pleural thickening adjacent to the subpleural region.

negative: Focal status epilepticus as unique clinical feature of COVID-19: a case report Abstract SARS-CoV-2, a novel zoonotic coronavirus, is currently spreading all over the world, causing a pandemic disease defined coronavirus disease 2019 (COVID-19). The spectrum of COVID-19 ranges from asymptomatic or mild infection to rapidly progressive, acute respiratory distress syndrome and death 1 .To the best of our knowledge, status epilepticus has never been described as initial presentation of COVID-19. We report a patient affected by COVID-19 whose primary presentation was a focal status epilepticus.

negative: COVID-19 Tragic Pandemic: Concerns over Unintentional “Directed Accelerated Evolution” of Novel Coronavirus (SARS-CoV-2) and Introducing a Modified Treatment Method for ARDS Global health authorities are trying to work out the current status of the novel coronavirus (COVID-19) outbreak and explore methods to reduce the rate of its transmission to healthy individuals. In this viewpoint we provide insights concerning how health care professionals can unintentionally shift the novel coronavirus type to more drug-resistant forms. It is worth noting that viruses usually have different sensitivities to physical and chemical damaging agents such antiviral drugs, UV and heat ranging from extremely sensitive (ES) to extremely resistant (ER) based on a bell-shaped curve. Given this consideration, the widespread infection of people with such ER viruses would be a real disaster. Here, we introduce a modified treatment method for COVID-19-associated pneumonia. In this proposed method, COVID-19 patients will receive a single dose of 100, 180 or 250 mSv X-ray radiation that is less than the maximum annual radiation dose of the residents of high background radiation areas of Ramsar that is up to 260 mSv. In contrast with antiviral drugs, a single dose of either 100, 180 or 250 mSv of low LET X-rays cannot exert a significant selective pressure on the novel coronavirus (SARS-CoV-2) and hence does not lead to directed accelerated evolution of these viruses. Moreover, Low Dose Radiation (LDR) has the capacity of modulating excessive inflammatory responses, regulating lymphocyte counts, and controling bacterial co-infections in patients with COVID-19.

negative: Responding to COVID-19: Perspectives from the Chinese Society of Gastroenterology

negative: Pulmonary High-Resolution Computed Tomography (HRCT) Findings of Patients with Early-Stage Coronavirus Disease 2019 (COVID-19) in Hangzhou, China BACKGROUND: The aim of this study was to investigate the imaging manifestations of early-stage coronavirus disease 2019 (COVID-19) and to provide imaging basis for early detection of suspected cases and stratified intervention. MATERIAL/METHODS: From 20 January 2020 to 2 February 2020, 6 patients diagnosed with COVID-19, including 1 male and 5 females, were retrospectively reviewed in Zhejiang Hospital. These cases were clinically assessed and classified as common COVID-19. All patients underwent thoracic high-resolution computed tomography (HRCT) within 2 days after the onset of symptoms, and their images were viewed by 2 radiologists who were blind to their clinical records. RESULTS: CT images of 6 confirmed patients were collected. Two of the 6 patients (33.3%) had bilateral lung involvements and 4 (66.7%) had single-lung involvement. Two cases (33.3%) had a single lesion, 2 cases (33.3%) had 2 lesions, and 2 cases (33.3%) had multiple lesions. There were 2 cases (33.3%) with focal subpleural distribution and 1 case (16.7%) along the bronchial vascular bundle. Five cases (83.3%) had ground-glass opacities, 4 cases (66.7%) had ground-glass nodules, 1 case (16.7%) had thickened lobular septum, 2 cases (33.3%) had thickened bronchial wall, 2 cases (33.3%) had halo sign, 1 case (16.7%) had crazy-paving sign, and 1 case (16.7%) had tree-in-bud sign. CONCLUSIONS: The imaging manifestations of early-stage COVID-19 are relatively mild, and the imaging findings of some patients are not typical, which can easily lead to missed diagnoses. Thus, suspected cases need to be closely monitored, and epidemiological history and clinical laboratory examination should also be considered during diagnosis.

negative: 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.

negative: First genome sequences of buffalo coronavirus from water buffaloes in Bangladesh We report the complete genome sequences of a buffalo coronavirus (BufCoV HKU26) detected from the faecal samples of two domestic water buffaloes (Bubalus bubalis) in Bangladesh. They possessed 98–99% nucleotide identities to bovine coronavirus (BCoV) genomes, supporting BufCoV HKU26 as a member of Betacoronavirus 1. Nevertheless, BufCoV HKU26 possessed distinct accessory proteins between spike and envelope compared to BCoV. Sugar-binding residues in the N-terminal domain of S protein in BCoV are conserved in BufCoV HKU26.

negative: An early test and treat strategy for SARS-CoV-2 As COVID-19 cases and deaths continue to expand globally, there is an urgent need to develop, test and approve effective antiviral therapies. Currently a majority of clinical trials are evaluating therapies in patients who are already hospitalized with SARS Co-V-2 infection. Given that the median time between development of symptoms and need for hospitalization is a week, a golden opportunity to intervene early is being missed. Indeed, for many other viral infections, early treatment soon after development of symptoms is associated with decreased mortality, lower hospitalization rates and lower likelihood of transmission to others. Here, we advocate for randomized double-blind placebo controlled clinical trials to evaluate promising agents early during SARS Co-V-2 infection.

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: Rhinovirus Infections in Hematopoietic Stem Cell Transplant Recipients with Pneumonia Little is known about the impact of human rhinovirus (HRV) and coronavirus infections in hematopoietic stem cell transplant (HSCT) recipients. We tested bronchoalveolar lavage (BAL) samples obtained from HSCT recipients with acute pulmonary infiltrates for HRV (n = 122) and coronavirus (n = 46) by reverse-transcriptase polymerase chain reaction. HRV RNA was detected in 6 (8%) of 77 patients, and coronavirus RNA was detected in 0 of 46 of BAL samples from HSCT recipients. The fatality rate in HRV-infected patients was high (83%), but all patients had significant coinfections, and the overall mortality rate was not different from that of patients who were negative for HRV in BAL samples. These results suggest that HRV may be a cause of lower respiratory tract infections in HSCT recipients and that its detection in BAL samples is associated with frequent copathogens. Whether the poor prognosis is due to HRV or the copathogen is not clear.

negative: 2019-nCoV (Wuhan virus), a novel Coronavirus: human-to-human transmission, travel-related cases, and vaccine readiness. On 31 December 2019 the Wuhan Health Commission reported a cluster of atypical pneumonia cases that was linked to a wet market in the city of Wuhan, China. The first patients began experiencing symptoms of illness in mid-December 2019. Clinical isolates were found to contain a novel coronavirus with similarity to bat coronaviruses. As of 28 January 2020, there are in excess of 4,500 laboratory-confirmed cases, with > 100 known deaths. As with the SARS-CoV, infections in children appear to be rare. Travel-related cases have been confirmed in multiple countries and regions outside mainland China including Germany, France, Thailand, Japan, South Korea, Vietnam, Canada, and the United States, as well as Hong Kong and Taiwan. Domestically in China, the virus has also been noted in several cities and provinces with cases in all but one provinence. While zoonotic transmission appears to be the original source of infections, the most alarming development is that human-to-human transmission is now prevelant. Of particular concern is that many healthcare workers have been infected in the current epidemic. There are several critical clinical questions that need to be resolved, including how efficient is human-to-human transmission? What is the animal reservoir? Is there an intermediate animal reservoir? Do the vaccines generated to the SARS-CoV or MERS-CoV or their proteins offer protection against 2019-nCoV? We offer a research perspective on the next steps for the generation of vaccines. We also present data on the use of in silico docking in gaining insight into 2019-nCoV Spike-receptor binding to aid in therapeutic development. Diagnostic PCR protocols can be found at https://www.who.int/health-topics/coronavirus/laboratory-diagnostics-for-novel-coronavirus.

negative: Abstracts for the 29th Annual Meeting of the Japan Neuroscience Society (Neuroscience2006)

negative: Cryo-EM structure of infectious bronchitis coronavirus spike protein reveals structural and functional evolution of coronavirus spike proteins As cell-invading molecular machinery, coronavirus spike proteins pose an evolutionary conundrum due to their high divergence. In this study, we determined the cryo-EM structure of avian infectious bronchitis coronavirus (IBV) spike protein from the γ-genus. The trimeric IBV spike ectodomain contains three receptor-binding S1 heads and a trimeric membrane-fusion S2 stalk. While IBV S2 is structurally similar to those from the other genera, IBV S1 possesses structural features that are unique to different other genera, thereby bridging these diverse spikes into an evolutionary spectrum. Specifically, among different genera, the two domains of S1, the N-terminal domain (S1-NTD) and C-terminal domain (S1-CTD), diverge from simpler tertiary structures and quaternary packing to more complex ones, leading to different functions of the spikes in receptor usage and membrane fusion. Based on the above structural and functional comparisons, we propose that the evolutionary spectrum of coronavirus spikes follows the order of α-, δ-, γ-, and β-genus. This study has provided insight into the evolutionary relationships among coronavirus spikes and deepened our understanding of their structural and functional diversity.

negative: Household transmission of SARS-CoV-2 Summary Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an epidemic in China and many other countries. Many infected clusters have been found within familial households, but the data about secondary transmission among household contacts is limited. Methods In this retrospective case series, we enrolled 85 patients infected with SARS-CoV-2 and their household members in Wuhan. Patients were confirmed infected with SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (RT-PCR) assays on throat swabs. Epidemiological, clinical and laboratory data of the household members were collected. Results There were 155 close contacts in total. 104 contacts received RT-PCR assays, with 47 (30%) positive cases and 57 (37%) negative cases. 51 (33%) cases did not received RT-PCR tests for they showed no symptoms of pneumonia during the 2 weeks of quarantine. The infection rate of close contacts was 38% for households with 1 contact, 50% for households with 2 contacts, and 31% for households with 3 contacts. Conclusions The rate of secondary transmission among household contacts of patients with SARS-CoV-2 infection was 30%. Our data provide insight into the rate of secondary transmission of SARS-CoV-2 in home.

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: Early diagnosis of SARS: lessons from the Toronto SARS outbreak The clinical presentation of SARS is nonspecific and diagnostic tests do not provide accurate results early in the disease course. Initial diagnosis remains reliant on clinical assessment. To identify features of the clinical assessment that are useful in SARS diagnosis, the exposure status and the prevalence and timing of symptoms, signs, laboratory and radiographic findings were determined for all adult patients admitted with suspected SARS during the Toronto SARS outbreak. Findings were compared between patients with laboratory-confirmed SARS and those in whom SARS was excluded by laboratory or public health investigation. Of 364 cases, 273 (75%) had confirmed SARS, 30 (8%) were excluded, and 61 (17%) remained indeterminate. Among confirmed cases, exposure occurred in the healthcare environment (80%) or in the households of affected patients (17%); community or travel-related cases were rare (<3%). Fever occurred in 97% of patients by the time of admission. Respiratory findings including cough, dyspnea and pulmonary infiltrates evolved later and were present in only 59, 37 and 68% of patients, respectively, at admission. Direct exposure, fever on the first day of illness, and elevated temperature, pulmonary infiltrates, lymphopenia and thrombocytopenia at admission were associated with confirmed cases. Rhinorrhea, sore throat, and an elevated neutrophil count at admission were associated with excluded cases. In the absence of fever or significant exposure, SARS is unlikely. Other clinical, laboratory and radiographic findings further raise or lower the likelihood of SARS and provide a rational basis for estimating the likelihood of SARS and directing initial management.

negative: Transmissibility of 2019 Novel Coronavirus: zoonotic vs. human to human transmission, China, 2019-2020 Objectives: The novel coronavirus (2019-nCoV) originating from Wuhan has rapidly spread throughout China. While the origin of the outbreak remains uncertain, accumulating evidence links a wet market in Wuhan for the early spread of 2019-nCoV. Similarly, the influence of the marketplace on the early transmission dynamics is yet to be investigated. Methods: Using the daily series of COVID-19 incidenceincluding contact history with the market, we have conducted quantitative modeling analyses to estimate the reproduction numbers (R) for the market-to-human and human-to-human transmission together with the reporting probability and the early effects of public health interventions. Results: Our mean R estimates for China in 2019-2020 are estimated at 0.37 (95%CrI: 0.02-1.78) for market-to-human transmission, and 3.87 (95%CrI: 3.18-4.78) for human-to-human transmission, respectively. Moreover we estimated that the reporting rate cases stemming from market-to-human transmission was 3-31 fold higher than that for cases stemming from human-to-human transmission, suggesting that contact history with the wet market played a key role in identifying COVID-19 cases. Conclusions: Our findings suggest that the proportions of asymptomatic and subclinical patients constitute a substantial component of the epidemic's magnitude. Findings suggest that the development of rapid diagnostic tests could help bring the epidemic more rapidly under control.

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: Management of a patient presenting with anterior STEMI with concomitant COVID‐19 infection early in the course of the U.S. pandemic The coronavirus disease‐2019 (COVID‐19) is a viral illness with heterogenous clinical manifestations, ranging from mild symptoms to severe acute respiratory distress syndrome and shock caused by the severe acute respiratory syndrome coronavirus‐2. The global healthcare community is rapidly learning more about the effects of COVID‐19 on the cardiovascular system, as well as the strategies for management of infected patients with cardiovascular disease. There is minimal literature available surrounding the relationship between COVID‐19 infection and acute coronary syndrome. We describe the case of a woman who presented with an acute anterior ST‐elevation myocardial infarction managed by primary percutaneous coronary intervention, who subsequently developed severe COVID‐19 infection and ultimately succumbed to multisystem organ failure.

negative: Impact on mental health and perceptions of psychological care among medical and nursing staff in Wuhan during the 2019 novel coronavirus disease outbreak: A cross-sectional study Abstract The severe 2019 outbreak of novel coronavirus disease (COVID-19), which was first reported in Wuhan, would be expected to impact the mental health of local medical and nursing staff and thus lead them to seek help. However, those outcomes have yet to be established using epidemiological data. To explore the mental health status of medical and nursing staff and the efficacy, or lack thereof, of critically connecting psychological needs to receiving psychological care, we conducted a quantitative study. This is the first paper on the mental health of medical and nursing staff in Wuhan. Notably, among 994 medical and nursing staff working in Wuhan, 36.9% had subthreshold mental health disturbances (mean PHQ-9: 2.4), 34.4% had mild disturbances (mean PHQ-9: 5.4), 22.4% had moderate disturbances (mean PHQ-9: 9.0), and 6.2% had severe disturbance (mean PHQ-9: 15.1) in the immediate wake of the viral epidemic. The noted burden fell particularly heavily on young women. Of all participants, 36.3% had accessed psychological materials (such as books on mental health), 50.4% had accessed psychological resources available through media (such as online push messages on mental health self-help coping methods), and 17.5% had participated in counseling or psychotherapy. Trends in levels of psychological distress and factors such as exposure to infected people and psychological assistance were identified. Although staff accessed limited mental healthcare services, distressed staff nonetheless saw these services as important resources to alleviate acute mental health disturbances and improve their physical health perceptions. These findings emphasize the importance of being prepared to support frontline workers through mental health interventions at times of widespread crisis.

negative: Middle East Respiratory Syndrome Coronavirus Transmission Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes a spectrum of respiratory illness, from asymptomatic to mild to fatal. MERS-CoV is transmitted sporadically from dromedary camels to humans and occasionally through human-to-human contact. Current epidemiologic evidence supports a major role in transmission for direct contact with live camels or humans with symptomatic MERS, but little evidence suggests the possibility of transmission from camel products or asymptomatic MERS cases. Because a proportion of case-patients do not report direct contact with camels or with persons who have symptomatic MERS, further research is needed to conclusively determine additional mechanisms of transmission, to inform public health practice, and to refine current precautionary recommendations.

negative: Chloroquine diphosphate: a risk factor for herpes zoster in patients with dermatomyositis/polymyositis OBJECTIVES: Herpes zoster has been widely described in the context of different systemic autoimmune diseases but not dermatomyositis/polymyositis. Therefore, we analyzed the prevalence, risk factors and herpes zoster outcomes in this population. METHOD: A retrospective cohort study of herpes zoster infections in dermatomyositis/polymyositis patients was performed. The patients were followed at a tertiary center from 1991 to 2012. For the control group, each patient with herpes zoster was paired with two patients without herpes zoster. Patients were matched by gender and the type of myositis, age at myositis onset and disease duration. RESULTS: Of 230 patients, 24 (10.4%) had a histories of herpes zoster (19 with dermatomyositis and five with polymyositis, two-thirds female). The mean age of the patients with herpes zoster was 44.6±16.8 years. No difference between the groups was found regarding cumulative clinical manifestations. Disease activity, autoantibody, muscle and leukogram parameters were also comparable between the groups. No differences in immunosuppressive (alone or in association with other immunosuppressive therapies) or glucocorticoid (current use, medium dose and cumulative dose in the last two months) therapies were found between patients with and without herpes zoster. However, a higher proportion of patients in the herpes zoster group received chloroquine diphosphate compared to the control group. All of the patients received acyclovir; 58.3% of patients had postherpetic neuralgia and no cases of recurrence were reported. Furthermore, individuals who were taking high prednisone doses at the time of the herpes zoster diagnosis had reduced levels of postherpetic neuralgia. CONCLUSIONS: These data suggest that chloroquine diphosphate could predispose patients with dermatomyositis/polymyositis to developing herpes zoster, particularly women and dermatomyositis patients.

negative: Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study Summary Background Coronavirus disease 2019 (COVID-19) causes severe community and nosocomial outbreaks. Comprehensive data for serial respiratory viral load and serum antibody responses from patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not yet available. Nasopharyngeal and throat swabs are usually obtained for serial viral load monitoring of respiratory infections but gathering these specimens can cause discomfort for patients and put health-care workers at risk. We aimed to ascertain the serial respiratory viral load of SARS-CoV-2 in posterior oropharyngeal (deep throat) saliva samples from patients with COVID-19, and serum antibody responses. Methods We did a cohort study at two hospitals in Hong Kong. We included patients with laboratory-confirmed COVID-19. We obtained samples of blood, urine, posterior oropharyngeal saliva, and rectal swabs. Serial viral load was ascertained by reverse transcriptase quantitative PCR (RT-qPCR). Antibody levels against the SARS-CoV-2 internal nucleoprotein (NP) and surface spike protein receptor binding domain (RBD) were measured using EIA. Whole-genome sequencing was done to identify possible mutations arising during infection. Findings Between Jan 22, 2020, and Feb 12, 2020, 30 patients were screened for inclusion, of whom 23 were included (median age 62 years [range 37–75]). The median viral load in posterior oropharyngeal saliva or other respiratory specimens at presentation was 5·2 log10 copies per mL (IQR 4·1–7·0). Salivary viral load was highest during the first week after symptom onset and subsequently declined with time (slope −0·15, 95% CI −0·19 to −0·11; R 2=0·71). In one patient, viral RNA was detected 25 days after symptom onset. Older age was correlated with higher viral load (Spearman's ρ=0·48, 95% CI 0·074–0·75; p=0·020). For 16 patients with serum samples available 14 days or longer after symptom onset, rates of seropositivity were 94% for anti-NP IgG (n=15), 88% for anti-NP IgM (n=14), 100% for anti-RBD IgG (n=16), and 94% for anti-RBD IgM (n=15). Anti-SARS-CoV-2-NP or anti-SARS-CoV-2-RBD IgG levels correlated with virus neutralisation titre (R 2>0·9). No genome mutations were detected on serial samples. Interpretation Posterior oropharyngeal saliva samples are a non-invasive specimen more acceptable to patients and health-care workers. Unlike severe acute respiratory syndrome, patients with COVID-19 had the highest viral load near presentation, which could account for the fast-spreading nature of this epidemic. This finding emphasises the importance of stringent infection control and early use of potent antiviral agents, alone or in combination, for high-risk individuals. Serological assay can complement RT-qPCR for diagnosis. Funding Richard and Carol Yu, May Tam Mak Mei Yin, The Shaw Foundation Hong Kong, Michael Tong, Marina Lee, Government Consultancy Service, and Sanming Project of Medicine.

negative: COVID-19 pneumonia patient without clear epidemiological history outside Wuhan: An analysis of the radiographic and clinical features Abstract The purpose of this case report is to describe the CT and clinical features of a COVID-19 pneumonia patient without clear epidemiological history outside Wuhan, China.

negative: Loss of Paramedic Availability in an Urban Emergency Medical Services System during a Severe Acute Respiratory Syndrome Outbreak Objectives: To describe the loss of paramedic availability to Toronto Emergency Medical Services during a biphasic (SARS‐1 and SARS‐2) outbreak of severe acute respiratory syndrome (SARS). Methods:During the SARS outbreak, a dedicated paramedic surveillance and quarantine program was developed. The authors determined the number of paramedics on quarantine each day, the type of quarantine (either home quarantine [HQ] or work quarantine [WQ]), and the development of SARS‐like symptoms. Results: During the SARS outbreak, there were five cases of probable SARS and three cases of suspect SARS. SARS‐1 lasted 30 days, during which 234 paramedics were placed on HQ. The total number of HQ days was 1,615. During the five peak days of SARS‐1, the total number of HQ days was 664. SARS‐2 lasted 18 days, during which 292 paramedics were placed on either HQ or WQ, for a combined number of quarantine days of 1,637. During the five peak days of SARS‐2, the combined number of quarantine days was 910. Of these, paramedics were available for duty on 708 days (78%) due to the WQ program. The primary reason for quarantine was unprotected exposure to a health care institution experiencing a SARS outbreak. Under quarantine, SARS‐like symptoms developed in 68 paramedics, including cough (53 [78%]), myalgia (33 [48%]), fatigue (30 [44%]), headache (29 [43%]), fever (11 [16%]), and shortness of breath (7 [10%]). Conclusions: Paramedics were among the health care workers who developed SARS. During SARS‐2, WQ optimized the number of days on which paramedics were available for duty. Many paramedics developed SARS‐like symptoms without being diagnosed as having SARS. A dedicated paramedic surveillance and quarantine program provided a useful means to manage the paramedic resource during the SARS outbreak.

