query: which biomarkers predict the severe clinical course of 2019-nCOV infection?

positive: Clinical Features and Predictors for Patients with Severe SARS-CoV-2 Pneumonia: a retrospective multicenter cohort study Objectives: This study was performed to investigate clinical features of patients with severe SARS-CoV-2 pneumonia and identify risk factors for converting to severe cases in those who had mild to moderate diseases. Methods: In this retrospective, multicenter cohort study, patients with mild to moderate SARS-CoV-2 pneumonia were included. Demographic data, symptoms, laboratory values, and clinical outcomes were collected. Data were compared between non-severe and severe patients. Results: 58 patients were included in the final analysis. Compared with non-severe cases, severe patients with SARS-CoV-2 pneumonia had a longer: time to clinical recovery (p=0.0011), duration of viral shedding (p=0.0183), and hospital stay ( p=0.0211). Multivariate logistic regression indicated that lymphocyte count was significantly associated with the rate of converting to severe cases (odds ratio 1.28, 95%CI 1.06-1.54, per 0.1*10 9/L reduced; p=0.007), while using of low-to-moderate doses of systematic corticosteroids was associated with reduced likelihood of converting to a severe case (odds ratio 0.14, 95%CI 0.02-0.80; p=0.0275). Conclusions: The low peripheral blood lymphocyte count was an independent risk factor for SARS-CoV-2 pneumonia patients converting to severe cases. This finding may help clinicians more accurately predict prognosis, and triage priorities to improve clinical outcomes.

positive: Plasma levels of soluble ACE2 are associated with sex, Metabolic Syndrome, and its biomarkers in a large cohort, pointing to a possible mechanism for increased severity in COVID-19 We examined the associations between plasma concentrations of soluble ACE2 and biomarkers of Metabolic Syndrome in a large (N=2,051) sample of individuals who participated in a commercial wellness program and who underwent deep molecular phenotyping. sACE2 levels were significantly higher in men, compared to women, and in individuals with Metabolic Syndrome, compared to controls. sACE2 levels showed reliable associations with all individuals components of Metabolic Syndrome, including obesity, hypertension, insulin resistance, hyperlipidemia, and as well as markers of liver damage. This profile of associations was statistically significantly stronger in men, compared to women, and suggests that preexisting cardiometabolic conditions might confer increased severity of symptoms in some COVID-19 patients through increased expression of ACE2 in the liver.

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: [Diagnostic steps and estimation of disease prognosis in COVID-19-infected patients]. In December 2019, a new coronavirus outbreak hit his head in Wuhan, China. The identified pathogen is a new coronavirus named "severe acute respiratory syndrome coronavirus 2," or SARS-CoV-2, and the respiratory syndrome it elicits was named "coronavirus disease 2019," or COVID-19. The World Health Organization (WHO) classified the epidemic as a pandemic in March 2020. We reviewed the currently available international literature on the COVID-19 epidemic. In this paper, we summarize the relevant information for the diagnosis and prognosis of the new coronavirus. Details of the anamnestic factors and initial test results required to raise a clinical suspicion, the method of microbiological sampling, the basic information on the molecular diagnostic test - the 'gold-standard' real-time 'reverse transcriptase polymerase chain reaction (RT-PCR) - in particular the diagnostic current public health regulations for testing. We also place emphasis on the parameters of high-risk patients and how to identify them. The COVID-19 pandemic may also have significant epidemiological and health consequences in Hungary. In addition to epidemiological measures to slow down the epidemic, the timely identification and adequate hospital care of already infected individuals is also a key issue in terms of mortality. The chances of critically ill patients can only be improved with high-quality, careful intensive care, and to be able to provide the best, it is useful to use the experience of medical colleagues already working in endemic countries. Orv Hetil. 2020; 160 (17): 667-671.

positive: Lactate dehydrogenase, an independent risk factor of severe COVID-19 patients: a retrospective and observational study Background: The World Health Organization has declared coronavirus disease 2019 (COVID-19) a public health emergency of global concern. Updated analysis of cases might help identify the risk factors of illness severity. Results: The median age was 63 years, and 44.9% were severe cases. Severe patients had higher APACHE II (8.5 vs. 4.0) and SOFA (2 vs. 1) scores on admission. Among all univariable parameters, lymphocytes, CRP, and LDH were significantly independent risk factors of COVID-19 severity. LDH was positively related both with APACHE II and SOFA scores, as well as P/F ratio and CT scores. LDH (AUC = 0.878) also had a maximum specificity (96.9%), with the cutoff value of 344.5. In addition, LDH was positively correlated with CRP, AST, BNP and cTnI, while negatively correlated with lymphocytes and its subsets. Conclusions: This study showed that LDH could be identified as a powerful predictive factor for early recognition of lung injury and severe COVID-19 cases. Methods: We extracted data regarding 107 patients with confirmed COVID-19 from Renmin Hospital of Wuhan University. The degree of severity of COVID-19 patients (severe vs. non-severe) was defined at the time of admission according to American Thoracic Society guidelines for community acquired pneumonia.

positive: [Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia]. Objective: To analyze the clinical characteristics of 2019 novel coronavirus (2019-nCoV) pneumonia and to investigate the correlation between serum inflammatory cytokines and severity of the disease. Methods: 29 patients with 2019-ncov admitted to the isolation ward of Tongji hospital affiliated to Tongji medical college of Huazhong University of Science and Technology in January 2020 were selected as the study subjects. Clinical data were collected and the general information, clinical symptoms, blood test and CT imaging characteristics were analyzed. According to the relevant diagnostic criteria, the patients were divided into three groups: mild (15 cases), severe (9 cases) and critical (5 cases). The expression levels of inflammatory cytokines and other markers in the serum of each group were detected, and the changes of these indicators of the three groups were compared and analyzed, as well as their relationship with the clinical classification of the disease. Results: (1) The main symptoms of 2019-nCoV pneumonia was fever (28/29) with or without respiratory and other systemic symptoms. Two patients died with underlying disease and co-bacterial infection, respectively. (2) The blood test of the patients showed normal or decreased white blood cell count (23/29), decreased lymphocyte count (20/29), increased hypersensitive C reactive protein (hs-CRP) (27/29), and normal procalcitonin. In most patients, serum lactate dehydrogenase (LDH) was significantly increased (20/29), while albumin was decreased (15/29). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Tbil), serum creatinine (Scr) and other items showed no significant changes. (3) CT findings of typical cases were single or multiple patchy ground glass shadows accompanied by septal thickening. When the disease progresses, the lesion increases and the scope expands, and the ground glass shadow coexists with the solid shadow or the stripe shadow. (4) There were statistically significant differences in the expression levels of interleukin-2 receptor (IL-2R) and IL-6 in the serum of the three groups (P<0.05), among which the critical group was higher than the severe group and the severe group was higher than the mild group. However, there were no statistically significant differences in serum levels of tumor necrosis factor-alpha (TNF-α), IL-1, IL-8, IL-10, hs-CRP, lymphocyte count and LDH among the three groups (P>0.05). Conclusion: The clinical characteristics of 2019-nCoV pneumonia are similar to those of common viral pneumonia. High resolution CT is of great value in the differential diagnosis of this disease. The increased expression of IL-2R and IL-6 in serum is expected to predict the severity of the 2019-nCoV pneumonia and the prognosis of patients.

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

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

positive: Blood biomarker score identifies individuals at high risk for severe COVID-19 a decade prior to diagnosis: metabolic profiling of 105,000 adults in the UK Biobank Background: Identification of healthy people at high risk for severe COVID-19 is a global health priority. We investigated whether blood biomarkers measured by high-throughput metabolomics could be predictive of severe pneumonia and COVID-19 hospitalisation years after the blood sampling. Methods: Nuclear magnetic resonance metabolomics was used to quantify a comprehensive biomarker profile in 105,146 plasma samples collected in the UK Biobank during 2007-2010 (age range 39-70). The biomarkers were tested for association with severe pneumonia (2507 cases, defined as diagnosis in hospital or death record occurring during a median of 8.1-year follow-up) and with severe COVID-19 (195 cases, defined as diagnosis in hospital between mid-March to mid-June 2020). A multi-biomarker score was derived for prediction of severe pneumonia based on half of the study population and validated in the other half. We explored how this biomarker score relates to the risk of severe COVID-19. Findings: The biomarker associations with risk of severe COVID-19 followed an overall pattern similar to associations with risk of severe pneumonia (correlation 0.83). The multi-biomarker score, comprised of 25 blood biomarkers including inflammatory proteins, fatty acids, amino acids and advanced lipid measures, was strongly associated with risk of severe pneumonia (odds ratio 1.67 per standard deviation [95% confidence interval 1.59-1.76]; 3.8-fold risk increase for individuals in upper vs lower quintile). The multi-biomarker score was also associated with risk of severe COVID-19 (odds ratio 1.33 [1.17-1.53]; 2.5-fold risk for upper vs lower quintile) and remained significant when adjusting for body mass index, smoking, and existing respiratory and cardiometabolic diseases. Mimicking the decade lag from blood sampling to COVID-19, severe pneumonia events occurring after 7-11 years associated with the multi-biomarker score to a similar magnitude (odds ratio 1.43 [1.29-1.59]; 2.6-fold risk for upper vs lower quintile) as for severe COVID-19. However, the short-term risk of severe pneumonia events associated to the multi-biomarker score at even 3 times higher magnitude (odds ratio 2.21 [1.95-2.50]; 8.0-fold risk for upper vs lower quintile in analysis of the first 2 years after blood sampling). Interpretation: In decade-old blood samples from the UK Biobank, a biomarker score measured by high-throughput metabolomics is indicative of the risk for severe COVID-19. The molecular signature of biomarker changes reflective of risk for severe COVID-19 is similar to that for severe pneumonia, in particular when accounting for the time lag to the COVID-19 pandemic. The even stronger association of the biomarker score with 2-year risk for severe pneumonia lends support to promising screening possibilities for identifying people at high risk for severe COVID-19.

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

positive: An interpretable mortality prediction model for COVID-19 patients The sudden increase in COVID-19 cases is putting high pressure on healthcare services worldwide. At this stage, fast, accurate and early clinical assessment of the disease severity is vital. To support decision making and logistical planning in healthcare systems, this study leverages a database of blood samples from 485 infected patients in the region of Wuhan, China, to identify crucial predictive biomarkers of disease mortality. For this purpose, machine learning tools selected three biomarkers that predict the mortality of individual patients more than 10 days in advance with more than 90% accuracy: lactic dehydrogenase (LDH), lymphocyte and high-sensitivity C-reactive protein (hs-CRP). In particular, relatively high levels of LDH alone seem to play a crucial role in distinguishing the vast majority of cases that require immediate medical attention. This finding is consistent with current medical knowledge that high LDH levels are associated with tissue breakdown occurring in various diseases, including pulmonary disorders such as pneumonia. Overall, this Article suggests a simple and operable decision rule to quickly predict patients at the highest risk, allowing them to be prioritized and potentially reducing the mortality rate.

positive: Biomarkers in Pediatric ARDS: Future Directions Acute respiratory distress syndrome (ARDS) is common among mechanically ventilated children and accompanies up to 30% of all pediatric intensive care unit deaths. Though ARDS diagnosis is based on clinical criteria, biological markers of acute lung damage have been extensively studied in adults and children. Biomarkers of inflammation, alveolar epithelial and capillary endothelial disruption, disordered coagulation, and associated derangements measured in the circulation and other body fluids, such as bronchoalveolar lavage, have improved our understanding of pathobiology of ARDS. The biochemical signature of ARDS has been increasingly well described in adult populations, and this has led to the identification of molecular phenotypes to augment clinical classifications. However, there is a paucity of data from pediatric ARDS (pARDS) patients. Biomarkers and molecular phenotypes have the potential to identify patients at high risk of poor outcomes, and perhaps inform the development of targeted therapies for specific groups of patients. Additionally, because of the lower incidence of and mortality from ARDS in pediatric patients relative to adults and lack of robust clinical predictors of outcome, there is an ongoing interest in biological markers as surrogate outcome measures. The recent definition of pARDS provides additional impetus for the measurement of established and novel biomarkers in future pediatric studies in order to further characterize this disease process. This chapter will review the currently available literature and discuss potential future directions for investigation into biomarkers in ARDS among children.

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: Prediction and analysis of key protein structures of 2019-nCoV Aim: The purpose of this study was to predict and analyze the structure and function of 2019-novel Coronavirus (nCoV) key proteins. Materials & methods: We obtained the structure and sequence of proteins from related databases and studied them through multiple sequence alignment, homology modeling, sequence analysis, virtual screening, reverse mutation, protein structure overlap and surface property analysis. Results & conclusion: We found no significant changes in envelope protein, membrane protein, nucleocapsid protein and key proteases in open reading frame 1ab, and predicted results of proteins and performed molecular dynamics simulations. Based on the surface properties of spike protein and docking results with angiotensin-converting enzyme 2, we believe that the binding ability of spike protein to angiotensin-converting enzyme 2 may be similar to SARS. These studies will help us in fighting 2019-nCoV.

positive: Lactate dehydrogenase and caspase activity in nasopharyngeal secretions are predictors of bronchiolitis severity BACKGROUND: Bronchiolitis is the leading cause of hospitalization in infants. Biomarkers of disease severity might help in clinical management. OBJECTIVE: To determine the clinical predictiveness of NW-LDH, NW-caspase 3/7, and NW-LDH/NW-caspase 3/7 ratio in bronchiolitis. METHODS: Previously healthy children less than 24 months of age with bronchiolitis were recruited from the Texas Children's emergency room and intensive care unit from October 2010 to April 2011. Demographic, clinical information, and NW samples were obtained at enrollment. NW samples were analyzed for respiratory viruses, caspase 3/7, and LDH. RESULTS: A viral pathogen was detected in 91·6% of 131 children, with the most common being respiratory syncytial virus and human rhinovirus. A single infection was found in 61·8% of subjects and co-infection in 29·8%. Children admitted to ICU had significantly higher NW-LDH than children sent home from the ER or admitted to the general floor (P = 0·02). Children infected with RSV had the highest NW-LDH concentration (P = 0·03) compared with other viral infections. NW-LDH and NW-caspase were significantly correlated (r = 0·77, P < 0·0001). The univariate models showed NW-LDH and NW-LDH/NW- caspase 3/7 ratio were directly associated with hospitalization. Mutivariate regression analyses suggested a complex interaction between the biomarkers, demographics, and disposition. CONCLUSIONS: NW-LDH, NW-caspase 3/7 and NW-LDH/NW-caspase 3/7 ratio and their interactions with demographic factors are predictive of bronchiolitis severity and can help distinguish children requiring ICU-level care from those admitted to the general floor, or discharged home from the emergency center.

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

positive: Correlation of coagulation parameters with clinical outcomes in Coronavirus-19 affected minorities in United States: Observational cohort Importance: COVID-19 has caused a worldwide illness and New York has become the epicenter of COVID-19 in the United States. Currently Bronx has the highest prevalence per capita in New York. Objective: To investigate the coagulopathic presentation of COVID and its natural course and to investigate whether hematologic and coagulation parameters can be used to assess illness severity and death. Design: Retrospective case study of positive COVID inpatients between 3/20/2020-3/31/2020. Setting: Montefiore Health System main hospital, Moses, a large tertiary care center in the Bronx. Participants: Adult inpatients with positive COVID tests hospitalized at MHS. Exposure (for observational studies): Datasets of participants were queried for physiological, demographic (age, sex, socioeconomic status and self-reported race and/or ethnicity) and laboratory data. Main Outcome and Measures: Relationship and predictive value of measured parameters to mortality and illness severity. Results: Of the 217 in this case review, 70 died during hospitalization while 147 were discharged home. Only the admission PT and first D-Dimer could very significantly differentiate those who were discharged alive and those who died. Logistic regression analysis shows increased odds ratio for mortality by first D-Dimer within 48 hrs. of admission. The optimal cut-point for the initial D-Dimer to predict mortality was found to be 1.65 mcg/mL. Conclusions: We describe here a comprehensive assessment of hematologic and coagulation parameters in COVID and examine the relationship of these to mortality. We demonstrate that both initial and maximum D-Dimer values are biomarkers that can be used for survival assessments.

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

positive: Identification and validation of a novel clinical signature to predict the prognosis in confirmed COVID-19 patients BACKGROUND: This study aims to identify a prognostic biomarker to predict the disease prognosis and reduce the mortality rate of COVID-19, which has caused a worldwide pandemic. METHODS: COVID-19 patients were randomly divided into training and test groups. Univariate and multivariate Cox regression analyses were performed to identify the disease prognosis signature, which was selected to establish a risk model in the training group. Furthermore, the disease prognosis signature of COVID-19 was validated in the test group. RESULTS: The signature of COVID-19 was combined with five indicators, namely neutrophil count, lymphocyte count, procalcitonin, older age, and C-reactive protein. The signature stratified patients into high- and low-risk groups with significantly relevant disease prognosis (log-rank test, P<0.001) in the training group. The survival analysis indicated that the high-risk group displayed substantially lower survival probability than the low-risk group (log-rank test P<0.001). The area under ROC curve (AUC) showed that the signature of COVID-19 displayed the highest predictive accuracy regarding disease prognosis, which was 0.955 in the training group and 0.945 in the test group. The ROC analysis of both groups demonstrated that the predictive ability of the signature surpassed the use of each of the five indicators alone. CONCLUSION: The signature of COVID-19 presents a novel predictor and prognostic biomarker for closely monitoring patients and providing timely treatment for those who are severely or critically ill.

positive: Systemic hypoferraemia and severity of hypoxaemic respiratory failure in COVID-19 Coronavirus disease 2019 (COVID-19) mortality is associated with hypoxaemia, multiorgan failure, and thromboinflammation. However severity of disease varies considerably and understanding physiological changes that may link to poor outcomes is important. Although increased serum ferritin has been observed in COVID-19 patients consistent with inflammation, other iron parameters have not been examined to our knowledge. Because iron is required for immunity and oxygen utilisation, and dysregulated iron homeostasis has been observed in COPD, we investigated serum iron concentrations in 30 patients with COVID-19 requiring ICU admission. All patients had low serum iron but patients with severe hypoxemic respiratory failure had more profound hypoferraemia. The area under the curve for receiver operating characteristic curves for serum iron to identify severe hypoxemia was 0.95; the optimal Youden Index for distinguishing between severe and non-severe hypoxemia was a serum iron concentration of 2.9 micromol/L. By linear regression, serum iron was associated with lymphocyte count and PaO2/FiO2. In conclusion, profound hypoferraemia identifies COVID-19 patients with severe hypoxaemia. Serum iron is a simple biomarker that could be usefully employed to stratify patients and monitor disease. Severe hypoferraemia may plausibly impair critical iron-dependent processes such as lymphocyte responses and hypoxia sensing, contributing to pathology, and is potentially treatable.

positive: Association of cardiac biomarkers and comorbidities with increased mortality, severity, and cardiac injury in COVID-19 patients: A meta-regression and Decision tree analysis BACKGROUND: Coronavirus disease-2019 (COVID-19) has a deleterious effect on several systems, including the cardiovascular system. We aim to systematically explore the association of COVID-19 severity and mortality rate with the history of cardiovascular diseases and/or other comorbidities and cardiac injury laboratory markers. METHODS: The standardized mean difference (SMD) or odds ratio (OR) and 95% confidence intervals (CI) were applied to estimate pooled results from the 56 studies. The prognostic performance of cardiac markers for predicting adverse outcomes and to select the best cutoff threshold was estimated by ROC curve analysis. Decision tree analysis by combining cardiac markers with demographic and clinical features was applied to predict mortality and severity in COVID-19 patients. RESULTS: A meta-analysis of 17,794 patients showed patients with high cardiac troponin I (OR=5.22, 95%CI=3.73-7.31, p<0.001) and AST levels (OR=3.64, 95%CI=2.84-4.66, p<0.001) were more likely to develop adverse outcomes. High troponin I >13.75 ng/L combined with either advanced age >60 years or elevated AST level >27.72 U/L was the best model to predict poor outcomes. CONCLUSIONS: COVID-19 severity and mortality are complicated by myocardial injury. Assessment of cardiac injury biomarkers may improve the identification of those patients at the highest risk and potentially lead to improved therapeutic approaches. This article is protected by copyright. All rights reserved.

positive: Hematological findings and complications of COVID‐19 COVID‐19 is a systemic infection with a significant impact on the hematopoietic system and hemostasis. Lymphopenia may be considered as a cardinal laboratory finding, with prognostic potential. Neutrophil/lymphocyte ratio and peak platelet/lymphocyte ratio may also have prognostic value in determining severe cases. During the disease course, longitudinal evaluation of lymphocyte count dynamics and inflammatory indices, including LDH, CRP and IL‐6 may help to identify cases with dismal prognosis and prompt intervention in order to improve outcomes. Biomarkers, such high serum procalcitonin and ferritin have also emerged as poor prognostic factors. Furthermore, blood hypercoagulability is common among hospitalized COVID‐19 patients. Elevated D‐Dimer levels are consistently reported, whereas their gradual increase during disease course is particularly associated with disease worsening. Other coagulation abnormalities such as PT and aPTT prolongation, fibrin degradation products increase, with severe thrombocytopenia lead to life‐threatening disseminated intravascular coagulation (DIC), which necessitates continuous vigilance and prompt intervention. So, COVID‐19 infected patients, whether hospitalized or ambulatory, are at high risk for venous thromboembolism, and an early and prolonged pharmacological thromboprophylaxis with low molecular weight heparin is highly recommended. Last but not least, the need for assuring blood donations during the pandemic is also highlighted.

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: Prediction of the clinical outcome of COVID-19 patients using T lymphocyte subsets with 340 cases from Wuhan, China: a retrospective cohort study and a web visualization tool Background Wuhan, China was the epicenter of the 2019 coronavirus outbreak. As a designated hospital, Wuhan Pulmonary Hospital has received over 700 COVID-19 patients. With the COVID-19 becoming a pandemic all over the world, we aim to share our epidemiological and clinical findings with the global community. Methods In this retrospective cohort study, we studied 340 confirmed COVID-19 patients from Wuhan Pulmonary Hospital, including 310 discharged cases and 30 death cases. We analyzed their demographic, epidemiological, clinical and laboratory data and implemented our findings into an interactive, free access web application. Findings Baseline T lymphocyte Subsets differed significantly between the discharged cases and the death cases in two-sample t-tests: Total T cells (p < 2.2e-16), Helper T cells (p < 2.2e-16), Suppressor T cells (p = 1.8-14), and TH/TS (Helper/Suppressor ratio, p = 0.0066). Multivariate logistic regression model with death or discharge as the outcome resulted in the following significant predictors: age (OR 1.05, p 0.04), underlying disease status (OR 3.42, p 0.02), Helper T cells on the log scale (OR 0.22, p 0.00), and TH/TS on the log scale (OR 4.80, p 0.00). The McFadden pseudo R-squared for the logistic regression model is 0.35, suggesting the model has a fair predictive power. Interpretation While age and underlying diseases are known risk factors for poor prognosis, patients with a less damaged immune system at the time of hospitalization had higher chance of recovery. Close monitoring of the T lymphocyte subsets might provide valuable information of the patients condition change during the treatment process. Our web visualization application can be used as a supplementary tool for the evaluation.

positive: Lymphocyte Subset Counts in COVID‐19 Patients: A Meta‐Analysis A reduced peripheral blood absolute lymphocyte count with an elevated neutrophil count has been a consistent observation in hospitalized COVID‐19 patients. In this brief meta‐analysis, the reduction of lymphocyte subset counts in COVID‐19 patients was investigated across 20 peer‐reviewed studies meeting criteria for reporting lymphocyte subset counts and COVID‐19 disease severity. CD4+ T cell, CD8+ T cell, B cell, NK cell and total lymphocyte cell counts all showed statistically significant reduction in patients with severe/critical COVID‐19 disease compared to mild/moderate disease. T cell subsets showed the largest standardized magnitude of change. In some studies, multivariate analysis has shown that CD4 and/or CD8 T cells counts are independently predictive of patient outcomes.

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

positive: 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: Less expression of CD4(+) and CD8(+) T cells might reflect the severity of infection and predict worse prognosis in patients with COVID-19: evidence from a pooled analysis This study mainly focused on the very serious COVID-19 epidemic situation at present and provided a new insight for the treatment and monitor of patients with COVID-19. Through this meta-analysis, we could draw a conclusion that less expression of blood CD4(+) and CD8(+) T cells count might reflect the severity of infection and often accompanied by a poor prognosis. Hence, we inferred blood CD4+ and CD8+ T cells count could be a promising biomarker for disease assessment and monitor of patients with COVID-19.

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

positive: The diagnostic and predictive role of NLR, d-NLR and PLR in COVID-19 patients Abstract Aim To accumulate evidence that indicates the key role played by virus-triggered inflammation in the 2019-novel coronavirus disease (COVID-19) which emerged in Wuhan City and rapidly spread throughout China. Methods Age, neutrophil(NEU)-to-lymphocyte (LYM) ratio (NLR), lymphocyte-to-monocyte(MON) ratio, platelet-to-lymphocyte ratio(PLR), and C-reactive protein(CRP) of 93 patients with laboratory confirmed COVID-19 were investigated and compared. The receiver operating characteristic curve was applied to determine the thresholds for five bio-markers, and their prognostic values were assessed via the Kaplan–Meier curve and multivariate COX regression models. Results The median age was 46.4 years old, and 37cases were females. A total of 26.8% of patients had been to Wuhan, and 73.1% had contacted with people from Wuhan. Fever (83.8%) and cough (70.9%) were the two most common symptoms. Elevated NLR and age were significantly associated with illness severity. The binary logistic analysis identified elevated NLR (hazard risk [HR] 2.46, 95% confidence interval [CI] 1.98–4.57) and age (HR 2.52, 95% CI 1.65–4.83) as independent factors for poor clinical outcome of COVID-19. NLR exhibited the largest area under the curve at 0.841, with the highest specificity (63.6%) and sensitivity (88%). Conclusions Elevated age and NLR can be considered independent biomarkers for indicating poor clinical outcomes.

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

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

positive: Cardiac biomarker-based risk stratification algorithm in patients with severe COVID-19 BACKGROUND AND AIMS: Cardiac biomarkers like cardiac troponins and natriuretic peptides are elevated in a substantial proportion of patients with coronavirus disease 2019 (COVID-19). We propose an algorithmic approach using cardiac biomarkers to triage, risk-stratify and prognosticate patients with severe COVID-19. METHODS: We systematically searched the PubMed and Google Scholar databases until May 31st, 2020, and accessed the available data on the role of cardiac biomarkers in patients with COVID-19. RESULTS: COVID-19 is associated with acute cardiac injury in around 7–28% of patients, significantly increasing its associated complications and mortality. Patients with underlying cardiovascular disease are more prone to develop acute cardiac injury as a result of COVID-19. The use of cardiac biomarkers may aid in differentiating the cardiac cause of dyspnea in patients with severe COVID-19. Cardiac biomarkers may also aid in triaging, risk-stratification, clinical decision-making, and prognostication of patients with COVID-19. However, there are concerns that routine testing in all patients with COVID-19 irrespective of severity, may result in unnecessary downstream investigations which may be misleading. In this brief review, using an algorithmic approach, we have tried to rationalize the use of cardiac biomarkers among patients with severe COVID-19. This approach is also likely to lessen the infection exposure risk to the cardiovascular team attending patients with severe COVID-19. CONCLUSION: It appears beneficial to triage, risk-stratify, and prognosticate patients with COVID-19 based on the evidence of myocardial injury and the presence of underlying cardiovascular disease. Future research studies are, however, needed to validate these proposed benefits.

positive: Antibody response to infectious diseases and other factors accurately predict COVID-19 infection and severity risk 10–14 years later: a retrospective UK Biobank cohort study BACKGROUND: Several risk factors have emerged for novel 2019 coronavirus disease (COVID-19) infection and severity. Yet, it is unknown to what degree these risk factors alone or in combination can accurately predict who is most at risk. It is also worthwhile to consider serological antibody titers to non COVID-19 infectious diseases, which may influence host immunity to COVID-19. METHODS: In this retrospective study of multicenter UK Biobank participants, as of May 26(th) 2020, all COVID-19 testing data was collected by Public Health England for older adult in- and out-patients (69.6 ± 8.8 years). We used linear discriminant analysis with cross-validation and bootstrapping to determine the accuracy, specificity, and sensitivity of baseline data from 2006–2010 to predict COVID-19 infection and presumptive severity (i.e., testing at hospital). Receiver operating characteristic (ROC) curves were used to derive the area under the curve (AUC). FINDINGS: This retrospective study included 4,510 unique participants and 7,539 testing instances (i.e., test cases). Testing resulted in 5,329 negative cases and 2,210 positive cases, split into 996 mild and 1,214 severe disease outcomes. Baseline data including demographics, bioimpedance-derived body composition, vitals, serum biochemistry, self-reported illness/disability, and complete blood count. A randomized subset of 80 participants with 124 test cases also had antibody titers for 20 common to rare infectious diseases. Among all test cases, accuracy was modest for final diagnostic models of COVID-19 infection (70.2%; AUC=0.570, CI=0.556–0.584) and severity (58.3%; AUC=0.592, CI=0.568–0.615). In the serology sub-group, by contrast, final models predicted infection and severity with an accuracy of 93.5% (AUC=0.969, CI=0.934–1.000) and 74.4% (AUC=0.803, CI=0.663–0.943) respectively. Models included titers to common pathogens (e.g., human cytomegalovirus), age, blood cell counts, lipids, and other biochemical markers. INTERPRETATION: Risk profiles including serological titers and other risk factors could help policy makers and clinicians better identify who may get COVID-19 and require hospitalization.

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: The impact of 2019 novel coronavirus on heart injury: A Systematic review and Meta-analysis BACKGROUND: Evidence about COVID-19 on cardiac injury is inconsistent. OBJECTIVES: We aimed to summarize available data on severity differences in acute cardiac injury and acute cardiac injury with mortality during the COVID-19 outbreak. METHODS: We performed a systematic literature search across Pubmed, Embase and pre-print from December 1, 2019 to March 27, 2020, to identify all observational studies that reported cardiac specific biomarkers (troponin, creatine kinase-MB fraction, myoglobin, or NT-proBNP) during COVID-19 infection. We extracted data on patient demographics, infection severity, comorbidity history, and biomarkers during COVID-19 infection. Where possible, data were pooled for meta-analysis with standard (SMD) or weighted (WMD) mean difference and corresponding 95% confidence intervals (CI). RESULTS: We included 4189 confirmed COVID-19 infected patients from 28 studies. More severe COVID-19 infection is associated with higher mean troponin (SMD 0.53, 95% CI 0.30 to 0.75, p < 0.001), with a similar trend for creatine kinase-MB, myoglobin, and NT-proBNP. Acute cardiac injury was more frequent in those with severe, compared to milder, disease (risk ratio 5.99, 3.04 to 11.80; p < 0.001). Meta regression suggested that cardiac injury biomarker differences of severity are related to history of hypertension (p = 0.030). Also COVID19-related cardiac injury is associated with higher mortality (summary risk ratio 3.85, 2.13 to 6.96; p < 0.001). hsTnI and NT-proBNP levels increased during the course of hospitalization only in non-survivors. CONCLUSION: The severity of COVID-19 is associated with acute cardiac injury, and acute cardiac injury is associated with death. Cardiac injury biomarkers mainly increase in non-survivors. This highlights the need to effectively monitor heart health to prevent myocarditis in patients infected with COVID-19.

positive: Risk factors for disease progression in hospitalized patients with COVID-19: a retrospective cohort study Background: To investigate the risk factors related to aggravation and clinical outcomes in coronavirus disease 2019 (COVID-19) patients. Methods: We performed a retrospective study on the risk factors for disease progression of cases with COVID-19. Based on the clinical types, the patients were divided into a progression group and an improvement group. Multivariable logistic regression and ROC curve analysis were performed to explore the risk factors for disease progression. Results: A total of 101 patients were included in this study; diseases progression occurred in 17 patients, 84 patients improved, 6 were transferred to intensive care unit (ICU), and 5 died. The mean time to obtain negative nucleic acid results was 12.5 ± 5.0 days. Multivariate logistic analysis indicated that age (OR, 0.104; p = .002), C-reactive protein (CRP) (OR, 0.093; p < .001) and lymphocyte count (OR, 3.397; p = .022) were risk factors for disease progression. ROC curve analysis revealed that the AUC of age, CRP and lymphocyte count for disease progression were 0.873, 0.911 and 0.817, respectively. Conclusions: Older age increased CRP and decreased lymphocyte count resulted in potential risk factors for COVID-19 progression. This may be helpful in identifying patients whose condition worsens at an early stage.