negative: Geographical tracking and mapping of coronavirus disease COVID-19/severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic and associated events around the world: how 21st century GIS technologies are supporting the global fight against outbreaks and epidemics In December 2019, a new virus (initially called ‘Novel Coronavirus 2019-nCoV’ and later renamed to SARS-CoV-2) causing severe acute respiratory syndrome (coronavirus disease COVID-19) emerged in Wuhan, Hubei Province, China, and rapidly spread to other parts of China and other countries around the world, despite China’s massive efforts to contain the disease within Hubei. As with the original SARS-CoV epidemic of 2002/2003 and with seasonal influenza, geographic information systems and methods, including, among other application possibilities, online real-or near-real-time mapping of disease cases and of social media reactions to disease spread, predictive risk mapping using population travel data, and tracing and mapping super-spreader trajectories and contacts across space and time, are proving indispensable for timely and effective epidemic monitoring and response. This paper offers pointers to, and describes, a range of practical online/mobile GIS and mapping dashboards and applications for tracking the 2019/2020 coronavirus epidemic and associated events as they unfold around the world. Some of these dashboards and applications are receiving data updates in near-real-time (at the time of writing), and one of them is meant for individual users (in China) to check if the app user has had any close contact with a person confirmed or suspected to have been infected with SARS-CoV-2 in the recent past. We also discuss additional ways GIS can support the fight against infectious disease outbreaks and epidemics.

negative: COVID-19: A promising cure for the global panic Abstract The novel Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2, which is the causative agent of a potentially fatal disease that is of great global public health concern. The outbreak of COVID-19 is wreaking havoc worldwide due to inadequate risk assessment regarding the urgency of the situation. The COVID-19 pandemic has entered a dangerous new phase. When compared with SARS and MERS, COVID-19 has spread more rapidly, due to increased globalization and adaptation of the virus in every environment. Slowing the spread of the COVID-19 cases will significantly reduce the strain on the healthcare system of the country by limiting the number of people who are severely sick by COVID-19 and need hospital care. Hence, the recent outburst of COVID-19 highlights an urgent need for therapeutics targeting SARS-CoV-2. Here, we have discussed the structure of virus; varying symptoms among COVID-19, SARS, MERS and common flu; the probable mechanism behind the infection and its immune response. Further, the current treatment options, drugs available, ongoing trials and recent diagnostics for COVID-19 have been discussed. We suggest traditional Indian medicinal plants as possible novel therapeutic approaches, exclusively targeting SARS-CoV-2 and its pathways.

negative: Comorbid Diabetes Mellitus was Associated with Poorer Prognosis in Patients with COVID-19: A Retrospective Cohort Study Background The 2019 novel coronavirus disease (COVID-19) emerged in Wuhan, Hubei province, China, and was characterized as pandemic by the World Health Organization. Diabetes mellitus is an established risk factor for poor clinical outcomes, but the association of diabetes with the prognosis of COVID-19 have not been reported yet. Methods In this cohort study, we retrospectively reviewed 258 consecutive hospitalized COVID-19 patients with or without diabetes at the West Court of Union Hospital of Huazhong University of Science and Technology in Wuhan, China, recruited from January 29 to February 12, 2020. The cases were confirmed by real-time PCR and the demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Prognosis was defined as hospitalization, discharged survivor and death, which was followed up until March 12, 2020. Results Of the 258 hospitalized patients (63 with diabetes) with COVID-19, the median age was 64 years (range 23-91), and 138 (53.5%) were male. No significant differences in age and sex were identified between patients with and without diabetes. Common symptoms included fever (82.2%), dry cough (67.1%), polypnea (48.1%), and fatigue (38%). Patients with diabetes had significantly higher leucocyte and neutrophil counts, and higher levels of fasting blood glucose, serum creatinine, urea nitrogen and creatine kinase isoenzyme MB at admission compared with those without diabetes. COVID-19 patients with diabetes were more likely to develop severe or critical disease condition with more complications at presentation, and had higher incidence rates of antibiotic therapy, non-invasive and invasive mechanical ventilation, and death (11.1% vs. 4.1%). Cox proportional hazard model showed that diabetes (adjusted hazard ratio [aHR]=3.64; 95% confidence interval [CI]: 1.09, 12.21) and fasting blood glucose (aHR=1.19; 95% CI: 1.08, 1.31) were associated with the fatality of COVID-19, adjusting for potential confounders. Conclusions Diabetes mellitus is associated with greater disease severity and a higher risk of mortality in patients with COVID-19. Primary and secondary prevention strategies are needed for COVID-19 patients with diabetes.

negative: The effect of uncontrolled travelers and social distancing on the spread of novel coronavirus disease (COVID-19) in Colombia

negative: A Chinese Case of Coronavirus Disease 2019 (COVID-19) Did Not Show Infectivity During the Incubation Period: Based on an Epidemiological Survey Controversy remains over whether the coronavirus disease 2019 (COVID-19) virus may have infectivity during the incubation period before the onset of symptoms. The author had the opportunity to examine the infectivity of COVID-19 during the incubation period by conducting an epidemiological survey on a confirmed patient who had visited Jeju Island during the incubation period. The epidemiological findings support the claim that the COVID-19 virus does not have infectivity during the incubation period.

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

negative: Chapter 8 The Middle East Respiratory Syndrome Coronavirus: An Emerging Virus of Global Threat Abstract Middle East respiratory syndrome (MERS) is a viral respiratory illness caused by a coronavirus (CoV), first identified in Saudi Arabia in 2012. Since then, almost 2000 cases have been reported from 27 countries, with Saudi Arabia being the epicenter. This newly emerging virus is highly pathogenic and has a case mortality rate of 35%. It is similar to the CoV causing severe acute respiratory syndrome CoV (SARS-CoV) in that both belong to the genus beta CoVs that are of zoonotic origin and cause lower respiratory infection. The natural reservoir for MERS-CoV remains unknown. Serological studies indicate that most dromedary camels in the Middle East have been infected with this virus, and they maybe the potential intermediate host. However, the mode of transmission from camels to humans is poorly understood. The majority of confirmed human cases have resulted from human-to-human transmission, most probably via respiratory route. Patients most at risk of developing severe MERS-CoV infection appear to be those with underlying conditions such as diabetes, hypertension, obesity, cardiac diseases, chronic respiratory diseases, and cancer. Unlike SARS-CoV, MERS-CoV is considered an ongoing public health problem, particularly for the Middle East region. In this chapter, we outline the prevailing information regarding the emergence and epidemiology of this virus, its mode of transmission and pathogenicity, its clinical features, and the potential strategies for prevention.

negative: Prevalence and molecular epidemiology of human coronavirus HKU1 in patients with acute respiratory illness In 2005, human coronavirus HKU1 (HCoV‐HKU1) was isolated and identified from a 71‐year‐old man with pneumonia in Hong Kong. To identify and classify genotypes of HCoV‐HKU1 in Korea, a sensitive, specific, and quantitative real‐time polymerase chain reaction (PCR) assay was developed and analyzed the sequences of HCoV‐HKU1 isolated in Korea. A total of 1,985 respiratory specimens taken from patients with acute respiratory illness were tested for HCoV‐HKU1 from January 2007 to May 2008. The major clinical symptoms associated with HCoV‐HKU1 infection were examined statistically and sequence variations of the RNA‐dependent RNA polymerase (RdRp), spike, and nucleocapsid genes were also analyzed. Fifty cases (2.5%) HCoV‐HKU1 were identified by real‐time PCR and viral loads ranged from 6.7 × 10(4) to 1.6 × 10(9) copies/ml. The clinical symptoms of HCoV‐HKU1 infection included rhinorrhea (72%), cough (64%), nasal congestion (56%), fever (32%), sputum (30%), sore throat (18%), chills (16%), postnasal discharge (14%), and tonsillar hypertrophy (10%). There was a seasonal distribution of HCoV‐HKU1 infection, peaking in winter and spring. Both genotypes A and B were detected but no recombination between them was found. This is the first report on the identification and genotyping of HCoV‐HKU1 as a causative agent of acute respiratory illness in Korea. The data suggest that at least two genotypes, A and B, of HCoV‐HKU1 with scattered silent mutations were circulating in Korea from 2007 to 2008. J. Med. Virol. 85:309–314, 2013. © 2012 Wiley Periodicals, Inc.

negative: Respiratory Virus Infections in People Over 14 Years of Age in Poland in the Epidemic Season of 2017/18 People most at risk of influenza complications are the elderly with impaired immunity. Clinical picture of influenza virus infection includes symptoms such as chills, increased body temperature, dry cough, chest pain, or dizziness as well as headaches and muscle aches. In the diagnosis of influenza, quick and effective tests are necessary. Sensitive diagnostic methods of molecular biology require more time, but the result firmly confirm or exclude the presence of the genetic material of influenza or other respiratory viruses. Influenza vaccination plays an important role in combating influenza infection. Unfortunately, the awareness of vaccination benefits is insufficient in Poland. In this study we demonstrate the results of examination of 4,507 people aged over 14 years toward the influenza infection in the epidemic season of 2017/18. Most of the confirmed infections were reported in older people aged over 65, a high-risk population group. A low percentage of the vaccinated population may affect an increased number of confirmed influenza viruses in the elderly. The findings demonstrate a need to increase awareness of vaccination benefits, which is particularly essential to avoid influenza infection in the elderly.

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: Tropheryma whipplei in Children with Gastroenteritis Tropheryma whipplei, which causes Whipple disease, is found in human feces and may cause gastroenteritis. To show that T. whipplei causes gastroenteritis, PCRs for T. whipplei were conducted with feces from children 2–4 years of age. Western blotting was performed for samples from children with diarrhea who had positive or negative results for T. whipplei. T. whipplei was found in samples from 36 (15%) of 241 children with gastroenteritis and associated with other diarrheal pathogens in 13 (33%) of 36. No positive specimen was detected for controls of the same age (0/47; p = 0.008). Bacterial loads in case-patients were as high as those in patients with Whipple disease and significantly higher than those in adult asymptomatic carriers (p = 0.002). High incidence in patients and evidence of clonal circulation suggests that some cases of gastroenteritis are caused or exacerbated by T. whipplei, which may be co-transmitted with other intestinal pathogens.

negative: COVID-19 Outbreak in Pakistan: Model-Driven Impact Analysis and Guidelines Motivated by the rapid spread of COVID-19 all across the globe, we have performed simulations of a system dynamic epidemic spread model in different possible situations. The simulation, not only captures the model dynamic of the spread of the virus, but also, takes care of population and mobility data. The model is calibrated based on epidemic data and events specifically of Pakistan, which can easily be generalized. The simulation results are quite disturbing, indicating that, even with stringent social distancing and testing strategies and for a quite long time (even beyond one year), the spread would be significant (in tens of thousands). The real alarm is when some of these measures got leaked for a short time within this duration, which may result in catastrophic situation when millions of people would be infected.

negative: Pandemic dynamics of COVID-19 using epidemic stage, instantaneous reproductive number and pathogen genome identity (GENI) score: modeling molecular epidemiology Background: Global spread of COVID-19 created an unprecedented infectious disease crisis that progressed to a pandemic with >180,000 cases in >100 countries. Reproductive number (R) is an outbreak metric estimating the transmission of a pathogen. Initial R values were published based on the early outbreak in China with limited number of cases with whole genome sequencing. Initial comparisons failed to show a direct relationship viral genomic diversity and epidemic severity was not established for SARS-Cov-2. Methods: Each country's COVID-19 outbreak status was classified according to epicurve stage (index, takeoff, exponential, decline). Instantaneous R estimates (Wallinga and Teunis method) with a short and standard serial interval examined asymptomatic spread. Whole genome sequences were used to quantify the pathogen genome identity score that were used to estimate transmission time and epicurve stage. Transmission time was estimated based on evolutionary rate of 2 mutations/month. Findings: The country-specific R revealed variable infection dynamics between and within outbreak stages. Outside China, R estimates revealed propagating epidemics poised to move into the takeoff and exponential stages. Population density and local temperatures had variable relationship to the outbreaks. GENI scores differentiated countries in index stage with cryptic transmission. Integration of incidence data with genome variation directly increases in cases with increased genome variation. Interpretation: R was dynamic for each country and during the outbreak stage. Integrating the outbreak dynamic, dynamic R, and genome variation found a direct association between cases and genome variation. Synergistically, GENI provides an evidence-based transmission metric that can be determined by sequencing the virus from each case. We calculated an instantaneous country-specific R at different stages of outbreaks and formulated a novel metric for infection dynamics using viral genome sequences to capture gaps in untraceable transmission. Integrating epidemiology with genome sequencing allows evidence-based dynamic disease outbreak tracking with predictive evidence.

negative: 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.

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

negative: High-resolution CT features of the COVID-19 infection in Nanchong City: Initial and follow-up changes among different clinical types OBJECTIVE: To discuss the high resolution computed tomography (HRCT) manifestations of coronavirus disease 2019 (COVID-19) patients among different clinical types on initial and follow-up CT. METHODS: Seven COVID-19 patients admitted to the Affiliated Hospital of North Sichuan Medical Collage were enrolled. All patients underwent initial and follow-up chest HRCT. The main CT features and semi-quantitative score which represent disease severity among different clinical types were evaluated. RESULT: On initial CT, the main abnormalities observed in common and severe cases respectively were pure ground glass opacities (GGOs) and patchy consolidation surrounded by GGOs. Critical cases had multiple consolidation surrounded by wide range of GGOs distributed in the whole lung fields. The scope and density score in common (4.5 and 5), severe (9.5 and 9.5) and critical (19 and 12) cases were increased by gradient. On follow-up CT, common and severe types manifested as decreasing density of lesion, absorbed consolidation and GGOs. Critical cases showed progression of the disease. The extent and progression scores in common and severe patients were significantly decreased, while the range score of patients with critical disease reached the highest points, accompanied with an increase in the density score. CONCLUSION: CT scanning can accurately assess the severity of COVID-19, and help to monitor disease transformation during follow-up among different clinical conditions.

negative: PepMapper: A Collaborative Web Tool for Mapping Epitopes from Affinity-Selected Peptides Epitope mapping from affinity-selected peptides has become popular in epitope prediction, and correspondingly many Web-based tools have been developed in recent years. However, the performance of these tools varies in different circumstances. To address this problem, we employed an ensemble approach to incorporate two popular Web tools, MimoPro and Pep-3D-Search, together for taking advantages offered by both methods so as to give users more options for their specific purposes of epitope-peptide mapping. The combined operation of Union finds as many associated peptides as possible from both methods, which increases sensitivity in finding potential epitopic regions on a given antigen surface. The combined operation of Intersection achieves to some extent the mutual verification by the two methods and hence increases the likelihood of locating the genuine epitopic region on a given antigen in relation to the interacting peptides. The Consistency between Intersection and Union is an indirect sufficient condition to assess the likelihood of successful peptide-epitope mapping. On average from 27 tests, the combined operations of PepMapper outperformed either MimoPro or Pep-3D-Search alone. Therefore, PepMapper is another multipurpose mapping tool for epitope prediction from affinity-selected peptides. The Web server can be freely accessed at: http://informatics.nenu.edu.cn/PepMapper/

negative: Radiographic findings in 240 patients with COVID-19 pneumonia: time-dependence after the onset of symptoms OBJECTIVE: To analyze the most frequent radiographic features of COVID-19 pneumonia and assess the effectiveness of chest X-ray (CXR) in detecting pulmonary alterations. MATERIALS AND METHODS: CXR of 240 symptomatic patients (70% male, mean age 65 ± 16 years), with SARS-CoV-2 infection confirmed by RT-PCR, was retrospectively evaluated. Patients were clustered in four groups based on the number of days between symptom onset and CXR: group A (0–2 days), 49 patients; group B (3–5), 75 patients; group C (6–9), 85 patients; and group D (> 9), 31 patients. Alteration’s type (reticular/ground-glass opacity (GGO)/consolidation) and distribution (bilateral/unilateral, upper/middle/lower fields, peripheral/central) were noted. Statistical significance was tested using chi-square test. RESULTS: Among 240 patients who underwent CXR, 180 (75%) showed alterations (group A, 63.3%; group B, 72%; group C, 81.2%; group D, 83.9%). GGO was observed in 124/180 patients (68.8%), reticular alteration in 113/180 (62.7%), and consolidation in 71/180 (39.4%). Consolidation was significantly less frequent (p < 0.01). Distribution among groups was as follows: reticular alteration (group A, 70.9%; group B, 72.2%; group C, 57.9%; group D, 46.1%), GGO (group A, 67.7%; group B, 62.9%; group C, 71%; group D, 76.9%), and consolidation (group A, 35.5%; group B, 31.4%; group C, 47.8%; group D, 38.5%). Alterations were bilateral in 73.3%. Upper, middle, and lower fields were involved in 36.7%, 79.4%, and 87.8%, respectively. Lesions were peripheral in 49.4%, central in 11.1%, or both in 39.4%. Upper fields and central zones were significantly less involved (p < 0.01). CONCLUSIONS: The most frequent lesions in COVID-19 patients were GGO (intermediate/late phase) and reticular alteration (early phase) while consolidation gradually increased over time. The most frequent distribution was bilateral, peripheral, and with middle/lower predominance. Overall rate of negative CXR was 25%, which progressively decreased over time. KEY POINTS: • The predominant lung changes were GGO and reticular alteration, while consolidation was less frequent. • The typical distribution pattern was bilateral, peripheral, or both peripheral and central and involved predominantly the lower and middle fields. • Chest radiography showed lung abnormalities in 75% of patients with confirmed SARS-CoV-2 infection, range varied from 63.3 to 83.9%, respectively, at 0–2 days and > 9 days from the onset of symptoms.

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: Epidemiological and clinical characteristics of 26 asymptomatic SARS-CoV-2 carriers BACKGROUND: We retrospectively analysed 26 persistently asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) carriers. METHODS: Epidemiological and clinical characteristics from the 26 asymptomatic patients with positive results for SARS-CoV-2 RNA testing were obtained. RESULTS: Twenty-two patients (84.6%) correlated with clustering occurrence. The median period from contact to diagnosis and the last positive nucleic acid test was 19 (8–24 days) and 21.5 days (10–36 days), respectively. The median period from diagnosis to negative nucleic acid test was significantly different between patients with normal or atypical chest computed tomography (CT) findings (n=16, 61.5%; 7.5 days [2–20 days]) and patients with typical ground-glass or patchy opacities on CT(n=10, 38.5%; 12.5 days[8–22 days]; P<0.01). Seven patients (70.0%) with initial positive nucleic acid test results had a negative result simultaneously with improved CT findings. Obvious improvement in CT findings was observed in three patients (30.0%) despite positive nucleic acid test results. CONCLUSION: In asymptomatic patients, changes in biochemical and inflammatory variables are small and changes on chest CT can occur. It is worth noting the long existence of SARS-CoV-2 in some asymptomatic patients and false-negative results need to be considered in SARS-CoV-2nucleic acid test.

negative: Epidemiology, Diagnosis, and Management of Esophageal Adenocarcinoma. Esophageal adenocarcinoma (EAC) is rapidly increasing in incidence in Western cultures. Barrett's esophagus is the presumed precursor lesion for this cancer. Several other risk factors for this cancer have been described, including chronic heartburn, tobacco use, white race, and obesity. Despite these known associations, most patients with EAC present with symptoms of dysphagia from late-stage tumors; only a small number of patients are identified by screening and surveillance programs. Diagnostic analysis of EAC usually commences with upper endoscopy followed by cross-sectional imaging. Endoscopic ultrasonography is useful to assess the local extent of disease as well as the involvement of regional lymph nodes. T1a EAC may be treated endoscopically, and some patients with T1b disease may also benefit from endoscopic therapy. Locally advanced disease is generally managed with esophagectomy, often accompanied by neoadjuvant chemoradiotherapy or chemotherapy. The prognosis is based on tumor stage; patients with T1a tumors have an excellent prognosis, whereas few patients with advanced disease have long-term survival.

negative: Epidemiological and clinical characteristics of discharged patients infected with SARS-CoV-2 on the Qinghai plateau Since the outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, a series of confirmed cases of COVID-19 were found on the Qinghai-Tibet plateau. We aimed to describe the epidemiological, clinical characteristics, and outcomes of all confirmed cases in Qinghai, a province at high altitude. With efficient measures to stop the spread of coronavirus, no new cases were found in Qinghai Province for 60 consecutive days between Feb 6 and April 6, 2020. Of all 18 patients with confirmed SARS-CoV-2 infection, 15 patients comprising 4 transmission clusters were identified. Three patients were infected by direct contact without travel history to Wuhan. Seven patients were asymptomatic on admission. Of 18 patients, 10 patients showed bilateral pneumonia and 2 patients showed no abnormalities. Three patients with comorbidities such as hypertension, liver diseases or diabetes developed severe illness. High C-reactive protein levels and elevations of both ALT and AST were observed in 3 severely ill patients on admission. All 18 patients were eventually discharged, including the 3 severe patients who recovered after treatment with non-invasive mechanical ventilation, convalescent plasma and other therapies. Our findings confirmed human-to-human transmission of SARS-CoV-2 in clusters. The strategies of early diagnosis, early isolation, and early treatment are important to prevent the spread of COVID-19 and improve the cure rate. Patients with comorbidities are more likely to develop severe illness and could benefit from convalescent plasma transfusion.

negative: Social and administrative issues related to the COVID-19 pandemic in Pakistan: better late than never The study critically reviewed Pakistan’s provincial updates of coronavirus disease 2019 (COVID-19) and discussed the current challenges faced by the government in a given context. The coronavirus-associated death tolls have been increasing rapidly in a country. The provincial status of confirmed cases of coronavirus is higher in Punjab, followed by the Sindh, Khyber Pakhtunkhwa (KPK), and Balochistan. The case fatality ratio shows that KPK has a higher ratio, i.e., 5.11%, followed by the Punjab, i.e., 1.82%; Sindh, i.e., 1.80%; Balochistan, i.e., 1.28%; Gilgit-Baltistan, i.e., 0.71%; and Federal territory, i.e., 0.66%. The country has a less testing capacity to identify more suspected coronavirus patients. The study calculated that if we increase five times our testing capacity from the current date, the total registered cases will be reached to 137,370 and death tolls will increase up to 3090. It is highly needed to increase testing capacity across Pakistan in order to minimize the outbreak of coronavirus. The provincial government should follow the Federal Government instructions to contain coronavirus by increasing testing capacities, tracing suspected patients, smart lockdowns, emergency relief to the poor, and vigilant monitoring system.

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

negative: 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.

negative: Efficacy and safety of an antiviral Iota-Carrageenan nasal spray: a randomized, double-blind, placebo-controlled exploratory study in volunteers with early symptoms of the common cold BACKGROUND: The common cold, the most prevalent contagious viral disease in humans still lacks a safe and effective antiviral treatment. Iota-Carrageenan is broadly active against respiratory viruses in-vitro and has an excellent safety profile. This study investigated the efficacy and safety of an Iota-Carrageenan nasal spray in patients with common cold symptoms. METHODS: In a randomized, double-blind, placebo-controlled exploratory trial, 35 human subjects suffering from early symptoms of common cold received Iota-Carrageenan (0.12%) in a saline solution three times daily for 4 days, compared to placebo. RESULTS: Administration of Iota-Carrageenan nasal spray reduced the symptoms of common cold (p = 0.046) and the viral load in nasal lavages (p = 0.009) in patients with early symptoms of common cold. Pro-inflammatory mediators FGF-2, Fractalkine, GRO, G-CSF, IL-8, IL-1α, IP-10, IL-10, and IFN-α2 were reduced in the Iota-Carrageenan group. CONCLUSIONS: Iota-Carrageenan nasal spray appears to be a promising treatment for safe and effective treatment of early symptoms of common cold. Larger trials are indicated to confirm the results.

negative: Immunomodulator expression in trophoblasts from the feline immunodeficiency virus (FIV)-infected cat BACKGROUND: FIV infection frequently compromises pregnancy under experimental conditions and is accompanied by aberrant expression of some placental cytokines. Trophoblasts produce numerous immunomodulators that play a role in placental development and pregnancy maintenance. We hypothesized that FIV infection may cause dysregulation of trophoblast immunomodulator expression, and aberrant expression of these molecules may potentiate inflammation and compromise pregnancy. The purpose of this project was to evaluate the expression of representative pro-(TNF-α, IFN-γ, IL-1β, IL-2, IL-6, IL-12p35, IL-12p40, IL-18, and GM-CSF) and anti-inflammatory cytokines (IL-4, IL-5, and IL-10); CD134, a secondary co-stimulatory molecule expressed on activated T cells (FIV primary receptor); the chemokine receptor CXCR4 (FIV co-receptor); SDF-1α, the chemokine ligand to CXCR4; and FIV gag in trophoblasts from early-and late-term pregnancy. METHODS: We used an anti-cytokeratin antibody in immunohistochemistry to identify trophoblasts selectively, collected these cells using laser capture microdissection, and extracted total RNA from the captured cell populations. Real time, reverse transcription-PCR was used to quantify gene expression. RESULTS: We detected IL-4, IL-5, IL-6, IL-1β, IL-12p35, IL-12p40, and CXCR4 in trophoblasts from early-and late-term pregnancy. Expression of cytokines increased from early to late pregnancy in normal tissues. A clear, pro-inflammatory microenvironment was not evident in trophoblasts from FIV-infected queens at either stage of pregnancy. Reproductive failure was accompanied by down-regulation of both pro-and anti-inflammatory cytokines. CD134 was not detected in trophoblasts, and FIV gag was detected in only one of ten trophoblast specimens collected from FIV-infected queens. CONCLUSION: Feline trophoblasts express an array of pro-and anti-inflammatory immunomodulators whose expression increases from early to late pregnancy in normal tissues. Non-viable pregnancies were associated with decreased expression of immunomodulators which regulate trophoblast invasion in other species. The detection of FIV RNA in trophoblasts was rare, suggesting that the high rate of reproductive failure in FIV-infected queens was not a direct result of viral replication in trophoblasts. The influence of placental immune cells on trophoblast function and pregnancy maintenance in the FIV-infected cat requires additional study.

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: The COVID-19 pandemic and the use of MS disease-modifying therapies

negative: Coronavirus: hospitals must learn from past pandemics.

negative: Covid-19 by Race and Ethnicity: A National Cohort Study of 6 Million United States Veterans BACKGROUND: There is growing concern that racial and ethnic minority communities around the world are experiencing a disproportionate burden of morbidity and mortality from symptomatic SARS-Cov-2 infection or coronavirus disease 2019 (Covid-19). Most studies investigating racial and ethnic disparities to date have focused on hospitalized patients or have not characterized who received testing or those who tested positive for Covid-19. OBJECTIVE: To compare patterns of testing and test results for coronavirus 2019 (Covid-19) and subsequent mortality by race and ethnicity in the largest integrated healthcare system in the United States. DESIGN: Retrospective cohort study. SETTING: United States Department of Veterans Affairs (VA). PARTICIPANTS: 5,834,543 individuals in care, among whom 62,098 were tested and 5,630 tested positive for Covid-19 between February 8 and May 4, 2020. EXPOSURES: Self-reported race/ethnicity. MAIN OUTCOME MEASURES: We evaluated associations between race/ethnicity and receipt of Covid-19 testing, a positive test result, and 30-day mortality, accounting for a wide range of demographic and clinical risk factors including comorbid conditions, site of care, and urban versus rural residence. RESULTS: Among all individuals in care, 74% were non-Hispanic white (white), 19% non-Hispanic black (black), and 7% Hispanic. Compared with white individuals, black and Hispanic individuals were more likely to be tested for Covid-19 (tests per 1000: white=9.0, [95% CI 8.9 to 9.1]; black=16.4, [16.2 to 16.7]; and Hispanic=12.2, [11.9 to 12.5]). While individuals from minority backgrounds were more likely to test positive (black vs white: OR 1.96, 95% CI 1.81 to 2.12; Hispanic vs white: OR 1.73, 95% CI 1.53 to 1.96), 30-day mortality did not differ by race/ethnicity (black vs white: OR 0.93, 95% CI 0.64 to 1.33; Hispanic vs white: OR 1.07, 95% CI 0.61 to 1.87). CONCLUSIONS: Black and Hispanic individuals are experiencing an excess burden of Covid-19 not entirely explained by underlying medical conditions or where they live or receive care. While there was no observed difference in mortality by race or ethnicity, our findings may underestimate risk in the broader US population as health disparities tend to be reduced in VA.

negative: Recent progress in understanding 2019 novel coronavirus (SARS-CoV-2) associated with human respiratory disease: detection, mechanisms and treatment ABSTRACT Viral respiratory diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) always pose a severe threat to people. First identified in late December 2019, a novel coronavirus (2019-nCoV; SARS-CoV-2) has affected many provinces in China and multiple countries worldwide. The viral outbreak has aroused panic and a public-health emergency around the world, and the number of infections continues to rise. However, the causes and consequences of the pneumonia remain unknown. To effectively implement epidemic prevention, early identification and diagnosis are critical to disease control. Here we scrutinise a series of available studies by global scientists on the clinical manifestations, detection methods and treatment options for the disease caused by SARS-CoV-2, named coronavirus disease 2019 (COVID-19), and also propose potential strategies for preventing the infection.

negative: Determining Urgent/Emergent Status of Gastrointestinal Endoscopic Procedures in an Ambulatory Care Setting During the COVID-19 Pandemic: Additional Factors That Need To Be Considered

negative: Coronavirus-like particles in nonhuman primate feces Coronavirus-like particles were detected by electron microscopy in normal and diarrhea stool specimens from baboons, chimpanzees, macaques, and marmosets. There was a high prevalence of particles in both normal and diarrhea stools of older animals, whereas stools from nonweaned animals rarely contained these coronavirus-like particles.

negative: Clinical Manifestations, Laboratory Findings, and Treatment Outcomes of SARS Patients Clinical and laboratory data on severe acute respiratory syndrome (SARS), particularly on the temporal progression of abnormal laboratory findings, are limited. We conducted a prospective study on the clinical, radiologic, and hematologic findings of SARS patients with pneumonia, who were admitted to National Taiwan University Hospital from March 8 to June 15, 2003. Fever was the most frequent initial symptom, followed by cough, myalgia, dyspnea, and diarrhea. Twenty-four patients had various underlying diseases. Most patients had elevated C-reactive protein (CRP) levels and lymphopenia. Other common abnormal laboratory findings included leukopenia, thrombocytopenia, and elevated levels of aminotransferase, lactate dehydrogenase, and creatine kinase. These clinical and laboratory findings were exacerbated in most patients during the second week of disease. The overall case-fatality rate was 19.7%. By multivariate analysis, underlying disease and initial CRP level were predictive of death.

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: 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

negative: A British Society of Thoracic Imaging statement: considerations in designing local imaging diagnostic algorithms for the COVID-19 pandemic

negative: Interplay between SIN3A and STAT3 Mediates Chromatin Conformational Changes and GFAP Expression during Cellular Differentiation BACKGROUND: Neurons and astrocytes are generated from common neural precursors, yet neurogenesis precedes astrocyte formation during embryogenesis. The mechanisms of neural development underlying suppression and de-suppression of differentiation- related genes for cell fate specifications are not well understood. METHODOLOGY/PRINCIPAL FINDINGS: By using an in vitro system in which NTera-2 cells were induced to differentiate into an astrocyte-like lineage, we revealed a novel role for Sin3A in maintaining the suppression of GFAP in NTera-2 cells. Sin3A coupled with MeCP2 bound to the GFAP promoter and their occupancies were correlated with repression of GFAP transcription. The repression by Sin3A and MeCP2 may be an essential mechanism underlying the inhibition of cell differentiation. Upon commitment toward an astrocyte-like lineage, Sin3A- MeCP2 departed from the promoter and activated STAT3 simultaneously bound to the promoter and exon 1 of GFAP; meanwhile, olig2 was exported from nuclei to the cytoplasm. This suggested that a three-dimensional or higher-order structure was provoked by STAT3 binding between the promoter and proximal coding regions. STAT3 then recruited CBP/p300 to exon 1 and targeted the promoter for histone H3K9 and H3K14 acetylation. The CBP/p300-mediated histone modification further facilitates chromatin remodeling, thereby enhancing H3K4 trimethylation and recruitment of RNA polymerase II to activate GFAP gene transcription. CONCLUSIONS/SIGNIFICANCE: These results provide evidence that exchange of repressor and activator complexes and epigenetic modifications are critical strategies for cellular differentiation and lineage-specific gene expression.

negative: Potential magnitude of COVID-19-induced healthcare resource depletion in Ontario, Canada Background: The global spread of coronavirus disease 2019 (COVID-19) continues in several jurisdictions, causing significant strain to healthcare systems. The purpose of our study is to predict the impact of the COVID-19 pandemic on patient outcomes and the healthcare system in Ontario, Canada. Methods: We developed an individual-level simulation to model the flow of COVID-19 patients through the Ontario healthcare system. We simulated different combined scenarios of epidemic trajectory and healthcare capacity. Outcomes include numbers of patients needing admission to the ward, Intensive Care Unit (ICU), and requiring ventilation; days to resource depletion; and numbers of patients awaiting resources and deaths associated with limited access to resources. Findings: We demonstrate that with effective early public health measures system resources need not be depleted. For scenarios considering late or ineffective implementation of physical distancing, health system resources would be depleted within 14-26 days. Resource depletion was also avoided or delayed with aggressive measures to rapidly increase ICU, ventilator, and acute care hospital capacity. Interpretation: We found that without aggressive physical distancing measures the Ontario healthcare system would have been inadequately equipped to manage the expected number of patients with COVID-19, despite the rapid capacity increase. This overall lack of resources would have led to an increase in mortality. By slowing the spread of the disease via ongoing public health measures and having increased healthcare capacity, Ontario may have avoided catastrophic stresses to its health care system.

negative: CoVID-19 in Japan: What could happen in the future? COVID-19 has been impacting on the whole world critically and constantly Since December 2019. We have independently developed a novel statistical time delay dynamic model on the basis of the distribution models from CCDC. Based only on the numbers of confirmed cases in different regions in China, the model can clearly reveal that the containment of the epidemic highly depends on early and effective isolation. We apply the model on the epidemic in Japan and conclude that there could be a rapid outbreak in Japan if no effective quarantine measures are carried out immediately.

negative: The incubation period of 2019-nCoV infections among travellers from Wuhan, China Currently, a novel coronavirus 2019-nCoV causes an outbreak of viral pneumonia in Wuhan, China. Little is known about its epidemiological characteristics. Using the travel history and symptom onset of 88 confirmed cases that were detected outside Wuhan, we estimate the mean incubation period to be 6.4 (5.6 - 7.7, 95% CI) days, ranging from 2.1 to 11.1 days (2.5th to 97.5th percentile). These values help to inform case definitions for 2019-nCoV and appropriate durations for quarantine.

negative: Attenuation of a virulent swine acute diarrhea syndrome coronavirus strain via cell culture passage Abstract Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly identified enteric alphacoronavirus that causes fatal diarrhea in newborn piglets in China. Here, we propagated a virulent strain SADS-CoV/CN/GDWT/2017 in Vero cells for up to 83 passages. Four strains of SADS-CoV/GDWT-P7, -P18, -P48 and -P83 were isolated and characterized. Sequence alignments showed that these four novel strains exhibited 16 nucleotide mutations and resultant 10 amino acid substitutions in open reading frame 1a/1b, spike, NS3a, envelope, membrane and nucleocapsid proteins. Furthermore, a 58-bp deletion in NS7a/7b was found in P48 and P83 strains, which led to the loss of NS7b and 38 amino acid changes of NS7a. Pig infection studies showed that the P7 strain caused typical watery diarrhea, while the P83 strain induced none-to-mild, delayed and transient diarrhea. This is the first report on cell adaption of a virulent SADS-CoV strain, which gives information on the potential virulence determinants of SADS-CoV.

negative: Feasibility of controlling COVID-19 outbreaks by isolation of cases and contacts BACKGROUND: Isolation of cases and contact tracing is used to control outbreaks of infectious diseases, and has been used for coronavirus disease 2019 (COVID-19). Whether this strategy will achieve control depends on characteristics of both the pathogen and the response. Here we use a mathematical model to assess if isolation and contact tracing are able to control onwards transmission from imported cases of COVID-19. METHODS: We developed a stochastic transmission model, parameterised to the COVID-19 outbreak. We used the model to quantify the potential effectiveness of contact tracing and isolation of cases at controlling a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-like pathogen. We considered scenarios that varied in the number of initial cases, the basic reproduction number (R(0)), the delay from symptom onset to isolation, the probability that contacts were traced, the proportion of transmission that occurred before symptom onset, and the proportion of subclinical infections. We assumed isolation prevented all further transmission in the model. Outbreaks were deemed controlled if transmission ended within 12 weeks or before 5000 cases in total. We measured the success of controlling outbreaks using isolation and contact tracing, and quantified the weekly maximum number of cases traced to measure feasibility of public health effort. FINDINGS: Simulated outbreaks starting with five initial cases, an R(0) of 1·5, and 0% transmission before symptom onset could be controlled even with low contact tracing probability; however, the probability of controlling an outbreak decreased with the number of initial cases, when R(0) was 2·5 or 3·5 and with more transmission before symptom onset. Across different initial numbers of cases, the majority of scenarios with an R(0) of 1·5 were controllable with less than 50% of contacts successfully traced. To control the majority of outbreaks, for R(0) of 2·5 more than 70% of contacts had to be traced, and for an R(0) of 3·5 more than 90% of contacts had to be traced. The delay between symptom onset and isolation had the largest role in determining whether an outbreak was controllable when R(0) was 1·5. For R(0) values of 2·5 or 3·5, if there were 40 initial cases, contact tracing and isolation were only potentially feasible when less than 1% of transmission occurred before symptom onset. INTERPRETATION: In most scenarios, highly effective contact tracing and case isolation is enough to control a new outbreak of COVID-19 within 3 months. The probability of control decreases with long delays from symptom onset to isolation, fewer cases ascertained by contact tracing, and increasing transmission before symptoms. This model can be modified to reflect updated transmission characteristics and more specific definitions of outbreak control to assess the potential success of local response efforts. FUNDING: Wellcome Trust, Global Challenges Research Fund, and Health Data Research UK.

negative: Comparison of SARS-CoV-2 Exit Strategies Building Blocks We consider and compare various exit strategy building blocks and key measures to mitigate the current SARS-CoV-2 pandemic, some already proposed as well as improvements we suggest. Our comparison is based on a computerized simulation integrating accumulated SARS-CoV-2 epidemiological knowledge. Our results stress the importance of immediate on-symptom isolation of suspected cases and household members, and the beneficial effects of prompt testing capacity. Our findings expose significant epidemic-suppression differences among strategies with seemingly similar economic cost stressing the importance of not just the portion of population and business that is released, but also the pattern. The most effective building blocks are the ones that integrate several base strategies - they allow to release large portions of the population while still achieving diminishing viral spread. However, it may come with a price on somewhat more complex schemes. For example, our simulations indicate that dividing the population into two groups completely released except for taking turns on a long weekend (Fri-Tue) self-isolation once every two weeks, while protecting the 5% most sensitive population would reduce R below 1 even if ten percent of the population does not follow it. We further simulate the contrasting approach of a stratified population release in a hope to achieve herd immunity, which for the time being seems inferior to other suggested building blocks. Knowing the tradeoff between building blocks could help optimize exit strategies to be more effective and suitable for a particular area or country, while maximizing human life as well as economic value. Given our results, we believe that pandemic can be controlled within a reasonable amount of time and at a reasonable socio-economic burden.

negative: Radiological approaches to COVID-19 pneumonia COVID-19 pneumonia has high mortality rates. The symptoms are undiagnostic, the results of viral nucleic acid detection method (PCR) can delay, so that chest computerized tomography is often key diagnostic test in patients with possible COVID-19 pneumonia. In this review, we discussed the main radiological findings of this infection.

negative: Prediction of Number of Cases of 2019 Novel Coronavirus (COVID-19) Using Social Media Search Index Predicting the number of new suspected or confirmed cases of novel coronavirus disease 2019 (COVID-19) is crucial in the prevention and control of the COVID-19 outbreak. Social media search indexes (SMSI) for dry cough, fever, chest distress, coronavirus, and pneumonia were collected from 31 December 2019 to 9 February 2020. The new suspected cases of COVID-19 data were collected from 20 January 2020 to 9 February 2020. We used the lagged series of SMSI to predict new suspected COVID-19 case numbers during this period. To avoid overfitting, five methods, namely subset selection, forward selection, lasso regression, ridge regression, and elastic net, were used to estimate coefficients. We selected the optimal method to predict new suspected COVID-19 case numbers from 20 January 2020 to 9 February 2020. We further validated the optimal method for new confirmed cases of COVID-19 from 31 December 2019 to 17 February 2020. The new suspected COVID-19 case numbers correlated significantly with the lagged series of SMSI. SMSI could be detected 6–9 days earlier than new suspected cases of COVID-19. The optimal method was the subset selection method, which had the lowest estimation error and a moderate number of predictors. The subset selection method also significantly correlated with the new confirmed COVID-19 cases after validation. SMSI findings on lag day 10 were significantly correlated with new confirmed COVID-19 cases. SMSI could be a significant predictor of the number of COVID-19 infections. SMSI could be an effective early predictor, which would enable governments’ health departments to locate potential and high-risk outbreak areas.

negative: Influenza A (H1N1) Influenza A (H1N1) is an acute respiratory infectious disease caused by mutant influenza A virus subtype H1N1. The pathogen is a new virus emerging after virus gene recombination of swine influenza, avian influenza, and human influenza. Influenza A (H1N1) is transmitted commonly via respiratory droplets and direct or indirect contact. Clinically, influenza A (H1N1) is characterized by influenza-like symptoms such as fever, cough, and rhinorrhea. But in rare serious cases, the condition may progress rapidly, with occurrence of viral pneumonia, respiratory failure, and multiple organ failure. Even death occurs in serious cases, with a mortality rate of 23–25 %. On April 30, 2009, influenza A (H1N1) was officially listed into Class B infectious diseases in China. Since then, it has been managed according to the Infectious Disease Prevention and Control Act in China. Meanwhile, it has been introduced into the category of quarantinable infectious disease for management based on the Frontier Health and Quarantine Law of China.

negative: Update in the treatment of non-influenza respiratory virus infection in solid organ transplant recipients Introduction: Despite the improved outcomes in solid organ transplantation with regard to prevention of rejection and increased patient and graft survival, infection remains a common cause of morbidity and mortality. Respiratory viruses are a frequent and potentially serious cause of infection after solid organ transplantation. Furthermore, clinical manifestations of respiratory virus infection (RVI) may be more severe and unusual in solid organ transplant recipients (SOTRs) compared with the non-immunocompromised population. Areas covered: This article reviews the non-influenza RVIs that are commonly encountered in SOTRs. Epidemiologic and clinical characteristics are highlighted and available treatment options are discussed. Expert opinion: New diagnostic tools, particularly rapid molecular assays, have expanded the ability to identify specific RVI pathogens in SOTRs. This is not only useful from a treatment standpoint but also to guide infection control practices. More data are needed on RVIs in the solid organ transplant population, particularly regarding their effect on rejection and graft dysfunction. There is also a need for new antiviral agents active against these infections as well as markers that can identify which patients would most benefit from treatment.