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: Prediction of the severity of Corona Virus Disease 2019 and its adverse clinical outcomes This study aims to investigate blood and biochemical laboratory findings in patients with severe Corona Virus Disease 2019 (COVID-19) and to develop a joint predictor for predicting the likelihood of severe COVID-19 and its adverse clinical outcomes, to provide more information for treatment. We collected the data of 88 patients with laboratory-confirmed COVID-19. Then patients were divided into a non-severe group and a critical group (including critically ill cases). Univariate analysis showed that the absolute lymphocyte count, albumin level, albumin/globulin (A/G) ratio, lactate dehydrogenase (LDH) level, interleukin-6 (IL-6) level, erythrocyte count, globulin level, blood glucose level, and age were significantly correlated with the severity of COVID-19. The multivariate binary logistic regression model revealed that Age, absolute lymphocyte count, and IL-6 level were independent risk factors in patients with COVID-19. The receiver operating characteristic (ROC) curve revealed that the combination of IL-6 level, absolute lymphocyte count and age is superior to a single factor as predictors for predicting severe COVID-19, regardless of whether it is the area under curve (AUC) or the prediction sensitivity and specificity. Early application is beneficial to early identification of critically ill patients and timing individual treatments to reduce mortality.

positive: Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19 BACKGROUND: Coronavirus disease 2019 (COVID-19) can manifest as a viral-induced hyperinflammation with multiorgan involvement. Such patients often experience rapid deterioration and need for mechanical ventilation. Currently, no prospectively validated biomarker of impending respiratory failure is available. OBJECTIVE: We aimed to identify and prospectively validate biomarkers that allow the identification of patients in need of impending mechanical ventilation. METHODS: Patients with COVID-19 who were hospitalized from February 29 to April 9, 2020, were analyzed for baseline clinical and laboratory findings at admission and during the disease. Data from 89 evaluable patients were available for the purpose of analysis comprising an initial evaluation cohort (n = 40) followed by a temporally separated validation cohort (n = 49). RESULTS: We identified markers of inflammation, lactate dehydrogenase, and creatinine as the variables most predictive of respiratory failure in the evaluation cohort. Maximal IL-6 level before intubation showed the strongest association with the need for mechanical ventilation, followed by maximal CRP level. The respective AUC values for IL-6 and CRP levels in the evaluation cohort were 0.97 and 0.86, and they were similar in the validation cohort (0.90 and 0.83, respectively). The calculated optimal cutoff values during the course of disease from the evaluation cohort (IL-6 level > 80 pg/mL and CRP level > 97 mg/L) both correctly classified 80% of patients in the validation cohort regarding their risk of respiratory failure. CONCLUSION: The maximal level of IL-6, followed by CRP level, was highly predictive of the need for mechanical ventilation. This suggests the possibility of using IL-6 or CRP level to guide escalation of treatment in patients with COVID-19-related hyperinflammatory syndrome.

positive: Lymphopenia in severe coronavirus disease-2019 (COVID-19): systematic review and meta-analysis OBJECTIVE: Clinical and laboratory biomarkers to predict the severity of coronavirus disease 2019 (COVID-19) are essential in this pandemic situation of which resource allocation must be urgently prepared especially in the context of respiratory support readiness. Lymphocyte count has been a marker of interest since the first COVID-19 publication. We conducted a systematic review and meta-analysis in order to investigate the association of lymphocyte count on admission and the severity of COVID-19. We would also like to analyze whether patient characteristics such as age and comorbidities affect the relationship between lymphocyte count and COVID-19. METHODS: Comprehensive and systematic literature search was performed from PubMed, SCOPUS, EuropePMC, ProQuest, Cochrane Central Databases, and Google Scholar. Research articles in adult patients diagnosed with COVID-19 with information on lymphocyte count and several outcomes of interest, including mortality, acute respiratory distress syndrome (ARDS), intensive care unit (ICU) care, and severe COVID-19, were included in the analysis. Inverse variance method was used to obtain mean differences and its standard deviations. Maentel-Haenszel formula was used to calculate dichotomous variables to obtain odds ratios (ORs) along with its 95% confidence intervals. Random-effect models were used for meta-analysis regardless of heterogeneity. Restricted-maximum likelihood random-effects meta-regression was performed for age, gender, cardiac comorbidity, hypertension, diabetes mellitus, COPD, and smoking. RESULTS: There were a total of 3099 patients from 24 studies. Meta-analysis showed that patients with poor outcome have a lower lymphocyte count (mean difference − 361.06 μL [− 439.18, − 282.95], p < 0.001; I(2) 84%) compared to those with good outcome. Subgroup analysis showed lower lymphocyte count in patients who died (mean difference − 395.35 μL [− 165.64, − 625.07], p < 0.001; I(2) 87%), experienced ARDS (mean difference − 377.56 μL [− 271.89, − 483.22], p < 0.001; I(2) 0%), received ICU care (mean difference − 376.53 μL [− 682.84, − 70.22], p = 0.02; I(2) 89%), and have severe COVID-19 (mean difference − 353.34 μL [− 250.94, − 455.73], p < 0.001; I(2) 85%). Lymphopenia was associated with severe COVID-19 (OR 3.70 [2.44, 5.63], p < 0.001; I(2) 40%). Meta-regression showed that the association between lymphocyte count and composite poor outcome was affected by age (p = 0.034). CONCLUSION: This meta-analysis showed that lymphopenia on admission was associated with poor outcome in patients with COVID-19.

positive: Elevation of blood glucose level predicts worse outcomes in hospitalized patients with COVID-19: a retrospective cohort study INTRODUCTION: With intense deficiency of medical resources during COVID-19 pandemic, risk stratification is of strategic importance. Blood glucose level is an important risk factor for the prognosis of infection and critically ill patients. We aimed to investigate the prognostic value of blood glucose level in patients with COVID-19. RESEARCH DESIGN AND METHODS: We collected clinical and survival information of 2041 consecutive hospitalized patients with COVID-19 from two medical centers in Wuhan. Patients without available blood glucose level were excluded. We performed multivariable Cox regression to calculate HRs of blood glucose-associated indexes for the risk of progression to critical cases/mortality among non-critical cases, as well as in-hospital mortality in critical cases. Sensitivity analysis were conducted in patient without diabetes. RESULTS: Elevation of admission blood glucose level was an independent risk factor for progression to critical cases/death among non-critical cases (HR=1.30, 95% CI 1.03 to 1.63, p=0.026). Elevation of initial blood glucose level of critical diagnosis was an independent risk factor for in-hospital mortality in critical cases (HR=1.84, 95% CI 1.14 to 2.98, p=0.013). Higher median glucose level during hospital stay or after critical diagnosis (≥6.1 mmol/L) was independently associated with increased risks of progression to critical cases/death among non-critical cases, as well as in-hospital mortality in critical cases. Above results were consistent in the sensitivity analysis in patients without diabetes. CONCLUSIONS: Elevation of blood glucose level predicted worse outcomes in hospitalized patients with COVID-19. Our findings may provide a simple and practical way to risk stratify COVID-19 inpatients for hierarchical management, particularly where medical resources are in severe shortage during the pandemic.

positive: Development and External Validation of a Prognostic Tool for COVID-19 Critical Disease Background: The rapid spread of coronavirus disease 2019 (COVID-19) revealed significant constraints in critical care capacity. In anticipation of subsequent waves, reliable prediction of disease severity is essential for critical care capacity management and may enable earlier targeted interventions to improve patient outcomes. The purpose of this study is to develop and externally validate a prognostic model/clinical tool for predicting COVID-19 critical disease at presentation to medical care. Methods: This is a retrospective study of a prognostic model for the prediction of COVID-19 critical disease where critical disease was defined as ICU admission, ventilation, and/or death. The derivation cohort was used to develop a multivariable logistic regression model. Covariates included patient comorbidities, presenting vital signs, and laboratory values. Model performance was assessed on the validation cohort by concordance statistics. The model was developed with consecutive patients with COVID-19 who presented to University of California Irvine Medical Center in Orange County, California. External validation was performed with a random sample of patients with COVID-19 at Emory Healthcare in Atlanta, Georgia. Results: Of a total 3208 patients tested in the derivation cohort, 9% (299/3028) were positive for COVID-19. Clinical data including past medical history and presenting laboratory values were available for 29% (87/299) of patients (median age, 48 years [range, 21-88 years]; 64% [36/55] male). The most common comorbidities included obesity (37%, 31/87), hypertension (37%, 32/87), and diabetes (24%, 24/87). Critical disease was present in 24% (21/87). After backward stepwise selection, the following factors were associated with greatest increased risk of critical disease: number of comorbidities, body mass index, respiratory rate, white blood cell count, % lymphocytes, serum creatinine, lactate dehydrogenase, high sensitivity troponin I, ferritin, procalcitonin, and C-reactive protein. Of a total of 40 patients in the validation cohort (median age, 60 years [range, 27-88 years]; 55% [22/40] male), critical disease was present in 65% (26/40). Model discrimination in the validation cohort was high (concordance statistic: 0.94, 95% confidence interval 0.87-1.01). A web-based tool was developed to enable clinicians to input patient data and view likelihood of critical disease. Conclusions and Relevance: We present a model which accurately predicted COVID-19 critical disease risk using comorbidities and presenting vital signs and laboratory values, on derivation and validation cohorts from two different institutions. If further validated on additional cohorts of patients, this model/clinical tool may provide useful prognostication of critical care needs.

positive: Intensive Care Risk Estimation in COVID-19 Pneumonia Based on Clinical and Imaging Parameters: Experiences from the Munich Cohort The evolving dynamics of coronavirus disease 2019 (COVID-19) and the increasing infection numbers require diagnostic tools to identify patients at high risk for a severe disease course. Here we evaluate clinical and imaging parameters for estimating the need of intensive care unit (ICU) treatment. We collected clinical, laboratory and imaging data from 65 patients with confirmed COVID-19 infection based on polymerase chain reaction (PCR) testing. Two radiologists evaluated the severity of findings in computed tomography (CT) images on a scale from 1 (no characteristic signs of COVID-19) to 5 (confluent ground glass opacities in over 50% of the lung parenchyma). The volume of affected lung was quantified using commercially available software. Machine learning modelling was performed to estimate the risk for ICU treatment. Patients with a severe course of COVID-19 had significantly increased interleukin (IL)-6, C-reactive protein (CRP), and leukocyte counts and significantly decreased lymphocyte counts. The radiological severity grading was significantly increased in ICU patients. Multivariate random forest modelling showed a mean ± standard deviation sensitivity, specificity and accuracy of 0.72 ± 0.1, 0.86 ± 0.16 and 0.80 ± 0.1 and a receiver operating characteristic-area under curve (ROC-AUC) of 0.79 ± 0.1. The need for ICU treatment is independently associated with affected lung volume, radiological severity score, CRP, and IL-6.

positive: Clinical and pathological investigation of severe COVID-19 patients. BACKGROUND Severe acute respiratory coronavirus 2 (SARS-CoV-2) caused coronavirus disease 2019 (COVID-19) has become a pandemic. This study addressed the clinical and immunopathological characteristics of severe COVID-19. METHODS Sixty-nine COVID-19 patients were classified into as severe and non-severe groups to analyze their clinical and laboratory characteristics. A panel of blood cytokines was quantified over time. Biopsy specimens from two deceased cases were obtained for immunopathological, ultrastructural, and in situ hybridization examinations. RESULTS Circulating cytokines, including IL8, IL6, TNFα, IP10, MCP1, and RANTES, were significantly elevated in severe COVID-19 patients. Dynamic IL6 and IL8 were associated with disease progression. SARS-CoV-2 was demonstrated to infect type II, type I pneumocytes and endothelial cells, leading to severe lung damage through cell pyroptosis and apoptosis. In severe cases, lymphopenia, neutrophilia, depletion of CD4+ and CD8+ T lymphocytes, and massive macrophage and neutrophil infiltrates were observed in both blood and lung tissues. CONCLUSIONS A panel of circulating cytokines could be used to predict disease deterioration and inform clinical interventions. Severe pulmonary damage was predominantly attributed to both SARS-CoV-2 caused cytopathy and immunopathologic damage. Strategies that encourage pulmonary recruitment and overactivation of inflammatory cells by suppressing cytokine storm might improve the outcomes of severe COVID-19 patients.

positive: Review on Machine and Deep Learning Models for the Detection and Prediction of Coronavirus The novel Coronavirus disease has increased rapidly in the Wuhan city of China in December 2019. This fatal virus has spread across the whole world like a fire in different stages and affecting millions of population and thousands of deaths worldwide. Therefore, it is essential to classify the infected people, so that they can take the precaution in the earlier stages. Also, due to the increasing cases spread of Coronavirus, there are only limited numbers of polymerase change reaction kits available in the hospitals for testing Coronavirus patients. That why it is extremely important to develop artificial intelligence-based automatic diagnostic tools to classify the Coronavirus outbreak. The objective of this paper is to know the novel disease epidemiology, major prevention from spreading of Coronavirus Severe Acute Respiratory Syndrome, and to assess the machine and deep learning-based architectures performance that is proposed in the present year for classification of Coronavirus images such as, X-Ray and computed tomography. Specifically, advanced deep learning-based algorithms known as the Convolutional neural network, which plays a great effect on extracting highly essential features, mostly in terms of medical images. This technique, with using CT and X-Ray image scans, has been adopted in most of the recently published articles on the Coronavirus with remarkable results. Furthermore, according to this paper, this can be noted and said that deep learning technology has potential clinical applications.

positive: Delayed-Phase Thrombocytopenia in Patients of Coronavirus Disease 2019 (COVID-19) The pandemic COVID19 pneumonia has engulfed the entire world. Hematopoietic system can also be affected by COVID19. Thrombocytopenia at admission was prevalent, while late phase or delayed phase thrombocytopenia is obscure. This retrospective case series analyzed patients with COVID19 at the Union Hospital, Wuhan, China, from January 25th to March 9th, 2020. Analysis began on March 11th, 2020. COVID19 associated delayed phase thrombocytopenia was occurred in 11.8% percent of enrolled patients. The delayed phase thrombocytopenia in COVID19 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 ICU admission rate. Delayed phase nadir platelet counts demonstrated a high and significantly negative linear correlation with B cell percentages and serum IL 6 levels. We also presented bone marrow aspiration pathology of three patients with delayed phase thrombocytopenia, showing impaired maturation of megakaryocytes. We speculated that the delayed phase platelet destruction might be mediated by antibodies, and suggest immunoregulatory treatment in severe patients to improve outcomes. Besides, clinicians need to pay attention to the delayed phase thrombocytopenia especially at 3 to 4 weeks after symptom onset.

positive: Preliminary Identification of Potential Vaccine Targets for the COVID-19 Coronavirus (SARS-CoV-2) Based on SARS-CoV Immunological Studies The beginning of 2020 has seen the emergence of COVID-19 outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is an imminent need to better understand this new virus and to develop ways to control its spread. In this study, we sought to gain insights for vaccine design against SARS-CoV-2 by considering the high genetic similarity between SARS-CoV-2 and SARS-CoV, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV. By screening the experimentally-determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV, we identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins that map identically to SARS-CoV-2 proteins. As no mutation has been observed in these identified epitopes among the 120 available SARS-CoV-2 sequences (as of 21 February 2020), immune targeting of these epitopes may potentially offer protection against this novel virus. For the T cell epitopes, we performed a population coverage analysis of the associated MHC alleles and proposed a set of epitopes that is estimated to provide broad coverage globally, as well as in China. Our findings provide a screened set of epitopes that can help guide experimental efforts towards the development of vaccines against SARS-CoV-2.

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

positive: Using IL-2R/lymphocytes for predicting the clinical progression of patients with COVID-19 Effective laboratory markers for the estimation of disease severity and predicting the clinical progression of coronavirus disease-2019 (COVID-19) is urgently needed. Laboratory tests, including blood routine, cytokine profiles and infection markers, were collected from 389 confirmed COVID-19 patients. The included patients were classified into mild (n = 168), severe (n = 169) and critical groups (n = 52). The leukocytes, neutrophils, infection biomarkers [such as C-reactive protein (CRP), procalcitonin (PCT) and ferritin] and the concentrations of cytokines [interleukin (IL)-2R, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α] were significantly increased, while lymphocytes were significantly decreased with increased severity of illness. The amount of IL-2R was positively correlated with the other cytokines and negatively correlated with lymphocyte number. The ratio of IL-2R to lymphocytes was found to be remarkably increased in severe and critical patients. IL-2R/lymphocytes were superior compared with other markers for the identification of COVID-19 with critical illness, not only from mild but also from severe illness. Moreover, the cytokine profiles and IL-2R/lymphocytes were significantly decreased in recovered patients, but further increased in disease-deteriorated patients, which might be correlated with the outcome of COVID-19. Lymphopenia and increased levels of cytokines were closely associated with disease severity. The IL-2R/lymphocyte was a prominent biomarker for early identification of severe COVID-19 and predicting the clinical progression of the disease.

positive: Hematological findings and complications of COVID-19 COVID-19 is a systemic infection with a significant impact on the hematopoietic system and hemostasis. Lymphopenia may be considered as a cardinal laboratory finding, with prognostic potential. Neutrophil/lymphocyte ratio and peak platelet/lymphocyte ratio may also have prognostic value in determining severe cases. During the disease course, longitudinal evaluation of lymphocyte count dynamics and inflammatory indices, including LDH, CRP and IL-6 may help to identify cases with dismal prognosis and prompt intervention in order to improve outcomes. Biomarkers, such high serum procalcitonin and ferritin have also emerged as poor prognostic factors. Furthermore, blood hypercoagulability is common among hospitalized COVID-19 patients. Elevated D-Dimer levels are consistently reported, whereas their gradual increase during disease course is particularly associated with disease worsening. Other coagulation abnormalities such as PT and aPTT prolongation, fibrin degradation products increase, with severe thrombocytopenia lead to life-threatening disseminated intravascular coagulation (DIC), which necessitates continuous vigilance and prompt intervention. So, COVID-19 infected patients, whether hospitalized or ambulatory, are at high risk for venous thromboembolism, and an early and prolonged pharmacological thromboprophylaxis with low molecular weight heparin is highly recommended. Last but not least, the need for assuring blood donations during the pandemic is also highlighted.

positive: Clinical Analysis of 25 COVID-19 Infections in Children BACKGROUND: To describe the characteristics of clinical manifestations of children with 2019 novel coronavirus (2019-nCoV) infection in Chongqing. METHODS: All 25 children with laboratory-confirmed 2019-nCoV infection by real-time reverse transcription-PCR (RNA-PCR) were admitted from the 4 designated treatment hospitals of 2019-nCoV in Chongqing from January 19 to March 12, 2020. Clinical data and epidemiologic history of these patients were retrospectively collected and analyzed. RESULTS: The diagnosis was confirmed through RNA-PCR testing. Among the 25 cases, 14 were males and 11 were females. The median age was 11.0 (6.3-14.5) years (range 0.6-17.0 years). All children were related to a family cluster outbreak, and 7 children (28%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 8 (32%) asymptomatic, 4 (16%) very mild cases and 13 (52%) common cases. No severe or critical cases were identified. The most common symptoms were cough (13 cases, 52%) and fever (6 cases, 24%). The duration time of clinical symptoms was 13.0 (8.0-25.0) days. In the 25 cases, on admission, 21 cases (84%) had normal white blood cell counts, while only 2 cases (8%) more than 10 × 10/L and 2 cases (8%) less than 4 × 10/L, respectively; 22 cases(88%) had normal CD4+ T lymphocyte counts, while in the remaining 3 cases(8%) this increased mildly; 23 cases had normal CD8+ T lymphocyte counts, while in the remaining 2 cases (8%) CD8+ T lymphocyte counts were mildly increased as well. All Lymphocyte counts were normal. There were no statistical differences of lab results between the groups of asymptomatic cases, mild cases and common cases. There were only 13 cases with abnormal CT imaging, most of which were located in the subpleural area of the bottom of the lung. All patients were treated with interferon, 6 cases combined with Ribavirin, and 12 cases combined with lopinavir or ritonavir. The days from onset to RNA turning negative was 15.20 ± 6.54 days. There was no significant difference of RNA turning negative between the groups of interferon, interferon plus ribavirin and interferon plus lopinavir or ritonavir treatment. All the cases recovered and were discharged from hospital. CONCLUSIONS: The morbidity of 2019-nCoV infection in children is lower than in adults and the clinical manifestations and inflammatory biomarkers in children are nonspecific and milder than that in adults. RNA-PCR test is still the most reliable diagnostic method, especially for asymptomatic patients.

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

positive: Biomarkers associated with COVID-19 disease progression The coronavirus disease 2019 (COVID-19) pandemic is a scientific, medical, and social challenge. The complexity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is centered on the unpredictable clinical course of the disease that can rapidly develop, causing severe and deadly complications. The identification of effective laboratory biomarkers able to classify patients based on their risk is imperative in being able to guarantee prompt treatment. The analysis of recently published studies highlights the role of systemic vasculitis and cytokine mediated coagulation disorders as the principal actors of multi organ failure in patients with severe COVID-19 complications. The following biomarkers have been identified: hematological (lymphocyte count, neutrophil count, neutrophil–lymphocyte ratio (NLR)), inflammatory (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT)), immunological (interleukin (IL)-6 and biochemical (D-dimer, troponin, creatine kinase (CK), aspartate aminotransferase (AST)), especially those related to coagulation cascades in disseminated intravascular coagulation (DIC) and acute respiratory distress syndrome (ARDS). New laboratory biomarkers could be identified through the accurate analysis of multicentric case series; in particular, homocysteine and angiotensin II could play a significant role.

positive: Cytokine prediction of mortality in COVID19 patients Coronavirus disease 2019 (COVID19) is a life-threatening infection with uncertain progression and outcome. Assessing the severity of the disease for worsening patients is of importance in making decisions related to supportive mechanical ventilation and aggressive treatments. This was a prospective, non-randomized study that included hospitalized patients diagnosed with COVID19. Pro-inflammatory cytokines were assessed during hospitalization, and we calculated a prediction paradigm for 30-day mortality based on the serum levels of interleukin1β (IL1β), interleukin6 (IL6), interleukin8 (IL8), and tumor necrosis factor alpha (TNFα) measured by next-generation ELISA. Data of 71 COVID19 patients, mean age 62 years, SD13.8, 50 males, 21 females, were analyzed. Twelve (16.9%) patients died within 7–39 days of their first COVID19 positive nasopharyngeal test. Levels of IL6 and TNFα were significantly higher in patients that did not survive. IL6 predicted mortality at the cut-off value of 163.4 pg/ml, with a sensitivity of 91.7% and specificity of 57.6%. Our findings demonstrate that IL6 expression is significant for the prediction of 30-day mortality in hospitalized COVID19 patients and, therefore, may assist in treatment decisions.

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

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

positive: Soluble Urokinase Plasminogen Activator Receptor: A Biomarker for Predicting Complications and Critical Care Admission of COVID-19 Patients The novel coronavirus infection has spread worldwide, causing a wide spectrum of clinical manifestations. Most patients develop moderate clinical illness, but a substantial number will experience severe pneumonia, which may rapidly progress to acute respiratory distress syndrome and multiple organ failure. In this population, soluble urokinase plasminogen activator receptor (suPAR) could serve as a quick triage test and independent marker of clinical severity, hospital and intensive care unit admission, complications, and mortality.

positive: Cardiovascular Diseases and COVID-19 Mortality and Intensive Care Unit Admission: A Systematic Review and Meta-analysis Importance: On 11th March, the World Health Organization declared a pandemic of COVID-19. There are over 1 million cases around the world with this disease and it continues to raise. Studies on COVID-19 patients have reported high rate of cardiovascular disease (CVD) among them and patients with CVD had higher mortality rate. Objectives: Since there were controversies between different studies about CVD burden in COVID-19 patients, we aimed to study cardiovascular disease burden among COVID-19 patients using a systematic review and meta-analysis. Data Sources: We have systematically searched databases including PubMed, Embase, Cochrane Library, Scopus, Web of Science as well as medRxiv pre-print database. Hand searched was also conducted in journal websites and Google Scholar. Study Selection: Studies reported cardiovascular disease among hospitalized adult COVID-19 patients with mortality or ICU admission (primary outcomes) were included into meta-analysis. In addition, all of studies which reported any cardiovascular implication were included for descriptive meta-analysis. Cohort studies, case-control, cross-sectional, case-cohort and case series studies included into the study. Finally, 16 studies met the inclusion criteria for primary outcome and 59 studies for descriptive outcome. Data Extraction and Synthesis: Two investigators have independently evaluated quality of publications and extracted data from included papers. In case of disagreement a supervisor solved the issue and made the final decision. Quality assessment of studies was done using Newcastle-Ottawa Scale tool. Heterogeneity was assessed using I-squared test and in case of high heterogeneity (>%50) random effect model was used. Main Outcomes and Measures: Meta-analyses were carried out for Odds Ratio (OR) of mortality and Intensive Care Unit (ICU) admission for different CVDs and Standardized Mean Difference (SMD) was calculated for Cardiac Troponin I. We have also performed a descriptive meta-analysis on different CVDs. Results: Sixteen papers including 3473 patients entered into meta-analysis for ICU admission and mortality outcome and fifty-nine papers including 9509 patients for descriptive outcomes. Results of meta-analysis indicated that acute cardiac injury, (OR: 15.94, 95% CI 2.31-110.14), hypertension (OR: 1.92, 95% CI 1.92-2.74), heart Failure (OR: 11.73, 95% CI 5.17-26.60), other cardiovascular disease (OR: 1.95, 95% CI 1.17-3.24) and overall CVDs (OR: 3.37, 95% CI 2.06-5.52) were significantly associated with mortality in COVID-19 patients. Arrhythmia (OR: 22.17, 95%CI 4.47-110.04), acute cardiac injury (OR: 19.83, 95%CI 7.85-50.13), coronary heart disease (OR: 4.19, 95%CI 1.27-13.80), cardiovascular disease (OR: 4.17, 95%CI 2.52-6.88) and hypertension (OR: 2.69, 95%CI 1.55-4.67) were also significantly associated with ICU admission in COVID-19 patients. Conclusion: Our findings showed a high burden of CVDs among COVID-19 patients which was significantly associated with mortality and ICU admission. Proper management of CVD patients with COVID-19 and monitoring COVID-19 patients for acute cardiac conditions is highly recommended to prevent mortality and critical situations.

positive: Liver injury is associated with severe coronavirus disease 2019 (COVID-19) infection: A systematic review and meta-analysis of retrospective studies The coronavirus disease 2019 (COVID-19) outbreak is a major threat to human beings. Lung injury has been reported as the major outcome of COVID-19 infection. However, liver damage has also been considered to occur in severe cases. The current meta-analysis of retrospective studies was carried out to summarize available findings on the association between liver injury and severity of COVID-19 infection. Online databases including PubMed, Scopus, Web of Science, and Cochrane Library were searched to detect relevant publications up to 1 April 2020, using relevant keywords. To pool data, a fixed- or random-effects model was used depending on the heterogeneity between studies. Furthermore, publication bias test and sensitivity analysis were also applied. In total, 20 retrospective studies with 3428 COVID-19 infected patients (severe cases, n = 1455; mild cases, n = 1973), were included in this meta-analysis. Higher serum levels of aspartate aminotransferase (weighted mean difference, 8.84 U/L; 95% confidence interval [CI] 5.97 to 11.71; P < 0.001), alanine aminotransferase (weighted mean difference, 7.35 U/L; 95% CI, 4.77 to 9.93; P < 0.001), total bilirubin (weighted mean difference, 2.30 mmol/L; 95% CI, 1.24 to 3.36; P < 0.001), and lower serum levels of albumin (weighted mean difference, -4.24 g/L; 95% CI, -6.20 to -2.28; P < 0.001) were associated with a significant increase in the severity of COVID-19 infection. The incidence of liver injury, as assessed by serum analysis (aspartate aminotransferase, alanine aminotransferase, total bilirubin, and albumin levels), seems to be higher in patients with severe COVID-19 infection.

positive: Acute myocarditis and multisystem inflammatory emerging disease following SARS-CoV-2 infection in critically ill children BACKGROUND: A recent increase in children admitted with hypotensive shock and fever in the context of the COVID-19 outbreak requires an urgent characterization and assessment of the involvement of SARS-CoV-2 infection. This is a case series performed at 4 academic tertiary care centers in Paris of all the children admitted to the pediatric intensive care unit (PICU) with shock, fever and suspected SARS-CoV-2 infection between April 15th and April 27th, 2020. RESULTS: 20 critically ill children admitted for shock had an acute myocarditis (left ventricular ejection fraction, 35% (25–55); troponin, 269 ng/mL (31–4607)), and arterial hypotension with mainly vasoplegic clinical presentation. The first symptoms before PICU admission were intense abdominal pain and fever for 6 days (1–10). All children had highly elevated C-reactive protein (> 94 mg/L) and procalcitonin (> 1.6 ng/mL) without microbial cause. At least one feature of Kawasaki disease was found in all children (fever, n = 20, skin rash, n = 10; conjunctivitis, n = 6; cheilitis, n = 5; adenitis, n = 2), but none had the typical form. SARS-CoV-2 PCR and serology were positive for 10 and 15 children, respectively. One child had both negative SARS-CoV-2 PCR and serology, but had a typical SARS-CoV-2 chest tomography scan. All children but one needed an inotropic/vasoactive drug support (epinephrine, n = 12; milrinone, n = 10; dobutamine, n = 6, norepinephrine, n = 4) and 8 were intubated. All children received intravenous immunoglobulin (2 g per kilogram) with adjuvant corticosteroids (n = 2), IL 1 receptor antagonist (n = 1) or a monoclonal antibody against IL-6 receptor (n = 1). All children survived and were afebrile with a full left ventricular function recovery at PICU discharge. CONCLUSIONS: Acute myocarditis with intense systemic inflammation and atypical Kawasaki disease is an emerging severe pediatric disease following SARS-CoV-2 infection. Early recognition of this disease is needed and referral to an expert center is recommended. A delayed and inappropriate host immunological response is suspected. While underlying mechanisms remain unclear, further investigations are required to target an optimal treatment.

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: Retrospective analysis of laboratory testing in 54 patients with severe- or critical-type 2019 novel coronavirus pneumonia Timely analysis of the laboratory characteristics associated with 2019 novel coronavirus pneumonia (COVID-19) can assist with clinical diagnosis and prognosis. This study is a collection of clinical data from 54 hospitalized adult patients diagnosed with COVID-19 in the Zhongfa Xincheng district of China at Tongji Hospital of Huazhong University of Science and Technology from January 28, 2020 to February 11, 2020. The average age of the patients was 61.8 ± 14.5 years, and the predominant age group was 50-79. The proportion of critical-type patients with comorbidities was higher than that of severe-type patients. Lymphocyte counts were significantly reduced in routine bloodwork for all patients, but significantly lower in critical-type patients than that in severe-type patients. Prolongation of prothrombin times (PT) and elevation of fibrinogen degradation products (FDPs) and D-dimers (D-Ds) were detected in coagulation function tests, and more significant changes were observed in critical-type patients compared to severe-type patients. Serum ferritin levels were sensitive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection but could not be used for disease assessment. In addition, levels of two inflammatory factors, soluble interleukin-2 receptor (sIL-2R) and interleukin-6 (IL-6) were significantly increased in all patients, but higher in critical-type patients than in severe-type patients. Moreover, kidney injury was the second-most common organ affected by COVID-19 followed by heart and liver. Kidney and heart injury were more severe in critical-type patients than in severe-type patients. All of the 31 severe-type patients recovered. Of the critical-type patients, six died and 17 recovered. The length of hospital stay for critical-type patients was significantly longer for severe-type patients. In summary, increased lymphocyte counts, prolonged PT, secondary increases in fibrinolytic activity and increases in sIL-2R and IL-6 are typical features of COVID-19 and are associated with disease severity.

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

positive: A novel simple scoring model for predicting severity of patients with SARS-CoV-2 infection An outbreak of pneumonia caused by a novel coronavirus (COVID-19) began in Wuhan, China in December 2019 and quickly spread throughout the country and world. An efficient and convenient method based on clinical characteristics was needed to evaluate the potential deterioration in patients. We aimed to develop a simple and practical risk scoring system to predict the severity of COVID-19 patients on admission. We retrospectively investigated the clinical information of confirmed COVID-19 patients from 10 February 2020 to 29 February 2020 in Wuhan Union Hospital. Predictors of severity were identified by univariate and multivariate logistic regression analysis. A total of 147 patients with confirmed SARS-CoV-2 infection were grouped into non-severe (94 patients) and severe (53 patients) groups. We found that an increased level of white blood cells (WBC), neutrophils, D-dimer, fibrinogen (FIB), IL-6, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), α-hydroxybutyrate dehydrogenase (HBDH), serum amyloid A (SAA) and a decreased level of lymphocytes were important risk factors associated with severity. Furthermore, three variables were used to formulate a clinical risk scoring system named COVID-19 index = 3 × D-dimer (µg/L) + 2 × lgESR (mm/hr) - 4 × lymphocyte (×109 /L) + 8. The area under the receiver operating characteristic (ROC) curve was 0.843 (95% CI, 0.771-0.914). We propose an effective scoring system to predict the severity of COVID-19 patients. This simple prediction model may provide healthcare workers with a practical method and could positively impact decision-making with regard to deteriorating patients.

positive: Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19 Abstract Background The inflammatory response plays a critical role in coronavirus disease 2019 (COVID-19), and inflammatory cytokine storm increases the severity of COVID-19. Objective To investigate the ability of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT) to predict mild and severe cases of COVID-19. Study design This retrospective cohort study included 140 patients diagnosed with COVID-19 from January 18, 2020, to March 12, 2020. The study population was divided into two groups according to disease severity: a mild group (MG) (n = 107) and a severe group (SG) (n = 33). Data on demographic characteristics, baseline clinical characteristics, and the levels of IL-6, CRP, and PCT on admission were collected. Results Among the 140 patients, the levels of IL-6, CRP, and PCT increased in 95 (67.9 %), 91 (65.0 %), and 8 (5.7 %) patients on admission, respectively. The proportion of patients with increased IL-6, CRP, and PCT levels was significantly higher in the SG than in the MG. Cox proportional hazard model showed that IL-6 and CRP could be used as independent factors to predict the severity of COVID-19. Furthermore, patients with IL-6 > 32.1 pg/mL or CRP > 41.8 mg/L were more likely to have severe complications. Conclusion The serum levels of IL-6 and CRP can effectively assess disease severity and predict outcome in patients with COVID-19.