negative: Integrated analysis of bulk multi omic and single-cell sequencing data confirms the molecular origin of hemodynamic changes in Covid-19 infection explaining coagulopathy and higher geriatric mortality Besides severe respiratory distress, recent reports in Covid-19 patients have found a strong association between platelet counts and patient survival. Along with hemodynamic changes such as prolonged clotting time, high fibrin degradation products and D-dimers, increased levels of monocytes with disturbed morphology have also been identified. In this study, through an integrated analysis of bulk RNA-sequencing data from Covid-19 patients with data from single-cell sequencing studies on lung tissues, we found that most of the cell-types that contributed to the altered gene expression were of hematopoietic origin. We also found that differentially expressed genes in Covid-19 patients formed a significant pool of the expressing genes in phagocytic cells such as Monocytes and Platelets. Interestingly, while we observed a general enrichment for Monocytes in Covid-19 patients, we found that the signal for FCGRA3+ Monocytes was depleted. Further, we found evidence that age-associated gene expression changes in Monocytes and Platelets, associated with inflammation, mirror gene expression changes in Covid-19 patients suggesting that pro-inflammatory signalling during aging may worsen the infection in older patients. We identified more than 20 genes that change in the same direction between Covid-19 infection and aging cells that may act as potential therapeutic targets. Of particular interest were IL2RG, GNLY and GMZA expressed in Platelets, which facilitates cytokine signalling in Monocytes through an interaction with Platelets. To understand whether infection can directly manipulate the biology of Monocytes and Platelets, we hypothesize that these non-ACE2 expressing cells may be infected by the virus through the phagocytic route. We observed that phagocytic cells such as Monocytes, T-cells, and Platelets have a significantly higher expression of genes that are a part of the Covid-19 viral interactome. Hence these cell-types may have an active rather than a reactive role in viral pathogenesis to manifest clinical symptoms such as coagulopathy. Therefore, our results present molecular evidence for pursuing both anti-inflammatory and anticoagulation therapy for better patient management especially in older patients.

negative: Clinical Characteristics of Coronavirus Disease 2019 in China BACKGROUND: Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. METHODS: We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. RESULTS: The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. CONCLUSIONS: During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)

negative: Characteristics of registered clinical trials assessing treatments for COVID-19: a cross-sectional analysis OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has prompted many initiatives to identify safe and efficacious treatments, yet little is known regarding where early efforts have focused. We aimed to characterise registered clinical trials assessing drugs or plasma treatments for COVID-19. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional analysis of clinical trials for the treatment of COVID-19 that were registered in the USA or in countries contributing to the WHO’s International Clinical Trials Registry Platform. Relevant trial entries of drugs or plasma were downloaded on 26 March 2020, deduplicated, verified with reviews of major medical journals and WHO websites and independently analysed by two reviewers. MAIN OUTCOME(S): Trial intervention, sponsorship, critical design elements and specified outcomes RESULTS: Overall, 201 clinical trials were registered for testing the therapeutic benefits of 92 drugs or plasma, including 64 in monotherapy and 28 different combinations. Only eight (8.7%) products or combinations involved new molecular entities. The other test therapies had a wide range of prior medical uses, including as antivirals, antimalarials, immunosuppressants and oncology treatments. In 152 trials (75.7%), patients were randomised to treatment or comparator, including 55 trials with some form of blinding and 97 open-label studies. The 49 (24.4%) of trials without a randomised design included 29 single armed studies and 20 trials with some comparison group. Most trial designs featured multiple endpoints. Clinical endpoints were identified in 134 (66.7%) of trials and included COVID-19 symptoms, death, recovery, required intensive care and hospital discharge. Clinical scales were being used in 33 (16.4%) trials, most often measures of oxygenation and critical illness. Surrogate endpoints or biomarkers were studied in 88 (42.3%) of trials, primarily assays of viral load. Although the trials were initiated in more than 17 countries or regions, 100 (49.8%) were registered in China and 78 (37.8%) in the USA. Registered trials increased rapidly, with the number of registered trials doubling from 1 March to 26 March 2020. CONCLUSIONS: While accelerating morbidity and mortality from the COVID-19 pandemic has been paralleled by early and rapid clinical investigation, many trials lack features to optimise their scientific value. Global coordination and increased funding of high-quality research may help to maximise scientific progress in rapidly discovering safe and effective treatments.

negative: Evolving epidemiology and transmission dynamics of coronavirus disease 2019 outside Hubei province, China: a descriptive and modelling study BACKGROUND: The coronavirus disease 2019 (COVID-19) epidemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began in Wuhan city, Hubei province, in December, 2019, and has spread throughout China. Understanding the evolving epidemiology and transmission dynamics of the outbreak beyond Hubei would provide timely information to guide intervention policy. METHODS: We collected individual information from official public sources on laboratory-confirmed cases reported outside Hubei in mainland China for the period of Jan 19 to Feb 17, 2020. We used the date of the fourth revision of the case definition (Jan 27) to divide the epidemic into two time periods (Dec 24 to Jan 27, and Jan 28 to Feb 17) as the date of symptom onset. We estimated trends in the demographic characteristics of cases and key time-to-event intervals. We used a Bayesian approach to estimate the dynamics of the net reproduction number (R(t)) at the provincial level. FINDINGS: We collected data on 8579 cases from 30 provinces. The median age of cases was 44 years (33–56), with an increasing proportion of cases in younger age groups and in elderly people (ie, aged >64 years) as the epidemic progressed. The mean time from symptom onset to hospital admission decreased from 4·4 days (95% CI 0·0–14·0) for the period of Dec 24 to Jan 27, to 2·6 days (0·0–9·0) for the period of Jan 28 to Feb 17. The mean incubation period for the entire period was estimated at 5·2 days (1·8–12·4) and the mean serial interval at 5·1 days (1·3–11·6). The epidemic dynamics in provinces outside Hubei were highly variable but consistently included a mixture of case importations and local transmission. We estimated that the epidemic was self-sustained for less than 3 weeks, with mean Rt reaching peaks between 1·08 (95% CI 0·74–1·54) in Shenzhen city of Guangdong province and 1·71 (1·32–2·17) in Shandong province. In all the locations for which we had sufficient data coverage of Rt, Rt was estimated to be below the epidemic threshold (ie, <1) after Jan 30. INTERPRETATION: Our estimates of the incubation period and serial interval were similar, suggesting an early peak of infectiousness, with possible transmission before the onset of symptoms. Our results also indicate that, as the epidemic progressed, infectious individuals were isolated more quickly, thus shortening the window of transmission in the community. Overall, our findings indicate that strict containment measures, movement restrictions, and increased awareness of the population might have contributed to interrupt local transmission of SARS-CoV-2 outside Hubei province. FUNDING: National Science Fund for Distinguished Young Scholars, National Institute of General Medical Sciences, and European Commission Horizon 2020.

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

negative: RAN translation and frameshifting as translational challenges at simple repeats of human neurodegenerative disorders Repeat-associated disorders caused by expansions of short sequences have been classified as coding and noncoding and are thought to be caused by protein gain-of-function and RNA gain-of-function mechanisms, respectively. The boundary between such classifications has recently been blurred by the discovery of repeat-associated non-AUG (RAN) translation reported in spinocerebellar ataxia type 8, myotonic dystrophy type 1, fragile X tremor/ataxia syndrome and C9ORF72 amyotrophic lateral sclerosis and frontotemporal dementia. This noncanonical translation requires no AUG start codon and can initiate in multiple frames of CAG, CGG and GGGGCC repeats of the sense and antisense strands of disease-relevant transcripts. RNA structures formed by the repeats have been suggested as possible triggers; however, the precise mechanism of the translation initiation remains elusive. Templates containing expansions of microsatellites have also been shown to challenge translation elongation, as frameshifting has been recognized across CAG repeats in spinocerebellar ataxia type 3 and Huntington's disease. Determining the critical requirements for RAN translation and frameshifting is essential to decipher the mechanisms that govern these processes. The contribution of unusual translation products to pathogenesis needs to be better understood. In this review, we present current knowledge regarding RAN translation and frameshifting and discuss the proposed mechanisms of translational challenges imposed by simple repeat expansions.

negative: Lung involvement in patients with coronavirus disease-19 (COVID-19): a retrospective study based on quantitative CT findings Purpose: To explore lung involvement in patients with coronavirus disease-19 (COVID-19) using quantitative computed tomography (QCT). Methods: A total of 52 patients with COVID-19 who were admitted to three hospitals in China from January 23, 2020 to February 1, 2020 were retrospectively analyzed using QCT. The accuracy of QCT segmentation was assessed. The relationship between the time from symptom onset to initial CT and QCT parameters acquired on the initial CT were explored. Results: First, the ability of QCT to detect and segment lesions was investigated and it was unveiled that results of segmentation of the majority of cases (42/52) were satisfactory and for 8 out of 52 patients, the images depicted lesions with miss-segmentation; besides, 2 out of 52 cases had negative finding on chest CT achieved by both radiologists and QCT. QCT-related parameters showed to have a relationship with the time from symptom onset to initial CT. In the early-stage (0-3 days), the percentage of lung involvement was 4%, with a mean density of - 462 ± 99 HU. The peak density of lesions appeared at the range of - 500 to - 700 HU on density histogram. In the intermediate-stage (4-6 days), the mean percentage of lung involvement noticeably increased compared with that in early stage (7%, p < 0.05). In late stage (7-14 days), the percentage of lung involvement decreased to 5%. The mean density of lesions was the highest (- 430 ± 80), and heterogeneity density distribution showed a dual-peak on density histogram. Conclusion: COVID-19 can be promptly detected by QCT. In addition, the QCT-related parameters can highly facilitate assessment of pulmonary involvement.

negative: The role of customer service manual on workplace emotional burden in nationwide cross sectional study. Background We aim to discuss the overall effect of customer service manual (CSM) on service industry workers using Korean Working Condition Survey. Methods Out of 50,007 total survey participants, 11,946 customer service workers were included in the current study (5613 men, 6333 women). Answers to survey questions were used to define the use of CSM, emotional burden, emotional dissonance, engaging angry customers and other covariates. Emotional burden included either depressive event or stress level. Odds ratio (OR) with 95% confidence interval (95% CI) of experiencing emotional burden was calculated by logistic regression model. Interaction effect between CSM and engaging angry customer on emotional burden was also estimated. Results Out of 11,946 subjects, total of 3279 (27.4%) have experienced emotional burden. OR (95% CI) of experiencing emotional burden was 1.40 (1.19-1.64) in men and 1.25 (1.09-1.44) in women. There was gender difference in interaction effect between the use of CSM and engaging angry customers. In men, OR (95% CI) was 3.16 (1.38-7.23) with additive effect when always engaging angry customers with CSM compared to rarely engaging without CSM, while in women OR (95% CI) was 8.85 (3.96-19.75) with synergistic effect. Moreover, the risk of depressive event increased only in women with OR (95% CI) 2.22 (1.42-3.48). Conclusions Our current study highlighted association between emotional burden and CSM in both men and women service workers. Furthermore, women were affected more severely by CSM. The results from current study suggest that CSM should be changed appropriately to benefit workers.

negative: Clinical and Radiographic Presentations of COVID-19 among Patients Receiving Radiation Therapy for Thoracic Malignancies The 2019 novel coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a pandemic affecting healthcare centers across the globe. Patients with cancer have been reported to be particularly vulnerable to infection, morbidity, and severe events. Given the high proportion of asymptomatic carriers and concerns regarding speed and availability of laboratory testing, novel detection strategies are necessary to supplement traditional screening methods and facilitate mitigation of viral transmission. Recent data support the diagnostic consistency and potential value of computed tomography (CT) scans to aid early diagnosis of COVID-19. Volumetric CT image-guidance is commonly employed in patients undergoing radiotherapy and presents a unique opportunity to screen for COVID-specific lung changes. This case series describes the presentation of SARS-CoV-2 infections among three patients undergoing thoracic radiotherapy across multiple institutions. We highlight their clinical symptoms, imaging findings, potential confounders, and clinical workflow to triage these patients to the next level of care.

negative: ¿Es esperable que haya cuadros neurológicos por la pandemia por SARS-CoV-2? INTRODUCTION: There is growing evidence that SARS-CoV-2 can gain access to the central nervous system (CNS). We revise the literature on coronavirus infection of the CNS associated with neurological diseases. DEVELOPMENT: Neurological symptoms were rarely reported in the SARS-CoV and MERS-CoV epidemics, although isolated cases were described. There are also reports of cases of neurological symptoms associated with CoV-OC43 and CoV-229E infection. The presence of neurological lesions, especially demyelinating lesions in the mouse hepatitis virus model, may explain the mechanisms by which coronaviruses enter the CNS, particularly those related with the immune response. This may explain the presence of coronavirus in patients with multiple sclerosis. We review the specific characteristics of SARS-CoV-2 and address the question of whether the high number of cases may be associated with greater CNS involvement. CONCLUSION: Although neurological symptoms are not frequent in coronavirus epidemics, the high number of patients with SARS-CoV-2 infection may explain the presence of the virus in the CNS and increase the likelihood of early- or delayed-onset neurological symptoms. Follow-up of patients affected by the SARS-CoV-2 epidemic should include careful assessment of the CNS.

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: Mortality Rate of Infection With COVID-19 in Korea From the Perspective of Underlying Disease On December 31, 2019 the China National Health Commission (NHC) reported that an unknown cause of pneumonia had been detected in Wuhan in Hubei province. On February 12, the disease caused by the novel coronavirus (2019-nCoV) was given a formal name, COVID-19. On January 20, 2020, the first case of COVID-19 was confirmed in Korea. The age-specific death rate was the highest among patients over 70 years of age, with underlying diseases in their circulatory system, such as myocardial infarction, cerebral infraction, arrythmia, and hypertension. Patients with underlying disease who are 70 years of age or older should recognize that there is a high possibility of developing a serious disease in case of viral infection and follow strict precautions.

negative: 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: Pulmonary Pathology of Early Phase 2019 Novel Coronavirus Pneumonia

negative: Nonstructural proteins NS7b and NS8 are likely to be phylogenetically associated with evolution of 2019-nCoV Abstract The seventh novel human infecting Betacoronavirus that causes pneumonia (2019 novel coronavirus, 2019-nCoV) originated in Wuhan, China. The evolutionary relationship between 2019-nCoV and the other human respiratory illness-causing coronavirus is not closely related. We sought to characterize the relationship of the translated proteins of 2019-nCoV with other species of Orthocoronavirinae. A phylogenetic tree was constructed from the genome sequences. A cluster tree was developed from the profiles retrieved from the presence and absence of homologs of ten 2019-nCoV proteins. The combined data were used to characterize the relationship of the translated proteins of 2019-nCoV to other species of Orthocoronavirinae. Our analysis reliably suggests that 2019-nCoV is most closely related to BatCoV RaTG13 and belongs to subgenus Sarbecovirus of Betacoronavirus, together with SARS coronavirus and Bat-SARS-like coronavirus. The phylogenetic profiling cluster of homolog proteins of one annotated 2019-nCoV protein against other genome sequences revealed two clades of ten 2019-nCoV proteins. Clade 1 consisted of a group of conserved proteins in Orthocoronavirinae comprising Orf1ab polyprotein, Nucleocapsid protein, Spike glycoprotein, and Membrane protein. Clade 2 comprised six proteins exclusive to Sarbecovirus and Hibecovirus. Two of six Clade 2 nonstructural proteins, NS7b and NS8, were exclusively conserved among 2019-nCoV, BetaCoV_RaTG, and BatSARS-like Cov. NS7b and NS8 have previously been shown to affect immune response signaling in the SARS-CoV experimental model. Thus, we speculated that knowledge of the functional changes in the NS7b and NS8 proteins during evolution may provide important information to explore the human infective property of 2019-nCoV.

negative: Concerns for activated breathing control (ABC) with breast cancer in the era of COVID-19: Maximizing infection control while minimizing heart dose

negative: SARS-CoV-2 and Norovirus Co-Infection after Lung Transplantation Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spreading as a pandemic in 2020 Few reports on infections in thoracic transplantation have been published so far We present a case of COVID-19 in a 55-year old female lung transplant recipient infected 5 months posttransplant, who additionally was co-infected with a Norovirus Respiratory and gastrointestinal symptoms were observed without need of therapeutic escalation except for antibiotic therapy We observed a moderate disease evolution likely due to triple immunosuppression

negative: Clinical Outcome of Coronavirus Disease 2019 in Haemato‐oncology Patients Since being identified in China in December 2019, coronavirus disease 2019 (Covid‐19) has rapidly evolved into a global pandemic with over 4 million cases and more than 270,000 deaths.(1) Following the first reported cases in the United Kingdom (UK) in late January 2020, numbers have continued to rise with 223,060 cases and 32,065 deaths reported as of 11(th) May 2020.(2) Initial reports from China have indicated that Covid‐19 has an overall mortality rate of 1.4%. However, the prognosis varies widely between groups, with age over 60 years and underlying conditions including hypertension, diabetes, cardiovascular disease and cancer identified as risk factors for severe disease and death.(3) The initial reports from China show that patients with cancer are over‐represented among individuals who develop severe Covid‐19 after contracting the virus.(4) Patients with haematological malignancies are expected to be at increased risk of adverse outcomes from this viral infection, due being immunosuppressed as a consequence of the underlying cancer, and from the effects of therapy.

negative: The “Common Cold” in Frail Older Persons: Impact of Rhinovirus and Coronavirus in a Senior Daycare Center OBJECTIVE: To evaluate the incidence and impact of rhino‐virus and Coronavirus infections in older persons attending daycare. DESIGN: Prospective descriptive study. SETTING: Three senior daycare centers in Rochester, New York. PATIENTS: Frail older persons and staff members of the daycare centers who developed signs or symptoms of an acute respiratory illness MEASUREMENTS: Demographic, medical, and physical findings were recorded on subjects at baseline and during respiratory illness. Nasopharyngeal specimens for viral culture as well as acute and convalescent sera for Coronavirus 229E enzyme immunoassay (EIA) were obtained for all illnesses. RESULTS: During the 44 months of study, 352 older persons experienced 522 illnesses. Thirty‐five (7%) of 522 cultures were positive for rhinovirus and 37 (8%) of 451 serologies were positive for Coronavirus 229E infection. The clinical syndromes associated with rhinovirus and Coronavirus infection were similar and characterized by nasal congestion, cough, and constitutional symptoms. No patient died or was hospitalized, but approximately 50% had evidence of lower respiratory tract involvement. The average illness lasted 14 days. During the same period, 113 staff developed 338 respiratory illnesses. Eight percent were identified as Coronavirus and 9% as rhinovirus. Cough, sputum production, and constitutional symptoms were significantly more common among older persons. CONCLUSIONS: Rhinovirus and Coronavirus 229E are common causes of moderately debilitating acute respiratory illnesses among older persons attending daycare.

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

negative: Rhinosinusitis: Establishing definitions for clinical research and patient care Background There is a need for more research on all forms of rhinosinusitis. Progress in this area has been hampered by a lack of consensus definitions and the limited number of published clinical trials. Objectives To develop consensus definitions for rhinosinusitis and outline strategies useful in clinical trials. Study design Five national societies, The American Academy of Allergy, Asthma and Immunology; The American Academy of Otolaryngic Allergy; The American Academy of Otolaryngology Head and Neck Surgery; The American College of Allergy, Asthma and Immunology; and the American Rhinologic Society formed an expert panel from multiple disciplines. Over two days, the panel developed definitions for rhinosinusitis and outlined strategies for design of clinical trials. Results Committee members agreed to adopt the term “rhinosinusitis” and reached consensus on definitions and strategies for clinical research on acute presumed bacterial rhinosinusitis, chronic rhinosinusitis without polyposis, chronic rhinosinusitis with polyposis, and classic allergic fungal rhinosinusitis. Symptom and objective criteria, measures for monitoring research progress, and use of symptom scoring tools, quality-of-life instruments, radiologic studies, and rhinoscopic assessment were outlined for each condition. Conclusions The recommendations from this conference should improve accuracy of clinical diagnosis and serve as a starting point for design of rhinosinusitis clinical trials.

negative: Delayed‐Phase Thrombocytopenia in Patients of Coronavirus Disease 2019 (COVID‐19) COVID‐19 can affect the hematopoietic system. Thrombocytopenia at admission was prevalent, while late‐phase or delayed‐phase thrombocytopenia (occurred 14 days after symptom onset) is obscure. This retrospective single‐center study screened 450 COVID‐19 patients and enrolled 271 patients at the Union Hospital, Wuhan, China, from January 25th to March 9th, 2020. COVID‐19 associated delayed‐phase thrombocytopenia occurred in 11.8% percent of enrolling patients. The delayed‐phase thrombocytopenia in COVID‐19 is prone to develop in elderly patients or patients with low lymphocyte count on admission. The delayed‐phase thrombocytopenia is significantly associated with increased length of hospital stay and higher mortality rate. Delayed‐phase nadir platelet counts demonstrated a significantly negative correlation with B cell percentages. We also presented bone marrow aspiration pathology of three patients with delayed‐phase thrombocytopenia, showing impaired maturation of megakaryocytes. We speculated that immune mediated platelet destruction might account for the delayed‐phase thrombocytopenia in a group of patients. Besides, clinicians need to pay attention to the delayed‐phase thrombocytopenia especially at 3‐4 weeks after symptom onset.

negative: Clinical evaluation of an immunochromatographic IgM/IgG antibody assay and chest computed tomography for the diagnosis of COVID-19 Background: We evaluated the clinical performance of an immunochromatographic (IC) IgM/IgG antibody assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) and chest computed tomography (CT) for the diagnosis of Coronavirus disease 2019 (COVID-19). Methods: We examined 139 serum specimens collected from 112 patients with COVID-19 and 48 serum specimens collected from 48 non-COVID-19 patients. The presence of IgM/IgG antibody for SARS-CoV2 was determined using the One Step Novel Coronavirus (COVID-19) IgM/IgG Antibody Test. Chest CT was performed in COVID-19 patients on admission. Findings: Of the 139 COVID-19 serum specimens, IgM was detected in 27.8%, 48.0%, and 95.8% of the specimens collected within 1 week, 1-2 weeks, and >2 weeks after symptom onset and IgG was detected in 3.3%, 8.0%, and 62.5%, respectively. Among the 48 non-COVID-19 serum specimens, 1 generated a false-positive result for IgM. Thirty-eight of the 112 COVID-19 patients were asymptomatic, of whom 15 were positive for IgM, and 74 were symptomatic, of whom 22 were positive for IgM and 7 were positive for IgG. The diagnostic sensitivity of CT scan alone and in combination with the IC assay was 57.9 % (22/38) and 68.4% (26/38) for the asymptomatic patients and 74.3% (55/74) and 82.4% (61/74) for the symptomatic patients, respectively. Conclusion: The IC assay had low sensitivity during the early phase of infection, and thus IC assay alone is not recommended for initial diagnostic testing for COVID-19. If RT-qPCR is not available, the combination of chest CT and IC assay may be useful for diagnosing COVID-19.

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: 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.

negative: Coronavirus Epidemic and Extracorporeal Therapies in Intensive Care: si vis pacem para bellum

negative: Clinical and High-Resolution CT Features of the COVID-19 Infection: Comparison of the Initial and Follow-up Changes OBJECTIVES: In late December 2019, an outbreak of coronavirus disease (COVID-19) in Wuhan, China was caused by a novel coronavirus, newly named severe acute respiratory syndrome coronavirus 2. We aimed to quantify the severity of COVID-19 infection on high-resolution chest computed tomography (CT) and to determine its relationship with clinical parameters. MATERIALS AND METHODS: From January 11, 2020, to February 5, 2020, the clinical, laboratory, and high-resolution CT features of 42 patients (26–75 years, 25 males) with COVID-19 were analyzed. The initial and follow-up CT, obtained a mean of 4.5 days and 11.6 days from the illness onset were retrospectively assessed for the severity and progression of pneumonia. Correlations among clinical parameters, initial CT features, and progression of opacifications were evaluated with Spearman correlation and linear regression analysis. RESULTS: Thirty-five patients (83%) exhibited a progressive process according to CT features during the early stage from onset. Follow-up CT findings showed progressive opacifications, consolidation, interstitial thickening, fibrous strips, and air bronchograms, compared with initial CT (all P < 0.05). Before regular treatments, there was a moderate correlation between the days from onset and sum score of opacifications (R = 0.68, P < 0.01). The C-reactive protein, erythrocyte sedimentation rate, and lactate dehydrogenase showed significantly positive correlation with the severity of pneumonia assessed on initial CT (R(range), 0.36–0.75; P < 0.05). The highest temperature and the severity of opacifications assessed on initial CT were significantly related to the progression of opacifications on follow-up CT (P = 0.001–0.04). CONCLUSIONS: Patients with the COVID-19 infection usually presented with typical ground glass opacities and other CT features, which showed significant correlations with some clinical and laboratory measurements. Follow-up CT images often demonstrated progressions during the early stage from illness onset.

negative: Etiologies of Acute Respiratory Tract Infections

negative: Bioethical Implications of Globalization: An International Consortium Project of the European Commission The BIG project looks at some of the ethical concerns surrounding globalization and health.

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: Comment on ‘Two cases of COVID‐19 presenting with a clinical picture resembling chilblains: first report from the Middle East’: pernio unrelated to COVID‐19 Dear editor, we have read with interest Dr´s Alramthan and Aldaraji contribution to the spectrum of COVID-19 clinical manifestations.1 Since COVID-19 outbreak begin, new symptoms have been described.2 Some of them, were not initially highlighted and could be a distinguishing feature of COVID-19 infection, like anosmia or ageusia.3 Therefore, it is believed that a newly reported one, so-called acute acro-ischemia is another novel clinical manifestation of COVID-19 infection.4.

negative: Time Course of Lung Changes On Chest CT During Recovery From 2019 Novel Coronavirus (COVID-19) Pneumonia BACKGROUND: Chest CT is used to assess the severity of lung involvement in COVID-19 pneumonia. PURPOSE: To determine the change in chest CT findings associated with COVID-19 pneumonia from initial diagnosis until patient recovery. MATERIALS AND METHODS: This retrospective review included patients with RT-PCR confirmed COVID-19 infection presenting between 12 January 2020 to 6 February 2020. Patients with severe respiratory distress and/ or oxygen requirement at any time during the disease course were excluded. Repeat Chest CT was obtained at approximately 4 day intervals. The total CT score was the sum of lung involvement (5 lobes, score 1-5 for each lobe, range, 0 none, 25 maximum) was determined. RESULTS: Twenty one patients (6 males and 15 females, age 25-63 years) with confirmed COVID-19 pneumonia were evaluated. These patients under went a total of 82 pulmonary CT scans with a mean interval of 4±1 days (range: 1-8 days). All patients were discharged after a mean hospitalized period of 17±4 days (range: 11-26 days). Maximum lung involved peaked at approximately 10 days (with the calculated total CT score of 6) from the onset of initial symptoms (R2=0.25), p<0.001). Based on quartiles of patients from day 0 to day 26 involvement, 4 stages of lung CT were defined: Stage 1 (0-4 days): ground glass opacities (GGO) in 18/24 (75%) patients with the total CT score of 2±2; (2)Stage-2 (5-8d days): increased crazy-paving pattern 9/17 patients (53%) with a increase in total CT score (6±4, p=0.002); (3) Stage-3 (9-13days): consolidation 19/21 (91%) patients with the peak of total CT score (7±4); (4) Stage-4 (≥14 days): gradual resolution of consolidation 15/20 (75%) patients with a decreased total CT score (6±4) without crazy-paving pattern. CONCLUSION: In patients recovering from COVID-19 pneumonia (without severe respiratory distress during the disease course), lung abnormalities on chest CT showed greatest severity approximately 10 days after initial onset of symptoms.

negative: How to handle patients with autoimmune rheumatic and inflammatory bowel diseases in the COVID-19 era: An expert opinion • A correct patient risk stratification is of paramount importance for the proper management of economic and human resources. • It's fundamental to prioritize clinical trials evaluating dosing, prophylaxis, and treatment with immunosuppressant in COVID-19 in order to avoid either an overuse and a treatment shortage. • Future controlled studies may highlight in our patients a potential preventive role of immunosuppressant therapies in the development of severe forms of Covid-19. • Despite the overall risk of infection in rheumatic and gastroenterological diseases a conclusive association between these diseases and COVID −19 remains questionable.

negative: Association of “initial CT” findings with mortality in older patients with coronavirus disease 2019 (COVID-19) OBJECTIVES: To investigate the association of chest CT findings with mortality in clinical management of older patients. METHODS: From January 21 to February 14, 2020, 98 older patients (≥ 60 years) who had undergone chest CT scans (“initial CT”) on admission were enrolled. Manifestation and CT score were compared between the death group and the survival group. In each group, patients were sub-grouped based on the time interval between symptom onset and the “initial CT” scan: subgroup1 (interval ≤ 5 days), subgroup2 (interval between 6 and 10 days), and subgroup3 (interval > 10 days). Adjusted ROC curve after adjustment for age and gender was applied. RESULTS: Consolidations on CT images were more common in the death group (n = 46) than in the survival group (n = 52) (53.2% vs 32.0%, p < 0.001). For subgroup1 and subgroup2, a higher mean CT score was found for the death group (33.0 ± 17.1 vs 12.9 ± 8.7, p < 0.001; 38.8 ± 12.3 vs 24.3 ± 11.9, p = 0.002, respectively) and no significant difference of CT score was identified with respect to subgroup3 (p = 0.144). In subgroup1, CT score of 14.5 with a sensitivity of 83.3% and a specificity of 77.3% for the prediction of mortality was an optimal cutoff value, with an adjusted AUC of 0.881. In subgroup2, CT score of 27.5 with a sensitivity of 87.5% and a specificity of 70.6% for the prediction of mortality was an optimal cutoff value, with an adjusted AUC of 0.895. CONCLUSIONS: “Initial CT” scores may be useful to speculate prognosis and stratify patients. Severe manifestation on CT at an early stage may indicate poor prognosis for older patients with COVID-19. KEY POINTS: • Severe manifestation on CT at an early stage may indicate poor prognosis for older patients with COVID-19. • Radiologists should pay attention to the time interval between symptom onsets and CT scans of patients with COVID-19. • Consolidations on CT images were more common in death patients than in survival patients.

negative: Severe Acute Respiratory Syndrome: Pertinent Clinical Characteristics and Therapy Severe acute respiratory syndrome (SARS) is a newly emerged infection that is caused by a previously unrecognized virus–a novel coronavirus designated as SARS-associated coronavirus (SARS-CoV). From November 2002 to July 2003 the cumulative number of worldwide cases was >8000, with a mortality rate of close to 10%. The mortality has been higher in older patients and those with co-morbidities. SARS has been defined using clinical and epidemiological criteria and cases are considered laboratory-confirmed if SARS coronavirus is isolated, if antibody to SARS coronavirus is detected, or a polymerase chain reaction test by appropriate criteria is positive. At the time of writing (24 May 2004), no specific therapy has been recommended. A variety of treatments have been attempted, but there are no controlled data. Most patients have been treated throughout the illness with broad-spectrum antimicrobials, supplemental oxygen, intravenous fluids, and other supportive measures. Transmission of SARS is facilitated by close contact with patients with symptomatic infection. The majority of cases have been reported among healthcare providers and family members of SARS patients. Since SARS-CoV is contagious, measures for prevention center on avoidance of exposure, and infection control strategies for suspected cases and contacts. This includes standard precautions (hand hygiene), contact precautions (gowns, goggles, gloves) and airborne precautions (negative pressure rooms and high efficiency masks). In light of reports of new cases identified during the winter of 2003–4 in China, it seems possible that SARS will be an important cause of pneumonia in the future, and the screening of outpatients at risk for SARS may become part of the pneumonia evaluation.

negative: Rapid implementation of mobile technology for real-time epidemiology of COVID-19 The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic (COVID-19) presents challenges to the robust collection of population-scale data to address this global health crisis. We established the COronavirus Pandemic Epidemiology (COPE) consortium to bring together scientists with expertise in big data research and epidemiology to develop a COVID-19 Symptom Tracker mobile application that we launched in the UK on March 24, 2020 and the US on March 29, 2020 garnering more than 2.8 million users as of May 2, 2020. This mobile application offers data on risk factors, herald symptoms, clinical outcomes, and geographical hot spots. This initiative offers critical proof-of-concept for the repurposing of existing approaches to enable rapidly scalable epidemiologic data collection and analysis which is critical for a data-driven response to this public health challenge.

negative: Les infections à coronavirus humains Résumé Les coronavirus humains (HCoV) sont des virus à ARN simple brin. Il existe actuellement quatre coronavirus dits « classiques » ou « nouveaux », dont la circulation est hivernale. Ils sont à l’origine d’infections respiratoires modérées dans la population générale. Cependant, les infections peuvent être plus sévères dans les populations susceptibles. Notamment, les HCoV sont impliqués dans 2 à 7% des hospitalisations consécutives à une infection respiratoire, en particulier chez les enfants et les personnes âgées ou immunodéprimées. De ce fait, ils appartiennent au panel de virus respiratoires recherchés lors des diagnostics de routine des infections respiratoires par des outils de biologie moléculaire. Ces coronavirus dits circulants sont à distinguer des deux coronavirus émergents, le SARS-CoV et le MERS-CoV qui sont associés à des pathologies respiratoires plus sévères. Ils se distinguent des autres HCoV par leur potentiel épidémique plus élevé, leur impact sanitaire plus important et leur mode de circulation atypique. À l’instar des paramyxovirus et des virus Influenza, les coronavirus doivent être surveillés pour leur risque d’émergence dans la population humaine à partir d’un réservoir animal. Summary Human coronaviruses (HCoV) are single strand RNA viruses. To date, there are four so-called « classical » or « novel » HCoVs, characterized by a winter circulation. These coronaviruses are responsible for mild respiratory infection in general population. However, HCoVs are associated to more severe respiratory tract infection among susceptible population. Indeed, HCoVs account for 2 to 7% of hospitalizations due to a respiratory infection, particularly among children, immunocompromised or elderly people. Thereby, HCoVs are included in the panel of respiratory viruses detected in routine using molecular biology tools. These four circulating HCoVs have to be distinguished from the two emerging HCoVs: SARS-CoV and MERS-CoV. These later are associated to a more severe respiratory infection and differ from other HCoVs by their increased epidemic potential, their more important health impact, and their atypical circulation. Such as paramyxoviruses and Influenza viruses, coronaviruses have to be monitored due to their associated risk of emergence in human population from animal reservoirs.

negative: Risk scoring calculation for the current NHSx contact tracing app We consider how the NHS COVID-19 application will initially calculate a risk score for an individual based on their recent contact with people who report that they have coronavirus symptoms.

negative: A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19 BACKGROUND: Coronavirus disease 2019 (Covid-19) occurs after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For persons who are exposed, the standard of care is observation and quarantine. Whether hydroxychloroquine can prevent symptomatic infection after SARS-CoV-2 exposure is unknown. METHODS: We conducted a randomized, double-blind, placebo-controlled trial across the United States and parts of Canada testing hydroxychloroquine as postexposure prophylaxis. We enrolled adults who had household or occupational exposure to someone with confirmed Covid-19 at a distance of less than 6 ft for more than 10 minutes while wearing neither a face mask nor an eye shield (high-risk exposure) or while wearing a face mask but no eye shield (moderate-risk exposure). Within 4 days after exposure, we randomly assigned participants to receive either placebo or hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 additional days). The primary outcome was the incidence of either laboratory-confirmed Covid-19 or illness compatible with Covid-19 within 14 days. RESULTS: We enrolled 821 asymptomatic participants. Overall, 87.6% of the participants (719 of 821) reported a high-risk exposure to a confirmed Covid-19 contact. The incidence of new illness compatible with Covid-19 did not differ significantly between participants receiving hydroxychloroquine (49 of 414 [11.8%]) and those receiving placebo (58 of 407 [14.3%]); the absolute difference was −2.4 percentage points (95% confidence interval, −7.0 to 2.2; P=0.35). Side effects were more common with hydroxychloroquine than with placebo (40.1% vs. 16.8%), but no serious adverse reactions were reported. CONCLUSIONS: After high-risk or moderate-risk exposure to Covid-19, hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure. (Funded by David Baszucki and Jan Ellison Baszucki and others; ClinicalTrials.gov number, NCT04308668.)

negative: Oncology Nursing During a Pandemic: Critical Reflections in the Context of COVID-19 Abstract Objectives To provide a critical reflection of COVID-19 in the context of oncology nursing and provide recommendations for caring for people affected by cancer during this pandemic. Data sources Electronic databases including CINAHL, MEDLINE, PsychINFO, Scopus, professional websites, and grey literature were searched using Google scholar. Conclusion Nurses are key stakeholders in developing and implementing policies regarding standards of care during COVID-19 pandemic. This pandemic poses several challenges for oncology services. Oncology nurses are providing a pivotal role in the care and management of the novel COVID-19 in the year landmarked as the International Year of the Nurse. Implications for practice It is too early to tell what shape this pandemic will take and its impact on oncology care. However, several important clinical considerations have been discussed to inform oncology nursing care and practice.

negative: A systematic review on COVID-19: urological manifestations, viral RNA detection and special considerations in urological conditions PURPOSE AND OBJECTIVE: We performed a systematic review on COVID-19 and its potential urological manifestations. METHODS: A literature search was performed using combination of keywords (MeSH terms and free text words) relating to COVID-19, urology, faeces and stool on multiple databases. Primary outcomes were the urological manifestations of COVID-19, and SARS-CoV-2 viral RNA detection in urine and stool samples. Meta-analyses were performed when there were two or more studies reporting on the same outcome. Special considerations in urological conditions that were relevant in the pandemic of COVID-19 were reported in a narrative manner. RESULTS: There were a total of 21 studies with 3714 COVID-19 patients, and urinary symptoms were absent in all of them. In patients with COVID-19, 7.58% (95% CI 3.30–13.54%) developed acute kidney injury with a mortality rate of 93.27% (95% CI 81.46–100%) amongst them. 5.74% (95% CI 2.88–9.44%) of COVID-19 patients had positive viral RNA in urine samples, but the duration of viral shedding in urine was unknown. 65.82% (95% CI 45.71–83.51%) of COVID-19 patients had positive viral RNA in stool samples, which were detected from 2 to 47 days from symptom onset. 31.6% of renal transplant recipients with COVID-19 required non-invasive ventilation, and the overall mortality rate was 15.4%. CONCLUSIONS: Acute kidney injury leading to mortality is common amongst COVID-19 patients, likely as a result of direct viral toxicity. Viral RNA positivity was detected in both urine and stool samples, so precautions are needed when we perform transurethral or transrectal procedures. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00345-020-03246-4) contains supplementary material, which is available to authorized users.

negative: Epidemiology The common cold is the result of an upper respiratory tract infection causing an acute syndrome characterised by a combination of non-specific symptoms, including sore throat, cough, fever, rhinorrhoea, malaise, headache, and myalgia. Respiratory viruses, alone or in combination, are the most common cause. The course f illness can be complicated by bacterial agents, causing pharyngitis or sinusitis, but the are a rare cause of cold and flu-like illnesses (CFLIs). Our understanding of CFLI epidemiology has been enhanced by molecular detection methods, particularly polymerase chain reaction (PCR) testing. PCR has not only improved detection of previously known viruses, but within the last decade has resulted in the detection of many divergent novel respiratory virus species. Human rhinovirus (HRV) infections cause nearly all CFLIs and they can be responsible for asthma and chronic obstructive pulmonary disease exacerbations. HRVs are co-detected with other respiratory viruses in statistically significant patterns, with HRVs occurring in the lowest proportion of co-detections, compared to most other respiratory viruses. Some recently identified rhinoviruses may populate an entirely new putative HRV species; HRV C. Further work is required to confirm a causal role for these newly identified viruses in CFLIs. The burden of illness associated with CFLIs is poorly documented, but where data are available, the impact of CFLIs is considerable. Individual infections, although they do not commonly result in more severe respiratory tract illness, are associated with substantial direct and indirect resource use. The product of frequency and burden for CFLIs is likely to be greater in magnitude than for any other respiratory syndrome, but further work is required to document this. Our understanding of the viral causes of CLFIs, although incomplete, has improved in recent years. Documenting burden is also an important step in progress towards improved control and management of these illnesses.

negative: Sexual Dysfunction Female sexual dysfunction or dissatisfaction is a common complaint among obstetric-gynecology patients. These complaints may result from medical treatments and procedures, or may secondarily complicate the management and patient compliance of treatment for other medical issues. Therefore, it is important that clinicians treating females obtain basic information regarding human sexual function and dysfunction. This chapter presents an integration of the clinical research as well as the author’s experience regarding sexual function and the management of sexual problems often presented in an obstetricgynecology practice.

negative: Coronavirus disease 2019 (COVID-19): a clinical update Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has posed a significant threat to global health. It caused a total of 80 868 confirmed cases and 3101 deaths in Chinese mainland until March 8, 2020. This novel virus spread mainly through respiratory droplets and close contact. As disease progressed, a series of complications tend to develop, especially in critically ill patients. Pathological findings showed representative features of acute respiratory distress syndrome and involvement of multiple organs. Apart from supportive care, no specific treatment has been established for COVID-19. The efficacy of some promising antivirals, convalescent plasma transfusion, and tocilizumab needs to be investigated by ongoing clinical trials.

negative: MOUSE HEPATITIS VIRUS: MOLECULAR BIOLOGY AND IMPLICATIONS FOR PATHOGENESIS

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: Running a virtual allergy division and training program in the time of COVID-19 pandemic

negative: Viral RNA in Blood as Indicator of Severe Outcome in Middle East Respiratory Syndrome Coronavirus Infection We evaluated the diagnostic and clinical usefulness of blood specimens to detect Middle East respiratory syndrome coronavirus infection in 21 patients from the 2015 outbreak in South Korea. Viral RNA was detected in blood from 33% of patients at initial diagnosis, and the detection preceded a worse clinical course.

negative: Feasibility of a birth cohort study dedicated to assessing acute infections using symptom diaries and parental collection of biomaterials BACKGROUND: A birth cohort dedicated to studying infections in early childhood may be assisted by parental recording of symptoms on a daily basis and a collection of biomaterials. We aimed at testing the feasibility of this approach for use in a long-term study focusing on infections in children in Germany. METHODS: Parents of 1- to 3-year-old children (n = 75) were recruited in nursery schools. They were asked to complete a symptom diary on a daily basis and to take monthly and symptom-triggered nasal swabs and stool samples from their child over the study period of three months. Feasibility was measured by means of the return proportions of symptom diaries and bio samples; acceptance was assessed by a questionnaire delivered to participants at the end of the study. RESULTS: The majority of the participants filled in the symptom diary during the three months study for 75 or more days (77.3 %), and provided the monthly nasal swabs (62.7 %) and stool samples (65.3 %). The time needed for the tasks was acceptable for most participants (symptom diary: 92.3 %, nasal swabs: 98.5 %, stool samples: 100.0 %). In 64.3 % of the symptom-triggered nasal swabs, respiratory viruses were found compared to 55.5 % in throat swabs taken by health-care professionals within the “ARE surveillance Lower Saxony”, a special project by the Governmental Institute of Public Health of Lower Saxony to investigate causal pathogens for acute respiratory infections in children. CONCLUSIONS: The parental assessment of symptoms and collection of biomaterials in a birth cohort dedicated to studying infections appears feasible in a middle class German population. The success of the study will depend on the ability to maintain these activities over a long time period. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-1189-0) contains supplementary material, which is available to authorized users.