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

positive: Do not forget interaction: Predicting fatality of COVID-19 patients using logistic regression Amid the ongoing COVID-19 pandemic, whether COVID-19 patients with high risks can be recovered or not depends, to a large extent, on how early they will be treated appropriately before irreversible consequences are caused to the patients by the virus. In this research, we reported an explainable, intuitive, and accurate machine learning model based on logistic regression to predict the fatality rate of COVID-19 patients using only three important blood biomarkers, including lactic dehydrogenase, lymphocyte (%) and high-sensitivity C-reactive protein, and their interactions. We found that when the fatality probability produced by the logistic regression model was over 0.8, the model had the optimal performance in that it was able to predict patient fatalities more than 11.30 days on average with maximally 34.91 days in advance, an accumulative f1-score of 93.76% and and an accumulative accuracy score of 93.92%. Such a model can be used to identify COVID-19 patients with high risks with three blood biomarkers and help the medical systems around the world plan critical medical resources amid this pandemic.

positive: Recognizing COVID-19-related myocarditis: the possible pathophysiology and proposed guideline for diagnosis and management Abstract Human coronavirus-associated myocarditis is known, and a number of COVID-19-related myocarditis cases have been reported. The pathophysiology of COVID-19-related myocarditis is thought to be a combination of direct viral injury and cardiac damage due to the host’s immune response. COVID-19 myocarditis diagnosis should be guided by insights from previous coronavirus and other myocarditis experience. The clinical findings include changes in ECG, cardiac biomarkers, and impaired cardiac function. When cardiac MRI is infeasible, cardiac CT angiography with delayed myocardial imaging may serve to exclude significant coronary artery disease and identify myocardial inflammatory patterns. Because many COVID-19 patients have cardiovascular comorbidities, myocardial infarction should be considered. Where the diagnosis remains uncertain, an endomyocardial biopsy may help identify active cardiac infection through viral genome amplification and possibly refine the treatment risks of systemic immunosuppression. Arrhythmias are not uncommon in the COVID-19 patients; however, its pathophysiology is still speculative. Nevertheless, clinicians should be vigilant to provide prompt monitoring and treatments. The long-term impact of COVID-19 myocarditis, including in the majority of mild cases remains unknown.

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

positive: Correlation between Heart fatty acid binding protein and severe COVID-19: A case-control study BACKGROUND: Heart-fatty acid binding protein (HFABP) has been recognized as a highly heart-specific marker. However, it is currently unknown that its HFABP is also closely related to the severity of COVID-19. METHODS: We retrospectively screened 46 patients who met our inclusion criteria within 4 weeks. They were tested for HFABP after the diagnosis of COVID-19, and monitored for HFABP during their hospital stay. We tracked the patients during their hospital stay to determine if they had severe COVID-19 or mild-to-severe transition features. We calculated the chi-square test values found for HFABP to predict the correlation between HFABP levels and the severity of the COVID-19. RESULTS: Of these 46 cases, 16 cases with confirmed COVID-19 were tested for HFABP> 7 ng / mL upon admission; among them, 14 cases were diagnosed with severe COVID-19 within the hospitalization. The Odds ratio of the measured HFABP elevation was 6.81(95% confidence interval [CI] 5.23–8.40), and 3 patients with severe COVID-19 progressed in 5 patients with mild HFABP> 7 ng/mL. CONCLUSION: These data indicate that the elevation of HFABP is closely related to the severity of COVID-19 in the patients, and the elevated HFABP may cause rapid development of patients with mild COVID-19 into severe COVID-19. But serum HFABP negative maybe make patients with mild COVID-19 safer, the current data show no effect on the all-cause mortality. TRIAL REGISTRATION: Our study has been registered with the Chinese Clinical Trial Registry, the registration number: ChiCTR2000029829.

positive: Risk factors associated with disease progression in a cohort of patients infected with the 2019 novel coronavirus BACKGROUND: The emerging infection of the 2019 novel coronavirus (2019-nCoV) in late December, 2019 in Wuhan, China, has caused an extreme health concern, with many patients having progressed to acute respiratory disease or other complications in a short period. Meanwhile, the risk factors associated with the disease progression still remain elusive. METHODS: A cohort of 17 patients with laboratory-confirmed 2019-nCoV infections who were admitted to the Ninth Hospital of Nanchang between January 28 and February 6, 2020, were enrolled in this study. All the patients received standardized treatment. The disease progression was evaluated every 7 days after admission. The clinical, radiologic, and laboratory characteristics were retrospectively analyzed, and the factors associated with the disease progression were screened by binary logistic regression analysis. RESULTS: The cohort comprised 11 women (64.7%) and 6 men (35.3%) between the ages of 18 to 70 years old. All patients had a reported history of contact with infection-confirmed patients. Fever (11/64.7%) and cough (8/47.1%) were the most common symptoms, whereas dyspnea (2/11.8%) and fatigue (3/17.6%) were rare, and there was no patient with diarrhea symptoms. There were 5 patients with aggravated disease at the first disease progression evaluation, and no patient received mechanical ventilation, transferred to the intensive care unit (ICU), or progressed to acute respiratory distress syndrome, septic shock, refractory metabolic acidosis, coagulation dysfunction, or death. Based on the disease progression, patients were divided into the non-aggravation group (12 cases) and the aggravation group (5 cases). There were no significant differences between the 2 groups with respect to their clinical characteristics. Chest computed tomography (CT) on admission revealed there were 8 patients (47.1%) with invasive lesions found bilaterally on the lungs on multiple lobes, 4 patients (23.5%) with invasive lesions on 1 lobe, and 5 patients (29.4%) with normal chest CT. The aggravation group had1 patient (20.0%) with invasive lesions on one lobe, 3 (60.0%) with invasive lesions on multiple lobes, bilaterally, and 1 (20.0%) with normal chest CT; meanwhile, the nonaggravation group had 3 patients (25.0%) with invasive lesions on one lobe, 5 (41.7%) with invasive lesions on multiple lobes, bilaterally, and 4 (33.3%) with normal chest CT. No significant difference was found between the 2 groups. In the aggravation group, the total lymphocyte counts significantly decreased in comparison to that in the non-aggravation group. Further analysis showed that the CD4+ T cell count but not the CD8+ T cell count of the aggravation group was significantly lower than that of the non-aggravation group. Correlation analysis indicated total lymphocyte count was positively correlated with CD4+ T cell count, and no significant differences were found between the 2 groups in other laboratory measurements, including those of white blood cell (WBC) count, C-reactive protein (CRP), albumin, lactate dehydrogenase (LDH), and D-dimer. Finally, a binary logistic regression model was used to identify the factors associated with the disease progression. It was found that total lymphocyte count was a risk factor associated with disease progression in patients infected with 2019-nCoV. CONCLUSIONS: A higher cell count of total lymphocytes may indicate a better outcome of the disease, and immune response may be a vital factor for directing disease progression in the early stage of 2019-nCoV infection.

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

positive: Quantitative computed tomography analysis for stratifying the severity of Coronavirus Disease 2019 Abstract Purpose To examine the feasibility of using a computer tool for stratifying the severity of Coronavirus Disease 2019 (COVID-19) based on computed tomography (CT) images. Materials and methods We retrospectively examined 44 confirmed COVID-19 cases. All cases were evaluated separately by radiologists (visually) and through an in-house computer software. The degree of lesions was visually scored by the radiologist, as follows, for each of the 5 lung lobes: 0, no lesion present; 1, <1/3 involvement; 2, >1/3 and < 2/3 involvement; and 3, >2/3 involvement. Lesion density was assessed based on the proportion of ground-glass opacity (GGO), consolidation and fibrosis of the lesions. The parameters obtained using the computer tool included lung volume (mL), lesion volume (mL), lesion percentage (%), and mean lesion density (HU) of the whole lung, right lung, left lung, and each lobe. The scores obtained by the radiologists and quantitative results generated by the computer software were tested for correlation. A Chi-square test was used to test the consistency of radiologist- and computer-derived lesion percentage in the right/left lung, upper/lower lobe, and each of the 5 lobes. Result The results showed a strong to moderate correlation between lesion percentage scores obtained by radiologists and the computer software (r ranged from 0.7679 to 0.8373, P < 0.05), and a moderate correlation between the proportion of GGO and mean lesion density (r = −0.5894, P < 0.05), and proportion of consolidation and mean lesion density (r = 0.6282, P < 0.05). Computer-aided quantification showed a statistical significant higher lesion percentage for lower lobes than that assessed by the radiologists (χ2 = 8.160, P = 0.004). Conclusions Our experiments demonstrated that the computer tool could reliably and accurately assess the severity and distribution of pneumonia on CT scans.

positive: Elevated Plasma Surfactant Protein D (SP‐D) Levels and a Direct Correlation with Anti‐severe Acute Respiratory Syndrome Coronavirus‐specific IgG Antibody in SARS Patients Pulmonary SP‐D is a defence lectin promoting clearance of viral infections. SP‐D is recognized to bind the S protein of SARS‐CoV and enhance phagocytosis. Moreover, systemic SP‐D is widely used as a biomarker of alveolar integrity. We investigated the relation between plasma SP‐D, SARS‐type pneumonia and the SARS‐specific IgG response. Sixteen patients with SARS, 19 patients with community‐acquired pneumonia (CAP) (Streptococcus pneumonia) and 16 healthy control subjects were enrolled in the study. Plasma SP‐D and anti‐SARS‐CoV N protein IgG were measured using ELISA. SP‐D was significantly elevated in SARS‐type pneumonia [median (95% CI), 453 (379–963) ng/ml versus controls 218 (160–362) ng/ml, P < 0.05] like in patients with CAP. SP‐D significantly correlated with anti‐SARS‐CoV N protein IgG (r (2) = 0.5995, P = 0.02). The possible re‐emergence of SARS or SARS‐like infections suggests a need for minimal traumatic techniques for following the alveolar compartment, e.g. during testing of antivirals. We suggest that monitoring systemic SP‐D may be useful in monitoring the alveolar integrity in SARS‐type pneumonia. The significant correlation between plasma SP‐D and anti‐SARS‐CoV‐specific antibodies support the role for SP‐D in interlinking innate and adaptive immune pathways.

positive: Hemostatic laboratory derangements in COVID-19 with a focus on platelet count. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease in 2019 (COVID-19) which rapidly evolved from an outbreak in Wuhan, China into a pandemic that has resulted in over millions of infections and over hundreds of thousands of mortalities worldwide. Various coagulopathies have been reported in association with COVID-19, including disseminated intravascular coagulation (DIC), sepsis-induced coagulopathy (SIC), local microthrombi, venous thromboembolism (VTE), arterial thrombotic complications, and thrombo-inflammation. There is a plethora of publications and conflicting data on hematological and hemostatic derangements in COVID-19 with some data suggesting the link to disease progress, severity and/or mortality. There is also growing evidence of potentially useful clinical biomarkers to predict COVID-19 progression and disease outcomes. Of those, a link between thrombocytopenia and COVID-19 severity or mortality was suggested. In this opinion report, we examine the published evidence of hematological and hemostatic laboratory derangements in COVID-19 and the interrelated SARS-CoV-2 induced inflammation, with a focussed discussion on platelet count alterations. We explore whether thrombocytopenia could be a potential disease biomarker and we provide recommendations for future studies in this regard.

positive: The role of comorbidities and clinical predictors of severe disease in COVID-19: a systematic review and meta-analysis Background COVID_19 is unpredictable due to non-specific symptoms and clinical course diversity in different individuals. We analyzed studies regarding the factors associated with severe status of the disease to identify unique findings in severely affected patients. Methods We systematically searched the electronic databases, including PubMed, Scopus, EMBASE, Web of Science, and Google Scholar from inception to 12th of March 2020. Cochranes Q and I-square statistics were used to assess the existence of heterogeneity between the included studies. We used the random-effects model to pool the odds ratios (ORs) at 95% confidence intervals (CIs). Results Seventeen articles out of 3009 citations were included. These contained 3189 patients, of whom 732 were severely affected (severe group) and 3189 were in non-severe group. Using the random-effects model, our meta-analyses showed that the odds of comorbidities, including COPD, DM, HTN, CVD, CKD, and symptoms, including dyspnea, dizziness, anorexia, and cough, were significantly higher among the severe group compared with the non-severe group. There were no significant changes in odds of CVA, liver disease, immunodeficiency/immunosuppression, fever, fatigue, myalgia, headache, diarrhea, sore throat, nasal congestion, sputum, nausea, vomiting, chest pain between the two groups. Conclusions Early recognition and intervention can be critical in management, and might stop progression to severe disease. Predictive symptoms and comorbidities can be used as a predictor in patients who are at risk of severe disease.

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

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

positive: Clinical Laboratory Parameters Associated with Severe or Critical Novel Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-analysis Background: To date, several clinical laboratory parameters associated with COVID-19 severity have been reported. However, these parameters have not been observed consistently across studies. The aim of this review was to assess clinical laboratory parameters which may serve as markers or predictors of severe or critical COVID-19 disease Methods: We conducted a systematic search of MEDLINE, Embase, Web of Science, CINAHL and Google Scholar databases from 2019 through April 18, 2020, and reviewed bibliographies of eligible studies, relevant systematic reviews, and the medRxiv pre-print server. We included hospital-based observational studies reporting clinical laboratory parameters of confirmed cases of COVID-19 and excluded studies having large proportions (>10%) of children and pregnant women. Two authors independently carried out screening of articles, data extraction and quality assessment. Meta-analyses were done using random effects model. Meta-median difference (MMD) and 95% confidence interval (CI) was calculated for each laboratory parameter. Results: Forty-five studies in 6 countries were included. Compared to non-severe COVID-19 cases, severe or critical COVID-19 disease was characterised by higher neutrophil count (MMD: 1.23 [95% CI: 0.58 to 1.88] x109 cells/L), and lower lymphocyte and CD4 counts with MMD (95% CI) of -0.39 (-0.47, -0.31) x109 cells/L and -204.9 (-302.6, -107.1) cells/l, respectively. Other notable results were observed for C-reactive protein (MMD: 36.97 [95% CI: 27.58, 46.35] mg/L), interleukin-6 (MMD: 17.37 [95% CI: 4.74, 30.00] pg/ml,), Troponin I (MMD: 0.01 [0.00, 0.02] ng/ml), and D-dimer (MMD: 0.65 [0.45, 0.85] mg/ml). Conclusions and Relevance: Relative to non-severe COVID-19, severe or critical COVID-19 is characterised by increased markers of innate immune response, decreased markers of adaptive immune response, and increased markers of tissue damage and major organ failure. These markers could be used to recognise severe or critical disease and to monitor clinical course of COVID-19.

positive: A correlation study ofCT and clinical features of different clinical types of 2019 novel coronavirus pneumonia/ 中华放射学杂志 Objective@#To investigate the CT and clinical features of 2019 novel coronavirus (NCP) pneumonia.@*Methods@#Chest CT and clinical data of confirmed 103 patients with 2019 novel coronavirus pneumonia in January 2020, retrospectively. According to diagnosis and treatment of NCP infected pneumonia (trial version 5), all the patients were classified into mild(n=58), severe (n=36) and very severe (n=9) type, and their clinical findings, laboratory examination and CT finding were analyzed. CT features included lesions’ distribution, location, size, shape, edge, number, density, percentage of pneumonia lesions of the whole lung and extra-pulmonary manifestations. The CT features of different clinical subtypes were compared using χ2test or Fisher's exact probability. Comparisons between the percentage of pneumonic lesions to total lung volume were computed by using analysis of variance (normal distribution) or Kruskal-Wallis rank sum test (non-normal distribution).@*Results@#In terms of clinical manifestations, the patients with severe NCP were more common in elderly men, with a median age of 65 years. Fever was the first symptom in 49 (84%) of 58 patients with NCP, and fever was the first symptom in both severe and critical NCP patients. The incidence of cough in severe (25 / 36, 69%) and critical (6 /9, 67%) NCP patients was higher than that in general (20 /58, 34%). All critical patients have dyspnea. In terms of CT findings, common NCP showed double lung (40/58,71%) multiple (40 / 58,69%) ground glass (31/58,52%) or mixed (25 / 58,43%) lesions (56 / 58,97%); severe and critical NCP showed double lung lesions, heavy NCP mainly showed multiple (34 / 36,96%) patches (33 / 36,92%) mixed density lesions (26 / 36,72%); 9 severe NCP lesions were more than 3 cm Mixed density lesions. The percentage of pneumonia focus in the whole lung volume: the common type (12.5% ± 6.1%) was significantly lower than the severe type (25.9% ± 10.7%) and the critical type (47.2% ± 19.2%) NCP, the difference was statistically significant (P values were < 0.001 and 0.002 respectively), and the severe type NCP was also significantly lower than the critical type (P = 0.032).@*Conclusions@#CT and clinical features of different clinical types of NCP pneumonia are different. Chest CT findings have unique characteristic, which can not only make early diagnosis, but also evaluate its clinical course and severity.

positive: A Tool to Early Predict Severe 2019-Novel Coronavirus Pneumonia (COVID-19) : A Multicenter Study using the Risk Nomogram in Wuhan and Guangdong, China Background Severe cases of coronavirus disease 2019 (COVID-19) rapidly develop acute respiratory distress leading to respiratory failure, with high short-term mortality rates. At present, there is no reliable risk stratification tool for non-severe COVID-19 patients at admission. We aimed to construct an effective model for early identifying cases at high risk of progression to severe COVID-19. Methods SARS-CoV-2 infected patients from one center in Wuhan city and two centers in Guangzhou city, China were included retrospectively. All patients with non-severe COVID-19 during hospitalization were followed for more than 15 days after admission. Patients who deteriorated to severe or critical COVID-19 and patients who kept non-severe state were assigned to the severe and non-severe group, respectively. We compared the demographic, clinical, and laboratory data between severe and non-severe group. Based on baseline data, least absolute shrinkage and selection operator (LASSO) algorithm and logistic regression model were used to construct a nomogram for risk prediction in the train cohort. The predictive accuracy and discriminative ability of nomogram were evaluated by area under the curve (AUC) and calibration curve. Decision curve analysis (DCA) and clinical impact curve analysis (CICA) were conducted to evaluate the clinical applicability of our nomogram. Findings The train cohort consisted of 189 patients, while the two independent validation cohorts consisted of 165 and 18 patients. Among all cases, 72 (19.35%) patients developed severe COVID-19 and 107 (28.76%) patients had one of the following basic disease, including hypertension, diabetes, coronary heart disease, chronic respiratory disease, tuberculosis disease. We found one demographic and six serological indicators (age, serum lactate dehydrogenase, C-reactive protein, the coefficient of variation of red blood cell distribution width (RDW), blood urea nitrogen, albumin, direct bilirubin) are associated with severe COVID-19. Based on these features, we generated the nomogram, which has remarkably high diagnostic accuracy in distinguishing individuals who exacerbated to severe COVID-19 from non-severe COVID-19 (AUC 0.912 [95% CI 0.846-0.978]) in the train cohort with a sensitivity of 85.71 % and specificity of 87.58% ; 0.853 [0.790-0.916] in validation cohort with a sensitivity of 77.5 % and specificity of 78.4%. The calibration curve for probability of severe COVID-19 showed optimal agreement between prediction by nomogram and actual observation. DCA and CICA further indicated that our nomogram conferred significantly high clinical net benefit. Interpretation Our nomogram could help clinicians to early identify patients who will exacerbate to severe COVID-19. And this risk stratification tool will enable better centralized management and early treatment of severe patients, and optimal use of medical resources via patient prioritization and thus significantly reduce mortality rates. The RDW plays an important role in predicting severe COVID-19, implying that the role of RBC in severe disease is underestimated.

positive: Predictors of progression from moderate to severe coronavirus disease 2019: a retrospective cohort OBJECTIVE: Most cases of coronavirus disease 2019 (COVID-19) are identified as moderate, which is defined as having a fever or dry cough and lung imaging with ground-glass opacities. The risk factors and predictors of prognosis in such cohorts remain uncertain. METHODS: All adults with COVID-19 of moderate severity diagnosed using quantitative RT-PCR and hospitalized at the Central Hospital of Wuhan, China, from 1 January to 20 March 2020 were enrolled in this retrospective study. The main outcomes were progression from moderate to severe or critical condition or death. RESULTS: Among the 456 enrolled patients with moderate COVID-19, 251/456 (55.0%) had poor prognosis. Multivariate logistic regression analysis identified higher neutrophil count: lymphocyte count ratio (NLR) on admission (OR 1.032, 95% CI 1.042-1.230, p 0.004) and higher C-reactive protein (CRP) on admission (OR 3.017, 95% CI 1.941-4.690, p < 0.001) were associated with increased OR of poor prognosis. The area under the receiver operating characteristic curve (AUC) for NLR and CRP in predicting progression to critical condition was 0.77 (95% CI 0.694-0.846, p < 0.001) and 0.84 (95% CI 0.780-0.905, p < 0.001), with a cut-off value of 2.79 and 25.95 mg/L, respectively. The AUC of NLR and CRP in predicting death was 0.81 (95% CI 0.732-0.878, p < 0.001) and 0.89 (95% CI 0.825-0.946, p < 0.001), with a cut-off value of 3.19 and 33.4 mg/L, respectively. CONCLUSIONS: Higher levels of NLR and CRP at admission were associated with poor prognosis of individuals with moderate COVID-19. NLR and CRP were good predictors of progression to critical condition and death.

positive: Retrospective analysis of laboratory testing in 54 patients with severe- or critical-type 2019 novel coronavirus pneumonia Timely analysis of the laboratory characteristics associated with 2019 novel coronavirus pneumonia (COVID-19) can assist with clinical diagnosis and prognosis. This study is a collection of clinical data from 54 hospitalized adult patients diagnosed with COVID-19 in the Zhongfa Xincheng district of China at Tongji Hospital of Huazhong University of Science and Technology from January 28, 2020 to February 11, 2020. The average age of the patients was 61.8 ± 14.5 years, and the predominant age group was 50–79. The proportion of critical-type patients with comorbidities was higher than that of severe-type patients. Lymphocyte counts were significantly reduced in routine bloodwork for all patients, but significantly lower in critical-type patients than that in severe-type patients. Prolongation of prothrombin times (PT) and elevation of fibrinogen degradation products (FDPs) and D-dimers (D-Ds) were detected in coagulation function tests, and more significant changes were observed in critical-type patients compared to severe-type patients. Serum ferritin levels were sensitive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection but could not be used for disease assessment. In addition, levels of two inflammatory factors, soluble interleukin-2 receptor (sIL-2R) and interleukin-6 (IL-6) were significantly increased in all patients, but higher in critical-type patients than in severe-type patients. Moreover, kidney injury was the second-most common organ affected by COVID-19 followed by heart and liver. Kidney and heart injury were more severe in critical-type patients than in severe-type patients. All of the 31 severe-type patients recovered. Of the critical-type patients, six died and 17 recovered. The length of hospital stay for critical-type patients was significantly longer for severe-type patients. In summary, increased lymphocyte counts, prolonged PT, secondary increases in fibrinolytic activity and increases in sIL-2R and IL-6 are typical features of COVID-19 and are associated with disease severity.

positive: Lactate dehydrogenase, a Risk Factor of Severe COVID-19 Patients BACKGROUND The World Health Organization (WHO) has recently declared coronavirus disease 2019 (COVID-19) a public health emergency of global concern. Updated analysis of cases might help identify the characteristic and risk factors of the illness severity. METHODS We extracted data regarding 47 patients with confirmed COVID-19 from Renmin Hospital of Wuhan University between February 1 and February 18, 2020. The degree of severity of COVID-19 patients (severe vs. non-severe) was defined at the time of admission according to American Thoracic Society (ATS) guidelines for community-acquired pneumonia (CAP). RESULTS The median age was 64.91 years, 26 cases (55.31%) were male of which, and 70.83% were severe cases. Severe patients had higher APACHE II (9.92 vs 4.74) and SOFA (3.0 vs 1.0) scores on admission, as well as the higher PSI (86.13 vs 61.39), Curb-65 (1.14 vs 0.48) and CT semiquantitative scores (5.0 vs 2.0) when compared with non-severe patients. Among all univariable parameters, APACHE II, SOFA, lymphocytes, CRP, LDH, AST, cTnI, BNP, et al were significantly independent risk factors of COVID-19 severity. Among which, LDH was most positively related both with APACHE II (R = 0.682) and SOFA (R = 0.790) scores, as well as PSI (R = 0.465) and CT (R = 0.837) scores. To assess the diagnostic value of these selected parameters, LDH (0.9727) had maximum sensitivity (100.00%) and specificity (86.67%), with the cutoff value of 283. As a protective factor, lymphocyte counts less than 1.045 x 109 /L showed a good accuracy for identification of severe patients with AUC = 0.9845 (95%CI 0.959-1.01), the maximum specificity (91.30%) and sensitivity (95.24%). In addition, LDH was positively correlated with CRP, AST, BNP and cTnI, while negatively correlated with lymphocyte cells and its subsets, including CD3+, CD4+ and CD8+ T cells (P < 0.01). CONCLUSIONS This study showed that LDH coule be identified as a powerful predictive factor for early recognition of lung injury and severe COVID-19 cases. And importantly, lymphocyte counts, especially CD3+, CD4+, and CD8+ T cells in the peripheral blood of COVID-19 patients, which was relevant with serum LDH, were also dynamically correlated with the severity of the disease. FUNDING Key Project of Shanghai Municipal Health Bureau (2016ZB0202)

positive: Coagulopathy of Coronavirus Disease 2019 Recent studies have reported a high prevalence of thrombotic events in coronavirus disease 2019. However, the significance of thromboembolic complications has not been widely appreciated. The purpose of this review is to provide current knowledge of this serious problem. DESIGN: Narrative review. DATA SOURCES: Online search of published medical literature through PubMed using the term “COVID-19,” “SARS,” “acute respiratory distress syndrome,” “coronavirus,” “coagulopathy,” “thrombus,” and “anticoagulants.” STUDY SELECTION AND DATA EXTRACTION: Articles were chosen for inclusion based on their relevance to coagulopathy and thrombosis in coronavirus disease 2019, and anticoagulant therapy. Reference lists were reviewed to identify additional relevant articles. DATA SYNTHESIS: Coronavirus disease 2019 is associated with a strikingly high prevalence of coagulopathy and venous thromboembolism that may contribute to respiratory deterioration. Monitoring coagulation variables is important, as abnormal coagulation tests are related to adverse outcomes and may necessitate adjuvant antithrombotic interventions. In the initial phase of the infection, d-dimer and fibrinogen levels are increased, while activated partial prothrombin time, prothrombin time, and platelet counts are often relatively normal. Increased d-dimer levels three times the upper limit of normal may trigger screening for venous thromboembolism. In all hospitalized patients, thromboprophylaxis using low-molecular-weight heparin is currently recommended. The etiology of the procoagulant responses is complex and thought to be a result of specific interactions between host defense mechanisms and the coagulation system. Although the coagulopathy is reminiscent of disseminated intravascular coagulation and thrombotic microangiopathy, it has features that are markedly distinct from these entities. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2/coronavirus disease 2019 frequently induces hypercoagulability with both microangiopathy and local thrombus formation, and a systemic coagulation defect that leads to large vessel thrombosis and major thromboembolic complications, including pulmonary embolism in critically ill hospitalized patients. d-dimers and fibrinogen levels should be monitored, and all hospitalized patients should undergo thromboembolism prophylaxis with an increase in therapeutic anticoagulation in certain clinical situations.

positive: 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.

positive: An interpretable mortality prediction model for COVID-19 patients - alternative approach The pandemic spread of coronavirus leads to increased burden on healthcare services worldwide. Experience shows that required medical treatment can reach limits at local clinics and fast and secure clinical assessment of the disease severity becomes vital. In L. Yan et al. a model is presented for predicting the mortality of COVID-19 patients from their biomarkers. Three biomarkers have been selected by ranking with a supervised Multi-tree XGBoost classifier. The prediction model is built up as a binary decision tree with depth three and achieves AUC scores of up to 97.84 pm 0.37 and 95.06 pm 2.21 for training and external test data sets, resp. In human assessment and decision making influencing parameters usually are not considered as sharp numbers but rather as Fuzzy terms, and inferencing primarily yields Fuzzy terms or continuous grades rather than binary decisions. Therefore, I examined a Sugeno-type Fuzzy classifier for disease assessment and decision support. In addition, I used an artificial neural network (SOM, [4]) for selecting the biomarkers. Modelling and validation was done with the identical data base provided by L. Yan et al.. With the complete training and test data sets, the Fuzzy prediction model achieves improved AUC scores of up to 98.59 or 95.12 The improvements with the Fuzzy classifier obviously become clear as physicians can inter- pret output grades to belong to positive or negative class more or less strongly. An extension of the Fuzzy model, which takes into account the trend in key features over time, provides excellent results with the training data, which, however, could not be finally verified due to the lack of suitable test data. The generation and training of the Fuzzy models was fully automatic and without additional adjustment with the help of ANFIS from Matlab(c).

positive: Elevated serum levels of S100A8/A9 and HMGB1 at hospital admission are correlated with inferior clinical outcomes in COVID-19 patients

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

positive: Validation of predictors of disease severity and outcomes in COVID-19 patients: a descriptive and retrospective study Abstract Background The severity and outcome of COVID-19 cases has been associated with percentage of circulating lymphocytes (LYM%), levels of C-reactive protein (CRP), interleukin 6 (IL-6), procalcitonin (PCT), lactic acid (LA) and viral load (ORF1ab Ct). However, the predictive power of each of these indicators in disease classification and prognosis remains largely unclear. Methods we retrospectively collected information on the above parameters in 142 patients with COVID-19, stratifying them by survival or disease severity. Findings CRP, PCT, IL-6, LYM% and ORF1ab Ct were significantly altered between survivors and non-survivors. LYM%, CRP and IL-6 were the most sensitive and reliable factors in distinguishing between survivors and non-survivors. These indicators were significantly different between critically ill and severe/moderate patients. Only LYM% levels were significantly different between severe and moderate types. Among all the investigated indicators, LYM% was the most sensitive and reliable in discriminating between critically ill, severe and moderate types, and between survivors and non-survivors. Conclusions CRP, PCT, IL-6, LYM% and ORF1ab Ct, but not LA, could predict prognosis and guide classification of COVID-19 patients. LYM% was the most sensitive and reliable predictor for disease typing and prognosis. We recommend that LYM% be further investigated in the management of COVID-19.

positive: A cohort study of 223 patients explores the clinical risk factors for the severity diagnosis of COVID-19 BACKGROUND: Coronavirus Disease 2019 (COVID-19) has recently become a public emergency and a worldwide pandemic. The clinical symptoms of severe and non-severe patients vary, and the case-fatality rate (CFR) in severe COVID-19 patients is very high. However, the information on the risk factors associated with the severity of COVID-19 and of their prognostic potential is limited. METHODS: In this retrospective study, the clinical characteristics, laboratory findings, treatment and outcome data were collected and analyzed from 223 COVID-19 patients stratified into 125 non-severe patients and 98 severe patients. In addition, a pooled large-scale meta-analysis of 1646 cases was performed. RESULTS: We found that the age, gender and comorbidities are the common risk factors associated with the severity of COVID-19. For the diagnosis markers, we found that the levels of D-dimer, C-reactive protein (CRP), lactate dehydrogenase (LDH), procalcitonin (PCT) were significantly higher in severe group compared with the non-severe group on admission (D-Dimer: 87.3% vs. 35.3%, P<0.001; CRP, 65.1% vs. 13.5%, P<0.001; LDH: 83.9% vs. 22.2%, P<0.001; PCT: 35.1% vs. 2.2%, P<0.001), while the levels of aspartate aminotransferase (ASP) and creatinine kinase (CK) were only mildly increased. We also made a large scale meta-analysis of 1646 cases combined with 4 related literatures, and further confirmed the relationship between the COVID-19 severity and these risk factors. Moreover, we tracked dynamic changes during the process of COVID-19, and found CRP, D-dimer, LDH, PCT kept in high levels in severe patient. Among all these markers, D-dimer increased remarkably in severe patients and mostly related with the case-fatality rate (CFR). We found adjuvant antithrombotic treatment in some severe patients achieved good therapeutic effect in the cohort. CONCLUSIONS: The diagnosis markers CRP, D-dimer, LDH and PCT are associated with severity of COVID-19. Among these markers, D-dimer is sensitive for both severity and CFR of COVID-19. Treatment with heparin or other anticoagulants may be beneficial for COVID-19 patients.

positive: Lymphocyte subset (CD4+, CD8+) counts reflect the severity of infection and predict the clinical outcomes in patients with COVID-19

positive: The clinical study on the relationship between serum albumin concentration and lymphocyte levels in patients with 2019-novel coronavirus pneumonia/ 中华急诊医学杂志 Objective@#To explore the relationship between different serum albumin and lymphocyte levels in patients with 2019-novel coronavirus (2019-nCoV) pneumonia (COVID-19).@*Methods@#A retrospective study was performed to identify the characteristics of the clinical data of 205 COVID-19 patients who were hospitalized in the Happy Street of Hanchuan People's Hospital, Xiaogan, Hubei Province from January 24 to February 12, 2020, including their general information, serum albumin (ALB) levels, lymphocyte counts (LYM), percentage of lymphocytes (LYM%) and other laboratory parameter levels. Low ALB group and normal ALB group were demarcated by the concentration of 35g/L, further to identify the differences of LYM and LYM% levels and the incidence of LYM and LYM% decline at different ALB levels between groups,as well as the correlation between ALB and LYM, LYM% levels in hypoalbuminemia conditions .@*Results@#17.5% of COVID-19 patients were associated with hypoalbuminemia. The levels of LYM and LYM% in the low ALB group were significantly lower than those in the normal ALB group (P <0.001). The incidence of LYM and LYM% decline in the low ALB group was significantly higher than those in the normal ALB group (P <0.001). The levels of LYM and LYM% in the low ALB group were significantly positively correlated with serum ALB concentrations (P <0.05).@*Conclusions@#The decrease of lymphocyte levels in COVID-19 patients may be correlated to hypoalbuminemia. COVID-19 patients complicated by hypoalbuminemia should be actively intervened to maintain serum albumin in the normal range.

positive: 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.

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

positive: Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): A meta-analysis

positive: Emerging key laboratory tests for patients with COVID-19

positive: 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.

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

positive: Myocardial characteristics as the prognosis for COVID-19 patients Background Amid the crisis of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), front-line clinicians in collaboration with backstage medical researchers analyzed clinical characteristics of COVID-19 patients and reported the prognosis using myocardial data records upon hospitalization. Methods We reported 135 cases of laboratory-confirmed COVID-19 patients admitted in The First People's Hospital of Jiangxia District in Wuhan, China. Demographic data, medical history, and laboratory parameters were taken from inpatient records and compared between patients at the Intensive Care Unit (ICU) and non-ICU isolation wards for prognosis on disease severity. In particular, survivors and non-survivors upon ICU admission were compared for prognosis on disease mortality. Results For COVID-19 patients, blood test results showed more significantly deranged values in the ICU group than those in non-ICU. Among those parameters for ICU patients, myocardial variables including troponin T, creatine kinase isoenzymes, myoglobin, were found significantly higher in non-survivors than in survivors. Conclusions Upon hospitalization abnormal myocardial metabolism in COVID-19 patients could be prognostic indicators of a worsened outcome for disease severity and mortality.

positive: 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.

positive: Potential biochemical markers to identify severe cases among COVID-19 patients There is a high mortality and long hospitalization period for severe cases with 2019 novel coronavirus disease (COVID-19) pneumonia. Therefore, it makes sense to search for a potential biomarker that could rapidly and effectively identify severe cases early. Clinical samples from 28 cases of COVID-19 (8 severe cases, 20 mild cases) in Zunyi District from January 29, 2020 to February 21, 2020 were collected and otherwise statistically analysed for biochemical markers. Serum urea, creatinine (CREA) and cystatin C (CysC) concentrations in severe COVID-19 patients were significantly higher than those in mild COVID-19 patients (P<0.001), and there were also significant differences in serum direct bilirubin (DBIL), cholinesterase (CHE) and lactate dehydrogenase (LDH) concentrations between severe and mild COVID-19 patients (P<0.05). Serum urea, CREA, CysC, DBIL, CHE and LDH could be used to distinguish severe COVID-19 cases from mild COVID-19 cases. In particular, serum biomarkers, including urea, CREA, CysC, which reflect glomerular filtration function, may have some significance as potential indicators for the early diagnosis of severe COVID-19 and to distinguish it from mild COVID-19. Glomerular filtration function injury in severe COVID-19 patients should also be considered by clinicians.

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: Key Points of Clinical and CT Imaging Features of 2019 Novel Coronavirus (2019-nCoV) Imported Pneumonia Based On 21 Cases Analysis Background and Objective: WHO Director-General declared that the 2019-nCoV outbreak constitutes a Public Health Emergency of International Concern,and the outbreak is still on-going.Chest CT had been a key component of the diagnostic workup for patients with suspected infection. In this retrospective study, we attempt to summarize and analyze the chest CT features of 2019-nCov infections, and to identify the typical features to improved the diagnostic accuracy of new coronavirus pneumonia (NCP). Methods:Chest CT scans and Clinical data of 21 patients confirmed NCP in our hospital were enrolled.These patients were divided into mild and sever group according to clinical manifestations described by the 6th clinical practice guideline of NCP in China. Main clinical and chest CT features were analyzed and identify. Results: Fever (85.7%) and cough (80.9%) were the two main symptoms of NCP patients.More significantly higher incidence (85.7%) of shortness of breath in the severe cases. Multiple lesions in both lungs and with incidence of GGO(100%),vascular enlargement (76.5%) and cobblestone/reticular pattern(70.6%) were the major feature.The incidence of consolidation, mixed pattern and vascular enlargement features were up to 100% in the severe group, significantly higher than that of patients in mild group. In addition, the incidence of air-bronchogram, dilated bronchi with thickened wall and fibrosis in the severe group was significantly higher than that in the mild group. Conclusions: Fever and cough are the typical clinical features of NCP patients, and chest CT mainly manifested as multiple lesions in both lungs, often accompanied by GGO, vascular enlargement and cobblestone/reticular pattern.Changes in these main CT features can indicate development of the disease.

positive: C-reactive protein correlates with computed tomographic findings and predicts severe COVID-19 early COVID-19 has developed into a worldwide pandemic; early identification of severe illness is critical for controlling it and improving the prognosis of patients with limited medical resources. The present study aimed to analyze the characteristics of severe COVID-19 and identify biomarkers for differential diagnosis and prognosis prediction. In total, 27 consecutive patients with COVID-19 and 75 patients with flu were retrospectively enrolled. Clinical parameters were collected from electronic medical records. The disease course was divided into four stages: initial, progression, peak, and recovery stages, according to computed tomography (CT) progress. to mild COVID-19, the lymphocytes in the severe COVID-19 progressively decreased at the progression and the peak stages, but rebound in the recovery stage. The levels of C-reactive protein (CRP) in the severe group at the initial and progression stages were higher than those in the mild group. Correlation analysis showed that CRP (R = .62; P < .01), erythrocyte sedimentation rate (R = .55; P < .01) and granulocyte/lymphocyte ratio (R = .49; P < .01) were positively associated with the CT severity scores. In contrast, the number of lymphocytes (R = -.37; P < .01) was negatively correlated with the CT severity scores. The receiver-operating characteristic analysis demonstrated that area under the curve of CRP on the first visit for predicting severe COVID-19 was 0.87 (95% CI 0.10-1.00) at 20.42 mg/L cut-off, with sensitivity and specificity 83% and 91%, respectively. CRP in severe COVID-19 patients increased significantly at the initial stage, before CT findings. Importantly, CRP, which was associated with disease development, predicted early severe COVID-19.

positive: Diagnosis and clinical management of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection: an operational recommendation of Peking Union Medical College Hospital (V2.0): Working Group of 2019 Novel Coronavirus, Peking Union Medical College Hospital Since December 2019, China has been experiencing an outbreak of a new infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical features include fever, coughing, shortness of breath, and inflammatory lung infiltration. China rapidly listed SARS-CoV-2-related pneumonia as a statutory infectious disease. To standardize the diagnosis and treatment of this new infectious disease, an operational recommendation for the diagnosis and management of SARS-CoV-2 infection is developed by Peking Union Medical College Hospital.

positive: COVID-19: Clinical course and outcomes of 36 maintenance hemodialysis patients from a single center in Spain. SARS-CoV-2-pneumonia emerged in Wuhan, China in December 2019. Unfortunately, there is lack of evidence about the optimal management of novel coronavirus disease 2019 (COVID-19), even less in patients on maintenance hemodialysis (MHD) therapy than in the general population. In this retrospective observational single-center study we analyzed the clinical course and outcomes of all MHD patients hospitalized with COVID-19 from March 12(th) to April 10(th), 2020 as confirmed by real time polymerase chain reaction. Baseline features, clinical course, laboratory data, and different therapies were compared between survivors and non-survivors to identify risk factors associated with mortality. Among the 36 patients, 11 (30.5%) died and 7 could be discharged within the observation period. Clinical and radiological evolution during the first week of admission were predictive of mortality. Among the 36 patients, 18 had worsening of their clinical status, as defined by severe hypoxia with oxygen therapy requirements greater than 4 Liters/minute and radiological worsening. Significantly 11 out of those 18 patients (61.1%) died. None of the classical cardiovascular risk factors in the general population were associated with higher mortality. However, a longer time on hemodialysis (hazard ratio 1.008(95% confidence interval 1.001-1.015) per year), increased LDH levels (1.006(1.001-1.011), and lower lymphocyte count (0.996 (0.992-1.000) one week after clinical onset were all significantly associated with higher mortality risk. Thus, the mortality among hospitalized hemodialysis patients diagnosed with COVID-19 is high. Lymphopenia and increased LDH levels were associated with poor prognosis.

positive: Risk factors related to hepatic injury in patients with corona virus disease 2019 Aims: Corona virus disease 2019 (COVID-19) has rapidly become the most severe public health issue all over the world. Despite respiratory symptoms, hepatic injury has also been observed in clinical settings. This study aimed to investigate the risk factors involved with hepatic injury in the patients with COVID-19. Methods: A total of 85 hospitalized patients who were diagnosed with COVID-19 in Beijing Youan Hospital were retrospectively analyzed. According to liver function, they were divided into ALT normal group (n=52) and ALT elevation group (n=33). Clinical features and laboratory data were compared between the two groups. The independent risk factors for liver injury were analyzed. Results: There were 33 patients with hepatic injury in our study, accounting for 38.8% (33/85). The patients in ALT elevation group were older than those in ALT normal group. The levels of lactic acid, CRP, myoglobin, and neutrophils were significantly higher in ALT elevation group. The lymphocytes and albumin were significantly lower in ALT elevation group. The proportion of severe and critical patients in ALT elevation group was significantly higher. Multivariate logistic regression analysis showed CRP ≥20 mg/L and lymphocyte count< 1.1*10^9/L were independently related to hepatic injury. Conclusions: Lymphopenia and CRP may serve as the risk factors related to hepatic injury in patients with COVID-19, which might be related to inflammatory cytokine storm in liver injury. Early detection and timely treatment of hepatic injury in patients with COVID-19 are necessary.

positive: Novel coronavirus 2019-nCoV: prevalence, biological and clinical characteristics comparison with SARS-CoV and MERS-CoV OBJECTIVE: Human infections with zoonotic coronavirus contain emerging and reemerging pathogenic characteristics which have raised great public health concern. This study aimed at investigating the global prevalence, biological and clinical characteristics of novel coronavirus, Wuhan China (2019-nCoV), Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection outbreaks. MATERIALS AND METHODS: The data on the global outbreak of "2019-nCoV, SARS-CoV, and MERS-CoV" were obtained from World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), concerned ministries and research institutes. We also recorded the information from research documents published in global scientific journals indexed in ISI Web of Science and research centers on the prevalence, biological and clinical characteristics of 2019-nCoV, SARS-CoV, and MERS-CoV. RESULTS: Worldwide, SARS-CoV involved 32 countries, with 8422 confirmed cases and 916 (10.87%) casualties from November 2002 to August 2003. MERS-CoV spread over 27 states, causing 2496 cases and 868 (34.77%) fatalities during the period April 2012 to December 2019. However, the novel coronavirus 2019-nCoV spread swiftly the global borders of 27 countries. It infected 34799 people and resulted in 724 (2.08%) casualties during the period December 29, 2019 to February 7, 2020. The fatality rate of coronavirus MERS-CoV was (34.77%) higher than SARS-CoV (10.87%) and 2019-nCoV (2.08%); however, the 2019-nCoV transmitted rapidly in comparison to SARS-CoV and MERS-CoV. CONCLUSIONS: The novel coronavirus 2019-nCoV has diverse epidemiological and biological characteristics, making it more contagious than SARS-CoV and MERS-CoV. It has affected more people in a short time period compared to SARS-CoV and MERS-CoV, although the fatality rate of MERS-CoV was higher than SARS-CoV and 2019-nCoV. The major clinical manifestations in coronavirus infections 2019-nCoV, MERS-CoV, and SARS CoV are fever, chills, cough, shortness of breath, generalized myalgia, malaise, drowsy, diarrhea, confusion, dyspnea, and pneumonia. Global health authorities should take immediate measures to prevent the outbreaks of such emerging and reemerging pathogens across the globe to minimize the disease burden locally and globally.

positive: Prognostic value of Cardiac Biomarkers in COVID-19 Infection: A Meta-analysis Background Multiple Biomarkers have recently been shown to be elevated in COVID-19, a respiratory infection with multi-organ dysfunction; however, information regarding the prognostic value of cardiac biomarkers as it relates to disease severity and cardiac injury are inconsistent. Research Question The goal of this meta-analysis was to summarize the evidence regarding the prognostic relevance of cardiac biomarkers from data available in published reports. Study Design and Methods PubMed was searched from inception through April 2020 for studies comparing median values of cardiac biomarkers in critically ill versus non-critically ill COVID-19 patients, or patients who died versus those who survived. The weighted mean differences (WMD) and 95% confidence interval (CI) between the groups were calculated for each study and combined using a random effects meta-analysis model. The odds ratio (OR) for mortality based on cardiac injury was combined from studies reporting it. Results Troponin levels were significantly higher in COVID-19 patients who died or were critically ill versus those who were alive or not critically ill (WMD 0.58, 95% CI 0.42-0.71, p<0.001). Cardiac injury was independently associated with significantly increased odds of mortality (OR 6.641, 95% CI 1.26 - 35.1, p=0.03). No difference in BNP was seen between the two groups. A significant difference in levels of D-dimer was seen in those who died or were critically ill. CK levels were only significantly higher in those who died versus those who were alive (WMD 0.47 95% CI 0.09-0.84, p=0.014). Interpretation Cardiac biomarkers add prognostic value to the determination of the severity of COVID-19 and can predict mortality.

positive: Using IL‐2R/lymphocytes for predicting the clinical progression of patients with COVID‐19 Effective laboratory markers for the estimation of disease severity and predicting the clinical progression of coronavirus disease‐2019 (COVID‐19) is urgently needed. Laboratory tests, including blood routine, cytokine profiles and infection markers, were collected from 389 confirmed COVID‐19 patients. The included patients were classified into mild (n = 168), severe (n = 169) and critical groups (n = 52). The leukocytes, neutrophils, infection biomarkers [such as C‐reactive protein (CRP), procalcitonin (PCT) and ferritin] and the concentrations of cytokines [interleukin (IL)‐2R, IL‐6, IL‐8, IL‐10 and tumor necrosis factor (TNF)‐α] were significantly increased, while lymphocytes were significantly decreased with increased severity of illness. The amount of IL‐2R was positively correlated with the other cytokines and negatively correlated with lymphocyte number. The ratio of IL‐2R to lymphocytes was found to be remarkably increased in severe and critical patients. IL‐2R/lymphocytes were superior compared with other markers for the identification of COVID‐19 with critical illness, not only from mild but also from severe illness. Moreover, the cytokine profiles and IL‐2R/lymphocytes were significantly decreased in recovered patients, but further increased in disease‐deteriorated patients, which might be correlated with the outcome of COVID‐19. Lymphopenia and increased levels of cytokines were closely associated with disease severity. The IL‐2R/lymphocyte was a prominent biomarker for early identification of severe COVID‐19 and predicting the clinical progression of the disease.

positive: Prediction of severe illness due to COVID-19 based on an analysis of initial Fibrinogen to Albumin Ratio and Platelet count Concomitant coagulation disorder can occur in severe patients withCOVID-19, but in-depth studies are limited. This study aimed to describe the parameters of coagulation function of patients with COVID-19 and reveal the risk factors of developing severe disease. This study retrospectively analyzed 113patients with SARS-CoV-2 infection in Taizhou Public Health Center. Clinical characteristics and indexes of coagulation function were collected. A multivariate Cox analysis was performed to identify potential biomarkers for predicting disease progression. Based on the results of multivariate Cox analysis, a Nomogram was built and the predictive accuracy was evaluated through the calibration curve, decision curve, clinical impact curve, and Kaplan–Meier analysis. Sensitivity, specificity, predictive values were calculated to assess the clinical value. The data showed that Fibrinogen, FAR, and D-dimer were higher in the severe patients, while PLTcount, Alb were much lower. Multivariate Cox analysis revealed that FAR and PLT count were independent risk factors for disease progression. The optimal cutoff values for FAR and PLT count were 0.0883 and 135*10(9)/L, respectively. The C-index [0.712 (95% CI = 0.610–0.814)], decision curve, clinical impact curve showed that Nomogram could be used to predict the disease progression. In addition, the Kaplan–Meier analysis revealed that potential risk decreased in patients with FAR<0.0883 and PLT count>135*10(9)/L.The model showed a good negative predictive value [(0.9474 (95%CI = 0.845–0.986)].This study revealed that FAR and PLT count were independent risk factors for severe illness and the severity of COVID-19 might be excluded when FAR<0.0883 and PLT count>135*10(9)/L.

positive: ACE2, COVID19 and serum ACE as a possible biomarker to predict severity of disease

positive: 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.

positive: Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19 BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 was first reported in Wuhan, December 2019, and continuously poses a serious threat to public health, highlighting the urgent need of identifying biomarkers for disease severity and progression. OBJECTIVE: We sought to identify biomarkers for disease severity and progression of COVID-19. METHODS: Forty-eight cytokines in the plasma samples from 50 COVID-19 cases including 11 critically ill, 25 severe, and 14 moderate patients were measured and analyzed in combination with clinical data. RESULTS: Levels of 14 cytokines were found to be significantly elevated in COVID-19 cases and showed different expression profiles in patients with different disease severity. Moreover, expression levels of IFN-Î³-induced protein 10, monocyte chemotactic protein-3, hepatocyte growth factor, monokine-induced gamma IFN, and macrophage inflammatory protein 1 alpha, which were shown to be highly associated with disease severity during disease progression, were remarkably higher in critically ill patients, followed by severe and then the moderate patients. Serial detection of the 5 cytokines in 16 cases showed that continuously high levels were associated with deteriorated progression of disease and fatal outcome. Furthermore, IFN-Î³-induced protein 10 and monocyte chemotactic protein-3 were excellent predictors for the progression of COVID-19, and the combination of the 2 cytokines showed the biggest area under the curve of the receiver-operating characteristics calculations with a value of 0.99. CONCLUSIONS: In this study, we report biomarkers that are highly associated with disease severity and progression of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of severe acute respiratory syndrome coronavirus 2 infection, and provide potential therapeutic targets and strategies.

positive: Interleukin-6 as a potential biomarker of COVID-19 progression

positive: Laboratory abnormalities in children with mild and severe coronavirus disease 2019 (COVID-19): A pooled analysis and review Limited data exists to-date on the laboratory findings in children with COVID-19, warranting the conduction of this study, in which we pool the currently available literature data on the laboratory findings seen in children with mild and severe COVID-19. Following an extensive literature search, we identified 24 eligible studies, including a total of 624 pediatric cases with laboratory-confirmed COVID-19, which report data on 27 different biomarkers. We then performed a meta-analysis to calculate the pooled prevalence estimates (PPE) for these laboratory abnormalities in mild COVID-19. As data was too limited for children with severe COVID-19 to allow pooling, results were presented descriptively in a summary of findings table. Our data show an inconsistent pattern of change in the leukocyte index of mild and severe cases of COVID-19 in children. Specifically, changes in leukocyte counts were only observed in 32% of the mild pediatric cases (PPE: 13% increase, 19% decrease). In mild disease, creatine kinase-MB (CK-MB) was frequently elevated, with a PPE of 33%. In severe disease, c-reactive protein (CRP), procalcitonin (PCT), and lactate dehydrogenase (LDH) were frequently elevated. Based on data obtained from early COVID-19 studies, leukocyte indices in children appear inconsistent, differing from those reported in adults that highlight specific leukocyte trends. This brings into question the utility and reliability of such parameters in monitoring disease severity in the pediatric population. Instead, we suggest physicians to serially monitor CRP, PCT, and LDH to track the course of illness in hospitalized children. Finally, elevated CK-MB in mild pediatric COVID-19 cases is indicative of possible cardiac injury. This highlights the importance of monitoring cardiac biomarkers in hospitalized patients and the need for further investigation of markers such as cardiac troponin in future studies.

positive: The diagnostic and predictive role of NLR, d-NLR and PLR in COVID-19 patients AIM: To accumulate evidence that indicated the key role played by virus-triggered inflammation in the 2019-novel coronavirus disease (COVID-19) which emerged in Wuhan City and rapidly spread throughout China. METHODS: Age, neutrophil(NEU)-to-lymphocyte (LYM) ratio (NLR), lymphocyte-to-monocyte (MON) ratio, platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) of 93 patients with laboratory confirmed COVID-19 were investigated and compared. The receiver operating characteristic curve was applied to determine the thresholds for five bio-markers, and their prognostic values were assessed via the Kaplan-Meier curve and multivariate COX regression models. RESULTS: The median age was 46.4 years old, and 37cases were females. A total of 27.8% of patients had been to Wuhan, and 73.1% had contacted with people from Wuhan. Fever (83.8%) and cough (70.9%) were the two most common symptoms. Elevated NLR and age were significantly associated with illness severity. The binary logistic analysis identified elevated NLR (hazard risk [HR] 2.46, 95% confidence interval [CI] 1.98-4.57) and age (HR 2.52, 95% CI 1.65-4.83) as independent factors for poor clinical outcome of COVID-19. NLR exhibited the largest area under the curve at 0.841, with the highest specificity (63.6%) and sensitivity (88%). CONCLUSIONS: Elevated age and NLR can be considered independent biomarkers for indicating poor clinical outcomes.

positive: Prognostic value of Carcinoembryonic antigen on outcome in patients with Coronavirus disease 2019

positive: Clinical course of severe and critically ill patients with coronavirus disease 2019 (COVID-19): a comparative study

positive: Tumor biomarkers predict clinical outcome of COVID-19 patients

positive: Clinical and historical features associated with severe COVID-19 infection: a systematic review Background: There is an urgent need for rapid assessment methods to guide pathways of care for COVID-19 patients, as frontline providers need to make challenging decisions surrounding rationing of resources. This study aimed to evaluate existing literature for factors associated with COVID-19 illness severity. Methods: A systematic review identified all studies published between 1/12/19 and 19/4/20 that used primary data and inferential statistics to assess associations between the outcome of interest - disease severity - and historical or clinical variables. PubMed, Scopus, Web of Science, and the WHO Database of Publications on Coronavirus Disease were searched. Data were independently extracted and cross-checked independently by two reviewers using PRISMA guidelines, after which they were descriptively analysed. Quality and risk of bias in available evidence were assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. This review was registered with PROSPERO, registration number CRD42020178098. Results: Of the 6202 relevant articles found, 63 were eligible for inclusion; these studies analysed data from 17648 COVID-19 patients. The majority (n=57, 90.5%) were from China and nearly all (n=51, 90.5%) focussed on admitted adult patients. Patients had a median age of 52.5 years and 52.8% were male. The predictors most frequently associated with COVID-19 disease severity were age, absolute lymphocyte count, hypertension, lactate dehydrogenase (LDH), C-reactive protein (CRP), and history of any pre-existing medical condition. Conclusion: This study identified multiple variables likely to be predictive of severe COVID-19 illness. Due to the novelty of SARS-CoV-2 infection, there is currently no severity prediction tool designed to, or validated for, COVID-19 illness severity. Findings may inform such a tool that can offer guidance on clinical treatment and disposition, and ultimately reduce morbidity and mortality due to the pandemic.

positive: Weathering the Cytokine Storm in Susceptible Patients with Severe SARS-CoV-2 Infection

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

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: C reactive protein level may predict the risk of COVID-19 aggravation BACKGROUND: Clinical findings indicated that a fraction of Corona Virus Disease 2019 (COVID-19) patients diagnosed as mild early may progress to severe cases. However, it is difficult to distinguish these patients in the early stage. The present study was to describe the clinical characteristics of these patients, analyze related factors and explore predictive markers of the disease aggravation. METHODS: Clinical and laboratory data of non-severe adult COVID-19 patients in Changsha, China, were collected and analyzed on admission. A logistic regression model was adopted to analyze the association between the disease aggravation and related factors. Receiver operating characteristic curve (ROC) was utilized to analyze the prognostic ability of C-reactive protein (CRP). RESULTS: About 7.7% (16/209) non-severe adult COVID-19 patients progressed to severe cases after admission. Compared with non-severe patients, the aggravated patients had much higher levels of CRP (median, 43.8 mg/L [range: 12.3-101.9] vs 12.1 mg/L [range: 0.1-91.4]; P = 0.000). The regression analysis showed CRP was significantly associated with the aggravation of non-severe COVID-19 patients, with an area under the curves (AUC) of 0.844 (95% CI, 0.761 - 0.926) and the optimal threshold value of 26.9 mg/L. CONCLUSIONS: CRP could be a valuable marker to anticipate the possibility of aggravation of non-severe adult COVID-19 patients, with the optimal threshold value of 26.9 mg/L.

positive: Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19 Abstract Background 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, December 2019, and continuously poses a serious threat to public health, highlighting the urgent need of identifying biomarkers for disease severity and progression. Objective To identify biomarkers for disease severity and progression of COVID-19. Methods Forty-eight cytokines in the plasma samples from 50 COVID-19 cases including 11 critically ill, 25 severe and 14 moderate patients were measured and analyzed in combination with clinical data. Results Fourteen cytokines were found to be significantly elevated in COVID-19 cases and showed different expression profiles in patients with different disease severity. Moreover, expression levels of IP-10, MCP-3, HGF, MIG and MIP-1α, which were shown to be highly associated with disease severity during disease progression, were remarkably higher in critically ill patients, followed by severe and then the moderate patients. Serial detection of the five cytokines in 16 cases showed that continuously high levels were associated with deteriorated progression of disease and fatal outcome. Furthermore, IP-10 and MCP-3 were excellent predictors for the progression of COVID-19, and the combination of the two cytokines showed the biggest area under the curve (AUC) of the receiver-operating characteristics (ROC) calculations with a value of 0.99. Conclusion In this study, we report biomarkers that highly associated with disease severity and progression of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of SARS-CoV-2 infection, and provide potential therapeutic targets and strategies.

positive: Plasma Metabolomic and Lipidomic Alterations Associated with COVID-19 The pandemic of the coronavirus disease 2019 (COVID-19) has become a global public health crisis. The symptoms of COVID-19 range from mild to severe conditions. However, the physiological changes associated with COVID-19 are barely understood. In this study, we performed targeted metabolomic and lipidomic analyses of plasma from a cohort of COVID-19 patients who had experienced different symptoms. We found the metabolite and lipid alterations exhibit apparent correlation with the course of disease in these COVID-19 patients, indicating that the development of COVID-19 affected whole-body metabolism of the patients. In particular, malic acid of the TCA cycle and carbamoyl phosphate of urea cycle reveal the altered energy metabolism and hepatic dysfunction, respectively. It should be noted that carbamoyl phosphate is profoundly down-regulated in fatal patients compared with mild patients. And more importantly, guanosine monophosphate (GMP), which is mediated by not only GMP synthase but also CD39 and CD73, is significantly changed between healthy subjects and COVID-19 patients, as well as between the mild and fatal groups. In addition, the dyslipidaemia was observed in COVID-19 patients. Overall, the disturbed metabolic patterns have been found to align with the progress and severity of COVID-19. This work provides valuable knowledge about plasma biomarkers associated with COVID-19 and potential therapeutic targets, as well as important resource for further studies of COVID-19 pathogenesis.

positive: Erythrocyte sedimentation rate is associated with severe coronavirus disease 2019 (COVID-19): a pooled analysis

positive: Clinical value of immune-inflammatory parameters to assess the severity of coronavirus disease 2019 Abstract Objective To explore the clinical value of immune-inflammatory markers to assess the severity of coronavirus disease 2019 (COVID-19). Methods 127 consecutive hospitalized patients with confirmed COVID-19 were enrolled in this study, and classified into non-severe and severe groups. Demographics, symptoms, underlying diseases and laboratory data were collected and assessed for predictive value. Results Of 127 COVID-19 patients, 16 cases (12.60%) were classified into the severe group. High level of interleukin-6 (IL-6), C-reaction protein (CRP) and hypertension were independent risk factors for the severity of COVID-19. The risk model based on IL-6, CRP and hypertension had the highest area under the receiver operator characteristic curve (AUROC). Additionally, the baseline IL-6 was positively correlated with other immune-inflammatory parameters and the dynamic change of IL-6 in the severe cases were parallel to the amelioration of the disease. Conclusion Our study showed that high level of IL-6, CRP and hypertension were independent risk factors for assessing the severity of COVID-19. The risk model established upon IL-6, CRP and hypertension had the highest predictability in this study. Besides, IL-6 played a pivotal role in the severity of COVID-19 and had a potential value for monitoring the process of severe cases.

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: Laboratory Biomarkers Predicting COVID-19 Severity in the Emergency Room Infection of novel Coronavirus has been declared pandemic by the WHO and now is a world public health crisis. Laboratory activity becames essential for the timely diagnosis. Few parameters, such Lymphocytes count, SaO2 and CRP serum level can be used to assess the severity of COVID-19 in emergency room.

positive: Risk assessment of progression to severe conditions for patients with COVID-19 pneumonia: a single-center retrospective study Background: Management of high mortality risk due to significant progression requires prior assessment of time-to-progression. However, few related methods are available for COVID-19 pneumonia. Methods: We retrospectively enrolled 338 adult patients admitted to one hospital between Jan 11, 2020 to Feb 29, 2020. The final follow-up date was March 8, 2020. We compared characteristics between patients with severe and non-severe outcome, and used multivariate survival analyses to assess the risk of progression to severe conditions. Results: A total of 76 (31.9%) patients progressed to severe conditions and 3 (0.9%) died. The mean time from hospital admission to severity onset is 3.7 days. Age, body mass index (BMI), fever symptom on admission, co-existing hypertension or diabetes are associated with severe progression. Compared to non-severe group, the severe group already demonstrated, at an early stage, abnormalities in biomarkers indicating organ function, inflammatory responses, blood oxygen and coagulation function. The cohort is characterized with increasing cumulative incidences of severe progression up to 10 days after admission. Competing risks survival model incorporating CT imaging and baseline information showed an improved performance for predicting severity onset (mean time-dependent AUC = 0.880). Conclusions: Multiple predisposition factors can be utilized to assess the risk of progression to severe conditions at an early stage. Multivariate survival models can reasonably analyze the progression risk based on early-stage CT images that would otherwise be misjudged by artificial analysis.

positive: Diagnostic and prognostic value of hematological and immunological markers in COVID-19 infection: A meta-analysis of 6320 patients Objective Evidence-based characterization of the diagnostic and prognostic value of the hematological and immunological markers related to the epidemic of Coronavirus Disease 2019 (COVID-19) is critical to understand the clinical course of the infection and to assess in development and validation of biomarkers. Methods Based on systematic search in Web of Science, PubMed, Scopus, and Science Direct up to April 22, 2020, a total of 52 eligible articles with 6,320 laboratory-confirmed COVID-19 cohorts were included. Pairwise comparison between severe versus mild disease, Intensive Care Unit (ICU) versus general ward admission, and expired versus survivors were performed for 36 laboratory parameters. The pooled standardized mean difference (SMD) and 95% confidence intervals (CI) were calculated using the DerSimonian Laird method/random effects model and converted to Odds ratio (OR). The decision tree algorithm was employed to identify the key risk factor(s) attributed to severe COVID-19 disease. Results Cohorts with elevated levels of white blood cells (WBCs) (OR=1.75), neutrophil count (OR=2.62), D-dimer (OR=3.97), prolonged prothrombin time (PT) (OR=1.82), fibrinogen (OR=3.14), erythrocyte sedimentation rate (OR=1.60), procalcitonin (OR=4.76), IL-6 (OR=2.10), and IL-10 (OR=4.93) had higher odds of progression to severe phenotype. Decision tree model (sensitivity=100%, specificity=81%) showed the high performance of neutrophil count at a cut-off value of more than 3.74 x109/L for identifying patients at high risk of severe COVID-19. Likewise, ICU admission was associated with higher levels of WBCs (OR=5.21), neutrophils (OR=6.25), D-dimer (OR=4.19), and prolonged PT (OR=2.18). Patients with high IL-6 (OR=13.87), CRP (OR=7.09), D-dimer (OR=6.36), and neutrophils (OR=6.25) had the highest likelihood of mortality. Conclusions Several hematological and immunological markers, in particular neutrophilic count, could be helpful to be included within the routine panel for COVID-19 infection evaluation to ensure risk stratification and effective management.