negative: Chinese experts’ consensus on the Internet of Things-aided diagnosis and treatment of coronavirus disease 2019 (COVID-19) Abstract The aim is to diagnose COVID-19 earlier and to improve its treatment by applying medical technology, the “COVID-19 Intelligent Diagnosis and Treatment Assistant Program (nCapp)” based on the Internet of Things. Terminal eight functions can be implemented in real-time online communication with the “cloud” through the page selection key. According to existing data, questionnaires, and check results, the diagnosis is automatically generated as confirmed, suspected, or suspicious of 2019 novel coronavirus (2019-nCoV) infection. It classifies patients into mild, moderate, severe or critical pneumonia. nCapp can also establish an online COVID-19 real-time update database, and it updates the model of diagnosis in real time based on the latest real-world case data to improve diagnostic accuracy. Additionally, nCapp can guide treatment. Front-line physicians, experts, and managers are linked to perform consultation and prevention. nCapp also contributes to the long-term follow-up of patients with COVID-19. The ultimate goal is to enable different levels of COVID-19 diagnosis and treatment among different doctors from different hospitals to upgrade to the national and international through the intelligent assistance of the nCapp system. In this way, we can block disease transmission, avoid physician infection, and epidemic prevention and control as soon as possible.

negative: Two X‐linked agammaglobulinemia patients develop pneumonia as COVID‐19 manifestation but recover BACKGROUND: The recent SARS‐CoV‐2 pandemic, which has recently affected Italy since February 21, constitutes a threat to normal subjects, as the coronavirus disease‐19 (COVID‐19) can manifest with a broad spectrum of clinical phenotypes ranging from asymptomatic cases to pneumonia or even death. There is evidence that older age and several comorbidities can affect the risk to develop severe pneumonia and possibly the need of mechanic ventilation in subjects infected with SARS‐CoV‐2. Therefore, we evaluated the outcome of SARS‐CoV‐2 infection in patients with inborn errors of immunity (IEI) such as X‐linked agammaglobulinemia (XLA). METHODS: When the SARS‐CoV‐2 epidemic has reached Italy, we have activated a surveillance protocol of patients with IEI, to perform SARS‐CoV‐2 search by nasopharyngeal swab in patients presenting with symptoms that could be a manifestation of COVID‐19, such as fever, cough, diarrhea, or vomiting. RESULTS: We describe two patients with X‐linked agammaglobulinemia (XLA) aged 34 and 26 years with complete absence of B cells from peripheral blood who developed COVID‐19, as diagnosed by SARS‐CoV‐2 detection by nasopharyngeal swab, while receiving immunoglobulin infusions. Both patients developed interstitial pneumonia characterized by fever, cough, and anorexia and associated with elevation of CRP and ferritin, but have never required oxygen ventilation or intensive care. CONCLUSION: Our report suggests that XLA patients might present with high risk to develop pneumonia after SARS‐CoV‐2 infection, but can recover from infection, suggesting that B‐cell response might be important, but is not strictly required to overcome the disease. However, there is a need for larger observational studies to extend these conclusions to other patients with similar genetic immune defects.

negative: Human iPSC-Derived Cardiomyocytes are Susceptible to SARS-CoV-2 Infection Coronavirus disease 2019 (COVID-19) is a viral pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is predominantly defined by respiratory symptoms, but cardiac complications including arrhythmias, heart failure, and viral myocarditis are also prevalent. Although the systemic ischemic and inflammatory responses caused by COVID-19 can detrimentally affect cardiac function, the direct impact of SARS-CoV-2 infection on human cardiomyocytes is not well-understood. We used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as a model system to examine the mechanisms of cardiomyocyte-specific infection by SARS-CoV-2. Microscopy and immunofluorescence demonstrated that SARS-CoV-2 can enter and replicate within hiPSC-CMs, localizing at perinuclear locations within the cytoplasm. Viral cytopathic effect induced hiPSC-CM apoptosis and cessation of beating after 72 hours of infection. These studies show that SARS-CoV-2 can infect hiPSC-CMs in vitro, establishing a model for elucidating the mechanisms of infection and potentially a cardiac-specific antiviral drug screening platform.

negative: Molecular epidemiology and characterization of human coronavirus in Thailand, 2012–2013 BACKGROUND: Coronavirus causes respiratory infections in humans. To determine the prevalence of human coronavirus (HCoV) infection among patients with influenza-like illness, 5833 clinical samples from nasopharyngeal swabs and aspirates collected between January 2012 and December 2013 were examined. RESULTS: HCoV was found in 46 (0.79 %) samples. There were 19 (0.32 %) HCoV-HKU1, 19 (0.32 %) HCoV-NL63, 5 (0.09 %) HCoV-229E, and 3 (0.05 %) HCoV-OC43. None of the sample tested positive for MERS-CoV. The majority (54 %) of the HCoV-positive patients were between the ages of 0 and 5 years. HCoV was detected throughout the 2-year period and generally peaked from May to October, which coincided with the rainy season. Phylogenetic trees based on the alignment of the spike (S) gene sequences suggest an emergence of a new clade for HCoV-229E. CONCLUSIONS: The data in this study provide an insight into the prevalence of the recent circulating HCoVs in the region.

negative: COVID‐19 and gastrointestinal endoscopy: Importance of reducing SARS‐CoV‐2 infection risks of medical workers and preserving personal protective equipment resources In December 2019, the World Health Organization (WHO) was informed of cases of pneumonia of unknown etiology detected in Wuhan, China. Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), a novel coronavirus, was identified and SARS‐CoV‐2 related disease, called coronavirus disease 2019 (COVID‐19), has spread worldwide. The WHO has declared COVID‐19 to be a pandemic on March 11, 2020. Clinical symptoms of the COVID‐19 includes cough (67.8%), fever (43.8%), fatigue (38.1%), production of sputum (33.7%), and shortness of breath (18.7%). Gastrointestinal symptoms of COVID‐19 include nausea or vomiting (5.0%), as well as diarrhea (3.8%) (1). It is estimated that 1.2% of infected subjects are asymptomatic, but the rate of severe disease is 13.9% with an overall mortality rate of 2.3% (2).

negative: Symptom Severity Patterns in Experimental Common Colds and Their Usefulness in Timing Onset of Illness in Natural Colds Mean total symptom severity scores for subjects with experimental rhinovirus colds peak 48 h after viral inoculation. Also, total symptom scores for natural rhinovirus and nonrhinovirus colds peaked on day 2 of illness in a long-term, noncompensated epidemiology study. In contrast, the mean total symptom scores for compensated patients receiving placebo in natural cold treatment trials peaked on day 1. Comparisons by day indicated that scores for symptoms reported as occurring on day 1 in the natural cold treatment trials corresponded with experimental cold scores for symptoms reported 48 h after viral inoculation. Comparisons of frequency and cumulative distribution scores for the 2 groups indicated that natural colds in the treatment trials were of longer duration than reported. A mean total symptom severity score of ⩽7 would capture 95% of experimental colds 24 h after inoculation while excluding 30.5% of natural colds on day 1 of illness. Histories given by compensated patients in natural cold treatment trials are inaccurate.

negative: Prevalence of psychiatric morbidity and psychological adaptation of the nurses in a structured SARS caring unit during outbreak: A prospective and periodic assessment study in Taiwan Abstract To assess the rapidly changing psychological status of nurses during the acute phase of the 2003 SARS outbreak, we conducted a prospective and periodic evaluation of psychiatric morbidity and psychological adaptation among nurses in SARS units and non-SARS units. Nurse participants were from two SARS units (regular SARS [N =44] and SARS ICU [N =26]) and two non-SARS units (Neurology [N =15] and CCU [N =17]). Participants periodically self-evaluated their depression, anxiety, post-traumatic stress symptoms, sleep disturbance, attitude towards SARS and family support. Results showed that depression (38.5% vs. 3.1%) and insomnia (37% vs. 9.7%) were, respectively, greater in the SARS unit nurses than the non-SARS unit nurses. No difference between these two groups was found in the prevalence of post-traumatic stress symptoms (33% vs. 18.7%), yet, three unit subjects (SARS ICU, SARS regular and Neurology) had significantly higher rate than those in CCU (29.7% vs. 11.8%, respectively) (p <0.05). For the SARS unit nurses, significant reduction in mood ratings, insomnia rate and perceived negative feelings as well as increasing knowledge and understanding of SARS at the end of the study (all p <0.001) indicated that a gradual psychological adaptation had occurred. The adjustment of nurses in the more structured SARS ICU environment, where nurses care for even more severely ill patients, may have been as good or better than that of nurses in the regular SARS unit. Occurrence of psychiatric symptoms was linked to direct exposure to SARS patient care, previous mood disorder history, younger age and perceived negative feelings. Positive coping attitude and strong social and family support may have protected against acute stress. In conclusion, the psychological impact on the caring staffs facing future bio-disaster will be minimized with lowered risk factors and a safer and more structured work environment.

negative: Advances in the Relationship Between Coronavirus Infection and Cardiovascular Diseases The outbreak of coronavirus disease 2019 (COVID-19) has once again aroused people's concern about coronavirus. Seven human coronaviruses (HCoVs) have been discovered so far, including HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU115, severe acute respiratory syndrome coronavirus, Middle East respiratory syndrome coronavirus and severe acute respiratory syndrome coronavirus 2. Existing studies show that the cardiovascular disease increased the incidence and severity of coronavirus infection. At the same time, myocardial injury caused by coronavirus infection is one of the main factors contributing to poor prognosis. In this review, the recent clinical findings about the relationship between coronaviruses and cardiovascular diseases and the underlying pathophysiological mechanisms are discussed. This review aimed to provide assistance for the prevention and treatment of COVID-19.

negative: The Impact of Model Building on the Transmission Dynamics under Vaccination: Observable (Symptom-Based) versus Unobservable (Contagiousness-Dependent) Approaches BACKGROUND: The way we formulate a mathematical model of an infectious disease to capture symptomatic and asymptomatic transmission can greatly influence the likely effectiveness of vaccination in the presence of vaccine effect for preventing clinical illness. The present study aims to assess the impact of model building strategy on the epidemic threshold under vaccination. METHODOLOGY/PRINCIPAL FINDINGS: We consider two different types of mathematical models, one based on observable variables including symptom onset and recovery from clinical illness (hereafter, the “observable model”) and the other based on unobservable information of infection event and infectiousness (the “unobservable model”). By imposing a number of modifying assumptions to the observable model, we let it mimic the unobservable model, identifying that the two models are fully consistent only when the incubation period is identical to the latent period and when there is no pre-symptomatic transmission. We also computed the reproduction numbers with and without vaccination, demonstrating that the data generating process of vaccine-induced reduction in symptomatic illness is consistent with the observable model only and examining how the effective reproduction number is differently calculated by two models. CONCLUSIONS: To explicitly incorporate the vaccine effect in reducing the risk of symptomatic illness into the model, it is fruitful to employ a model that directly accounts for disease progression. More modeling studies based on observable epidemiological information are called for.

negative: Coronavirus disease 2019 (covid-19): a guide for UK GPs.

negative: SARS: Just another viral acronym? Abstract Recent observations and experimental evidence have purported that a virus causes SARS, but such viruses have been isolated in only less than half of SARS patients in some studies and virologist Vincent Plummer of Winnipeg’s National Microbiology Laboratory found that indeed 1 in 5 perfectly healthy Canadians with a history of recent travel to Asia had the virus. Therfore SARS microbiologic origins remain unclear. Outbreaks of multi-drug resistant (MDR) tuberculosis and the atypical mycobacteria simulate SARS on clinical, radiologic, epidemiologic, and diagnostic laboratory grounds and it is only logical then to include them in the differential to find a definitive cause and cure for SARS.

negative: A Clathrin Independent Macropinocytosis-Like Entry Mechanism Used by Bluetongue Virus-1 during Infection of BHK Cells Acid dependent infection of Hela and Vero cells by BTV-10 occurs from within early-endosomes following virus uptake by clathrin-mediated endocytosis (Forzan et al., 2007: J Virol 81: 4819–4827). Here we report that BTV-1 infection of BHK cells is also dependent on a low endosomal pH; however, virus entry and infection were not inhibited by dominant-negative mutants of Eps15, AP180 or the ‘aa’ splice variant of dynamin-2, which were shown to inhibit clathrin-mediated endocytosis. In addition, infection was not inhibited by depletion of cellular cholesterol, which suggests that virus entry is not mediated by a lipid-raft dependent process such as caveolae-mediated endocytosis. Although virus entry and infection were not inhibited by the dominant-negative dynamin-2 mutant, entry was inhibited by the general dynamin inhibitor, dynasore, indicating that virus entry is dynamin dependent. During entry, BTV-1 co-localised with LAMP-1 but not with transferrin, suggesting that virus is delivered to late-endosomal compartments without first passing through early-endosomes. BTV-1 entry and infection were inhibited by EIPA and cytochalasin-D, known macropinocytosis inhibitors, and during entry virus co-localised with dextran, a known marker for macropinocytosis/fluid-phase uptake. Our results extend earlier observations with BTV-10, and show that BTV-1 can infect BHK cells via an entry mechanism that is clathrin and cholesterol-independent, but requires dynamin, and shares certain characteristics in common with macropinocytosis.

negative: Factors associated with depression, anxiety, and PTSD symptomatology during the COVID-19 pandemic: Clinical implications for U.S. young adult mental health This study sought to identify factors associated with depression, anxiety, and PTSD symptomatology in U.S. young adults (18-30 years) during the COVID-19 pandemic. This cross-sectional online study assessed 898 participants from April 13, 2020 to May 19, 2020, approximately one month after the U.S. declared a state of emergency due to COVID-19 and prior to the initial lifting of restrictions across 50 U.S. states. Respondents reported high levels of depression (43.3%, PHQ-8 scores ≥ 10), high anxiety scores (45.4%, GAD-7 scores ≥ 10), and high levels of PTSD symptoms (31.8%, PCL-C scores ≥ 45). High levels of loneliness, high levels of COVID-19-specific worry, and low distress tolerance were significantly associated with clinical levels of depression, anxiety, and PTSD symptoms. Resilience was associated with low levels of depression and anxiety symptoms but not PTSD. Most respondents had high levels of social support; social support from family, but not from partner or peers, was associated with low levels of depression and PTSD. Compared to Whites, Asian Americans were less likely to report high levels across mental health symptoms, and Hispanic/Latinos were less likely to report high levels of anxiety. These factors provide initial guidance regarding the clinical management for COVID-19-related mental health problems.

negative: Gulf War Servicemen and Servicewomen: The Long Road Home and the Role of Health Care Professionals to Enhance the Troops' Health and Healing

negative: World Heart Federation Briefing on Prevention: Coronavirus Disease 2019 (COVID-19) in Low-Income Countries In December 2019, the novel coronavirus Coronavirus Disease 2019 (COVID-19) outbreak started in Wuhan, the capital of Hubei province in China. Since then it has spread to many other regions, including low-income countries.

negative: Severe acute respiratory syndrome (SARS) in children: epidemiology, presentation and management Abstract Severe acute respiratory syndrome (SARS) is a newly recognised and highly contagious respiratory infection caused by a new strain of coronavirus. The disease can result in progressive respiratory failure in adults and the mortality rate has been reported to be 8–15%. This infection spreads by droplet transmission and children appear to acquire SARS through close household contact exposure to infected adults. Disease severity is, however, much milder in the paediatric age group. The common laboratory findings in infected children and adolescents include lymphopaenia and elevated levels of lactate dehydrogenase and creatinine phosphokinase. Air space consolidation is commonly seen during the course of the illness although chest radiographs are normal on presentation in half of the cases. The pathophysiology of SARS appears to be related to immunological dysregulation in response to the coronavirus infection. The optimal treatment of SARS in children remains to be determined. No case fatality in infected children has been reported. The early and proper isolation of infected adults, meticulous infection control measures in the hospital setting, exhaustive contact tracing and quarantine measures are important steps in preventing the spread of the disease among health care workers and into the community. The development of a sensitive and rapid test for early diagnosis is underway. Further controlled trials are necessary to define the optimal treatment of this infection in children.

negative: High transmissibility of COVID-19 near symptom onset Background The dynamics of coronavirus disease 2019 (COVID-19) transmissibility after symptom onset remains unknown. Methods We conducted a prospective case-ascertained study on laboratory-confirmed COVID-19 cases and their contacts. Secondary clinical attack rate (considering symptomatic cases only) was analyzed for different exposure windows after symptom onset of index cases and for different exposure settings. Results Thirty-two confirmed patients were enrolled and 12 paired data (index-secondary cases) were identified among the 1,043 contacts. The secondary clinical attack rate was 0.9% (95% CI 0.5-1.7%). The attack rate was higher among those whose exposure to index cases started within five days of symptom onset (2.4%, 95% CI 1.1-4.5%) than those who were exposed later (zero case from 605 close contacts, 95% CI 0-0.61%). The attack rate was also higher among household contacts (13.6%, 95% CI 4.7-29.5%) and non-household family contacts (8.5%, 95% CI 2.4-20.3%) than that in healthcare or other settings. The higher secondary clinical attack rate for contacts near symptom onset remained when the analysis was restricted to household and family contacts. There was a trend of increasing attack rate with the age of contacts (p for trend < 0.001). Conclusions High transmissibility of COVID-19 near symptom onset suggests that finding and isolating symptomatic patients alone may not suffice to contain the epidemic, and more generalized social distancing measures are required. Rapid reduction of transmissibility over time implies that prolonged hospitalization of mild cases might not be necessary in large epidemics.

negative: Allium fistulosum congee as a home remedy to ward off the corona virus at an early stage

negative: Coronavirus Pandemic as Black Swan Event Nowadays coronavirus is the hottest break news around the world. This paper aims to study why coronavirus became so meaningful for worldwide life. On one side many countries closed their boarders to prevent coronavirus spreading. On another side some people said that coronavirus is no scared than simple influence. Where is true? The health effects and mortality of coronavirus and influenza were compared. Situation Reports of World Health Organization have been analyzed and signs of Black Swan event considered. Total confirmed cases, total, deaths, and Rate of coronavirus distribution was calculated based on Situation Reports of the World Health Organization. To conclude this paper Coronavirus Pandemic recognized as Black Swan event according to considered figures and facts from recent references.

negative: Pneumonia in the Non–HIV-Infected Immunocompromised Patient

negative: Endothelial cell dysfunction: a major player in SARS-CoV-2 infection (COVID-19)? Coronavirus disease 2019 (COVID-19) represents a public health crisis of pandemic proportions. Caused by SARS-CoV-2, which stands for severe acute respiratory syndrome (SARS) coronavirus 2, the symptoms most commonly reported include cough, fever, and shortness of breath, but also extra-pulmonary symptoms, such as neurological and gastroenterological manifestations.

negative: Connected health: cancer symptom and quality-of-life assessment using a tablet computer: a pilot study. Incorporation of tablet computers (TCs) into patient assessment may facilitate safe and secure data collection. We evaluated the usefulness and acceptability of a TC as an electronic self-report symptom assessment instrument. Research Electronic Data Capture Web-based application supported data capture. Information was collected and disseminated in real time and a structured format. Completed questionnaires were printed and given to the physician before the patient visit. Most participants completed the survey without assistance. Completion rate was 100%. The median global quality of life was high for all. More than half reported pain. Based on Edmonton Symptom Assessment System, the top 3 most common symptoms were tiredness, anxiety, and decreased well-being. Patient and physician acceptability for these quick and useful TC-based surveys was excellent.

negative: Typical radiological progression and clinical features of patients with coronavirus disease 2019 We aimed to describe typical radiological features and progression of Coronavirus disease 2019 (COVID-19) patients. We reviewed the chest CT scans, laboratory findings, and clinical records of 66 COVID-19 patients who were admitted to affiliated hospitals of Nanchang university, Nanchang, China, from Jan 21 to Feb 2, 2020. CT was used to evaluate the radiological characteristics of COVID-19 patients. Only 4 patients (4/66, 6%) claimed their exposure to COVID-19 pneumonia patients. The major symptoms were fever (60/66, 91%) and cough (37/66, 56%). The predominant features of lesion were scattered (43/66, 65%), bilateral (50/66, 76%), ground-glass opacity (64/66, 97%), and air bronchogram sign (47/66, 71%). Forty-eight patients (48/66, 73%) had more than two lobes involved. Right lower lobe (58/66, 88%) and left lower lobe (49/66, 74%) were most likely invaded. Twelve patients (12/66, 18%) had at least one comorbid condition. Pleural traction (29/66, 44%), crazy paving (15/66, 23%), interlobular septal thickening (11/66, 17%), and consolidation (7/66, 11%) were also observed. The typical radiology features of COVID-19 patients are scattered ground-glass opacity in the bilateral lobes. Fever and cough are the major symptoms. Evaluating chest CT, clinical symptoms, and laboratory results could facilitate the early diagnosis of COVID-19, and judge disease progression.

negative: Epidemiology and Clinical Characteristics of COVID-19. Since December 2019, there has been an outbreak of a novel coronavirus (COVID-19) infection in Wuhan, China. Meanwhile, the outbreak also drew attention and concern from the World Health Organization (WHO). COVID-19 is another human infectious disease caused by coronavirus. The transmission of COVID-19 is potent and the infection rate is fast. Since there is no specific drug for COVID-19, the treatment is mainly symptomatic supportive therapy. In addition, it should be pointed out that patients with severe illness need more aggressive treatment and meticulous care. Recently, accurate RNA detection has been decisive for the diagnosis of COVID-19. The development of highly sensitive RT-PCR has facilitated epidemiological studies that provide insight into the prevalence, seasonality, clinical manifestations and course of COVID-19 infection. In this review, we summarize the epidemiology and characteristics of 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: The indispensable role of chest CT in the detection of coronavirus disease 2019 (COVID-19)

negative: First case diagnosed with both COVID-19 and dengue virus infections in Bangladesh: Possible dengue prevention strategies amid COVID-19 outbreak

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: Should we expect neurological symptoms in the SARS-CoV-2 epidemic? Abstract Introduction There is growing evidence that SARS-CoV-2 can gain access to the central nervous system (CNS). We revise the literature on coronavirus infection of the CNS associated with neurological diseases. Development Neurological symptoms were rarely reported in the SARS-CoV and MERS-CoV epidemics, although isolated cases were described. There are also reports of cases of neurological symptoms associated with CoV-OC43 and CoV-229E infection. The presence of neurological lesions, especially demyelinating lesions in the mouse hepatitis virus model, may explain the mechanisms by which coronaviruses enter the CNS, particularly those related with the immune response. This may explain the presence of coronavirus in patients with multiple sclerosis. We review the specific characteristics of SARS-CoV-2 and address the question of whether the high number of cases may be associated with greater CNS involvement. Conclusion Although neurological symptoms are not frequent in coronavirus epidemics, the high number of patients with SARS-CoV-2 infection may explain the presence of the virus in the CNS and increase the likelihood of early- or delayed-onset neurological symptoms. Follow-up of patients affected by the SARS-CoV-2 epidemic should include careful assessment of the CNS.