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

positive: A novel simple scoring model for predicting severity of patients with SARS‐CoV‐2 infection An outbreak of pneumonia caused by a novel coronavirus (COVID‐19) began in Wuhan, China in December 2019 and quickly spread throughout the country and world. An efficient and convenient method based on clinical characteristics was needed to evaluate the potential deterioration in patients. We aimed to develop a simple and practical risk scoring system to predict the severity of COVID‐19 patients on admission. We retrospectively investigated the clinical information of confirmed COVID‐19 patients from February 10, 2020 to February 29, 2020 in Wuhan Union Hospital. Predictors of severity were identified by univariate and multivariate logistic regression analysis. A total of 147 patients with confirmed SARS‐CoV‐2 infection were grouped into non‐severe (94 patients) and severe (53 patients) groups. We found that an increased level of white blood cells (WBC), neutrophils, D‐dimer, fibrinogen (FIB), IL‐6, C‐reactive protein (CRP), erythrocyte sedimentation rate (ESR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), α‐hydroxybutyrate dehydrogenase (HBDH), serum amyloid A (SAA) and a decreased level of lymphocytes were important risk factors associated with severity. Furthermore, three variables were used to formulate a clinical risk scoring system named COVID‐19 index = 3×D‐dimer (µg/L)+2×lgESR (mm/h)‐4×lymphocyte (×10(9)/L)+8. The area under the receiver operating characteristic (ROC) curve was 0.843 (95% CI, 0.771‐0.914). We propose an effective scoring system to predict the severity of COVID‐19 patients. This simple prediction model may provide health‐care workers with a practical method and could positively impact decision‐making with regard to deteriorating patients.

positive: Level of IL-6 predicts respiratory failure in hospitalized symptomatic COVID-19 patients The pandemic Coronavirus-disease 19 (COVID-19) is characterized by a heterogeneous clinical course. While most patients experience only mild symptoms, a relevant proportion develop severe disease progression with increasing hypoxia up to acute respiratory distress syndrome. The substantial number of patients with severe disease have strained intensive care capacities to an unprecedented level. Owing to the highly variable course and lack of reliable predictors for deterioration, we aimed to identify variables that allow the prediction of patients with a high risk of respiratory failure and need of mechanical ventilation Patients with PCR proven symptomatic COVID-19 infection hospitalized at our institution from 29th February to 27th March 2020 (n=40) were analyzed for baseline clinical and laboratory findings. Patients requiring mechanical ventilation 13/40 (32.5%) did not differ in age, comorbidities, radiological findings, respiratory rate or qSofa score. However, elevated interleukin-6 (IL-6) was strongly associated with the need for mechanical ventilation (p=1.2.10-5). In addition, the maximal IL-6 level (cutoff 80 pg/ml) for each patient during disease predicted respiratory failure with high accuracy (p=1.7.10-8, AUC=0.98). The risk of respiratory failure for patients with IL-6 levels of ≥ 80 pg/ml was 22 times higher compared to patients with lower IL-6 levels. In the current situation with overwhelmed intensive care units and overcrowded emergency rooms, correct triage of patients in need of intensive care is crucial. Our study shows that IL-6 is an effective marker that might be able to predict upcoming respiratory failure with high accuracy and help physicians correctly allocate patients at an early stage.

positive: Coronavirus 2019-nCoV: A brief perspective from the front line Abstract A novel coronavirus, designated as 2019-nCoV, hit the central Chinese city of Wuhan in late December 2019, and subsequently spread rapidly to all provinces of China and multiple countries. As of 0:00 am February 9, 2020, a total of 37,287 cases have been confirmed infection of 2019-nCoV in China mainland, and 302 cases have also been cumulatively reported from 24 countries. According to the latest data, a total of 813 deaths occurred in China mainland, with the mortality reaching approximately 2.2%. At present, there is no vaccine or specific drugs for the human coronavirus. Therefore, it is critical to understand the nature of the virus and its clinical characteristics, in order to respond to the 2019-nCoV outbreak. Thus, the present study briefly but comprehensively summarizes the not much but timely reports on the 2019-nCoV.

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

positive: The value of clinical parameters in predicting the severity of COVID‐19 To study the relationship between clinical indexes and the severity of coronavirus disease 2019 (COVID‐19), and to explore its role in predicting the severity of COVID‐19. Clinical data of 443 patients with COVID‐19 admitted to our hospital were retrospectively analyzed, which were divided into nonsevere group (n = 304) and severe group (n = 139) according to their condition. Clinical indicators were compared between different groups. The differences in sex, age, the proportion of patients with combined heart disease, leukocyte, neutrophil‐to‐lymphocyte ratio (NLR), neutrophil, lymphocyte, platelet, D‐dimer, C‐reactive protein (CRP), procalcitonin, lactate dehydrogenase, and albumin on admission between the two groups were statistically significant (P < .05). Multivariate logistic regression analysis showed NLR and CRP were independent risk factors for severe COVID‐19. Platelets were independent protective factors for severe COVID‐19. The receiver operating characteristic (ROC) curve analysis demonstrated area under the curve of NLR, platelet, CRP, and combination was 0.737, 0.634, 0.734, and 0.774, respectively. NLR, CRP, and platelets can effectively assess the severity of COVID‐19, among which NLR is the best predictor of severe COVID‐19, and the combination of three clinical indicators can further predict severe COVID‐19.

positive: Machine Learning to Predict Mortality and Critical Events in COVID-19 Positive New York City Patients Coronavirus 2019 (COVID-19), caused by the SARS-CoV-2 virus, has become the deadliest pandemic in modern history, reaching nearly every country worldwide and overwhelming healthcare institutions. As of April 20, there have been more than 2.4 million confirmed cases with over 160,000 deaths. Extreme case surges coupled with challenges in forecasting the clinical course of affected patients have necessitated thoughtful resource allocation and early identification of high-risk patients. However, effective methods for achieving this are lacking. In this paper, we present a decision tree-based machine learning model trained on electronic health records from patients with confirmed COVID-19 at a single center within the Mount Sinai Health System in New York City. We then externally validate our model by predicting the likelihood of critical event or death within various time intervals for patients after hospitalization at four other hospitals and achieve strong performance, notably predicting mortality at 1 week with an AUC-ROC of 0.84. Finally, we establish model interpretability by calculating SHAP scores to identify decisive features, including age, inflammatory markers (procalcitonin and LDH), and coagulation parameters (PT, PTT, D-Dimer). To our knowledge, this is one of the first models with external validation to both predict outcomes in COVID-19 patients with strong validation performance and identification of key contributors in outcome prediction that may assist clinicians in making effective patient management decisions.

positive: The Association Between Biomarkers and Clinical Outcomes in Novel Coronavirus (COVID-19) Pneumonia in a U.S. Cohort Background: The global pandemic caused by COVID-19 remains poorly understood by clinicians. Identifying biologic markers associated with prognosis can help clinicians recognize disease severity. Objective: To describe the association between D-dimer, CRP, IL-6, ferritin, LDH, and clinical outcomes in a cohort of COVID-19 patients treated on the inpatient medical service at a university hospital in Washington, DC. Design: In this retrospective study, we included all adults admitted to the inpatient medicine service at George Washington University Hospital between March 12, 2020 and May 9, 2020 with laboratory confirmed COVID-19. Clinical and laboratory data were extracted from electronic medical records and compared between survivors not requiring ICU transfer, survivors requiring ICU transfer, survivors requiring intubation, and non-survivors. Key Results: 299 patients were included in our study, of whom 69 required transfer to the ICU, 39 required intubation, and 71 died. Threshold values for IL-6 (>50 pg/mL), D-dimer (>3 mcg/mL), ferritin (>450 ng/mL), CRP (>100 mg/L), and LDH (1,200 u/L) were found to be statistically significant and independently associated with higher odd of clinical deterioration and death. Hypertension, CVA and heart disease independently had an increased risk of all three outcomes, while CKD had only an increased risk of death. Patient co-morbidities had no effect on the different biomarkers' significant association with poor patient clinical outcomes, except cancer. Conclusion: Laboratory markers of inflammation and coagulopathy can help clinicians identify patients who are at high risk for clinical deterioration, independent of clinically significant medical comorbidities

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

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 to successful treatment of COVID-19: accurate identification of severe risks and early intervention of disease progression Abstract Background COVID-19 is a new and highly contagious respiratory disease that has caused global spread, high case fatality rate in severe patients, and a huge medical burden due to invasive mechanical ventilation. The current diagnosis and treatment guidelines are still need to be improved, and more excellent clinical experience is needed to provide reference. Methods We analyzed and summarized clinical data of 97 confirmed COVID-19 adult patients (including 26 severe cases) admitted to the Fifth Affiliated Hospital of Sun Yat-sen University from January 17, 2020 to March 10, 2020,included laboratory examination results, imaging findings, treatment effect, prognosis , etc, in order to put forward prediction index of severe COVID-19 patients, principles of early intervention and methylprednisolone usages in COVID-19 patients. Results 1.Hypoxemia, hyperlactic acid, hypoproteinemia, and hypokalemia were prevalent in COVID-19 patients.The significant low lymphocyte count, hypoproteinemia, hypokalemia, the persistent or worsen high CRP, high D-dimer, and high BNP, and the occurrence of hemoptysis and novel coronavirus (SARS-CoV-2) viremia were important indicators for early diagnosis and prediction of severe disease progression. 2.Characteristic images of lung CT had a clear change in COVID - 19, Ground-glass opacity (GGO) and high-density linear combinations may indicate different pathological changes. Rapid lobular progression of GGO suggests the possibility of severe disease. 3.Basic principles of early intervention treatment of COVID-19: on the premise of no effective antiviral drugs, treatment is based on supportive and symptomatic therapy (albumin supplementation, supplement of potassium, supplement blood plasma, etc.) in order to maintain the stability of the intracellular environment and adequately reactivate body immunity to clean up SARS-CoV-2 . 4. According to severity, oxygenation index, body weight, age, underlying diseases, appropriate amount methylprednisolone application on severe/critical COVID-19 patients on demand, improved blood oxygen and reduced the utilization rate of invasive mechanical ventilation, case fatality rate and medical burden significantly. The most common indications for invasive mechanical ventilation should be strictly control in critical COVID-19 patients. Conclusions: 1.Accurate and timely identification of clinical features in severe risks, and early and appropriate intervention can block disease progression. 2.Appropriate dose of methylprednisolone can effectively avoid invasive mechanical ventilation and reduce case fatality rate in critical COVID-19 patients.

positive: The profile of peripheral blood lymphocyte subsets and serum cytokines in children with 2019 novel coronavirus pneumonia 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.

positive: Association between chest CT features and clinical course of Coronavirus Disease 2019 PURPOSE: This retrospective study aims to illustrate the radiographic characteristics of Coronavirus Disease 2019 and the correlation with the clinical course. METHODS: 195 hospitalized patients confirmed as Coronavirus Disease 2019 at First Hospital of Changsha, Hunan Province from December 31, 2019 to February 20, 2020 were enrolled. Chest computed tomography scan, clinical data and laboratory tests results were collected accordingly. Variable characteristics were recorded, radiographic evolution and outcome were analyzed along with the time course. Representative laboratory tests results were analyzed based on the image findings. RESULTS: Majority of the patients showed bilateral (73.8%), multiple lobes involvements (75.9%), peripheral distribution (83.1%), ground-glass opacification (41.0%), increased vascular margins (63.1%), long axis parallelism (55.9%), patchy ground-glass opacities beneath the pleura (51.3%) and consolidation (45.6%). According to the repeated radiology analysis, patients of improving/stable group tended to have younger age compared with worsening group (45.3 ± 15.0 VS. 59.3 ± 13.5, P = 0.001). Based on the laboratory test results, patients with positive image findings shared elder age, 46.0 (35.0-60.0)VS.31.0 (12.0-37.0) P < 0.001, and higher chance developing fever(P < 0.05); higher level of lymphocytes, C-reactive protein, erythrocyte sedimentation rate and lactate dehydrogenase; lower level of white blood cells, neutrophil and albumin(P < 0.001). CONCLUSIONS: There are several specific image changes along with the disease progression may be helpful in early recognition and differential diagnosis of Coronavirus Disease 2019. Comprehensive assessments of both imaging feature and laboratory test results may offer an intact knowledge of Coronavirus Disease 2019.

positive: Characteristics of lymphocyte subsets and their predicting values for the severity of COVID-19 patients Severe COVID-19 patients showed worse clinical outcomes compared to mild and moderate patients. However, effective indicators are still lacking to predict the severity of the disease. In the present study, we retrospectively analyzed the clinical and laboratory data of 16 COVID-19 patients and found that the absolute counts of three T-cells (CD3+, CD4+, and CD8+) were significantly lower in the moderate and severe patients than those in mild patients and were significantly lower in severe patients than in moderate patients on admission. With the recovery of the COVID-19, serum levels of inflammatory biomarkers (CRP, PCT, and IL6) of moderate and severe patients gradually decreased. In contrast, the counts of lymphocytes and their subsets including CD3+, CD4+, and CD8+ T cells gradually increased in severe patients, and eventually showed comparable levels with moderate patients. ROC analysis showed that the counts of CD3+, CD4+, and CD8+ T-cells with AUC > 0.9 have potential values for predicting the severity of COVID-19 patients. In conclusion, the reduction of CD3+, CD4+, and CD8+ T-cells is related to the severity of COVID-19 and dynamic detection of these T-lymphocyte subsets may help predict the outcome of the patients.

positive: Inflammatory markers in Covid-19 Patients: a systematic review and meta-analysis. Introduction Diagnosis of COVID-19 is based on clinical manifestation, history of exposure, positive findings on chest CT and laboratory tests. It has been shown that inflammation plays a role in pathogenesis of COVID-19. Method We used the necessary transformations to convert the median and IQR to mean and SD Random-effect model using Der Simonian, and Laird methods was used if heterogeneity between studies was significant, the homogeneity among studies was assessed with I2 Statistic, values above 50%, and for the chi-square test, P-values <0.1 was supposed statistically significant Results Twelve studies were included in the analysis that all of which were conducted in China in the year 2020. The result of combining 12 articles with 772 participants showed that the pooled estimate of the mean of lymphocyte with 95% CI was (Mean: 1.01; 95% CI (0.76-1.26); p-value<0.001). About WBC the pooled result of 9 studies with 402 participants was (Mean: 5.11; 95% CI (3.90-6.32); p-value<0.001) Also the pooled mean estimate of 9 studies with 513 patients for the ratio of Neutrophil/lymphocyte was (Mean: 3.62; 95% CI (1.48-5.77); p-value=0.001). The pooled mean from the combination of 7 studies with 521 patients on CRP was (Mean: 28.75; 95% CI (8.04-49.46). Conclusion Inflammatory Markers increase in patients with Covid-19, which can be a good indicator to find patients.

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

positive: Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan, Hubei province, and rapidly spread to many provinces in China as well as other countries. Here we report the epidemiological, clinical, laboratory, and radiological characteristics, as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen, China. All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS). The most common laboratory abnormalities were hypoalbuminemia, lymphopenia, decreased percentage of lymphocytes (LYM) and neutrophils (NEU), elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased CD8 count. The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity. ALB, LYM, LYM (%), LDH, NEU (%), and CRP were highly correlated to the acute lung injury. Age, viral load, lung injury score, and blood biochemistry indexes, albumin (ALB), CRP, LDH, LYM (%), LYM, and NEU (%), may be predictors of disease severity. Moreover, the Angiotensin II level in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury. Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection.

positive: Analysis of hospitalized COVID-19 patients in the Mount Sinai Health System using electronic medical records (EMR) reveals important prognostic factors for improved clinical outcomes COVID-19 is a novel threat to human health worldwide. There is an urgent need to understand patient characteristics of having COVID-19 disease and evaluate markers of critical illness and mortality. Objective: To assess association of clinical features on patient outcomes. Design, Setting, and Participants: In this observational case series, patient-level data were extracted from electronic medical records for 28,336 patients tested for SARS-CoV-2 at the Mount Sinai Health System from 2/24/ to 4/15/2020, including 6,158 laboratory-confirmed cases. Exposures: Confirmed COVID-19 diagnosis by RT-PCR assay from nasal swabs. Main Outcomes and Measures: Effects of race on positive test rates and mortality were assessed. Among positive cases admitted to the hospital (N = 3,273), effects of patient demographics, hospital site and unit, social behavior, vital signs, lab results, and disease comorbidities on discharge and death were estimated. Results: Hispanics (29%) and African Americans (25%) had disproportionately high positive case rates relative to population base rates (p<2e-16); however, no differences in mortality rates were observed in the hospital. Outcome differed significantly between hospitals (Gray's T=248.9; p<2e-16), reflecting differences in average baseline age and underlying comorbidities. Significant risk factors for mortality included age (HR=1.05 [95% CI, 1.04-1.06]; p=1.15e-32), oxygen saturation (HR=0.985 [95% CI, 0.982-0.988]; p=1.57e-17), care in ICU areas (HR=1.58 [95% CI, 1.29-1.92]; p=7.81e-6), and elevated creatinine (HR=1.75 [95% CI, 1.47-2.10]; p=7.48e-10), alanine aminotransferase (ALT) (HR=1.002, [95% CI 1.001-1.003]; p=8.86e-5) and body-mass index (BMI) (HR=1.02, [95% CI 1.00-1.03]; p=1.09e-2). Asthma (HR=0.78 [95% CI, 0.62-0.98]; p=0.031) was significantly associated with increased length of hospital stay, but not mortality. Deceased patients were more likely to have elevated markers of inflammation. Baseline age, BMI, oxygen saturation, respiratory rate, white blood cell (WBC) count, creatinine, and ALT were significant prognostic indicators of mortality. Conclusions and Relevance: While race was associated with higher risk of infection, we did not find a racial disparity in inpatient mortality suggesting that outcomes in a single tertiary care health system are comparable across races. We identified clinical features associated with reduced mortality and discharge. These findings could help to identify which COVID-19 patients are at greatest risk and evaluate the impact on survival.

positive: Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, it has rapidly spread across many other countries. While the majority of patients were considered mild, critically ill patients involving respiratory failure and multiple organ dysfunction syndrome are not uncommon, which could result death. We hypothesized that cytokine storm is associated with severe outcome. We enrolled 102 COVID-19 patients who were admitted to Renmin Hospital (Wuhan, China). All patients were classified into moderate, severe and critical groups according to their symptoms. 45 control samples of healthy volunteers were also included. Inflammatory cytokines and C-Reactive Protein (CRP) profiles of serum samples were analyzed by specific immunoassays. Results showed that COVID-19 patients have higher serum level of cytokines (TNF-α, IFN-Î³, IL-2, IL-4, IL-6 and IL-10) and CRP than control individuals. Within COVID-19 patients, serum IL-6 and IL-10 levels are significantly higher in critical group (n = 17) than in moderate (n = 42) and severe (n = 43) group. The levels of IL-10 is positively correlated with CRP amount (r = 0.41, P < 0.01). Using univariate logistic regression analysis, IL-6 and IL-10 are found to be predictive of disease severity and receiver operating curve analysis could further confirm this result (AUC = 0.841, 0.822 respectively). Our result indicated higher levels of cytokine storm is associated with more severe disease development. Among them, IL-6 and IL-10 can be used as predictors for fast diagnosis of patients with higher risk of disease deterioration. Given the high levels of cytokines induced by SARS-CoV-2, treatment to reduce inflammation-related lung damage is critical.

positive: Biochemical biomarkers alterations in Coronavirus Disease 2019 (COVID-19) Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory disease, which can evolve into multi-organ failure (MOF), leading to death. Several biochemical alterations have been described in COVID-19 patients. To date, many biomarkers reflecting the main pathophysiological characteristics of the disease have been identified and associated with the risk of developing severe disease. Lymphopenia represents the hallmark of the disease, and it can be detected since the early stage of infection. Increased levels of several inflammatory biomarkers, including c-reactive protein, have been found in COVID-19 patients and associated with an increased risk of severe disease, which is characterised by the so-called "cytokine storm". Also, the increase of cardiac and liver dysfunction biomarkers has been associated with poor outcome. In this review, we provide an overview of the main biochemical characteristics of COVID-19 and the associated biomarkers alterations.

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

positive: Higher level of neutrophil-to-lymphocyte is associated with severe COVID-19 In December 2019, cases of severe coronavirus 2019 (COVID-19) infection rapidly progressed to acute respiratory failure. This study aims to assess the association between the neutrophil-to-lymphocyte ratio (NLR) and the incidence of severe COVID-19 infection. A retrospective cohort study was conducted on 210 patients with COVID-19 infection who were admitted to the Central Hospital of Wuhan from 27 January 2020 to 9 March 2020. Peripheral blood samples were collected and examined for lymphocyte subsets by flow cytometry. Associations between tertiles of NLR and the incidence of severe illness were analysed by logistic regression. Of the 210 patients with COVID-19, 87 were diagnosed as severe cases. The mean NLR of the severe group was higher than that of the mild group (6.6 vs. 3.3, P < 0.001). The highest tertile of NLR (5.1–19.7) exhibited a 5.9-fold (95% CI 1.3–28.5) increased incidence of severity relative to that of the lowest tertile (0.6–2.5) after adjustments for age, diabetes, hypertension and other confounders. The number of T cells significantly decreased in the severe group (0.5 vs. 0.9, P < 0.001). COVID-19 might mainly act on lymphocytes, particularly T lymphocytes. NLR was identified as an early risk factor for severe COVID-19 illness. Patients with increased NLR should be admitted to an isolation ward with respiratory monitoring and supportive care.

positive: The Australasian COVID-19 Trial (ASCOT) to assess clinical outcomes in hospitalised patients with SARS-CoV-2 infection (COVID-19) treated with lopinavir/ritonavir and/or hydroxychloroquine compared to standard of care: A structured summary of a study protocol for a randomised controlled trial OBJECTIVES: To determine if lopinavir/ritonavir +/- hydroxychloroquine will reduce the proportion of participants who survive without requiring ventilatory support, 15 days after enrolment, in adult participants with non-critically ill SARS-CoV-2 infection. TRIAL DESIGN: ASCOT is an investigator-initiated, multi-centre, open-label, randomised controlled trial. Participants will have been hospitalised with confirmed COVID-19, and will be randomised 1:1:1:1 to receive lopinavir /ritonavir, hydroxychloroquine, both or neither drug in addition to standard of care management. PARTICIPANTS: Participants will be recruited from >80 hospitals across Australia and New Zealand, representing metropolitan and regional centres in both public and private sectors. Admitted patients will be eligible if aged ≥ 18 years, have confirmed SARS-CoV-2 by nucleic acid testing in the past 12 days and are expected to remain an inpatient for at least 48 hours from the time of randomisation. Potentially eligible participants will be excluded if admitted to intensive care or requiring high level respiratory support, are currently receiving study drugs or their use is contraindicated due to allergy, drug interaction or comorbidities (including baseline QTc prolongation of 470ms for women or 480ms for men), or death is anticipated imminently. INTERVENTION AND COMPARATOR: Participants will be randomised 1:1:1:1 to: Group 1: standard of care; Group 2: lopinavir (400mg) / ritonavir (100mg) twice daily for 10 days in tablet form; Group 3: hydroxychloroquine (800mg) 4x200mg administered 12 hours apart on Day 1, followed by 400mg twice a day for 6 days; Group 4: lopinavir /ritonavir plus hydroxychloroquine. MAIN OUTCOMES: Proportion of participants alive and not having required intensive respiratory support (invasive or non-invasive ventilation) at 15 days after enrolment. A range of clinical and virological secondary outcomes will also be evaluated. RANDOMISATION: The randomisation schedule will be generated by an independent statistician. Randomisation will be stratified by site and will be in permuted blocks of variable block size. The randomised sequence allocation will only be accessible to the data management group, and site investigators will have individual participant allocation provided through a web-based trial enrolment platform. BLINDING (MASKING): This is an open-label study, with researchers assessing the laboratory outcomes blinded to treatment allocation. No unblinding procedures relating to potential adverse effects are therefore required. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): We assumed that 5% of participants receiving standard of care would meet the primary outcome, aimed to evaluate whether interventions could lead to a relative risk of 0.5, assuming no interaction between intervention arms. This corresponds to a required sample size of 610 per arm, with a 5% two-sided significance level (alpha) and 80% power. The total sample size therefore is planned to be 2440. TRIAL STATUS: ASCOT protocol version 3, May 5, 2020. Recruitment opened April 4, 2020 and is ongoing, with planned completion of enrolment July 31, 2021. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12620000445976). Prospectively registered April 6, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

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

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: The value of clinical parameters in predicting the severity of COVID-19 To study the relationship between clinical indexes and the severity of coronavirus disease 2019 (COVID-19), and to explore its role in predicting the severity of COVID-19. Clinical data of 443 patients with COVID-19 admitted to our hospital were retrospectively analyzed, which were divided into nonsevere group (n = 304) and severe group (n = 139) according to their condition. Clinical indicators were compared between different groups. The differences in sex, age, the proportion of patients with combined heart disease, leukocyte, neutrophil-to-lymphocyte ratio (NLR), neutrophil, lymphocyte, platelet, D-dimer, C-reactive protein (CRP), procalcitonin, lactate dehydrogenase, and albumin on admission between the two groups were statistically significant (P < .05). Multivariate logistic regression analysis showed NLR and CRP were independent risk factors for severe COVID-19. Platelets were independent protective factors for severe COVID-19. The receiver operating characteristic (ROC) curve analysis demonstrated area under the curve of NLR, platelet, CRP, and combination was 0.737, 0.634, 0.734, and 0.774, respectively. NLR, CRP, and platelets can effectively assess the severity of COVID-19, among which NLR is the best predictor of severe COVID-19, and the combination of three clinical indicators can further predict severe COVID-19.

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: 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: Quantitative Computed Tomography of the Coronavirus Disease 2019 (COVID-19) Pneumonia Abstract Objective To quantify coronavirus diseases 2019 (COVID-19) pneumonia and to explore whether quantitative computer tomography (CT) could be used to assess severity on admission. Materials and Methods From January 17 to February 9, 2020, 38 hospitalized patients with COVID-19 pneumonia were consecutively enrolled in our hospitals. All clinical data and the chest CT on admission were retrospectively reviewed and analyzed. Firstly, a quantitative method based on multi-scale convolutional neural networks was used to assess the infected lung segments and this was compared with the semi-quantitative method. Secondly, the quantitative method was tested with laboratory results and the pneumonia severity index (PSI) by correlation analyses. Thirdly, both quantitative and semi-quantitative parameters between patients with different PSI were compared. Results Thirty cases were finally enrolled: 16 (53.33%) of them were male, and the mean age was 48 years old. The interval from onset symptoms to first chest CT scan was 8 days. The proportion of ground glass opacity (GGO), consolidation and the total lesion based on the quantitative method was positively correlated with the semi-quantitative CT score (P < 0.001 for all; rs=0.88, 0.87, 0.90), CRP (P=0.0278, 0.0168, 0.0078; rs=0.40, 0.43, 0.48) and ESR (P=0.0296, 0.0408, 0.0048; rs=0.46, 0.44, 0.58), respectively, and was negatively correlated with the lymphocyte count (P=0.0222, 0.0024, 0.0068; rs=-0.42, -0.53, -0.48). There was a positive correlation trend between the proportion of total infection and the pneumonia severity index (P=0.0994; rs=0.30) and a tendency that patients with severe COVID-19 pneumonia had higher percentage of consolidation and total infection (P=0.0903, 0.0989). Conclusions Quantitative CT may have potential in assessing the severity of COVID-19 pneumonia on admission.

positive: Elevated interleukin-6, interleukin-10 and neutrophil : lymphocyte ratio as identifiers of severe coronavirus disease 2019

positive: Correlation between Heart fatty acid binding protein and severe COVID-19: A case-control study BACKGROUND: Heart-fatty acid binding protein (HFABP) has been recognized as a highly heart-specific marker. However, it is currently unknown that its HFABP is also closely related to the severity of COVID-19. METHODS: We retrospectively screened 46 patients who met our inclusion criteria within 4 weeks. They were tested for HFABP after the diagnosis of COVID-19, and monitored for HFABP during their hospital stay. We tracked the patients during their hospital stay to determine if they had severe COVID-19 or mild-to-severe transition features. We calculated the chi-square test values found for HFABP to predict the correlation between HFABP levels and the severity of the COVID-19. RESULTS: Of these 46 cases, 16 cases with confirmed COVID-19 were tested for HFABP> 7 ng / mL upon admission; among them, 14 cases were diagnosed with severe COVID-19 within the hospitalization. The Odds ratio of the measured HFABP elevation was 6.81(95% confidence interval [CI] 5.23-8.40), and 3 patients with severe COVID-19 progressed in 5 patients with mild HFABP> 7 ng/mL. CONCLUSION: These data indicate that the elevation of HFABP is closely related to the severity of COVID-19 in the patients, and the elevated HFABP may cause rapid development of patients with mild COVID-19 into severe COVID-19. But serum HFABP negative maybe make patients with mild COVID-19 safer, the current data show no effect on the all-cause mortality. TRIAL REGISTRATION: Our study has been registered with the Chinese Clinical Trial Registry, the registration number: ChiCTR2000029829.

positive: 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.

positive: Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis Background As coronavirus disease 2019 (COVID-19) pandemic rages on, there is urgent need for identification of clinical and laboratory predictors for progression towards severe and fatal forms of this illness. In this study we aimed to evaluate the discriminative ability of hematologic, biochemical and immunologic biomarkers in patients with and without the severe or fatal forms of COVID-19. Methods An electronic search in Medline (PubMed interface), Scopus, Web of Science and China National Knowledge Infrastructure (CNKI) was performed, to identify studies reporting on laboratory abnormalities in patients with COVID-19. Studies were divided into two separate cohorts for analysis: severity (severe vs. non-severe and mortality, i.e. non-survivors vs. survivors). Data was pooled into a meta-analysis to estimate weighted mean difference (WMD) with 95% confidence interval (95% CI) for each laboratory parameter. Results A total number of 21 studies was included, totaling 3377 patients and 33 laboratory parameters. While 18 studies (n = 2984) compared laboratory findings between patients with severe and non-severe COVID-19, the other three (n = 393) compared survivors and non-survivors of the disease and were thus analyzed separately. Patients with severe and fatal disease had significantly increased white blood cell (WBC) count, and decreased lymphocyte and platelet counts compared to non-severe disease and survivors. Biomarkers of inflammation, cardiac and muscle injury, liver and kidney function and coagulation measures were also significantly elevated in patients with both severe and fatal COVID-19. Interleukins 6 (IL-6) and 10 (IL-10) and serum ferritin were strong discriminators for severe disease. Conclusions Several biomarkers which may potentially aid in risk stratification models for predicting severe and fatal COVID-19 were identified. In hospitalized patients with respiratory distress, we recommend clinicians closely monitor WBC count, lymphocyte count, platelet count, IL-6 and serum ferritin as markers for potential progression to critical illness.

positive: The role of biomarkers in diagnosis of COVID-19 - A systematic review AIMS: As of the 28th April 2020, the COVID-19 pandemic has infiltrated over 200 countries and affected over three million confirmed people. We review different biomarkers to evaluate if they are able to predict clinical outcomes and correlate with the severity of COVID-19 disease. METHODS: A systematic review of the literature was carried out to identify relevant articles using six different databases. Keywords to refine the search included 'COVID-19', 'SARS-CoV2', 'Biomarkers', among others. Only studies which reported data on pre-defined outcomes were included. KEY FINDINGS: Thirty-four relevant articles were identified which reviewed the following biomarkers: C-reactive protein, serum amyloid A, interleukin-6, lactate dehydrogenase, neutrophil-to-lymphocyte ratio, D-dimer, cardiac troponin, renal biomarkers, lymphocytes and platelet count. Of these, all but two, showed significantly higher levels in patients with severe complications of COVID-19 infection compared to their non-severe counterparts. Lymphocytes and platelet count showed significantly lower levels in severe patients compared to non-severe patients. SIGNIFICANCE: Although research is still in its early stages, the discovery of how different biomarkers behave during the course of the disease could help clinicians in identifying severe disease earlier and subsequently improve prognosis. Nevertheless, we urge for more research across the globe to corroborate these findings.

positive: Clinical characteristics associated with COVID-19 severity in California Given the rapidly progressing COVID-19 pandemic, this report on a US cohort of 54 COVID-19 patients from Stanford Hospital and data regarding risk factors for severe disease obtained at initial clinical presentation is of high importance and is immediately clinically relevant. We identified low presenting oxygen saturation as predictive of severe disease outcomes, such as diagnosis of pneumonia, acute respiratory distress syndrome (ARDS), and admission to the ICU, and also replicated data from China suggesting a link between hypertension and disease severity. Clinicians will benefit by tools to rapidly risk stratify patients at presentation by likelihood of progression to severe disease.

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

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: Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients Abstract Background The dynamic changes of lymphocyte subsets and cytokines profiles of patients with novel coronavirus disease (COVID-19) and their correlation with the disease severity remain unclear. Methods Peripheral blood samples were longitudinally collected from 40 confirmed COVID-19 patients and examined for lymphocyte subsets by flow cytometry and cytokine profiles by specific immunoassays. Findings Of the 40 COVID-19 patients enrolled, 13 severe cases showed significant and sustained decreases in lymphocyte counts [0•6 (0•6-0•8)] but increases in neutrophil counts [4•7 (3•6-5•8)] than 27 mild cases [1.1 (0•8-1•4); 2•0 (1•5-2•9)]. Further analysis demonstrated significant decreases in the counts of T cells, especially CD8+ T cells, as well as increases in IL-6, IL-10, IL-2 and IFN-γ levels in the peripheral blood in the severe cases compared to those in the mild cases. T cell counts and cytokine levels in severe COVID-19 patients who survived the disease gradually recovered at later time points to levels that were comparable to those of the mild cases. Moreover, the neutrophil-to-lymphocyte ratio (NLR) (AUC=0•93) and neutrophil-to-CD8+ T cell ratio (N8R) (AUC =0•94) were identified as powerful prognostic factors affecting the prognosis for severe COVID-19. Interpretation The degree of lymphopenia and a proinflammatory cytokine storm is higher in severe COVID-19 patients than in mild cases, and is associated with the disease severity. N8R and NLR may serve as a useful prognostic factor for early identification of severe COVID-19 cases. Funding The National Natural Science Foundation of China, the National Science and Technology Major Project, the Health Commission of Hubei Province, Huazhong University of Science and Technology, and the Medical Faculty of the University Hospital Essen, Germany.

positive: Paying close attention to diabetic patients with novel coronavirus infection/ 中华内分泌代谢杂志 A major infectious disease associated with severe acute respiratory syndrome coronavirus 2 (2019-nCoV)has emerged in Wuhan, China. Current clinical studies have shown that diabetes is commonly complicated with this disorder. Hyperglycemia is a risk factor for severe infection, and also an independent risk factor for the progression of mild infection to severe infection. This may be related to the immune deficiency of diabetics. Besides, virus may cause direct damage to the islets and induce acute stress hyperglycemia. Special attention should be payed to diabetics with 2019-nCoV infection. Systemic steroid hormones should be used with particular caution in patients with 2019-nCoV infection, especially those with diabetes.

positive: Prognostic value of C-reactive protein in patients with COVID-19 BACKGROUND: Elevated serum C-reactive protein (CRP) level was observed in most patients with COVID-19. METHODS: Data of COVID-19 patients with clinical outcome in a designated hospital in Wuhan, China, were retrospectively collected and analyzed from Jan 30 to Feb 20, 2020. The prognostic value of admission CRP was evaluated in patients with COVID-19. RESULTS: Out of 298 patients enrolled, 84 died and 214 recovered. Most non-survivors tended to be males, old aged, or with chronic diseases. Compared to survivors, non-survivors showed significantly elevated white blood cell and neutrophil count, neutrophil to lymphocyte ratio (NLR), systemic immune-inflammation index (SII, defined by platelet count multiply by NLR), CRP, procalcitonin, and D-dimer, and decreased red blood cell, lymphocyte, and platelet count. Age, neutrophil count, platelet count, and CRP were identified as independent predictors of adverse outcome. The area under the receiver operating characteristic (ROC) curve (AUC) of CRP (0.896) was significantly higher than that of age (0.833), neutrophil count (0.820), and platelet count (0.678) in outcome prediction (all p<0.05). With a cut-off value of 41.4, CRP exhibited sensitivity 90.5%, specificity 77.6%, positive predictive value 61.3%, and negative predictive value 95.4%. Subgroup analysis revealed that CRP remained robust accuracy in adverse outcome prediction in patients with different disease severity (AUC 0.832, z=10.23, p<0.001; AUC 0.989, z=44.04, p<0.001). CRP was also an independent discriminator of severe/critical illness on admission (AUC 0.783, z=10.69, p<0.001). CONCLUSIONS: In patients with COVID-19, admission CRP correlated with disease severity and tended to be a good predictor of adverse outcome.

positive: Interleukin-6 as prognosticator in patients with COVID-19: IL-6 and Covid-19

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

positive: IL-6 may be a good biomarker for earlier detection of COVID-19 progression

positive: Neutrophil to lymphocyte ratio as prognostic and predictive factor in patients with coronavirus disease 2019: A retrospective cross‐sectional study This retrospective study was designed to explore whether neutrophil to lymphocyte ratio (NLR) is a prognostic factor in patients with coronavirus disease 2019 (COVID‐19). A cohort of patients with COVID‐19 admitted to the Tongren Hospital of Wuhan University from 11 January 2020 to 3 March 2020 was retrospectively analyzed. Patients with hematologic malignancy were excluded. The NLR was calculated by dividing the neutrophil count by the lymphocyte count. NLR values were measured at the time of admission. The primary outcome was all‐cause in‐hospital mortality. A multivariate logistic analysis was performed. A total of 1004 patients with COVID‐19 were included in this study. The mortality rate was 4.0% (40 cases). The median age of nonsurvivors (68 years) was significantly older than survivors (62 years). Male sex was more predominant in nonsurvival group (27; 67.5%) than in the survival group (466; 48.3%). NLR value of nonsurvival group (median: 49.06; interquartile range [IQR]: 25.71‐69.70) was higher than that of survival group (median: 4.11; IQR: 2.44‐8.12; P < .001). In multivariate logistic regression analysis, after adjusting for confounding factors, NLR more than 11.75 was significantly correlated with all‐cause in‐hospital mortality (odds ratio = 44.351; 95% confidence interval = 4.627‐425.088). These results suggest that the NLR at hospital admission is associated with in‐hospital mortality among patients with COVID‐19. Therefore, the NLR appears to be a significant prognostic biomarker of outcomes in critically ill patients with COVID‐19. However, further investigation is needed to validate this relationship with data collected prospectively.

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

positive: Association between D-Dimer levels and mortality in patients with coronavirus disease 2019 (COVID-19): a systematic review and pooled analysis Abstract Background: Several observational studies have reported elevated baseline D-dimer levels in patients hospitalized for moderate to severe coronavirus disease 2019 (COVID-19). These elevated baseline D-dimer levels have been associated with disease severity and mortality in retrospective cohorts. Objectives: To review current available data on the association between D-Dimer levels and mortality in patients admitted to hospital for COVID-19. Methods: We performed a systematic review of published studies using MEDLINE and EMBASE through 13 April 2020. Two authors independently screened all records and extracted the outcomes. A random effects model was used to estimate the standardized mean difference (SMD) with 95% confidence intervals (CI). Results: Six original studies enrolling 1355 hospitalized patients with moderate to critical COVID-19 (391 in the non-survivor group and 964 in the survivor group) were considered for the final pooled analysis. When pooling together the results of these studies, D-Dimer levels were found to be higher in non-survivors than in-survivors. The SMD in D-Dimer levels between non-survivors and survivors was 3.59 µg/L (95% CI 2.79–4.40 µg/L), and the Z-score for overall effect was 8.74 (p < 0.00001), with a high heterogeneity across studies (I²=95%). Conclusions: Despite high heterogeneity across included studies, the present pooled analysis indicates that D-Dimer levels are significantly associated with the risk of mortality in COVID-19 patients. Early integration of D-Dimer testing, which is a rapid, inexpensive, and easily accessible biological test, can be useful to better risk stratification and management of COVID-19 patients.

positive: Epidemiological characteristics and clinical features of 32 critical and 67 noncritical cases of COVID-19 in Chengdu Abstract Background In December 2019, Wuhan, China, experienced an outbreak of coronavirus (COVID-19). The number of cases has increased rapidly, but information on the clinical characteristics remains limited. Objectives This paper describes the epidemiological and clinical characteristics of COVID-19. Early detection and identification of critically ill patients is necessary to facilitate scientific classification and treatment. Study design This study included a retrospective, single-center case series of 99 consecutively hospitalized patients with confirmed COVID-19 at Chengdu Public Health Clinical Medical Center in Chengdu, China, from January 16 to February 20, 2020. The final date of follow-up was February 23, 2020. We collected and analyzed epidemiological, demographic, clinical, laboratory, radiological, and treatment data. We compared outcomes of critically ill patients and noncritically ill patients. Results Of the 99 hospitalized patients with COVID-19, the median age was 49 years (minimum, 3 months; maximum, 87 years) and 51 (52 %) were men; 42 (42 %) had traveled to or lived in Wuhan and 48 (49 %) had come into close contact with patients with new coronavirus pneumonia; 41 (41 %) patients had underlying disease. Common symptoms included fever (85 [86 %]), dry cough (84 [85 %]), and fatigue (72 [73 %]). We analyzed the clinical characteristics of patients. We expressed the measurement data as mean ± standard deviation. We collected data for age (49.39 ± 18.45 years), number of hospital days (12.32 ± 6.70 days), and laboratory indicators. We compared critically ill and noncritically ill patients: p-values for age, C-reactive protein, high-sensitivity troponin T, prothrombin time, fibrin degradation products, D-Dimer, and CD4+ count were p < 0.001; and p-values for hospital days, white blood cell, neutrophil, lymphocyte, creatine kinase isoenzyme, myoglobin, N-terminal brain natriuretic peptide, and CD8+ count were p < 0.05. Conclusions We collected data from a single-center case series of 32 hospitalized patients who were critically ill with confirmed COVID-19 in Chengdu, China, and compared data with 67 noncritically ill patients. Elderly patients had chronic underlying diseases, notably cardiovascular disease. Higher C-reactive protein levels, higher levels of myocardial damage, and higher brain natriuretic peptide levels; lower white blood cells, neutrophils, and lymphocytes; and lower CD4 and CD8 counts could be used for early detection and identification of critically ill patients, and dynamic Data observation was more important than at a single moment.

positive: Predictive factors for disease progression in hospitalized patients with Coronavirus Disease 2019 in Wuhan, China Abstract Background A few studies have revealed the clinical characteristics of hospitalized patients with COVID-19. However, predictive factors for the outcomes remain unclear. Objective Attempted to determine the predictive factors for the poor outcomes of patients with COVID-19. Study design This is a single-center, retrospective study. Clinical, laboratory, and treatment data were collected and analyzed from 111 hospitalized patients with laboratory-confirmed COVID-19 in Union Hospital. The gathered data of discharged and deteriorated patients were compared. Results Among these 111 patients, 93 patients were discharged and 18 patients were deteriorated. The lymphocyte count (0.56 G/L [0.47-0.63] vs 1.30 G/L [0.95-1.65]) was lower in the deteriorated group than those in the discharged group. The numbers of pulmonary lobe involved (5.00 [5.00–5.00] vs 4.00 [2.00-5.00]), serum C‐reactive protein (CRP, 79.52 mg/L [61.25-102.98] vs 7.93 mg/L [3.14-22.50]), IL-6 (35.72 pg/ml [9.24-85.19] vs 5.09 pg/ml [3.16-9.72]), and IL-10 (5.35 pg/ml [4.48-7.84] vs 3.97 pg/ml [3.34-4.79]) concentrations in deteriorated patients were elevated compared with discharged patients. Multivariate logistic regression analysis showed that male gender (OR, 24.8 [1.8-342.1]), comorbidity (OR, 52.6 [3.6-776.4]), lymphopenia (OR, 17.3 [1.1-261.8]), and elevated CRP (OR, 96.5 [4.6-2017.6]) were the independent risk factors for the poor prognosis in COVID-19 patients. Conclusions This finding would facilitate the early identification of high-risk COVID-19 patients.

positive: A score-based risk model for predicting severe COVID-19 infection as a key component of lockdown exit strategy Background: As many countries consider and employ various lockdown exit strategies, health authorities seek tools to provide differential targeted advice for social distancing based on personal risk for severe COVID-19. However, striking a balance between a scientifically precise multivariable risk prediction model, and a model which can easily be used by the general public, remains a challenge. A list of risk criteria, as defined by the CDC for example, provides a simple solution, but may be too inclusive by classifying a substantial portion of the population at high risk. Score-based risk classification tools may provide a good compromise between accuracy and simplicity. Objective: To create a score-based risk classification tool for severe COVID-19. Methods: The outcome was defined as a composite of being labeled severe during hospitalization or dying due to COVID-19. The risk classification tool was developed using retrospective data from all COVID-19 patients that were diagnosed until April 1st, 2020 in a large healthcare organization ("training set"). The developed tool combines 10 risk factors using simple summation, and defines three risk levels according to the patient's age and number of accumulated risk points - basic risk, high risk and very-high risk (the last two levels are also considered together as the elevated risk group). The tool's performance in accurately identifying individuals at risk was evaluated using a "temporal test set" of COVID-19 patients diagnosed between April 2nd and April 22nd, 2020, later than those used for model development. The tool's performance was also compared to that of the CDC's criteria. The healthcare organization's general population was used to evaluate the proportion of patients that would be classified to each of the model's risk levels and as elevated risk by the CDC criteria. Results: A total of 2,421, 2,624 and 4,631,168 individuals were included in the training, test, and general population cohorts, respectively. The outcome rate in the training and test sets was 5%. Overall, 18% of the general population would be classified at elevated risk by the model, with a resulting sensitivity of 92%, compared to 35% that would be defined as elevated risk by the CDC criteria, with a resulting sensitivity of 96%. Within the model's elevated risk groups, the high and very-high risk groups comprised 15% and 3% of the general population, with an incidence rate (PPV) of 15% and 33%, respectively. Discussion: A simple to communicate score-based risk classification tool classifies at elevated risk about half of the population that is considered to have an elevated risk by the CDC risk criteria, with only a 4% reduction in sensitivity. The model's ability to further divide the elevated risk population into two markedly different subgroups allows providing more refined recommendations to the general public and limiting the restrictions of social distancing to a smaller and more manageable subset of the population. This model was adopted by the Israeli ministry of health as its risk classification tool for COVID-19 lab tests prioritization and for targeting its instructions on risk management during the lockdown exit strategy.

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

positive: [Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV] Objective: To explore the clinical characteristics and prognosis of the new coronavirus 2019-nCoV patients combined with cardiovascular disease (CVD). Methods: A retrospective analysis was performed on 112 COVID-19 patients with CVD admitted to the western district of Union Hospital in Wuhan, from January 20, 2020 to February 15, 2020. They were divided into critical group (ICU, n=16) and general group (n=96) according to the severity of the disease and patients were followed up to the clinical endpoint. The observation indicators included total blood count, C-reactive protein (CRP), arterial blood gas analysis, myocardial injury markers, coagulation function, liver and kidney function, electrolyte, procalcitonin (PCT), B-type natriuretic peptide (BNP), blood lipid, pulmonary CT and pathogen detection. Results: Compared with the general group, the lymphocyte count (0.74×10(9) (0.34×10(9), 0.94×10(9))/L vs. 0.99×10(9) (0.71×10(9), 1.29×10(9))/L, P=0.03) was extremely lower in the critical group, CRP (106.98 (81.57, 135.76) mg/L vs. 34.34 (9.55,76.54) mg/L, P<0.001) and PCT (0.20 (0.15,0.48) µg/L vs. 0.11 (0.06,0.20)µg/L, P<0.001) were significantly higher in the critical group. The BMI of the critical group was significantly higher than that of the general group (25.5 (23.0, 27.5) kg/m(2) vs. 22.0 (20.0, 24.0) kg/m(2), P=0.003). Patients were further divided into non-survivor group (17, 15.18%) group and survivor group (95, 84.82%). Among the non-survivors, there were 88.24% (15/17) patients with BMI> 25 kg/m(2), which was significantly higher than that of survivors (18.95% (18/95), P<0.001). Compared with the survived patients, oxygenation index (130 (102, 415) vs. 434 (410, 444), P<0.001) was significantly lower and lactic acid (1.70 (1.30, 3.00) mmol/L vs. 1.20 (1.10, 1.60) mmol/L, P<0.001) was significantly higher in the non-survivors. There was no significant difference in the proportion of ACEI/ARB medication between the critical group and the general group or between non-survivors and survivors (all P>0.05). Conclusion: COVID-19 patients combined with CVD are associated with a higher risk of mortality. Critical patients are characterized with lower lymphocyte counts. Higher BMI are more often seen in critical patients and non-survivor. ACEI/ARB use does not affect the morbidity and mortality of COVID-19 combined with CVD. Aggravating causes of death include fulminant inflammation, lactic acid accumulation and thrombotic events.

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

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

positive: Expressions of multiple inflammation markers in the patients with 2019 novel coronavirus pneumonia and their clinical values/ 中华检验医学杂志 Objective@#To explore the Expressions of multiple inflammation markers in the patients with 2019 novel coronavirus pneumonia (COVID-19) and their clinical values, and to provide theoretical basis for clinical diagnosis and treatment.@*Methods@#A total of 164 patients, diagnosed with COVID-19 and admitted to Guangzhou Eighth People's Hospital from January to February 2020, were selected as the research group and divided into three groups (ordinary, severe, and critically severe pneumonia) according to the disease severity. Meandwhile 66 non-infected patients during the same period were selected as negative control group. The expressions of WBC, LYM, CRP, SAA, and PCT were retrospective studied and compared between groups. The diagnostic values of WBC, CRP, SAA and the combination of these three markers in all patients with COVID-19 and in different severity groups were analyzed by ROC curve.@*Results@#Compared with control group (WBC count :8.13(6.51,9.42)×109/L, LYM count:2.00(1.28,2.43)×109/L), WBC count [4.94(4.05, 6.67) ×109/L] and LYM count [1.33(0.94, 1.96) ×109/L] of COVID-19 patients were significantly reduced (Z=-7.435, P<0.01; Z=-4.906, P<0.01) . Compared with the control group [CRP: 1.36 (0.57~5.67) mg/ml; SAA:[4.98 (4.80~15.75) mg/mL], CRP [7.93 (2.45~23.98) mg/ml] and SAA [34.13 (4.83~198.40) mg/ml] were increased in research group (Z=-5.72, P<0.01; Z=-4.166, P<0.01) . PCT in the control group and the research group were 0.100 0(0.030 6~0.100 0)ng/ml and 0.044 5(0.031 6~0.077 0)ng/ml, respectively. There was no statistical difference between two groups (Z=-1.451, P=0.147) . The areas under the ROC curve (AUC) of WBC, CRP and SAA in patients with COVID-19 were 0.814, 0.742, 0.673, respectively (P<0.01), while the AUC of the combination of three indexes for COVID-19 diagnosis was 0.882, with 83.33%(55/66) specificity and 84.76% (139/164) sensitivity, P<0.01.The AUCs of WBC, CRP, and SAA for predicting severe and critically severe COVID-19 were 0.799, 0.779, and 0.886 , respectively (P<0.01), and the AUC of the combination of three indexes for the diagnosis of severe and critically severe COVID-19 was 0.924, with 78.67% (118/150) specificity and 14/14 sensitivity (P<0.01).@*Conclusion@#Combining detection of WBC, CRP and SAA can improve the specificity and sensitivity of COVID-19 diagnosis, with a high diagnostic value for severe and critically severe COVID-19.

positive: Predicting the receptor-binding domain usage of the coronavirus based on kmer frequency on spike protein

positive: The Novel Coronavirus: A Bird's Eye View The novel coronavirus (2019-nCoV) outbreak, which initially began in China, has spread to many countries around the globe, with the number of confirmed cases increasing every day. With a death toll exceeding that of the SARS-CoV outbreak back in 2002 and 2003 in China, 2019-nCoV has led to a public health emergency of international concern, putting all health organizations on high alert. Herein, we present on an overview of the currently available information on the pathogenesis, epidemiology, clinical presentation, diagnosis, and treatment of this virus.

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

positive: Plasma CRP level is positively associated with the severity of COVID-19 AIMS: The coronavirus disease 2019 (COVID-19) is characterized as highly contagious and deadly; however there is no credible and convenient biomarker to predict the severity of the disease. The aim of the present study was to estimate whether the CRP level is able to act as a marker in indicating the severity of COVID-19. METHODS: Patients who complained cough or chest pain with or without fever were enrolled after laboratory confirmed of SARS-CoV-2 viral nucleic acid via qRT-PCR. Chest computed tomography (CT) was then performed to classify the patients into mild, moderate and severe pneumonia groups according to the interim management guideline. Then linear regression models were applied to analyze the association between c-reactive protein (CRP) levels and severity of COVID-19 pneumonia. RESULTS: When compared to mild pneumonia, the adjusted-Odds Ratio were 11.46, p = 0.029 and 23.40, p = 0.025 in moderate and severe pneumonia, respectively. The area under receiver operation curve was 0.898 (95% CI 0.835, 0.962, p < 0.001). Higher plasma CRP level indicated severe COVID-19 pneumonia and longer inpatients duration. CONCLUSIONS: The level of plasma CRP was positively correlated to the severity of COVID-19 pneumonia. Our findings could assist to discern patients of moderate to severe COVID-19 pneumonia from the mild ones. Our findings may be useful as an earlier indicator for severe illness and help physicians to stratify patients for intense care unit transfer.

positive: Acute myocardial injury in patients hospitalized with COVID-19 infection: A review The Coronavirus Disease 2019 (COVID-19) is now a global pandemic with millions affected and millions more at risk for contracting the infection. The COVID-19 virus, SARS-CoV-2, affects multiple organ systems particularly the lungs and heart. Elevation of cardiac biomarkers, particularly high-sensitivity troponin and/or creatine kinase MB, is common in patients with COVID-19 infection. In our review of clinical studies, we found that in 26 studies including 11,685 patients, the weighted pooled prevalence of acute myocardial injury was 20% (ranged from 5% to 38% depending on the criteria used). The plausible mechanisms of myocardial injury include, 1) hyperinflammation and cytokine storm mediated through pathologic T-cells and monocytes leading to myocarditis, 2) respiratory failure and hypoxemia resulting in damage to cardiac myocytes, 3) down regulation of ACE2 expression and subsequent protective signaling pathways in cardiac myocytes, 4) hypercoagulability and development of coronary microvascular thrombosis, 5) diffuse endothelial injury and ‘endotheliitis’ in several organs including heart, and, 6) inflammation and/or stress causing coronary plaque rupture or supply-demand mismatch leading to myocardial ischemia/infarction. Cardiac biomarkers can be used to aid in diagnosis as well as risk stratification. In patients with elevated hs-troponin, clinical context is important and myocarditis as well as stress induced cardiomyopathy should be considered in the differential, along with type I and type II myocardial infarction. Irrespective of etiology, patients with acute myocardial injury should be prioritized for treatment. Clinical decisions including interventions should be individualized and carefully tailored after thorough review of risks/benefits. Given the complex interplay of SARS-CoV-2 with the cardiovascular system, further investigation into potential mechanisms is needed to guide effective therapies. Randomized trials are urgently needed to investigate treatment modalities to reduce the incidence and mortality associated with COVID-19 related acute myocardial injury.

positive: Characteristics and prognostic factors of disease severity in patients with COVID-19: The Beijing experience Abstract COVID-19 has become one of the worst infectious disease outbreaks of recent times, with over 2.1 million cases and 120,000 deaths so far. Our study investigated the demographic, clinical, laboratory and imaging features of 63 patients with COVID-19 in Beijing. Patients were classified into four groups, mild, moderate, severe and critically ill. The mean age of our patients was 47 years of age (range 3–85) and there was a slight male predominance (58.7%). Thirty percent of our patients had severe or critically ill disease, but only 20% of severe and 33% of critically ill patients had been to Wuhan. Fever was the most common presentation (84.1%), but cough was present in only slightly over half of the patients. We found that lymphocyte and eosinophils count were significantly decreased in patients with severe disease (p = 0.001 and p = 0.000, respectively). Eosinopenia was a feature of higher levels of severity. Peripheral CD4+, CD8+ T lymphocytes, and B lymphocytes were significantly decreased in severe and critically ill patients, but there was only a non-statistically significant downward trend in NK cell numbers with severity. Of note is that liver function test including AST, ALT, GGT and LDH were elevated, and albumin was decreased. The inflammatory markers CRP, ESR and ferritin were elevated in patients with severe disease or worse. IL-6 levels were also higher, indicating that the presence of a hyperimmune inflammatory state portends higher morbidity and mortality. In a binary logistic regression model, C-reactive protein level (OR 1.073, [CI, 1.013–1.136]; p = 0.017), CD8 T lymphocyte counts (OR 0.989, [CI, 0.979–1.000]; p = 0.043), and D-dimer (OR 5.313, [CI, 0.325–86.816]; p = 0.241) were independent predictors of disease severity.

positive: Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. BACKGROUND A relatively high mortality of severe coronavirus disease 2019 (COVID-19) is worrying, the application of heparin in COVID-19 has been recommended by some expert consensus due to the risk of disseminated intravascular coagulation and venous thromboembolism. However, its efficacy remains to be validated. METHODS Coagulation results, medications and outcomes of consecutive patients being classified as severe COVID-19 in Tongji hospital were retrospectively analysed. The 28-day mortality between heparin users and nonusers were compared, also in different risk of coagulopaphy which was stratified by the sepsis-induced coagulopathy (SIC) score or D-dimer result. RESULTS There were 449 patients with severe COVID-19 enrolled into the study, 99 of them received heparin (mainly with low molecular weight heparin, LMWH) for 7 days or longer. The D-dimer, prothrombin time and age were positively, and platelet count was negatively, correlated with 28-day mortality in multivariate analysis. No difference on 28-day mortality was found between heparin users and nonusers (30.3% vs 29.7%, P=0.910). But the 28-day mortality of heparin users were lower than nonusers In patients with SIC score ≥4 (40.0% vs 64.2%, P=0.029), or D-dimer > 6 fold of upper limit of normal (32.8% vs 52.4%, P=0.017). CONCLUSIONS Anticoagulant therapy mainly with LMWH appears to be associated with better prognosis in severe COVID-19 patients meeting SIC criteria or with markedly elevated D-dimer.

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

positive: Predictive factors of severe coronavirus disease 2019 in previously healthy young adults: a single-center, retrospective study BACKGROUND: Several previously healthy young adults have developed Coronavirus Disease 2019 (COVID-19), and a few of them progressed to the severe stage. However, the factors are not yet determined. METHOD: We retrospectively analyzed 123 previously healthy young adults diagnosed with COVID-19 from January to March 2020 in a tertiary hospital in Wuhan. Patients were classified as having mild or severe COVID-19 based on their respiratory rate, SpO(2), and PaO(2)/FiO(2) levels. Patients’ symptoms, computer tomography (CT) images, preadmission drugs received, and the serum biochemical examination on admission were compared between the mild and severe groups. Significant variables were enrolled into logistic regression model to predict the factors affecting disease severity. A receiver operating characteristic (ROC) curve was applied to validate the predictive value of predictors. RESULT: Age; temperature; anorexia; and white blood cell count, neutrophil percentage, platelet count, lymphocyte count, C-reactive protein, aspartate transaminase, creatine kinase, albumin, and fibrinogen values were significantly different between patients with mild and severe COVID-19 (P < 0.05). Logistic regression analysis confirmed that lymphopenia (P = 0.010) indicated severe prognosis in previously healthy young adults with COVID-19, with the area under the curve (AUC) was 0.791(95% Confidence Interval (CI) 0.704–0.877)(P < 0.001). CONCLUSION: For previously healthy young adults with COVID-19, lymphopenia on admission can predict severe prognosis.

positive: Profiling COVID-19 pneumonia progressing into the cytokine storm syndrome: results from a single Italian Centre study on tocilizumab versus standard of care. Background Approximately 5% of patients with coronavirus disease 2019 (COVID-19) develop a life-threatening pneumonia that often occurs in the setting of increased inflammation or "cytokine storm". Anti-cytokine treatments are being evaluated but optimal patient selection remains unclear. Methods Between February 29 to April 6, 2020, 111 consecutive hospitalized patients with COVID-19 pneumonia were evaluated in a single centre retrospective study. Patients were divided in two groups: 42 severe cases (TOCI) with adverse prognostic features including raised CRP and IL-6 levels, who underwent anti-cytokine treatments, mostly tocilizumab, and 69 standard of care patients (SOC). Findings In the TOCI group, all received anti-viral therapy and 40% also received glucocorticoids. In TOCI, 62% of cases were ventilated and there were 3 deaths (17.8+/-10.6 days, mean follow up) with 7/26 cases remaining on ventilators, without improvement, and 17/26 developed bacterial superinfection. One fatality occurred in the 15 TOCI cases treated on noninvasive ventilation and 1 serious bacterial superinfection. Of the 69 cases in SOC, there was no fatalities and no bacterial complications. The TOCI group had higher baseline CRP and IL-6 elevations (p<0.0001 for both) and higher neutrophils and lower lymphocyte levels (p= 0.04 and p=0.001, respectively) with the TOCI ventilated patients having higher markers than non-ventilated TOCI patients. Interpretation Higher inflammatory markers, more superimposed infections and worse outcomes characterized ventilated TOCI cases compared to ward based TOCI therapy. Despite the confounding factors, this study suggests that therapy time in anti-cytokine randomized clinical trials will be key.

positive: Leucocyte Subsets Effectively Predict the Clinical Outcome of Patients With COVID-19 Pneumonia: A Retrospective Case-Control Study Background: The clinical characteristics of coronavirus disease 2019 (COVID-19) have been well-studied, while effective predictors for clinical outcome and research on underlying mechanisms are scarce. Methods: Hospitalized COVID-19 pneumonia patients with definitive clinical outcome (cured or died) were retrospectively studied. The diagnostic performance of the leucocyte subsets and other parameters were compared using the area under the receiver operating characteristic curve (AUC). Further, the correlations between leucocyte subsets and inflammation-related factors associated with clinical outcome were subsequently investigated. Results: Among 95 subjects included, 56 patients were cured, and 39 died. Older age, elevated aspartate aminotransferase, total bilirubin, serum lactate dehydrogenase, blood urea nitrogen, prothrombin time, D-dimer, Procalcitonin, and C-reactive protein levels, decreased albumin, elevated serum cytokines (IL2R, IL6, IL8, IL10, and TNF-α) levels, and a decreased lymphocyte count indicated poor outcome in patients with COVID-19 pneumonia. Lymphocyte subset (lymphocytes, T cells, helper T cells, suppressor T cells, natural killer cells, T cells+B cells+NK cells) counts were positively associated with clinical outcome (AUC: 0.777; AUC: 0.925; AUC: 0.900; AUC: 0.902; AUC: 0.877; AUC: 0.918, resp.). The neutrophil-to-lymphocyte ratio (NLR), neutrophil to T lymphocyte count ratio (NTR), neutrophil percentage to T lymphocyte ratio (NpTR) effectively predicted mortality (AUC: 0.900; AUC: 0.905; AUC: 0.932, resp.). Binary logistic regression showed that NpTR was an independent prognostic factor for mortality. Serum IL6 levels were positively correlated with leucocyte count, neutrophil count, and eosinophil count and negatively correlated with lymphocyte count. Conclusion: These results indicate that leucocyte subsets predict the clinical outcome of patients with COVID-19 pneumonia with high efficiency. Non-self-limiting inflammatory response is involved in the development of fatal pneumonia.

positive: Neutrophil-to-lymphocyte ratio and clinical outcome in COVID-19: a report from the Italian front line. • Clinicians are looking for a reliable prognostic marker for patients with COVID-19; • In our cohort, clinical improvement was predicted by younger age and a NLR below 3; • Transfer to ICU was instead predicted by a NLR over 4 (p=0.046); • NLR is a fast, widely available and relatively inexpensive assessment; • NLR may be a useful tool in the early screening of patients with COVID-19.

positive: A comprehensive appraisal of laboratory biochemistry tests as major predictors of COVID-19 severity. Context: A relevant portion of COVID-19 patients develop severe disease with negative outcomes. Several biomarkers have been proposed to predict COVID-19 severity, but no definite interpretative criteria have been established to date for stratifying risk. Objective: To evaluate six serum biomarkers (C-reactive protein, lactate dehydrogenase, D-dimer, albumin, ferritin and cardiac troponin T) for predicting COVID-19 severity and to define related cut-offs able to aid clinicians in risk stratification of hospitalized patients. Design: A retrospective study of 427 COVID-19 patients was performed. Patients were divided into groups based on their clinical outcome: non-survivors vs. survivors and patients admitted to intensive care unit vs. others. ROC curves and likelihood ratios were employed to define predictive cut-offs for evaluated markers. Results: Marker concentrations at peak were significantly different between groups for both selected outcomes. At univariate logistic regression analysis, all parameters were significantly associated with higher odds of death and intensive care. At the multivariate analysis, high concentrations of lactate dehydrogenase and low concentrations of albumin in serum remained significantly associated with higher odds of death, while only low lactate dehydrogenase activities remained associated with lower odds of intensive care admission. The best cut-offs for death prediction were >731 U/L for lactate dehydrogenase and ≤18 g/L for albumin, while a lactate dehydrogenase activity <425 U/L was associated with a negative likelihood ratio of 0.10 for intensive treatment. Conclusions: Our study identifies which biochemistry tests represent major predictors of COVID-19 severity and defines the best cut-offs for their use.

positive: A descriptive study of the impact of diseases control and prevention on the epidemics dynamics and clinical features of SARS-CoV-2 outbreak in Shanghai, lessons learned for metropolis epidemics prevention Objective: To describe and evaluate the impact of diseases control and prevention on epidemics dynamics and clinical features of SARS-CoV-2 outbreak in Shanghai. Design: A retrospective descriptive study Setting: China Participants: Epidemiology information was collected from publicly accessible database. 265 patients admitted to Shanghai Public Health Center with confirmed COVID-19 were enrolled for clinical features analysis. Main outcome measure: Prevention and control measures taken by Shanghai government, epidemiological, demographic, clinical, laboratory and radiology data were collected. Weibull distribution, Chi-square test, Fisher's exact test, t test or Mann-Whitney U test were used in statistical analysis. Results: COVID-19 transmission rate within Shanghai had reduced over 99% than previous speculated, and the exponential growth has been stopped so far. Epidemic was characterized by the first stage mainly composed of imported cases and the second stage where >50% of cases were local. The incubation period was 6.4 (95% CI 5.3 to 7.6) days and the mean onset-admission interval was 5.5 days (95% CI, 5.1 to 5.9). Median time for COVID-19 progressed to severe diseases were 8.5 days (IQR: 4.8-11.0 days). By February 11th, proportion of patients being mild, moderate, severe and critically ill were 1.9%(5/265), 89.8%(238/265), 3.8%(10/265), 4.5%(12/265), respectively; 47 people in our cohort were discharged, and 1 patient died. Conclusion: Strict controlling of the transmission rate at the early stage of an epidemic in metropolis can quickly prohibit the spread of the diseases. Controlling local clusters is the key to prevent outbreaks from imported cases. Most COVID-19 severe cases progressed within 14 days of disease onset. Multiple systemic laboratory abnormalities had been observed before significant respiratory dysfunction. Keyword: COVID-19, SARS-CoV-2, epidemics dynamics, diseases control, clinical features

positive: Predictive factors of poor outcomes in the COVID-19 epidemic: Consider the inflammatory response

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: Prediction of the severity of Corona Virus Disease 2019 and its adverse clinical outcomes. This study aims to investigate blood and biochemical laboratory findings in patients with severe Corona Virus Disease 2019 (COVID-19) and to develop a joint predictor for predicting the likelihood of severe COVID-19 and its adverse clinical outcomes, to provide more information for treatment. We collected the data of 88 patients with laboratory-confirmed COVID-19. Then patients were divided into a non-severe group and a critical group (including critically ill cases). Univariate analysis showed that the absolute lymphocyte count, albumin level, albumin/globulin (A/G) ratio, lactate dehydrogenase (LDH) level, interleukin-6 (IL-6) level, erythrocyte count, globulin level, blood glucose level, and age were significantly correlated with the severity of COVID-19. The multivariate binary logistic regression model revealed that Age, absolute lymphocyte count, and IL-6 level were independent risk factors in patients with COVID-19. The receiver operating characteristic (ROC) curve revealed that the combination of IL-6 level, absolute lymphocyte count and age is superior to a single factor as predictors for predicting severe COVID-19, regardless of whether it is the area under curve (AUC) or the prediction sensitivity and specificity. Early application is beneficial to early identification of critically ill patients and timing individual treatments to reduce mortality.