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: What was the primary mode of smallpox transmission? Implications for biodefense The mode of infection transmission has profound implications for effective containment by public health interventions. The mode of smallpox transmission was never conclusively established. Although, “respiratory droplet” transmission was generally regarded as the primary mode of transmission, the relative importance of large ballistic droplets and fine particle aerosols that remain suspended in air for more than a few seconds was never resolved. This review examines evidence from the history of variolation, data on mucosal infection collected in the last decades of smallpox transmission, aerosol measurements, animal models, reports of smallpox lung among healthcare workers, and the epidemiology of smallpox regarding the potential importance of fine particle aerosol mediated transmission. I introduce briefly the term anisotropic infection to describe the behavior of Variola major in which route of infection appears to have altered the severity of disease.

negative: Potential inhibitors for 2019-nCoV coronavirus M protease from clinically approved medicines Starting from December 2019, a novel coronavirus, named 2019-nCoV, was found to cause Severe Acute Respiratory (SARI) symptoms and rapid pandemic in China. With the hope to identify candidate drugs for 2019-nCoV, we adopted a computational approach to screen for available commercial medicines which may function as inhibitors for the Mpro of 2019-nCoV. Up to 10 commercial medicines that may form hydrogen bounds to key residues within the binding pocket of 2019-nCoV Mpro were identified, which may have higher mutation tolerance than lopinavir/ritonavir and may also function as inhibitors for other coronaviruses with similar Mpro binding sites and pocket structures.

negative: Analysis and comparison of the tongue picture of 34 patients with severe acute respiratory syndrome Objective: To explore the changes of tongue pictures in the developing process of disease in patients with severe acute respiratory syndrome (SARS), and to compare the tongue pictures of SARS patients with those of suspected SARS patients.Methods: Materials of tongue picture were dynamically collected from 34 SARS patients and 35 suspected SARS patients, and the difference and similarity between them were analyzed. Meanwhile, the changes in clinic symptoms and tongue picture after integrative medicinal treatment were observed.Results: Characteristics of tongue picture in SARS patients were changed along with the progress of the disease, showing that there existed a tendency of the pathogen invading from exterior to interior, from surface to the deep. Also the tongue pictures were varied due to the coexistence of dampness pathogen; the time of the early stage was generally 1–1.5 days, shorter than that of other stages. While in the patients with suspected SARS, the tongue picture was mostly red with thin white or yellow coating, comparatively steady and showing no obvious change along with the development of the disease.Conclusion: Observing the tongue picture and its changes in different stages can be helpful to understanding the property of pathogenic evil and its developing rules, thus offering a basis for clinical treatment.

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: Disposition of patients with coronavirus disease 2019 (COVID-19) whose respiratory specimens remain positive for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) by polymerase chain reaction assay (PCR)

negative: Pathophysiology of Clinical Symptoms in Acute Viral Respiratory Tract Infections In this article we discuss the pathophysiology of common symptoms of acute viral respiratory infections (e.g., sneezing, nasal discharge, sore throat, cough, muscle pains, malaise, and mood changes). Since clinical symptoms are not sufficient to determine the etiology of viral respiratory tract infections, we believe that the host defense mechanisms are critical for the symptomatology. Consequently, this review of literature is focused on the pathophysiology of respiratory symptoms regardless of their etiology. We assume that despite a high prevalence of symptoms of respiratory infection, their pathogenesis is not widely known. A better understanding of the symptoms’ pathogenesis could improve the quality of care for patients with respiratory tract infections.

negative: Rhinoviruses significantly affect day-to-day respiratory symptoms of children with asthma Background Viruses are frequently associated with acute exacerbations of asthma, but the extent to which they contribute to the level of day-to-day symptom control is less clear. Objective We sought to explore the relationship between viral infections, host and environmental factors, and respiratory symptoms in children. Methods Sixty-seven asthmatic children collected samples twice weekly for an average of 10 weeks. These included nasal wash fluid and exhaled breath for PCR-based detection of viral RNA, lung function measurements, and records of medication use and asthma and respiratory symptoms in the previous 3 days. Atopy, mite allergen exposure, and vitamin D levels were also measured. Mixed-model regression analyses were performed. Results Human rhinoviruses (hRVs) were detected in 25.5% of 1232 nasal samples and 11.5% of breath samples. Non-hRV viruses were detected in less than 3% of samples. hRV in nasal samples was associated with asthma symptoms (cough and phlegm: odds ratio = 2.0; 95% CI = 1.4-2.86, P = .0001; wheeze and chest tightness: odds ratio = 2.34, 95% CI = 1.55-3.52, P < .0001) and with cold symptoms, as reported concurrently with sampling and 3 to 4 days later. No differences were found between the 3 hRV genotypes (hRV-A, hRV-B, and hRV-C) in symptom risk. A history of inhaled corticosteroid use, but not atopic status, mite allergen exposure, or vitamin D levels, modified the association between viruses and asthma symptoms. Conclusion The detection of nasal hRV was associated with a significantly increased risk of day-to-day asthma symptoms in children. Host, virus genotype, and environmental factors each had only a small or no effect on the relationship of viral infections to asthma symptoms.

negative: A confirmed asymptomatic carrier of 2019 novel coronavirus

negative: Changing dynamics of psychoneuroimmunology during COVID-19 pandemic The Coronavirus Disease-2019 (COVID-19) pandemic has led to a global health care crisis in recent times. Emerging research suggest an unanticipated impact of COVID-19 on mental and/or psychological health of both the general community and affected individuals. The fear of the COVID-19 epidemic and the consequent lockdown and economic crisis has led to globally increased psychological distress. The biological bases of immediate and new onset of psychiatric symptoms in individuals with COVID-19 are not yet known. COVID-19 infection may lead to activated immune-inflammatory pathways and cytokine storm. Activated immune-inflammatory pathways, especially chronic low-grade inflammation, are associated with major psychiatric disorders in at least a subset of individuals. We propose that both the (sub)chronic inflammatory response and cytokine storm might crucially be involved in the immediate manifestation of neuropsychiatric symptoms in individuals with COVID-19 infection as well as heightened expression of psychiatric symptoms in COVID-19 infected individuals with prior psychiatric conditions. These events might expand concepts in psychoneuroimmunology, with the importance of chronic-low grade inflammation augmented by the cytokine storm hypothesis. Additionally, this might augment and refine diagnosis and prognostic management as well as treatment.

negative: COVID‐19, chronicle of an expected pandemic What is COVID‐19? What are the causes, parameters, and effects of this disease? What are the short‐ and long‐term prospects? Philippe Sansonetti, Infectious disease specialist and Chief Editor of EMBO Molecular Medicine, explains why the fate of the epidemic is in our hands.[Image: see text]

negative: Chapter 38 Animal Models of Human Viral Diseases Abstract As the threat of exposure to emerging and reemerging viruses within a naive population increases, it is vital that the basic mechanisms of pathogenesis and immune response be thoroughly investigated. By using animal models in this endeavor, the response to viruses can be studied in a more natural context to identify novel drug targets, and assess the efficacy and safety of new products. This is especially true in the advent of the Food and Drug Administration's animal rule. Although no one animal model is able to recapitulate all the aspects of human disease, understanding the current limitations allows for a more targeted experimental design. Important facets to be considered before an animal study are the route of challenge, species of animals, biomarkers of disease, and a humane endpoint. This chapter covers the current animal models for medically important human viruses, and demonstrates where the gaps in knowledge exist.

negative: Severe acute respiratory syndrome and dentistry A retrospective view ABSTRACT Background Severe acute respiratory syndrome, or SARS, which has created panic in Asia and in some parts of North America, is the first epidemic of the new century. Although it has been well-contained, sporadic cases continue to emerge. Objectives The authors trace the emergence of the SARS outbreak from southern China and its spread worldwide, discuss the viral etiology of the infection and its clinical features, and review the infection control guidelines issued during the outbreak by the health authorities in Hong Kong, the Centers for Disease Control and Prevention, the World Health Organization and the American Dental Association. They also review the prospects for a new outbreak and preventive measures. Overview The disease, which is caused by a novel coronavirus termed the “SARS coronavirus,” or SARS-CoV, essentially spreads through droplet infection and affects people of any age. It has a mortality rate ranging from 10 to 15 percent. A major hallmark of this disease has been the rate at which it has affected health care workers through nosocomial transmission; in some countries, up to one-fourth to one-third of those infected were in this category. However, no dental health care worker has been affected by SARS in a nosocomial or dental setting. Conclusions and Clinical Implications Researchers believe that a combination of factors, including the universal infection control measures that the dental community has implemented and/or the low degree of viral shedding in the prodromal phase of SARS, may have obviated the spread of the disease in dental settings. The dental community should reflect on this outbreak to reinforce the currently applied infection control measures.

negative: A Commentary on Rural‐Urban Disparities in COVID‐19 Testing Rates per 100,000 and Risk Factors

negative: The Pace and Pulse of the Fight against Coronavirus across the US, A Google Trends Approach The coronavirus pandemic is impacting our lives at unprecedented speed and scale - including how we eat and work, what we worry about, how much we move, and our ability to earn. Google Trends can be used as a proxy for what people are thinking, needing, and planning. We use it to provide both insights into, and potential indicators of, important changes in information-seeking patterns during pandemics like COVID-19. Key questions we address are: (1) What is the relationship between the coronavirus outbreak and internet searches related to healthcare seeking, government support programs, media sources of different ideologies, planning around social activities, travel, and food, and new coronavirus-specific behaviors and concerns?; (2) How does the popularity of search terms differ across states and regions and can we explain these differences?; (3) Can we find distinct, tangible search patterns across states suggestive of policy gaps to inform pandemic response? (4) Does Google Trends data correlate with and potentially precede real-life events? We suggest strategic shifts for policy makers to improve the precision and effectiveness of non-pharmaceutical interventions (NPIs) and recommend the development of a real-time dashboard as a decision-making tool. Methods used include trend analysis of US search data; geographic analyses of the differences in search popularity across US states during March 1st to April 15th, 2020; and Principal Component Analyses (PCA) to extract search patterns across states.

negative: Cardiac Tamponade Secondary to COVID-19 Abstract A 67-year-old female presented with upper respiratory symptoms and was diagnosed with COVID-19. She was found to have a large hemorrhagic pericardial effusion with echocardiographic signs of tamponade and mild left ventricular impairment. Clinical course was complicated by development of Takotsubo cardiomyopathy. She was treated with pericardiocentesis, colchicine, corticosteroids and hydroxychloroquine with improvement in symptoms.

negative: Lessons learned from a double-blind randomised placebo-controlled study with a iota-carrageenan nasal spray as medical device in children with acute symptoms of common cold BACKGROUND: Common cold is caused by a variety of respiratory viruses. The prevalence in children is high, and it potentially contributes to significant morbidity. Iota-carragenan, a polymer derived from red seaweed, has reduced viral load in nasal secretions and alleviated symptoms in adults with common cold. METHODS: We have assessed the antiviral and therapeutic activity of a nasal spray containing iota-carrageenan in children with acute symptoms of common cold. A cohort of 153 children between 1–18 years (mean age 5 years), displaying acute symptoms of common cold were randomly assigned to treatment with a nasal spray containing iota-carrageenan (0.12%) as verum or 0.9% sodium chloride solution as placebo for seven days. Symptoms of common cold were recorded and the viral load of respiratory viruses in nasal secretions was determined at two consecutive visits. RESULTS: The results of the present study showed no significant difference between the iota carrageenan and the placebo group on the mean of TSS between study days 2–7. Secondary endpoints, such as reduced time to clearance of disease (7.6 vs 9.4 days; p = 0.038), reduction of viral load (p = 0.026), and lower incidence of secondary infections with other respiratory viruses (p = 0.046) indicated beneficial effects of iota-carrageenan in this population. The treatment was safe and well tolerated, with less side effects observed in the verum group compared to placebo. CONCLUSION: In this study iota-carrageenan did not alleviate symptoms in children with acute symptoms of common cold, but significantly reduced viral load in nasal secretions that may have important implications for future studies. TRIAL REGISTRATION: ISRCTN52519535, http://www.controlled-trials.com/ISRCTN52519535/

negative: SARS Abstract Severe acute respiratory syndrome (SARS) emerged in southern China in late 2002. It first spread within Guangdong Province and then to other parts of China. Via air travelers, it quickly reached various countries around the globe, causing several major hospital outbreaks. Within weeks, the causative agent, a previously unknown coronavirus (SARS-CoV), was identified, thanks to an unprecedented international effort led by the World Health Organization (WHO). Its origin was quickly traced to wild animals traded locally for culinary purposes. Masked palm civet and some other species seem to have acted as intermediate hosts. Since then, SARS-like coronaviruses were found in different bat species in China and elsewhere, and bats are now regarded as the wildlife reservoir for SARS-CoV. Fortunately, the SARS outbreak could be contained within months. Until July 2003, it had caused 8096 cases, with 774 deaths. Once adequate measures such as isolating patients and quarantining their contacts were strictly adhered to, further transmission between human beings could be interrupted. SARS is an example of how rapidly an infectious agent can spread in the modern world. At the same time, it should serve as a showcase of how international cooperation and modern science can help to combat the spread of infectious diseases.

negative: Differential diagnosis of pandemic (H1N1) 2009 infection by detection of haemagglutinin with an enzyme-linked immunoassay A sensitive and convenient immunoassay that can directly differentiate pandemic (H1N1) 2009 (pH1N1) virus from seasonal influenza virus can play an important role in the clinic. In the presented study, a double-sandwich ELISA (pH1N1 ELISA), based on two monoclonal antibodies against haemagglutinin (HA) of the pH1N1 virus, was developed. After laboratory determination of the sensitivity and specificity characteristics, the performance of this assay was evaluated in a cohort of 904 patients with influenza-like illness. All seven strains of pH1N1 virus tested were positive by pH1N1 ELISA, with an average lower detection limit of 10(3.0 ± 0.4) tissue culture infective dose (TCID)(50)/mL (or 0.009 ± 0.005 HA titre). Cross-reaction of the assay with seasonal influenza virus and other common respiratory pathogens was rare. In pH1N1-infected patients, the sensitivity of the pH1N1 ELISA was 92.3% (84/91, 95% CI 84.8–96.9%), which is significantly higher than that of the BD Directigen EZ Flu A + B test (70.3%, p <0.01). The specificity of pH1N1 ELISA in seasonal influenza A patients was 100.0% (171/171, 95% CI 97.9–100.0%), similar to that in non-influenza A patients (640/642, 99.7%, 95% CI 98.9–100.0%). The positive predictive value for pH1N1 ELISA was 97.7% and the negative predictive value was 99.1% in this study population with a pH1N1 prevalence of 10.1%. In conclusion, detection of HA of pH1N1 virus by immunoassay appears to be a convenient and reliable method for the differential diagnosis of pH1N1 from other respiratory pathogens, including seasonal influenza virus.

negative: Dual Mutation Events in the Haemagglutinin-Esterase and Fusion Protein from an Infectious Salmon Anaemia Virus HPR0 Genotype Promote Viral Fusion and Activation by an Ubiquitous Host Protease In Infectious salmon anaemia virus (ISAV), deletions in the highly polymorphic region (HPR) in the near membrane domain of the haemagglutinin-esterase (HE) stalk, influence viral fusion. It is suspected that selected mutations in the associated Fusion (F) protein may also be important in regulating fusion activity. To better understand the underlying mechanisms involved in ISAV fusion, several mutated F proteins were generated from the Scottish Nevis and Norwegian SK779/06 HPR0. Co-transfection with constructs encoding HE and F were performed, fusion activity assessed by content mixing assay and the degree of proteolytic cleavage by western blot. Substitutions in Nevis F demonstrated that K276 was the most likely cleavage site in the protein. Furthermore, amino acid substitutions at three sites and two insertions, all slightly upstream of K276, increased fusion activity. Co-expression with HE harbouring a full-length HPR produced high fusion activities when trypsin and low pH were applied. In comparison, under normal culture conditions, groups containing a mutated HE with an HPR deletion were able to generate moderate fusion levels, while those with a full length HPR HE could not induce fusion. This suggested that HPR length may influence how the HE primes the F protein and promotes fusion activation by an ubiquitous host protease and/or facilitate subsequent post-cleavage refolding steps. Variations in fusion activity through accumulated mutations on surface glycoproteins have also been reported in other orthomyxoviruses and paramyxoviruses. This may in part contribute to the different virulence and tissue tropism reported for HPR0 and HPR deleted ISAV genotypes.

negative: Clinical time course of COVID-19, its neurological manifestation and some thoughts on its management Coronavirus disease-2019 (COVID‐19) has become a global pandemic. COVID-19 runs its course in two phases, the initial incubation phase and later clinical symptomatic phase. Patients in the initial incubation phase often have insidious clinical symptoms, but they are still highly contagious. At the later clinical symptomatic phase, the immune system is fully activated and the disease may enter the severe infection stage in this phase. Although many patients are known for their respiratory symptoms, they had neurological symptoms in their first 1–2 days of clinical symptomatic phase, and ischaemic stroke occurred 2 weeks after the onset of the clinical symptomatic phase. The key is to prevent a patient from progressing to this severe infection from mild infection. We are sharing our experience on prevention and management of COVID-19.

negative: Clinical Description of a Completed Outbreak of SARS in Vietnam, February–May, 2003 We investigated the clinical manifestations and course of all probable severe acute respiratory syndrome (SARS) patients in the Vietnam outbreak. Probable SARS cases were defined by using the revised World Health Organization criteria. We systematically reviewed medical records and undertook descriptive statistical analyses. All 62 patients were hospitalized. On admission, the most prominent symptoms were malaise (82.3%) and fever (79.0%). Cough, chest pain, and shortness of breath were present in approximately one quarter of the patients; 79.0% had lymphopenia; 40.3% had thrombocytopenia; 19.4% had leukopenia; and 75.8% showed changes on chest radiograph. Fever developed on the first day of illness onset, and both respiratory symptoms and radiographic changes occurred on day 4. On average, maximal radiographic changes were observed on day 10, and fevers subsided by day 13. Symptoms on admission were nonspecific, although fever, malaise, and lymphopenia were common. The complications of SARS included invasive intubation and ventilation (11.3%) and death (9.7%).

negative: How to protect the protectors: 10 lessons to learn for doctors fighting the COVID-19 coronavirus

negative: Asymptomatic cases in a family cluster with SARS-CoV-2 infection

negative: The association between age, COVID-19 symptoms, and social distancing behavior in the United States BACKGROUND: Public health authorities recommend that people practice social distancing, especially if they have symptoms of coronavirus disease (COVID-19), or are older and more at risk of serious illness if they become infected. We test the hypothesis that these groups are following these recommendations and are more likely to undertake social distancing. METHODS: We conducted an open online survey of 4,676 U.S. adults aged 18 and older between April 4 and April 7, 2020. We model the effects of age and common COVID-19 symptoms in the last two weeks on going out of the home for non-healthcare reasons the day before taking the survey, using a logistic model and the number of close contacts (within 6 feet) that respondents had with non-household members, using a Poisson count model. Our models control for several covariates, including other flu-like symptoms, sex, education, income, whether the respondent worked in February, household size, population density in the respondent’s ZIP code, state fixed effects, and the day of completion of the survey. We also weight our analyses to make the sample representative of the U.S. adult population. FINDINGS: About 52 percent of the adult United States population went out of their home the previous day. On average, adults had close contact with 1.9 non-household members. We find that having at least one COVID-19 symptom (fever, dry cough, or shortness of breath) increased the likelihood of going out the previous day and having additional close contacts with non-household members; however, the estimates were not statistically significant. When disaggregating our analysis by COVID-19 symptoms, we find no strong evidence of greater social distancing by people with a fever or cough in the last two weeks, but we do find that those who experienced shortness of breath have fewer close contacts, with an incidence rate ratio (IRR) of 0.49 (95% CI: 0.30–0.78). Having other flu-like symptoms reduces the odds of going out by 0.32 (95% CI: 0.18–0.60) and the incidence rate of having close contacts by 42 percent (IRR = 0.58; 95% CI: 0.38–0.88). We find that older people are just as likely to leave their homes as younger people, but people over the age of 50 had less than half the predicted number of close contacts than those who were younger than 30. Our approach has the limitation that the survey sample is self-selected. Our findings may therefore be subject to selection bias that is not adequately controlled for by weighting. In addition, the possibility exists of confounding of the results due to omitted variable bias. CONCLUSIONS: We provide evidence that older people are having significantly fewer close contacts than younger people, which is in line with the public health authorities’ recommendations. We also find that people experiencing shortness of breath are practicing more intense social distancing. However, we find that those with two other common COVID-19 symptoms, fever and dry cough, are not engaging in greater social distancing, suggesting that increased targeting on relevant symptoms, and messaging, may be required.

negative: Coronavirus Disease 2019 (COVID-19) CT Findings: A Systematic Review and Meta-analysis Abstract Purpose To date, considerable knowledge gaps remain regarding the chest CT imaging features of COVID-19. We performed a systematic review and meta-analysis of results from published studies to date to provide a summary of evidence on detection of COVID-19 by chest CT and the expected CT imaging manifestations. Methods Studies were identified by searching PubMed database for articles published between December 2019 and February 2020. Pooled CT positive rate of COVID-19 and pooled incidence of CT imaging findings were estimated using a random-effect model. Results A total of 13 studies met inclusion criteria. The pooled positive rate of the CT imaging was 89.76% and 90.35% when only including thin-section chest CT. Typical CT signs were ground glass opacities (83.31%), ground glass opacities with mixed consolidation (58.42%), adjacent pleura thickening (52.46%), interlobular septal thickening (48.46%), and air bronchograms (46.46%). Other CT signs included crazy paving pattern (14.81%), pleural effusion (5.88%), bronchiectasis (5.42%), pericardial effusion (4.55%), and lymphadenopathy (3.38%). The most anatomic distributions were bilateral lung infection (78.2%) and peripheral distribution (76.95%). The incidences were highest in the right lower lobe (87.21%), left lower lobe (81.41%), and bilateral lower lobes (65.22%). The right upper lobe (65.22%), right middle lobe (54.95%), and left upper lobe (69.43%) were also commonly involved. The incidence of bilateral upper lobes was 60.87%. A considerable proportion of patients had three or more lobes involved (70.81%). Conclusions The detection of COVID-19 chest CT imaging is very high among symptomatic individuals at high risk, especially using thin-section chest CT. The most common CT features in patients affected by COVID-19 included ground glass opacities and consolidation involving the bilateral lungs in a peripheral distribution.

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: Coronavirus Disease and New-Onset Atrial Fibrillation: Two Cases Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in a considerable amount of morbidity and mortality worldwide since December 2019. Patients with coronavirus disease (COVID-19) most commonly present with respiratory manifestations, while cardiac manifestations were reported as a complication and seldom as a presenting feature. We report two cases of new-onset atrial fibrillation occurring in middle-aged men with no significant past medical history. The first patient presented with symptomatic atrial fibrillation; however, during his hospitalization course, he developed a fever, which led to the diagnosis of infection with SARS-CoV-2. The second patient presented from urgent care after being diagnosed with COVID-19 associated with newly diagnosed atrial fibrillation. Both patients were treated symptomatically for COVID-19 and discharged home after reverting to sinus rhythm. Physicians should be aware of the variable clinical presentations of COVID-19, especially in new or worsening cardiac illnesses, in order to practice the appropriate personal protection practices. More studies are needed to identify the viral mechanisms leading to the dysregulation of cardiac rhythm.

negative: An experimental trial of recombinant human interferon alpha nasal drops to prevent coronavirus disease 2019 in medical staff in an epidemic area Objective To investigate the efficacy and safety of recombinant human interferon alpha1b (rhIFN-α) nasal drops in healthy medical staff to prevent 2019 novel coronavirus disease (COVID-19). Methods A prospective, open-label study was conducted. Starting January 21, 2020, at Taihe Hospital in Shiyan City, Hubei Province, 2944 medical staff members were recruited and allocated into a low-risk group or a high-risk group according to whether they were directly exposed to the coronavirus. Participants in the low-risk group received rhIFN-α nasal drops (2-3 drops/nostril/time, 4 times/day) for 28 days; those in the high-risk group received rhIFN-α nasal drops combined with thymosin-α1 (1.6 mg, hypodermic injection, once a week). The primary outcome was new-onset COVID-19 over 28 days. The secondary outcome was new-onset fever or respiratory symptoms but with negative pulmonary images. The results were compared with the number of new cases in medical staff in the same areas of Hubei Province (including Wuhan) during the same period. Adverse reactions to interferon nasal drops were also observed. Results Among the 2944 subjects in our study, 2415 were included in the low-risk group, including 997 doctors and 1418 nurses with average ages of 37.38 and 33.56 years, respectively; 529 were included in the high-risk group, including 122 doctors and 407 nurses with average ages of 35.24 and 32.16 years, respectively. The 28-day incidence of COVID-19 was zero in both the high- and low-risk groups. The 28-day incidence of new-onset clinical symptoms with negative images for pneumonia was also zero in both the high- and low-risk groups. As controls, a total of 2035 medical personnel with confirmed COVID-19 pneumonia from the same area (Hubei Province) was observed between January 21 to February 23, 2020. There were no serious adverse effects in the 2944 subjects treated during the intervention period. Conclusion In this investigator-initiated open-label study, we observed that rhIFN-α nasal drops can effectively prevent COVID-19 in treated medical personnel. Our results also indicate that rhIFN-α nasal drops have potential promise for protecting susceptible healthy people during the coronavirus pandemic.

negative: Initial CT imaging characters of an imported family cluster of COVID-19 Abstract The objective of this report is to better understand the initial CT imaging spectrum and the relationship between clinical characteristics and initial CT imaging features of an imported family cluster cases involving 7 laboratory-confirmed COVID-19 patients. We find that initial CT findings of 4 patients were positive within one week after the onset of symptoms and 1 patient was negative before the onset of symptoms. Two asymptomatic patients had typical CT abnormalities. The initial CT imaging manifestations are mainly peripheral or subpleural ground-glass opacities and ground-glass with consolidation. Our report is of potential guiding value for the initial CT screening of imported familial cluster cases since the imported cases have an identified time of infection.

negative: Positive selection of ORF3a and ORF8 genes drives the evolution of SARS-CoV-2 during the 2020 COVID-19 pandemic In this study, we analyzed full-length SARS-CoV-2 genomes from multiple countries to determine early trends in the evolutionary dynamics of the novel COVID-19 pandemic. Results indicated SARS-CoV-2 evolved early into at least three phylogenetic groups, characterized by positive selection at specific residues of the accessory proteins OFR3a and ORF8a. We also report evidence of epistatic interactions among sites in the genome that may be important in the generation of variants adapted to humans. These observations might impact not only public health, but also suggest more studies are needed to understand the genetic mechanisms that may affect the development of therapeutic and preventive tools, like antivirals and vaccines.

negative: Creating a Palliative Care Inpatient Response Plan for COVID-19—The UW Medicine Experience Abstract Context The coronavirus disease 2019 (COVID-19) pandemic is stressing health care systems throughout the world. Significant numbers of patients are being admitted to the hospital with severe illness, often in the setting of advanced age and underlying comorbidities. Therefore, palliative care is an important part of the response to this pandemic. The Seattle area and UW Medicine have been on the forefront of the pandemic in the U.S. Methods UW Medicine developed a strategy to implement a palliative care response for a multihospital health care system that incorporates conventional capacity, contingency capacity, and crisis capacity. The strategy was developed by our palliative care programs with input from the health care system leadership. Results In this publication, we share our multifaceted strategy to implement high-quality palliative care in the context of the COVID-19 pandemic that incorporates conventional, contingency, and crisis capacity and focuses on the areas of the hospital caring for the most patients: the emergency department, intensive care units, and acute care services. The strategy focuses on key content areas, including identifying and addressing goals of care, addressing moderate and severe symptoms, and supporting family members. Conclusion Strategy planning for delivery of high-quality palliative care in the context of the COVID-19 pandemic represents an important area of need for our health care systems. We share our experiences of developing such a strategy to help other institutions conduct and adapt such strategies more quickly.

negative: Disease Outbreaks: Critical Biological Factors and Control Strategies Disease outbreaks remain a major threat to human health and welfare especially in urban areas in both developed and developing countries. A large body of theoretical work has been devoted to modeling disease emergence, and critical factors that predict outbreak occurrence and severity have been proposed. In this chapter, we focus on biological factors that underlie both theoretical models and urban planning. We describe the SARS 2002–2003 pandemic as a case study of epidemic control of a human infectious disease. We then describe theoretical analyses of disease dynamics and control strategies. An important conclusion is that epidemic control will be strongly dependent on particular aspects of pathogen biology including host breadth, virulence, incubation time, and/or mutation rate. The probability, and potential cost, of future outbreaks, may be high and lessons from both past cases and theoretical work should inform urban design and policy. Interdisciplinary collaboration in planning, swiftness of information dissemination and response, and willingness to forgo personal liberties during a crisis may be key factors in resilience to infectious disease outbreaks.

negative: Remdesivir: A Review of Its Discovery and Development Leading to Emergency Use Authorization for Treatment of COVID-19 [Image: see text] The global pandemic of SARS-CoV-2, the causative viral pathogen of COVID-19, has driven the biomedical community to action—to uncover and develop antiviral interventions. One potential therapeutic approach currently being evaluated in numerous clinical trials is the agent remdesivir, which has endured a long and winding developmental path. Remdesivir is a nucleotide analogue prodrug that perturbs viral replication, originally evaluated in clinical trials to thwart the Ebola outbreak in 2014. Subsequent evaluation by numerous virology laboratories demonstrated the ability of remdesivir to inhibit coronavirus replication, including SARS-CoV-2. Here, we provide an overview of remdesivir’s discovery, mechanism of action, and the current studies exploring its clinical effectiveness.

negative: Novel coronavirus infection and pregnancy

negative: The Impact of Ambient Environmental Exposures to Microbial Products on Asthma Outcomes from Birth to Childhood PURPOSE OF REVIEW: Asthma is a chronic respiratory condition with increasing domestic and worldwide prevalence that burdens individuals and the healthcare system with high costs associated with long-term treatments and acute emergency room (ER) visits. It can be triggered by ambient microbes, including bacteria, viruses, and fungi. In this review, we examine the outcomes of asthma patients in relation to environmental exposures to ambient microbe products, focusing on whether exposure leads to asthma development from birth to childhood and if particular microbes are associated with worsened asthma exacerbations. RECENT FINDINGS: Bacterial endotoxin is more prominent in homes with pets and may cause cytokine cascades that lead to asthma exacerbation. However, some studies have demonstrated a protective effect with early exposure. Patients with positive Aspergillus skin testing are more prone to moderate-severe or severe-uncontrolled asthma. Fungal sensitization is also associated with earlier onset of asthma and demonstrates a dose-dependent relationship of symptom severity and duration. Among viruses, rhinovirus has the greatest association with decreased lung function, severe asthma, and asthma-related hospital admissions. Distribution of microbial products and associated asthma symptoms depends on the geographical climate. Genetic variations among individuals also mitigate the effects of microbial products on asthma development and symptom severity. SUMMARY: Microbial products of bacteria, fungi, and viruses are associated with the development of asthma, more severe asthma symptoms, and worse outcomes. However, some early exposure studies have also demonstrated a protective effect. Bacterial and fungal products are related to decreased lung function and earlier onset of asthma. Viral products are related to asthma-associated hospital admissions; and the climate and patient genetics can also temper or intensify the relationships between microbial products, asthma development, and asthma symptom severity. Further research should focus on the effects of early microbe exposure and its interaction with human immune systems and asthma-related outcomes.

negative: Computed tomography manifestations in super early stage 2019 novel coronavirus pneumonia. BACKGROUND The recent outbreak of pneumonia cases in Wuhan, PR China, was caused by a novel beta coronavirus, the 2019 novel coronavirus (COVID-19). PURPOSE To summarize chest computed tomography (CT) manifestations of the early stage of COVID-19 infection and provide a piece of reliable imaging evidence for initial screening and diagnosis. MATERIAL AND METHODS From 10 January 2020 to 10 February 2020, we continuously observed chest CT imaging of 14 patients with clinically suspected new coronavirus infection in the two weeks after onset of symptoms. Ground-glass opacity (GGO), consolidation, reticular pattern, and ground-glass mimic nodules in each patient's chest CT image were recorded. RESULTS We enrolled 14 patients, of which nine patients had the infection confirmed by reverse transcription polymerase chain reaction (RT-PCR). Five patients were highly suspected of infection. All cases had epidemiological evidence. GGO was a dominant imaging manifestation in the initial days of infection. GGO performance accounts for 40% in 1- 2 days, 90% in 3- 6 days, and 85% in 7- 10 days. With disease progression, consolidation appeared on follow-up CT. Consolidation performance accounts for 0% in 1- 2 days, 40% in 3- 6 days, and 71% in 7- 10 days. The lesions are mostly near the pleura. The number of lesions and the extent of the lesions increased as the disease progressed. CONCLUSION Patients with novel coronavirus pneumonia have characteristic CT features in the initial stage of infection, which can be used as an essential supplement for nucleic acid examination.

negative: Acute kidney injury in critically ill patients with 2009 influenza A (H1N1) viral pneumonia: an observational study OBJECTIVE: To describe the incidence, risk factors, and impact on mortality of acute kidney injury (AKI) in patients with 2009 influenza A (H1N1) viral pneumonia requiring mechanical ventilation. DESIGN: Observational cohort study. PATIENTS AND METHODS: AKI was defined as risk, injury or failure, according to the RIFLE classification. Early and late AKI were defined as AKI occurring on intensive care unit (ICU) day 2 or before, or after ICU day 2, respectively. Demographic data and information on organ dysfunction were collected daily. RESULTS: Of 84 patients, AKI developed in 43 patients (51%). Twenty (24%) needed renal replacement therapy. Early and late AKI were found in 28 (33%) and 15 (18%) patients, respectively. Patients with AKI, as compared with patients without AKI, had higher Acute Physiology and Chronic Health Evaluation (APACHE) II score and ICU mortality (72% versus 39%, p < 0.01) and presented on admission more marked cardiovascular, respiratory, and hematological dysfunction. Patients with early but not late AKI presented on admission higher APACHE II score and more marked organ dysfunction, as compared with patients without AKI. ICU mortality was higher in late versus early AKI (93% versus 61%, p < 0.001). On multivariate analysis, only APACHE II score and late but not early AKI [odds ratio (OR) 1.1 (95% confidence interval 1.0–1.1) and 15.1 (1.8–130.7), respectively] were associated with mortality. CONCLUSIONS: AKI is a frequent complication of 2009 influenza A (H1N1) viral pneumonia. AKI developing after 2 days in ICU appears to be associated with different risk factors than early AKI, and is related to a higher mortality rate.

negative: Prolonged shedding of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) RNA among patients with coronavirus disease 2019 (COVID-19)

negative: Coronavirus disease 2019: initial chest CT findings OBJECTIVES: To systematically analyze CT findings during the early and progressive stages of natural course of coronavirus disease 2019 and also to explore possible changes in pulmonary parenchymal abnormalities during these two stages. METHODS: We retrospectively reviewed the initial chest CT data of 62 confirmed coronavirus disease 2019 patients (34 men, 28 women; age range 20–91 years old) who did not receive any antiviral treatment between January 21 and February 4, 2020, in Chongqing, China. Patients were assigned to the early-stage group (onset of symptoms within 4 days) or progressive-stage group (onset of symptoms within 4–7 days) for analysis. CT characteristics and the distribution, size, and CT score of pulmonary parenchymal abnormalities were assessed. RESULTS: In our study, the major characteristic of coronavirus disease 2019 was ground-glass opacity (61.3%), followed by ground-glass opacity with consolidation (35.5%), rounded opacities (25.8%), a crazy-paving pattern (25.8%), and an air bronchogram (22.6%). No patient presented cavitation, a reticular pattern, or bronchial wall thickening. The CT scores of the progressive-stage group were significantly greater than those of the early-stage group (p = 0.004). CONCLUSIONS: Multiple ground-glass opacities with consolidations in the periphery of the lungs were the primary CT characteristic of coronavirus disease 2019. CT score can be used to evaluate the severity of the disease. If these typical alterations are found, then the differential diagnosis of coronavirus disease 2019 must be considered. KEY POINTS: • Multiple GGOs with consolidations in the periphery of the lungs were the primary CT characteristic of COVID-19. • The halo sign may be a special CT feature in the early-stage COVID-19 patients. • Significantly increased CT score may indicate the aggravation of COVID-19 in the progressive stage.

negative: Adrenal infections Summary Adrenal infections are an important but under-recognized clinical entity. The adrenal gland can be infected by a myriad of pathogens including fungi, viruses, parasites, and bacteria. Infection can directly or indirectly cause tissue damage and alteration in endocrine function. Direct damage occurs via microbial replication and local production of toxic compounds, such as endotoxins. Indirect damage results from alterations in the regulation of a host's immunologic and endocrine mediators in response to damage by a microbe at a distant site. Variations in pathogen tropism, adrenal anatomy, and host immune integrity contribute to the progression of active disease and discernable adrenal dysfunction. Early recognition and intervention in the case of adrenal infection can significantly improve outcome, demonstrating the need for increased clinical suspicion in the appropriate clinical setting.

negative: COVID-19: Knowns, Unknowns, and Questions The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the Hubei province in China in late 2019 demonstrates the epidemic potential of coronaviruses. The rapid spread of this virus across the world in only 2 months highlights the transmissibility of this family of viruses and the significant morbidity and mortality that they can cause. We highlight the current state of knowledge of coronavirus biology while answering questions concerning the current outbreak of SARS-CoV-2.

negative: Highlights for management of patients with Autoimmune Liver Disease during COVID-19 pandemia

negative: Rapidly fatal outcome of Covid-19 after successful emergency surgery during pandemic outbreak in Northern Italy INTRODUCTION: A pandemic outbreak of novel coronavirus, named SARS-CoV-2 and responsible of Coronavirus Disease 2019 (COVID-19), has rapidly spread from China to Europe, being Northern Italy the first focus outside Asia. Little is known about the evolution of SARS-CoV-2 infection in patients undergoing surgery. PRESENTATION OF CASE: Here we report the first confirmed case of early postoperative SARS-CoV-2 infection in a patient recovering after Hartmann’s procedure for acute diverticulitis. After an otherwise unevenful postoperative course, on post-operative day 8, the patient suddenly presented hyperpyrexia and cough, rapidly evolving to respiratory failure and death 36 h after symptoms onset. CT-scan identified bilateral, diffuse, interstitial pneumonitis and oropharyngeal swab test confirmed the presence of SARS-CoV-2. A previous contact with the partner, developing the same symptoms, remained unrecognized until ICU admission. DISCUSSION: During a pandemic outbreak, the early identification of SARS-CoV-2 infection of an inside patient initially considered to be infection-free has a pivotal importance not only for the prompt patient’s management, but also to avoid infection spreading to other patients and hospital personnel.In the reported case, a more precise information to the patient regarding the imperative necessity to inform the medical personnel of any person of his entourage presenting, at any time, any tell-tale sign, symptom or examination which may be attributed to COVID-19, may have had allowed to anticipate patient’s isolation and examinations and procedures aimed at identifying such an infection. CONCLUSION: Persistent hyperleucocytosis and increased CRP serum level in spite of uneventful postoperative course were the only, aspecific markers of an ongoing SARS-CoV-2 infection before symptoms’ onset, and should be considered in future clinical practice in order to adopt the prompt and appropriate patient management and limit COVID-19 contagion in surgical units.

negative: A New Measure for Assessing the Public Health Response to a Middle East Respiratory Syndrome Coronavirus Outbreak Contact monitoring is an essential component of the public health response to a Middle East respiratory syndrome coronavirus outbreak, and is required for an effective quarantine to contain the epidemic. The timeliness of a quarantine is associated with its effectiveness. This paper provides a conceptual framework to describe the process of contact monitoring, and proposes a new measure called the “timely quarantined proportion” as a tool to assess the adequacy of a public health response.

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

negative: Analysis of the COVID-19 epidemic in french overseas department Mayotte based on a modified deterministic and stochastic SEIR model In order to anticipate a future trends in the development of the novel coronavirus COVID-19 epidemic starting early at march 13, in the french overseas department Mayotte, we study in this paper a deterministic and stochastic epidemic model through several possible states: susceptible, exposed, infected including symptomatics and asymptomatics cases, simple or mild removed, severe removed (including hospitalized) and death cases. We first fit the constant transmission rate parameter to the epidemic data in Mayotte during an early exponential growth phase using an algorithm with a package of software R and based on a Likewook Maximum estimator. Thus, after the intervention and control measures imposed by the gouvernement, we introduce a simple temporally varying and exponentially decreasing transmission rate with a control parameter. This allows us to understand wheter these interventions are having the desired impact of controlling the epidemic by pointing out some percentages to maintain control which is critical in Mayotte given the fragility of its health infrastructure and the significant fraction of the population without access to water.

negative: Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to January 2020 Since December 2019, China has been experiencing a large outbreak of a novel coronavirus (2019-nCoV) which can cause respiratory disease and severe pneumonia. We estimated the basic reproduction number R(0) of 2019-nCoV to be around 2.2 (90% high density interval: 1.4–3.8), indicating the potential for sustained human-to-human transmission. Transmission characteristics appear to be of similar magnitude to severe acute respiratory syndrome-related coronavirus (SARS-CoV) and pandemic influenza, indicating a risk of global spread.

negative: Pre-Existing Characteristics Associated with Covid-19 Illness Severity Background. Certain individuals, when infected by SARS-CoV-2, tend to develop more severe forms of Covid-19 illness for reasons that remain unclear. Objective. To determine the demographic and pre-existing clinical characteristics associated with increased severity of Covid-19 infection. Design. Retrospective observational study. We curated data from the electronic health record, and used multivariable logistic regression to examine the association of pre-existing traits with a Covid-19 illness severity defined by level of required care: need for hospital admission, need for intensive care, and need for intubation. Setting. A large, multihospital healthcare system in Southern California. Participants. All patients with confirmed Covid-19 infection (N=442). Results. Of all patients studied, 48% required hospitalization, 17% required intensive care, and 12% required intubation. In multivariable-adjusted analyses, patients requiring a higher levels of care were more likely to be older (OR 1.5 per 10 years, P<0.001), male (OR 2.0, P=0.001), African American (OR 2.1, P=0.011), obese (OR 2.0, P=0.021), with diabetes mellitus (OR 1.8, P=0.037), and with a higher comorbidity index (OR 1.8 per SD, P<0.001). Several clinical associations were more pronounced in younger compared to older patients (Pinteraction<0.05). Of all hospitalized patients, males required higher levels of care (OR 2.5, P=0.003) irrespective of age, race, or morbidity profile. Conclusion. In our healthcare system, greater Covid-19 illness severity is seen in patients who are older, male, African American, obese, with diabetes, and with greater overall comorbidity burden. Certain comorbidities paradoxically augment risk to a greater extent in younger patients. In hospitalized patients, male sex is the main determinant of needing more intensive care. Further investigation is needed to understand the mechanisms underlying these findings.