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: COVID-19 and the Heart Infection with the severe acute respiratory syndrome novel coronavirus produces a clinical syndrome known as 2019 novel coronavirus disease (COVID-19). When severe, COVID-19 is a systemic illness characterized by hyperinflammation, cytokine storm, and elevations of cardiac injury biomarkers. Here, we review what is known about the pathophysiology of COVID-19, its cardiovascular manifestations, and emerging therapeutic prospects. In this rapidly moving field, this review was comprehensive as of April 3, 2020.

positive: Incidence and risk factors of kidney impairment on patients with COVID-19: a systematic review and meta-analysis Background: The novel coronavirus is pandemic around the world. Several researchers have given the evidence of impacts of COVID-19 on the respiratory, cardiovascular and gastrointestinal system. Studies still have debated on kidney injury of COVID-19 patients. The purpose of the meta-analysis was to evaluate the association of kidney impairment with the development of COVID-19. Methods: The PubMed, Embase and MedRxiv databases were searched until April 1, 2020. We extracted data from eligible studies to summarize the clinical manifestations and laboratory indexes of kidney injury on COVID-19 infection patients and further compared the prevalence of acute kidney injury (AKI) and the mean differences of three biomarkers between in ICU/severe and non-ICU/non-severe cases. Heterogeneity was evaluated using the I2 method. Results: In the sum of 19 studies with 4375 patients were included in this analysis. The pooled prevalence of AKI, increased serum creatinine (Scr), increased blood urea nitrogen (BUN), increased D-dimer, proteinuria and hematuria in patients with COVID-19 were 7.7%, 6.6%, 6.2%, 49.8%, 42% and 30.3% respectively. Moreover, the means of Scr, BUN and D-dimer were shown 6-folds, 1.8-folds and 0.68-folds, respectively, higher in ICU/severe cases than in corresponding non-ICU/non-severe patients. The prevalence of AKI was about 17 folds higher in ICU/severe patients compared with the non-ICU/non-severe cases. Conclusions: Overall, we assessed the incidences of the clinic and laboratory features of kidney injury in COVID-19 patients. And kidney dysfunction may be a risk factor for COVID-19 patients developing into the severe condition. In reverse, COVID-19 can also cause damage to the kidney.

positive: Neutrophil to CD4+ lymphocyte ratio as a potential biomarker in predicting virus negative conversion time in COVID-19 BACKGROUND: Since December 2019, novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19) occurred in Wuhan, and rapidly spread throughout China. Our study aimed to evaluate the robustness of neutrophil to CD4+ lymphocyte ratio (NCD4LR) in predicting the negative conversion time (NCT) of SARS-CoV-2 in COVID-19 patients. METHODS: Univariate and multivariate analysis were conducted to evaluate the independency of NCD4LR in predicting NCT. Receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) were used to assess the diagnostic accuracy. RESULTS: Compared with low NCD4LR patients, patients with high NCD4LR had an older age; higher incidence of fever, fatigue, chest distress/breath shortness, severer disease assessment on admission; higher levels of inflammatory indicators; low levels of lymphocyte subsets, and a longer NCT. Multivariate analysis also identified NCD4LR as an independent risk factor for delayed NCT. ROC analysis showed that NCD4LR had a better performance than neutrophil to lymphocyte ratio in predicting the virus negative conversion within 2 weeks (AUC = 0.772), 3 weeks (AUC = 0.710), 4 weeks (AUC = 0.728), or 5 weeks (AUC = 0.815). CONCLUSION: This study suggests that NCD4LR is a potential and useful biomarker for predicting the virus negative conversion time in COVID-19 patients. Furthermore, due to the NCDLR value is easily calculated, it can be widely used as a clinical biomarker for disease progression and clinical outcomes in COVID-19 patients.

positive: Development and validation of an early warning score (EWAS) for predicting clinical deterioration in patients with coronavirus disease 2019 Background: Since the pandemic outbreak of coronavirus disease 2019 (COVID-19), the health system capacity in highly endemic areas has been overwhelmed. Approaches to efficient management are urgently needed. We aimed to develop and validate a score for early prediction of clinical deterioration of COVID-19 patients. Methods: In this retrospective multicenter cohort study, we included 1138 mild to moderate COVID-19 patients admitted to 33 hospitals in Guangdong Province from December 27, 2019 to March 4, 2020 (N =818; training cohort), as well as two hospitals in Hubei Province from January 21 to February 22, 2020 (N =320; validation cohort) in the analysis. Results: The 14-day cumulative incidences of clinical deterioration were 7.9% and 12.1% in the training and validation cohorts, respectively. An Early WArning Score (EWAS) (ranging from 0 to 4.5), comprising of age, underlying chronic disease, neutrophil to lymphocyte ratio, C-reactive protein, and D-dimer levels, was developed (AUROC: 0.857). By applying the EWAS, patients were categorized into low-, medium-, and high risk groups (cut-off values: two and three). The 14-day cumulative incidence of clinical deterioration in the low-risk group was 1.8%, which was significantly lower than the incidence rates in the medium- (14.4%) and high-risk (40.9%) groups (P <.001). The predictability of EWAS was similar in the validation cohort (AUROC =0.781), patients in the low-, medium-, and high-risk groups had 14-day cumulative incidences of 2.6%, 10.0%, and 25.7%, respectively (P <.001). Conclusion: The EWAS, which is based on five common parameters, can predict COVID-19-related clinical deterioration and may be a useful tool for a rapid triage and establishing a COVID-19 hierarchical management system that will greatly focus clinical management and medical resources to reduce mortality in highly endemic areas.

positive: Predictive factors for disease progression in hospitalized patients with coronavirus disease 2019 in Wuhan, China BACKGROUND: A few studies have revealed the clinical characteristics of hospitalized patients with COVID-19. However, predictive factors for the outcomes remain unclear. OBJECTIVE: Attempted to determine the predictive factors for the poor outcomes of patients with COVID-19. STUDY DESIGN: This is a single-center, retrospective study. Clinical, laboratory, and treatment data were collected and analyzed from 111 hospitalized patients with laboratory-confirmed COVID-19 in Union Hospital. The gathered data of discharged and deteriorated patients were compared. RESULTS: Among these 111 patients, 93 patients were discharged and 18 patients were deteriorated. The lymphocyte count (0.56 G/L [0.47-0.63] vs 1.30 G/L [0.95-1.65]) was lower in the deteriorated group than those in the discharged group. The numbers of pulmonary lobe involved (5.00 [5.00-5.00] vs 4.00 [2.00-5.00]), serum C-reactive protein (CRP, 79.52 mg/L [61.25-102.98] vs 7.93 mg/L [3.14-22.50]), IL-6 (35.72 pg/mL [9.24-85.19] vs 5.09 pg/mL [3.16-9.72]), and IL-10 (5.35 pg/mL [4.48-7.84] vs 3.97 pg/mL [3.34-4.79]) concentrations in deteriorated patients were elevated compared with discharged patients. Multivariate logistic regression analysis showed that male gender (OR, 24.8 [1.8-342.1]), comorbidity (OR, 52.6 [3.6-776.4]), lymphopenia (OR, 17.3 [1.1-261.8]), and elevated CRP (OR, 96.5 [4.6-2017.6]) were the independent risk factors for the poor prognosis in COVID-19 patients. CONCLUSIONS: This finding would facilitate the early identification of high-risk COVID-19 patients.

positive: The clinical characteristics of myocardial injury in severe and very severe patients with 2019 novel coronavirus disease

positive: Laboratory Abnormalities in Children with Mild and Severe Coronavirus Disease 2019 (COVID-19): a pooled analysis and review Limited data exists to-date on the laboratory findings in children with COVID-19, warranting the conduction of this study, in which we pool the currently available literature data on the laboratory findings seen in children with mild and severe COVID-19. Following an extensive literature search, we identified 24 eligible studies, including a total of 624 pediatric cases with laboratory-confirmed COVID-19, which report data on 27 different biomarkers. We then performed a meta-analysis to calculate the pooled prevalence estimates (PPE) for these laboratory abnormalities in mild COVID-19. As data was too limited for children with severe COVID-19 to allow pooling, results were presented descriptively in a summary of findings table. Our data show an inconsistent pattern of change in the leukocyte index of mild and severe cases of COVID-19 in children. Specifically, changes in leukocyte counts were only observed in 32% of the mild pediatric cases (PPE: 13% increase, 19% decrease). In mild disease, creatine kinase-MB (CK-MB) was frequently elevated, with a PPE of 33%. In severe disease, c-reactive protein (CRP), procalcitonin (PCT), and lactate dehydrogenase (LDH) were frequently elevated. Based on data obtained from early COVID-19 studies, leukocyte indices in children appear inconsistent, differing from those reported in adults that highlight specific leukocyte trends. This brings into question the utility and reliability of such parameters in monitoring disease severity in the pediatric population. Instead, we suggest physicians to serially monitor CRP, PCT, and LDH to track the course of illness in hospitalized children. Finally, elevated CK-MB in mild pediatric COVID-19 cases is indicative of possible cardiac injury. This highlights the importance of monitoring cardiac biomarkers in hospitalized patients and the need for further investigation of markers such as cardiac troponin in future studies.

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

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

positive: Dynamic changes of D-dimer and neutrophil-lymphocyte count ratio as prognostic biomarkers in COVID-19 BACKGROUND: Since December 2019, the outbreak of COVID-19 caused a large number of hospital admissions in China. Many patients with COVID-19 have symptoms of acute respiratory distress syndrome, even are in danger of death. This is the first study to evaluate dynamic changes of D-Dimer and Neutrophil-Lymphocyte Count Ratio (NLR) as a prognostic utility in patients with COVID-19 for clinical use. METHODS: In a retrospective study, we collected data from 349 hospitalized patients who diagnosed as the infection of the COVID-19 in Wuhan Pulmonary Hospital. We used ROC curves and Cox regression analysis to explore critical value (optimal cut-off point associated with Youden index) and prognostic role of dynamic changes of D-Dimer and NLR. RESULTS: Three hundred forty-nine participants were enrolled in this study and the mortality rate of the patients with laboratory diagnosed COVID-19 was 14.9%. The initial and peak value of D-Dimer and NLR in deceased patients were higher statistically compared with survivors (P < 0.001). There was a more significant upward trend of D-Dimer and NLR during hospitalization in the deceased patients, initial D-Dimer and NLR were lower than the peak tests (MD) -25.23, 95% CI: − 31.81- -18.64, P < 0.001; (MD) -43.73, 95% CI:-59.28- -31.17, P < 0.001. The test showed a stronger correlation between hospitalization days, PCT and peak D-Dimer than initial D-Dimer. The areas under the ROC curves of peak D-Dimer and peak NLR tests were higher than the initial tests (0.94(95%CI: 0.90–0.98) vs. 0.80 (95% CI: 0.73–0.87); 0.93 (95%CI:0.90–0.96) vs. 0.86 (95%CI:0.82–0.91). The critical value of initial D-Dimer, peak D-Dimer, initial NLR and peak NLR was 0.73 mg/L, 3.78 mg/L,7.13 and 14.31 respectively. 35 (10.03%) patients were intubated. In the intubated patients, initial and peak D-Dimer and NLR were much higher than non-intubated patients (P < 0.001). The critical value of initial D-Dimer, peak D-Dimer, initial NLR and peak NLR in prognosticate of intubation was 0.73 mg/L, 12.75 mg/L,7.28 and 27.55. The multivariable Cox regression analysis showed that age (HR 1.04, 95% CI 1.00–1.07, P = 0.01), the peak D-Dimer (HR 1.03, 95% CI 1.01–1.04, P < 0.001) were prognostic factors for COVID-19 patients’ death. CONCLUSIONS: To dynamically observe the ratio of D-Dimer and NLR was more valuable during the prognosis of COVID-19. The rising trend in D-Dimer and NLR, or the test results higher than the critical values may indicate a risk of death for participants with COVID-19.

positive: Preliminary study to identify severe from moderate cases of COVID-19 using combined hematology parameters Background: The third fatal coronavirus is the novel coronavirus (SARS-CoV-2) that causes novel coronavirus pneumonia (COVID-19) which first broke out in December 2019 Patients will develop rapidly if there is no any intervention, so the risk identification of severe patients is critical The aim of this study was to investigate the characteristics and rules of hematology changes in patients with COVID-19, and to explore the possibility differentiating moderate and severe patients using conventional hematology parameters or combined parameters Methods: The clinical data of 45 moderate and severe type patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Jingzhou Central Hospital from January 23 to February 13, 2020 were collected The epidemiological indexes, clinical symptoms, and laboratory test results of the patients were retrospectively analyzed Those parameters with significant differences between moderate and severe cases were analyzed, and the combination parameters with the best diagnostic performance were selected using the linear discriminant analysis (LDA) method Results: Of the 45 patients with the novel 2019 corona virus (COVID-19) (35 moderate and 10 severe cases), 23 were male and 22 were female, with ages ranging from 16 to 62 years The most common clinical symptoms were fever (89%) and dry cough (60%) As the disease progressed, white blood cell count (WBC), neutrophil count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), red blood cell distribution width-coefficient of variation (RDW-CV), and red cell volume distribution width-standard deviation (RDW-SD) parameters in the severe group were significantly higher than those in the moderate group (P<0 05);meanwhile, lymphocyte count (Lym#), eosinophil count (Eos#), high fluorescent cell percentage (HFC%), red blood cell count (RBC), hemoglobin (HGB), and hematocrit (HCT) parameters in the severe group were significantly lower than those in the moderate group (P<0 05) For NLR parameter, it's area under the curve (AUC), cutoff, sensitivity and specificity were 0 890, 13 39, 83 3% and 82 4% respectively;meanwhile, for PLR parameter, it's AUC, cutoff, sensitivity and specificity were 0 842, 267 03, 83 3% and 74 0% respectively The combined parameters of NLR and RDW-SD had the best diagnostic efficiency (AUC =0 938), and when the cutoff value was 1 046, the sensitivity and the specificity were 90 0% and 84 7% respectively, followed by the combined parameter NLR&RDW-CV (AUC =0 923) When the cut-off value was 0 62, the sensitivity and the specificity for distinguishing severe type from moderate cases of COVID-19 were 90 0% and 82 4% respectively Conclusions: The combined NLR and RDW-SD parameter is the best hematology index It may help clinicians to predict the severity of COVID-19 patients and can be used as a useful indicator to help prevent and control the epidemic

positive: Combined use of the neutrophil-to-lymphocyte ratio and CRP to predict 7-day disease severity in 84 hospitalized patients with COVID-19 pneumonia: a retrospective cohort study. Background Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide from Wuhan. An easy-to-use index capable of the early identification of inpatients who are at risk of becoming critically ill is urgently needed in clinical practice. Hence, the aim of this study was to explore an easy-to-use nomogram and a model to triage patients into risk categories to determine the likelihood of developing a critical illness. Methods A retrospective cohort study was conducted. We extracted data from 84 patients with laboratory-confirmed COVID-19 from one designated hospital. The primary endpoint was the development of severe/critical illness within 7 days after admission. Predictive factors of this endpoint were selected by LASSO Cox regression model. A nomogram was developed based on selected variables. The predictive performance of the derived nomogram was evaluated by calibration curves and decision curves. Additionally, the predictive performances of individual and combined variables under study were evaluated by receiver operating characteristic curves. The developed model was also tested in a separate validation set with 71 laboratory-confirmed COVID-19 patients. Results None of the 84 inpatients were lost to follow-up in this retrospective study. The primary endpoint occurred in 23 inpatients (27.4%). The neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) were selected as the final prognostic factors. A nomogram was developed based on the NLR and CRP. The calibration curve and decision curve indicated that the constructed nomogram model was clinically useful. The AUCs for the NLR, CRP and Combined Index in both training set and validation sets were 0.685 (95% CI: 0.574-0.783), 0.764 (95% CI: 0.659-0.850), 0.804 (95% CI: 0.702-0.883), and 0.881 (95% CI: 0.782-0.946), respectively. Conclusions Our results demonstrated that the nomogram and Combined Index calculated from the NLR and CRP are potential and reliable predictors of COVID-19 prognosis and can triage patients at the time of admission.

positive: COVID-19 severity is predicted by earlier evidence of accelerated aging With no known treatments or vaccine, COVID-19 presents a major threat, particularly to older adults, who account for the majority of severe illness and deaths. The age-related susceptibility is partly explained by increased comorbidities including dementia and type II diabetes. While it is unclear why these diseases predispose risk, we hypothesize that increased biological age, rather than chronological age, may be driving disease-related trends in COVID-19 severity with age. To test this hypothesis, we applied our previously validated biological age measure (PhenoAge) composed of chronological age and nine clinical chemistry biomarkers to data of 347,751 participants from a large community cohort in the United Kingdom (UK Biobank), recruited between 2006 and 2010. Other data included disease diagnoses (to 2017), mortality data (to 2020), and the UK national COVID-19 test results (to May 31, 2020). Accelerated aging 10-14 years prior to the start of the COVID-19 pandemic was associated with test positivity (OR=1.15 per 5-year acceleration, 95% CI: 1.08 to 1.21, p=3.2x10-6) and all-cause mortality with test-confirmed COVID-19 (OR=1.25, per 5-year acceleration, 95% CI: 1.09 to 1.44, p=0.002) after adjustment for demographics including current chronological age and pre-existing diseases or conditions. The corresponding areas under the curves were 0.669 and 0.803, respectively. Biological aging, as captured by PhenoAge, is a better predictor of COVID-19 severity than chronological age, and may inform risk stratification initiatives, while also elucidating possible underlying mechanisms, particularly those related to inflammaging.

positive: 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.

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: 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.

positive: Relationship between Chest CT manifestations and immune response in COVID-19 patients Abstract Objectives To study the and correlations of lymphocytes and cytokines between changes of lung lesion volumes in patients with COVID-19, and to predict their correlation. Methods 93 patients with COVID-19 were divided into mild and severe groups. The data of lymphocyte subgroups and cytokines were collected, the imaging characteristics were measured and correlation analysis was performed to analyze the differences. Results 60 mild and 33 severe patients were included, Lymphocyte subsets decreased in both groups. The percentages of reduction of absolute lymphocytes value in mild and severe groups were 32% and 64% respectively. The lung CT lesion volume of all patients was 241.45 ± 282.92 cm3, among which the mild group was 151.29 ± 226.04 cm3 and the severe group was 405.38 ± 304.90 cm3, respectively. In critically ill patients, the decrease of absolute value of CD4 + T cells and increase of IL-6 level are significantly correlated with the volume of lung lesions. Conclusions The absolute values of CD3+, CD4+, and CD8 + T cells are lower in patients with COVID-19, the levels of IL-6 and IL-10 are increased. The severity of lung lesions predicts poor clinical outcomes and may be a predictor of the transition from mild to severe.

positive: Prediction of severe illness due to COVID-19 based on an analysis of initial Fibrinogen to Albumin Ratio and Platelet count Concomitant coagulation disorder can occur in severe patients withCOVID-19, but in-depth studies are limited. This study aimed to describe the parameters of coagulation function of patients with COVID-19 and reveal the risk factors of developing severe disease. This study retrospectively analyzed 113patients with SARS-CoV-2 infection in Taizhou Public Health Center. Clinical characteristics and indexes of coagulation function were collected. A multivariate Cox analysis was performed to identify potential biomarkers for predicting disease progression. Based on the results of multivariate Cox analysis, a Nomogram was built and the predictive accuracy was evaluated through the calibration curve, decision curve, clinical impact curve, and Kaplan-Meier analysis. Sensitivity, specificity, predictive values were calculated to assess the clinical value. The data showed that Fibrinogen, FAR, and D-dimer were higher in the severe patients, while PLTcount, Alb were much lower. Multivariate Cox analysis revealed that FAR and PLT count were independent risk factors for disease progression. The optimal cutoff values for FAR and PLT count were 0.0883 and 135*109/L, respectively. The C-index [0.712 (95% CI = 0.610-0.814)], decision curve, clinical impact curve showed that Nomogram could be used to predict the disease progression. In addition, the Kaplan-Meier analysis revealed that potential risk decreased in patients with FAR<0.0883 and PLT count>135*109/L.The model showed a good negative predictive value [(0.9474 (95%CI = 0.845-0.986)].This study revealed that FAR and PLT count were independent risk factors for severe illness and the severity of COVID-19 might be excluded when FAR<0.0883 and PLT count>135*109/L.

positive: Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Background As coronavirus disease 2019 (COVID-19) pandemic rages on, there is urgent need for identification of clinical and laboratory predictors for progression towards severe and fatal forms of this illness. In this study we aimed to evaluate the discriminative ability of hematologic, biochemical and immunologic biomarkers in patients with and without the severe or fatal forms of COVID-19. Methods An electronic search in Medline (PubMed interface), Scopus, Web of Science and China National Knowledge Infrastructure (CNKI) was performed, to identify studies reporting on laboratory abnormalities in patients with COVID-19. Studies were divided into two separate cohorts for analysis: severity (severe vs. non-severe and mortality, i.e. non-survivors vs. survivors). Data was pooled into a meta-analysis to estimate weighted mean difference (WMD) with 95% confidence interval (95% CI) for each laboratory parameter. Results A total number of 21 studies was included, totaling 3377 patients and 33 laboratory parameters. While 18 studies (n = 2984) compared laboratory findings between patients with severe and non-severe COVID-19, the other three (n = 393) compared survivors and non-survivors of the disease and were thus analyzed separately. Patients with severe and fatal disease had significantly increased white blood cell (WBC) count, and decreased lymphocyte and platelet counts compared to non-severe disease and survivors. Biomarkers of inflammation, cardiac and muscle injury, liver and kidney function and coagulation measures were also significantly elevated in patients with both severe and fatal COVID-19. Interleukins 6 (IL-6) and 10 (IL-10) and serum ferritin were strong discriminators for severe disease. Conclusions Several biomarkers which may potentially aid in risk stratification models for predicting severe and fatal COVID-19 were identified. In hospitalized patients with respiratory distress, we recommend clinicians closely monitor WBC count, lymphocyte count, platelet count, IL-6 and serum ferritin as markers for potential progression to critical illness.

positive: Laboratory tests and outcome for patients with COVID-19: A systematic review and meta-analysis BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (COVID-19) poses substantial challenges for health care systems. With a vastly expanding amount of publications on COVID-19, clinicians need evidence synthesis to produce guidance for handling patients with COVID-19. In this systematic review and meta-analysis, we examine which routine laboratory tests are associated with severe COVID-19 disease. CONTENT: PubMed (Medline), Scopus, and Web of Science were searched until the 22(nd) of March 2020 for studies on COVID-19. Eligible studies were original articles reporting on laboratory tests and outcome of patients with COVID-19. Data were synthesised and we conducted random effects meta-analysis and estimated mean difference (MD) and standard mean difference at biomarker level for disease severity. Risk of bias and applicability concern was evaluated using the Quality Assessment of Diagnostic Accuracy Studies -2. SUMMARY: 45 studies were included, of which 21 publications were used for the meta-analysis. Studies were heterogeneous, but had low risk of bias and applicability concern in terms of patient selection and reference standard. Severe disease was associated with higher white blood cell count (MD 1.28 x 10(9)/L), neutrophil count (MD 1.49 x 10(9)/L), C-reactive protein (MD 49.2 mg/L), lactate dehydrogenase (MD 196 U/L), D-dimer (SMD 0.58), and aspartate aminotransferase (MD 8.5 U/L), all p < 0.001. Furthermore, low lymphocyte count (MD -0.32 x 10(9)/L), platelet count (MD -22.4 x 10(9)/L), and haemoglobin (MD -4.1 g/L), all p < 0.001, were also associated with severe disease. In conclusion, several routine laboratory tests are associated with disease severity in COVID-19.

positive: Association between age and clinical characteristics and outcomes of COVID-19

positive: Predictors for imaging progression on chest CT from coronavirus disease 2019 (COVID-19) patients Objective: This study aimed to investigate the potential parameters associated with imaging progression on chest CT from coronavirus disease 19 (COVID-19) patients. Results: The average age of 273 COVID-19 patients enrolled with imaging progression were older than those without imaging progression (p = 0.006). The white blood cells, platelets, neutrophils and acid glycoprotein were all decreased in imaging progression patients (all p < 0.05), and monocytes were increased (p = 0.025). The parameters including homocysteine, urea, creatinine and serum cystatin C were significantly higher in imaging progression patients (all p < 0.05), while eGFR decreased (p < 0.001). Monocyte-lymphocyte ratio (MLR) was significantly higher in imaging progression patients compared to that in imaging progression-free ones (p < 0.001). Logistic models revealed that age, MLR, homocysteine and period from onset to admission were factors for predicting imaging progression on chest CT at first week from COVID-19 patients (all p < 0.05). Conclusion: Age, MLR, homocysteine and period from onset to admission could predict imaging progression on chest CT from COVID-19 patients. Methods: The primary outcome was imaging progression on chest CT. Baseline parameters were collected at the first day of admission. Imaging manifestations on chest CT were followed-up at (6±1) days.

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

positive: Dynamic changes of D-dimer and neutrophil-lymphocyte count ratio as prognostic biomarkers in COVID-19 BACKGROUND: Since December 2019, the outbreak of COVID-19 caused a large number of hospital admissions in China. Many patients with COVID-19 have symptoms of acute respiratory distress syndrome, even are in danger of death. This is the first study to evaluate dynamic changes of D-Dimer and Neutrophil-Lymphocyte Count Ratio (NLR) as a prognostic utility in patients with COVID-19 for clinical use. METHODS: In a retrospective study, we collected data from 349 hospitalized patients who diagnosed as the infection of the COVID-19 in Wuhan Pulmonary Hospital. We used ROC curves and Cox regression analysis to explore critical value (optimal cut-off point associated with Youden index) and prognostic role of dynamic changes of D-Dimer and NLR. RESULTS: Three hundred forty-nine participants were enrolled in this study and the mortality rate of the patients with laboratory diagnosed COVID-19 was 14.9%. The initial and peak value of D-Dimer and NLR in deceased patients were higher statistically compared with survivors (P < 0.001). There was a more significant upward trend of D-Dimer and NLR during hospitalization in the deceased patients, initial D-Dimer and NLR were lower than the peak tests (MD) -25.23, 95% CI: - 31.81- -18.64, P < 0.001; (MD) -43.73, 95% CI:-59.28- -31.17, P < 0.001. The test showed a stronger correlation between hospitalization days, PCT and peak D-Dimer than initial D-Dimer. The areas under the ROC curves of peak D-Dimer and peak NLR tests were higher than the initial tests (0.94(95%CI: 0.90-0.98) vs. 0.80 (95% CI: 0.73-0.87); 0.93 (95%CI:0.90-0.96) vs. 0.86 (95%CI:0.82-0.91). The critical value of initial D-Dimer, peak D-Dimer, initial NLR and peak NLR was 0.73 mg/L, 3.78 mg/L,7.13 and 14.31 respectively. 35 (10.03%) patients were intubated. In the intubated patients, initial and peak D-Dimer and NLR were much higher than non-intubated patients (P < 0.001). The critical value of initial D-Dimer, peak D-Dimer, initial NLR and peak NLR in prognosticate of intubation was 0.73 mg/L, 12.75 mg/L,7.28 and 27.55. The multivariable Cox regression analysis showed that age (HR 1.04, 95% CI 1.00-1.07, P = 0.01), the peak D-Dimer (HR 1.03, 95% CI 1.01-1.04, P < 0.001) were prognostic factors for COVID-19 patients' death. CONCLUSIONS: To dynamically observe the ratio of D-Dimer and NLR was more valuable during the prognosis of COVID-19. The rising trend in D-Dimer and NLR, or the test results higher than the critical values may indicate a risk of death for participants with COVID-19.

positive: Risk factors for disease progression in hospitalized patients with COVID-19: a retrospective cohort study Background: To investigate the risk factors related to aggravation and clinical outcomes in coronavirus disease 2019 (COVID-19) patients.Methods: We performed a retrospective study on the risk factors for disease progression of cases with COVID-19. Based on the clinical types, the patients were divided into a progression group and an improvement group. Multivariable logistic regression and ROC curve analysis were performed to explore the risk factors for disease progression.Results: A total of 101 patients were included in this study; diseases progression occurred in 17 patients, 84 patients improved, 6 were transferred to intensive care unit (ICU), and 5 died. The mean time to obtain negative nucleic acid results was 12.5 ± 5.0 days. Multivariate logistic analysis indicated that age (OR, 0.104; p = .002), C-reactive protein (CRP) (OR, 0.093; p < .001) and lymphocyte count (OR, 3.397; p = .022) were risk factors for disease progression. ROC curve analysis revealed that the AUC of age, CRP and lymphocyte count for disease progression were 0.873, 0.911 and 0.817, respectively.Conclusions: Older age increased CRP and decreased lymphocyte count resulted in potential risk factors for COVID-19 progression. This may be helpful in identifying patients whose condition worsens at an early stage.

positive: SARS-CoV-2 inflames the heart. The importance of awareness of myocardial injury in COVID-19 patients

positive: Radiographic Findings and other Predictors in Adults with Covid-19 As of March 20, 2020, there were 234,073 confirmed cases of coronavirus disease 2019 (Covid-19) and 9,840 deaths worldwide. Older age and elevated d-dimer are reported risk factors for Covid-19. However, whether early radiographic change is a predictor of fatality remains unknown. We retrospectively reviewed records of all laboratory-confirmed patients admitted to a quarantine unit at Tongji Hospital, a large regional hospital in Wuhan, China, between January 31 and March 5, 2020. The Tongji Hospital ethics committee approved this study. A total of 128 patients were admitted. 102 patients were confirmed to have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using RNA detection. As of March 20, 82 confirmed patients were discharged, 15 died, and 5 remained hospitalized. The median age was 57 years (range, 27 - 85), 59 (58%) were male, and 44 (43%) patients had a comorbidity. The most common symptoms were fever, cough, and dyspnea. When compared with survivors, non-survivors were older and more likely to have lymphopenia, elevated lactate dehydrogenase (LDH), elevated d-dimer, and increased hypersensitive troponin I. In a multivariate regression model that included these predictors, older age and elevated LDH were independent risk factors for fatality. Twenty-one survivors and 11 non-survivors had CT scans within the first week. We used severity score to quantify the extent of lung opacification as described in the Supplementary Appendix. The total severity score and number of involved lung lobes within the first week were significantly greater in non-survivors compared to survivors . Using univariate logistic regression analysis, higher total severity score ([≥]15) (odds ratio 53, 95% CI 3-369; p = 0.003), and more involved lung lobes (5 involved lobes) (9, 2-53; p = 0.016) in CT images within the first week were significantly associated with fatality. Moreover, in this subset of patients with CT data within the first week, higher total severity score was the only independent risk factor in a multivariate analysis incorporated the predictors discussed above (older age, lymphocytopenia, elevated LDH, elevated d-dimer, and increased troponin I). For survivors with serial CT scans performed over four weeks, total severity score peaked in the second week. This report suggests that the extent of lung lesions in early CT images is a potential predictor of poor outcome of Covid-19. This will help clinicians to identify the patients with poor prognosis at early stage.

positive: Cytokine profile in plasma of severe COVID-19 does not differ from ARDS and sepsis Rationale: Elevated levels of inflammatory cytokines have been associated with poor outcomes among COVID-19 patients. It is unknown, however, how these levels compare to those observed in critically ill patients with ARDS or sepsis due to other causes. Objectives: To directly compare plasma levels of inflammatory cytokines, with a focus on 6 cytokines associated with cytokine storm (IL-1b, IL-1RA, IL-6, IL-8, IL-18, and TNF), between hospitalized COVID-19 patients and banked plasma samples from ARDS and sepsis patients from prior to the COVID-19 pandemic. Findings: 15 hospitalized COVID-19 patients, 9 of whom were critically ill, were compared to 28 critically ill patients with ARDS or sepsis. There were no statistically significant differences in baseline levels of IL-1b, IL-1RA, IL-6, IL-8, IL-18, and TNF between patients with severe COVID-19 and critically ill controls with ARDS or sepsis. Conclusions: Levels of inflammatory cytokines IL-1b, IL-1RA, IL-6, IL-8, IL-18, and TNF were not higher in critically ill COVID-19 patients than in critically ill patients admitted with ARDS or sepsis due to other causes in this small cohort. Broad use of immunosuppressive therapies in ARDS has failed in numerous Phase 3 studies; use of these therapies in unselected patients with COVID-19 is likely unwarranted.

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

positive: Predictors for imaging progression on chest CT from coronavirus disease 2019 (COVID-19) patients OBJECTIVE: This study aimed to investigate the potential parameters associated with imaging progression on chest CT from coronavirus disease 19 (COVID-19) patients. RESULTS: The average age of 273 COVID-19 patients enrolled with imaging progression were older than those without imaging progression (p = 0.006). The white blood cells, platelets, neutrophils and acid glycoprotein were all decreased in imaging progression patients (all p < 0.05), and monocytes were increased (p = 0.025). The parameters including homocysteine, urea, creatinine and serum cystatin C were significantly higher in imaging progression patients (all p < 0.05), while eGFR decreased (p < 0.001). Monocyte-lymphocyte ratio (MLR) was significantly higher in imaging progression patients compared to that in imaging progression-free ones (p < 0.001). Logistic models revealed that age, MLR, homocysteine and period from onset to admission were factors for predicting imaging progression on chest CT at first week from COVID-19 patients (all p < 0.05). CONCLUSION: Age, MLR, homocysteine and period from onset to admission could predict imaging progression on chest CT from COVID-19 patients. METHODS: The primary outcome was imaging progression on chest CT. Baseline parameters were collected at the first day of admission. Imaging manifestations on chest CT were followed-up at (6±1) days.

positive: 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.

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

positive: Epidemiological, clinical characteristics of cases of SARS-CoV-2 infection with abnormal imaging findings PURPOSE: To investigate the epidemiological and clinical characteristics of COVID-19 patients with abnormal imaging findings. METHODS: Patients confirmed with SARS-CoV-2 infection in Zhejiang province from January 17 to February 8 who had undergone CT or X-ray were enrolled. Epidemiological and clinical data were analyzed among those with abnormal or normal imaging findings. RESULTS: Excluding 72 patients with normal images, 230 of 573 patients showed abnormalities affecting more than two lung lobes. The median radiographic score was 2.0, and there was a negative correlation between that score and the oxygenation index (ρ = −0.657, P < 0.001). Patients with abnormal images were older (46.65 ± 13.82), with a higher rate of coexisting condition (28.8%), a lower rate of exposure history, and longer time between onset and confirmation (5 days) than non-pneumonia patients (all P < 0.05). A higher rate of fever, cough, expectoration and headache, a lower level of lymphocytes, albumin, and serum sodium levels and a higher total bilirubin, creatine kinase, lactate dehydrogenase, and C-reactive protein levels and a lower oxygenation index were observed in pneumonia patients (all P < 0.05). Muscle ache, shortness of breath, nausea and vomiting, lower lymphocytes levels, and higher serum creatinine and radiographic score at admission were predictive factors for the severe/critical subtype. CONCLUSION: Patients with abnormal images have more obvious clinical manifestations and laboratory changes. Combing clinical features and radiographic scores can effectively predict severe/critical types.

positive: Association of cardiac biomarkers and comorbidities with increased mortality, severity, and cardiac injury in COVID‐19 patients: A meta‐regression and Decision tree analysis BACKGROUND: Coronavirus disease‐2019 (COVID‐19) has a deleterious effect on several systems, including the cardiovascular system. We aim to systematically explore the association of COVID‐19 severity and mortality rate with the history of cardiovascular diseases and/or other comorbidities and cardiac injury laboratory markers. METHODS: The standardized mean difference (SMD) or odds ratio (OR) and 95% confidence intervals (CI) were applied to estimate pooled results from the 56 studies. The prognostic performance of cardiac markers for predicting adverse outcomes and to select the best cutoff threshold was estimated by ROC curve analysis. Decision tree analysis by combining cardiac markers with demographic and clinical features was applied to predict mortality and severity in COVID‐19 patients. RESULTS: A meta‐analysis of 17,794 patients showed patients with high cardiac troponin I (OR=5.22, 95%CI=3.73‐7.31, p<0.001) and AST levels (OR=3.64, 95%CI=2.84‐4.66, p<0.001) were more likely to develop adverse outcomes. High troponin I >13.75 ng/L combined with either advanced age >60 years or elevated AST level >27.72 U/L was the best model to predict poor outcomes. CONCLUSIONS: COVID‐19 severity and mortality are complicated by myocardial injury. Assessment of cardiac injury biomarkers may improve the identification of those patients at the highest risk and potentially lead to improved therapeutic approaches. This article is protected by copyright. All rights reserved.

positive: Neutrophil-to-lymphocyte ratio as a predictive biomarker for moderate-severe ARDS in severe COVID-19 patients ChiCTR, ChiCTR2000029758. Registered 12 February 2020 - Retrospectively registered

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: 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: Kidney manifestations of mild, moderate and severe coronavirus disease 2019: a retrospective cohort study BACKGROUND: Coronavirus disease 2019 (COVID-19) is a pandemic that has affected more than 3 million patients globally. Previous data from Wuhan city showed that acute kidney injury (AKI), proteinuria and hematuria occurred frequently in patients with severe COVID-19. However, the prevalence of kidney injury in milder cases remains unclear. METHODS: This retrospective study included two major consecutive cohorts of COVID-19 patients in Sichuan Province. Baseline characteristics, laboratory data including renal function, proteinuria and dipstick hematuria, and other laboratory parameters were collected. A subgroup of patients was followed up for 2–4 weeks to evaluate the short-term outcome of renal impairment. RESULTS: Overall, 168 COVID-19-positive patients were included in the study. The majority of patients (79.7%) were diagnosed with mild or moderate disease. Half of patients presented with fever; however, in The Tibetan cohort, fever only occurred in 13.4% of patients. On hospital admission, proteinuria and dipstick hematuria were noted in 18.4% and 17.4% of patients, respectively, while AKI only occurred in one patient. Further analysis showed that severe or critical COVID-19 was associated with higher risk of proteinuria [relative risk (RR) 7.37, 95% confidence interval (CI) 2.45–22.18, P = 3.8 × 10(−4)] and dipstick hematuria (RR 8.30, 95% CI 2.69–25.56, P = 2.3 × 10(−4)). Proteinuria, dipstick hematuria, or the combination of proteinuria and hematuria could significantly predict severe or critical severe COVID-19. CONCLUSIONS: Proteinuria and dipstick hematuria are not uncommon in patients with COVID-19 infection, especially in severe or critical cases.

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

positive: Fatal outcome of COVID-19 disease in a 5-month infant with comorbidities

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: Prognostic Factors for Severe Coronavirus Disease 2019 in Daegu, Korea BACKGROUND: Since its first detection in December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 infection has spread rapidly around the world. Although there have been several studies investigating prognostic factors for severe COVID-19, there have been no such studies in Korea. METHODS: We performed a retrospective observational study of 110 patients with confirmed COVID-19 hospitalized at a tertiary hospital in Daegu, Korea. Demographic, clinical, laboratory, and outcome data were collected and analyzed. Severe disease was defined as a composite outcome of acute respiratory distress syndrome, intensive care unit care, or death. RESULTS: Diabetes mellitus (odds ratio [OR], 19.15; 95% confidence interval [CI], 1.90–193.42; P = 0.012), body temperature ≥ 37.8°C (OR, 10.91; 95% CI, 1.35–88.36; P = 0.025), peripheral oxygen saturation < 92% (OR, 33.31; 95% CI, 2.45–452.22; P = 0.008), and creatine kinase-MB (CK-MB) > 6.3 (OR, 56.84; 95% CI, 2.64–1,223.78, P = 0.010) at admission were associated with higher risk of severe COVID-19. The likelihood of development of severe COVID-19 increased with an increasing number of prognostic factors. CONCLUSION: In conclusion, we found that diabetes mellitus, body temperature ≥ 37.8°C, peripheral oxygen saturation < 92%, and CK-MB > 6.3 are independent predictors of severe disease in hospitalized COVID-19 patients. Appropriate assessment of prognostic factors and close monitoring to provide the necessary interventions at the appropriate time in high-risk patients may reduce the case fatality rate of COVID-19.

positive: [Potential biomarkers predictors of mortality in COVID-19 patients in the Emergency Department]. OBJECTIVE Identify which biomarkers performed in the first emergency analysis help to stratify COVID-19 patients according to mortality risk. METHODS Observational, descriptive and cross-sectional study performed with data collected from patients with suspected COVID-19 in the Emergency Department from February 24 to March 16, 2020. The univariate and multivariate study was performed to find independent mortality markers and calculate risk by building a severity score. RESULTS A total of 163 patients were included, of whom 33 died and 29 of them were positive for the COVID-19 PCR test. We obtained as possible factors to conform the Mortality Risk Score age> 75 years ((adjusted OR = 12,347, 95% CI: 4,138-36,845 p = 0.001), total leukocytes> 11,000 cells / mm3 (adjusted OR = 2,649, 95% CI: 0.879-7.981 p = 0.083), glucose> 126 mg / dL (adjusted OR = 3.716, 95% CI: 1.247-11.074 p = 0.018) and creatinine> 1.1 mg / dL (adjusted OR = 2.566, 95% CI: 0.889- 7.403, p = 0.081) This score was called COVEB (COVID, Age, Basic analytical profile) with an AUC 0.874 (95% CI: 0.816-0.933, p <0.001; Cut-off point = 1 (sensitivity = 89.66 % (95% CI: 72.6% -97.8%), specificity = 75.59% (95% CI: 67.2% -82.8%). A score <1 has a negative predictive value = 100% (95% CI: 93.51% -100%) and a positive predictive value = 18.59% (95% CI: 12.82% -25.59%). CONCLUSIONS Clinical severity scales, kidney function biomarkers, white blood cell count parameters, the total neutrophils / total lymphocytes ratio and procalcitonin are early risk factors for mortality. The variables age, glucose, creatinine and total leukocytes stand out as the best predictors of mortality. A COVEB score <1 indicates with a 100% probability that the patient with suspected COVID-19 will not die in the next 30 days.

positive: 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.

positive: Association of clinical and radiographic findings with the outcomes of 93 patients with COVID-19 in Wuhan, China Rationale: To retrospectively analyze serial chest CT and clinical features in patients with coronavirus disease 2019 (COVID-19) for the assessment of temporal changes and to investigate how the changes differ in survivors and nonsurvivors. Methods: The consecutive records of 93 patients with confirmed COVID-19 who were admitted to Wuhan Union Hospital from January 10, 2020, to February 22, 2020, were retrospectively reviewed. A series of chest CT findings and clinical data were collected and analyzed. The serial chest CT scans were scored on a semiquantitative basis according to the extent of pulmonary abnormalities. Chest CT scores in different periods (0 - 5 days, 6 - 10 days, 11 - 15 days, 16 - 20 days, and > 20 days) since symptom onset were compared between survivors and nonsurvivors, and the temporal trend of the radiographic-clinical features was analyzed. Results: The final cohort consisted of 93 patients: 68 survivors and 25 nonsurvivors. Nonsurvivors were significantly older than survivors. For both survivors and nonsurvivors, the chest CT scores were not different in the first period (0 - 5 days) but diverged afterwards. The mortality rate of COVID-19 monotonously increased with chest CT scores, which positively correlated with the neutrophil-to-lymphocyte ratio, neutrophil percentage, D-dimer level, lactate dehydrogenase level and erythrocyte sedimentation rate, while negatively correlated with the lymphocyte percentage and lymphocyte count. Conclusions: Chest CT scores correlate well with risk factors for mortality over periods, thus they may be used as a prognostic indicator in COVID-19. While higher chest CT scores are associated with a higher mortality rate, CT images taken at least 6 days since symptom onset may contain more prognostic information than images taken at an earlier period.

positive: Presepsin as a predictive biomarker of severity in COVID‐19: a case series Guidelines for the diagnosis and treatment of the novel coronavirus disease 2019 (COVID‐19) present clear criteria, including respiratory rate, hemoglobin oxygen saturation (SaO(2)), and oxygenation indicator (PaO(2)/FiO(2))(1). This article is protected by copyright. All rights reserved.

positive: Potential effect of blood purification therapy in reducing cytokine storm as a late complication of critically ill COVID-19

positive: Hypoalbuminemia predicts the outcome of COVID‐19 independent of age and co‐morbidity The coronavirus disease 2019 (COVID‐19) has evolved into a pandemic rapidly. Most of the literature show that the elevated liver enzymes in COVID‐19 are of little clinical significance. Lower albumin level is seen in severe COVID‐19 and is not parallel to the changes in alanine aminotransferase and aspartate aminotransferase levels. We aimed to explore the impact of hypoalbuminemia in COVID‐19. This retrospective cohort study included adult patients with confirmed COVID‐19. The relationship between hypoalbuminemia and death was studied using binary logistic analysis. A total of 299 adult patients were included, 160 (53.5%) were males and the average age was 53.4 ± 16.7 years. The median time from the onset of illness to admission was 3 days (interquartile ranges, 2‐5). Approximately one‐third of the patients had comorbidities. Hypoalbuminemia (<35 g/L) was found in 106 (35.5%) patients. The difference in albumin was considerable between survivors and non‐survivors (37.6 ± 6.2 vs 30.5 ± 4.0, P < .001). Serum albumin level was inversely correlated to white blood cell (r = –.149, P = .01) and neutrophil to lymphocyte ratio (r = −.298, P < .001). Multivariate analysis showed the presence of comorbidities (OR, 6.816; 95% CI, 1.361‐34.133), lymphopenia (OR, 13.130; 95% CI, 1.632‐105.658) and hypoalbuminemia (OR, 6.394; 95% CI, 1.315‐31.092) were independent predictive factors for mortality. In conclusion, hypoalbuminemia is associated with the outcome of COVID‐19. The potential therapeutic value of albumin infusion in COVID‐19 should be further explored at the earliest.

positive: A link between inflammatory biomarkers and lung ultrasound observations in patients with SARS-CoV-2 infection ABSTRACT: Lung ultrasound (LUS) has shown to correlate well with the findings obtained by chest computed tomography (CT) in acute-phase COVID-19. Although there is a significant correlation between blood biomarkers and CT radiological findings, a potential correlation between biochemical parameters and LUS images is still unknown. Our purpose was to evaluate a potential association between lung lesions visualised by LUS and blood biomarkers as well as the ability to predict mortality from two different lung ultrasound scoring systems (LUSS). We performed a retrospective observational study on 45 patients aged >70 years with SARS-CoV-2 infection who required hospitalisation. LUS was carried out at admission and on day 7, when the clinical course was favourable or earlier in case of worsening. Disease severity was scored by means of LUSS in 8 (LUSS8) and in 12 (LUSS12) quadrants. LUS and blood draw for inflammatory marker analysis were performed at the same time. The correlation between biochemical parameters and either LUSS score was significant for ferritin levels. It was 0.486 (p=0.001) for LUSS8 and 0.458 (p=0.002) for LUSS12. Using a threshold score of 15 with LUSS12 predicted mortality in 86.7% of cases (ORcrude 31, CI 95% 4.79-200.51). Applying a threshold of 10 with LUSS8 predicted mortality in 88.9% (ORcrude 69.75, CI 95% 6.90-705.20). There is a correlation between ferritin levels and LUSS. The prognostic capacity of LUSS12 does not surpass that of LUSS8.

positive: Presepsin as a predictive biomarker of severity in COVID-19: A case series

positive: Time-series plasma cell-free DNA analysis reveals disease severity of COVID-19 patients Symptoms of coronavirus disease 2019 (COVID-19) range from asymptomatic to severe pneumonia and death. Detection of individuals at high risk for critical condition is crucial for control of the disease. Herein, for the first time, we profiled and analyzed plasma cell-free DNA (cfDNA) of mild and severe COVID-19 patients. We found that in comparison between mild and severe COVID-19 patients, Interleukin-37 signaling was one of the most relevant pathways; top significantly altered genes included POTEH, FAM27C, SPATA48, which were mostly expressed in prostate and testis; adrenal glands, small intestines and liver were tissues presenting most differentially expressed genes. Our data thus revealed potential tissue involvement, provided insights into mechanism on COVID-19 progression, and highlighted utility of cfDNA as a noninvasive biomarker for disease severity inspections.

positive: Risk factors for severe COVID-19: evidence from 167 hospitalized patients in Anhui, China

positive: Clinical Decision Support Tool and Rapid Point-of-Care Platform for Determining Disease Severity in Patients with COVID-19 SARS-CoV-2 is the virus that causes coronavirus disease (COVID-19) which has reached pandemic levels resulting in significant morbidity and mortality affecting every inhabited continent. The large number of patients requiring intensive care threatens to overwhelm healthcare systems globally. Likewise, there is a compelling need for a COVID-19 disease severity test to prioritize care and resources for patients at elevated risk of mortality. Here, an integrated point-of-care COVID-19 Severity Score and clinical decision support system is presented using biomarker measurements of C-reactive protein (CRP), N-terminus pro B type natriuretic peptide (NT-proBNP), myoglobin (MYO), D-dimer, procalcitonin (PCT), creatine kinase-myocardial band (CK-MB), and cardiac troponin I (cTnI). The COVID-19 Severity Score combines multiplex biomarker measurements and risk factors in a statistical learning algorithm to predict mortality. The COVID-19 Severity Score was trained and evaluated using data from 160 hospitalized COVID-19 patients from Wuhan, China. Our analysis finds that COVID-19 Severity Scores were significantly higher for the group that died versus the group that was discharged with median (interquartile range) scores of 59 (40–83) and 9 (6–17), respectively, and area under the curve of 0.94 (95% CI 0.89–0.99). These promising initial models pave the way for a point-of-care COVID-19 Severity Score system to impact patient care after further validation with externally collected clinical data. Clinical decision support tools for COVID-19 have strong potential to empower healthcare providers to save lives by prioritizing critical care in patients at high risk for adverse outcomes.

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: Bilirubin levels in patients with mild and severe Covid‐19: A pooled analysis The letter comments on a recent commentary published in Liver International entitled "COVID-19 and liver disease" by Sun et al., and describes a pooled analysis of data on bilirubin levels in patients with and without severe Covid-19. This is the first pooled analysis of data on bilirubin in Covid-19 patients. The results evidence that bilirubin levels are significantly associated with the severity of the disease.

positive: C-reactive protein: a promising biomarker for poor prognosis in COVID-19 infection BACKGROUND: The novel coronavirus disease 2019 (COVID-19) break out from Wuhan, China, spread over 227 countries and caused approximately 0.3 million death worldwide. Several biomolecules have been explored for possible biomarkers for prognosis outcome. Although increased C reactive protein (CRP) has been associated with death due to COVID-19 infections, results from different populations remain inconsistent. For a conclusive result, the present meta-analysis was performed. METHODS: We conducted a literature survey in PubMed and Scopus database for the association of CRP concentration with COVID-19 disease outcomes. A total of 16 eligible studies were enrolled in the present analysis comprising of 1896 survivors and 849 non-survivors cases. Concentrations of CRP were compared and analyzed by a meta-analysis. RESULTS: Egger’s regression analysis (intercept=0.04, P=0.98, 95%CI=-5.48 to 5.58) and funnel plot revealed an absence of publication bias in the included studies. Due to the presence of significant heterogeneity across the studies (Q=252.03, P(heterogeneity)= 0.000, I(2)=93.65) random model was used for the analysis of the present study. The results of the meta-analysis demonstrated a significant role of CRP in COVID-19 infection outcome (Standard difference in means= 1.371, P=0.000). CONCLUSIONS: Concentrations of CRP remained increased in patients who died in COVID-19 infection and could be a promising biomarker for accessing disease lethality.

positive: From Community Acquired Pneumonia to COVID-19: A Deep Learning Based Method for Quantitative Analysis of COVID-19 on thick-section CT Scans Background: Thick-section CT scanners are more affordable for the developing countries. Considering the widely spread COVID-19, it is of great benefit to develop an automated and accurate system for quantification of COVID-19 associated lung abnormalities using thick-section chest CT images. Purpose: To develop a fully automated AI system to quantitatively assess the disease severity and disease progression using thick-section chest CT images. Materials and Methods: In this retrospective study, a deep learning based system was developed to automatically segment and quantify the COVID-19 infected lung regions on thick-section chest CT images. 531 thick-section CT scans from 204 patients diagnosed with COVID-19 were collected from one appointed COVID-19 hospital from 23 January 2020 to 12 February 2020. The lung abnormalities were first segmented by a deep learning model. To assess the disease severity (non-severe or severe) and the progression, two imaging bio-markers were automatically computed, i.e., the portion of infection (POI) and the average infection HU (iHU). The performance of lung abnormality segmentation was examined using Dice coefficient, while the assessment of disease severity and the disease progression were evaluated using the area under the receiver operating characteristic curve (AUC) and the Cohen's kappa statistic, respectively. Results: Dice coefficient between the segmentation of the AI system and the manual delineations of two experienced radiologists for the COVID-19 infected lung abnormalities were 0.74 {+/-} 0.28 and 0.76 {+/-} 0.29, respectively, which were close to the inter-observer agreement, i.e., 0.79 {+/-} 0.25. The computed two imaging bio-markers can distinguish between the severe and non-severe stages with an AUC of 0.9680 (p-value < 0.001). Very good agreement ({kappa} = 0.8220) between the AI system and the radiologists were achieved on evaluating the changes of infection volumes. Conclusions: A deep learning based AI system built on the thick-section CT imaging can accurately quantify the COVID-19 associated lung abnormalities, assess the disease severity and its progressions.

positive: Abnormalities of peripheral blood system in patients with COVID-19 in Wenzhou, China Abstract Background In December 2019, coronavirus disease 2019 (COVID-19) was first found in Wuhan, China and soon was reported all around the world. Methods All confirmed cases with COVID-19 in Wenzhou from January 19 to February 20, 2020, were collected and analyzed. Of the 116 patients with COVID-19, 27 were diagnosed as severe cases. Among severe cases, 9 were treated in ICU. The data of blood routine examination were analyzed and compared among common patients (as common group), severe patients admitted to intensive care unit (as severe ICU group) and severe patients not admitted to ICU (as severe non-ICU group). The blood routine examination results were dynamically observed in the above groups after admission. Results Patients with COVID-19 have lower counts of leucocytes, lymphocytes, eosinophils, platelets, and hemoglobin, but have higher neutrophil-lymphocyte ratio (NLR) and monocyte-lymphocyte ratio (MLR), which were compared with controls (P < 0.001). In severe ICU group, patients have the lowest count of lymphocytes, but the highest neutrophil count and NLR among the above three groups (all P values < 0.05); NLR and MLR indicators were combined for diagnostic efficacy analysis of severe COVID-19, and its area under the curve reached 0.925. The odds ratio of the delay in days to the start of the increase of eosinophil count for predicting the outcome of patients with severe COVID-19 was 2.291 after age adjusted. Conclusions Patients with COVID-19 have abnormal peripheral blood routine examination results. Dynamic surveillance of peripheral blood system especially eosinophils is helpful in the prediction of severe COVID-19 cases.

positive: Prompt Predicting of Early Clinical Deterioration of Moderate-to-Severe COVID-19 Patients: Usefulness of a Combined Score Using IL-6 in a Preliminary Study BACKGROUND: The early identification of patients at risk of clinical deterioration is of interest considering the timeline of COVID-19 after the onset of symptoms. OBJECTIVE: The aim of our study was to evaluate the usefulness of testing serum IL-6 and other serological and clinical biomarkers, to predict a short-term negative clinical course of patients with noncritical COVID-19. METHODS: A total of 208 patients with noncritical COVID-19 pneumonia at admission were consecutively enrolled. Clinical and laboratory findings obtained on admission were analyzed by using survival analysis and stepwise logistic regression for variable selection. Three-day worsening as outcome in a logistic model to generate a prognostic score was used. RESULTS: Clinical worsening occurred in 63 patients (16 = died; 39 = transferred to intensive care unit; 8 worsening of respiratory failure). Forty-five of them worsened within 3 days after admission. The risk of clinical worsening was progressively enhanced along with increasing quartiles of IL-6 levels. Multivariate analysis showed that IL-6 (P = .005), C-reactive protein (CRP) (P = .003), and SaO2/FiO2 (P = .014) were the best predictors for clinical deterioration in the first 3 days after admission. The combined score yielded an area under the curve = 0.88 (95% confidence interval: 0.83-0.93). A nomogram predicting the probability of 3-day worsening was generated. The score also showed good performance for 7-day and 14- or 21-day worsening and in predicting death occurring during all the follow-up. CONCLUSIONS: Combining IL-6, CRP, and SaO2/FiO2 in a score may help clinicians to identify on admission those patients with COVID-19 who are at high risk for a further 3-day clinical deterioration.

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

positive: 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.

positive: Deep Learning COVID-19 Features on CXR using Limited Training Data Sets Under the global pandemic of COVID-19, the use of artificial intelligence to analyze chest X-ray (CXR) image for COVID-19 diagnosis and patient triage is becoming important. Unfortunately, due to the emergent nature of the COVID-19 pandemic, a systematic collection of the CXR data set for deep neural network training is difficult. To address this problem, here we propose a patch-based convolutional neural network approach with a relatively small number of trainable parameters for COVID-19 diagnosis. The proposed method is inspired by our statistical analysis of the potential imaging biomarkers of the CXR radiographs. Experimental results show that our method achieves state-of-the-art performance and provides clinically interpretable saliency maps, which are useful for COVID-19 diagnosis and patient triage.

positive: Coronavirus disease 2019 in elderly patients: Characteristics and prognostic factors based on 4-week follow-up Summary Objective To investigate the characteristics and prognostic factors in the elderly patients with COVID-19. Methods Consecutive cases over 60 years old with COVID-19 in Renmin Hospital of Wuhan University from Jan 1 to Feb 6, 2020 were included. The primary outcomes were death and survival till March 5. Data of demographics, clinical features, comorbidities, laboratory tests and complications were collected and compared for different outcomes. Cox regression was performed for prognostic factors. Results 339 patients with COVID-19 (aged 71±8 years,173 females (51%)) were enrolled, including 80 (23.6%) critical, 159 severe (46.9%) and 100 moderate (29.5%) cases. Common comorbidities were hypertension (40.8%), diabetes (16.0%) and cardiovascular disease (15.7%). Common symptoms included fever (92.0%), cough (53.0%), dyspnea (40.8%) and fatigue (39.9%). Lymphocytopenia was a common laboratory finding (63.2%). Common complications included bacterial infection (42.8%), liver enzyme abnormalities (28.7%) and acute respiratory distress syndrome (21.0%). Till Mar 5, 2020, 91 cases were discharged (26.8%), 183 cases stayed in hospital (54.0%) and 65 cases (19.2%) were dead. Shorter length of stay was found for the dead compared with the survivors (5 (3–8) vs. 28 (26–29), P < 0.001). Symptoms of dyspnea (HR 2.35, P = 0.001), comorbidities including cardiovascular disease (HR 1.86, P = 0.031) and chronic obstructive pulmonary disease (HR 2.24, P = 0.023), and acute respiratory distress syndrome (HR 29.33, P < 0.001) were strong predictors of death. And a high level of lymphocytes was predictive of better outcome (HR 0.10, P < 0.001). Conclusions High proportion of severe to critical cases and high fatality rate were observed in the elderly COVID-19 patients. Rapid disease progress was noted in the dead with a median survival time of 5 days after admission. Dyspnea, lymphocytopenia, comorbidities including cardiovascular disease and chronic obstructive pulmonary disease, and acute respiratory distress syndrome were predictive of poor outcome. Close monitoring and timely treatment should be performed for the elderly patients at high risk.

positive: Association between ages and clinical characteristics and outcomes of coronavirus disease 2019 Age significantly determined the clinical features and prognosis of the disease. The prognosis was worse in patients older than 60 years, calling for clinicians to pay more attention to patients on this special age. https://bit.ly/34DTI05

positive: AI-Driven CT-based quantification, staging and short-term outcome prediction of COVID-19 pneumonia Chest computed tomography (CT) is widely used for the management of Coronavirus disease 2019 (COVID-19) pneumonia because of its availability and rapidity. The standard of reference for confirming COVID-19 relies on microbiological tests but these tests might not be available in an emergency setting and their results are not immediately available, contrary to CT. In addition to its role for early diagnosis, CT has a prognostic role by allowing visually evaluating the extent of COVID-19 lung abnormalities. The objective of this study is to address prediction of short-term outcomes, especially need for mechanical ventilation. In this multi-centric study, we propose an end-to-end artificial intelligence solution for automatic quantification and prognosis assessment by combining automatic CT delineation of lung disease meeting performance of experts and data-driven identification of biomarkers for its prognosis. AI-driven combination of variables with CT-based biomarkers offers perspectives for optimal patient management given the shortage of intensive care beds and ventilators.

positive: 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.

positive: Elevations of serum cancer biomarkers correlate with severity of COVID‐19 In this retrospective study, we evaluated the levels of a series of serum biomarkers in coronavirus disease 2019 (COVID‐19) patients (mild: 131; severe: 98; critical: 23). We found that there were significant increases in levels of human epididymis protein 4 (HE4) (73.6 ± 38.3 versus 46.5 ± 14.7, p<0.001), cytokeratin‐19 fragment (CYFRA21‐1) (2.2 ± 0.9 versus 1.9 ± 0.8, p<0.001), carcinoembryonic antigen (CEA) (3.4 ± 2.2 versus 2.1 ± 1.2, p<0.001), carbohydrate antigens (CA) 125 (18.1 ± 13.5 versus 10.5 ± 4.6, p<0.001) and 153 (14.4 ± 8.9 versus 10.1 ± 4.4, p<0.001) in COVID‐19 mild cases as compared to normal control subjects; their levels showed continuous and significant increases in severe and critical cases (HE4, CYFRA21‐1 and CA125: p<0.001; CEA and CA153: p<0.01). Squamous cell carcinoma antigen (SCC) and CA199 increased significantly only in critical cases of COVID‐19 as compared with mild and severe cases and normal controls (p<0.01). There were positive associations between levels of C‐reactive protein and levels of HE4 (R= 0.631, p<0.001), CYFRA21‐1(R= 0.431, p<0.001), CEA (R= 0.316, p<0.001), SCC (R= 0.351, p<0.001), CA153 (R= 0.359, p<0.001) and CA125 (R= 0.223, p=0.031). We concluded that elevations of serum cancer biomarkers positively correlated with the pathological progressions of COVID‐19, demonstrating diffuse and acute lung injuries. This article is protected by copyright. All rights reserved.

positive: Cardiac injury is associated with mortality and critically ill pneumonia in COVID-19: A meta-analysis Abstract Background In this systematic review and meta-analysis, we aimed to explore the association between cardiac injury and mortality, the need for intensive care unit (ICU) care, acute respiratory distress syndrome (ARDS), and severe coronavirus disease 2019 (COVID-19) in patients with COVID-19 pneumonia. Methods We performed a comprehensive literature search from several databases. Definition of cardiac injury follows that of the included studies, which includes highly sensitive cardiac troponin I (hs-cTnl) >99th percentile.The primary outcome was mortality, and the secondary outcomes were ARDS, the need for ICU care, and severe COVID-19. ARDS and severe COVID-19 were defined per the World Health Organization (WHO) interim guidance of severe acute respiratory infection (SARI) of COVID-19. Results There were a total of 2389 patients from 13 studies. This meta-analysis showed that cardiac injury was associated with higher mortality (RR 7.95 [5.12, 12.34], p < 0.001; I2: 65%). Cardiac injury was associated with higher need for ICU care (RR 7.94 [1.51, 41.78], p = 0.01; I2: 79%), and severe COVID-19 (RR 13.81 [5.52, 34.52], p < 0.001; I2: 0%). The cardiac injury was not significant for increased risk of ARDS (RR 2.57 [0.96, 6.85], p = 0.06; I2: 84%). The level of hs-cTnI was higher in patients with primary + secondary outcome (mean difference 10.38 pg/mL [4.44, 16.32], p = 0.002; I2: 0%). Conclusion Cardiac injury is associated with mortality, need for ICU care, and severity of disease in patients with COVID-19.

positive: Correlation between the variables collected at admission and progression to severe cases during hospitalization among patients with COVID-19 in Chongqing Mortality is high among severe patients with 2019 novel coronavirus-infected disease (COVID-19). Early prediction of progression to severe cases is needed. We retrospectively collected patients with COVID-19 in two hospital of Chongqing from 1st January to 29th February 2020. At admission, we collected the demographics and laboratory tests to predict whether the patient would progress to severe cases in hospitalization. Severe case was confirmed when one of the following criteria occurred: (a) dyspnea, respiratory rate ≥30 breaths/min, (b) blood oxygen saturation ≤93%, and (c) PaO2 /FiO2 ≤ 300 mm Hg. At admission, 348 mild cases were enrolled in this study. Of them, 20 (5.7%) patients progressed to severe cases after median 4.0 days (interquartile range: 2.3-6.0). Pulmonary inflammation index, platelet counts, sodium, C-reactive protein, prealbumin, and PaCO2 showed good distinguishing power to predict progression to severe cases (each area under the curve of receiver operating characteristics [AUC] ≥ 0.8). Age, heart rate, chlorine, alanine aminotransferase, aspartate aminotransferase, procalcitonin, creatine kinase, pH, CD3 counts, and CD4 counts showed moderate distinguishing power (each AUC between 0.7-0.8). And potassium, creatinine, temperature, and D-dimer showed mild distinguishing power (each AUC between 0.6-0.7). In addition, higher C-reactive protein was associated with shorter time to progress to severe cases (r = -0.62). Several easily obtained variables at admission are associated with progression to severe cases during hospitalization. These variables provide a reference for the medical staffs when they manage the patients with COVID-19.

positive: Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis BACKGROUND: Coronavirus disease 2019 (COVID-19) is a novel infectious disease with lack of established laboratory markers available to evaluate illness severity. In this study, we investigate whether platelet count could differentiate between COVID-19 patients with or without severe disease. Additionally, we evaluate if thrombocytopenia is associated with severe COVID-19. METHODS: An electronic search in Medline, Scopus and Web of Science was performed to identify studies reporting data on platelet count in COVID-19 patients. A meta-analysis was performed, with calculation of weighted mean difference (WMD) of platelet number in COVID-19 patients with or without severe disease and odds ratio (OR) of thrombocytopenia for severe form of COVID-19. RESULTS: Nine studies with 1779 COVID-19 patients, 399 (22.4%) with severe disease, were included in the meta-analysis. The pooled analysis revealed that platelet count was significantly lower in patients with more severe COVID-19 (WMD -31 × 109/L; 95% CI, from -35 to -29 × 109/L). A subgroup analysis comparing patients by survival, found an even lower platelet count was observed with mortality (WMD, -48 × 109/L; 95% CI, -57 to -39 × 109/L. In the four studies (n = 1427) which reported data on rate of thrombocytopenia, a low platelet count was associated with over fivefold enhanced risk of severe COVID-19 (OR, 5.1; 95% CI, 1.8-14.6). CONCLUSIONS: Low platelet count is associated with increased risk of severe disease and mortality in patients with COVID-19, and thus should serve as clinical indicator of worsening illness during hospitalization.

positive: 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.

positive: Application of a portable instrument for rapid and reliable detection of SARS‐CoV‐2 infection in any environment The ongoing outbreak of the novel coronavirus (SARS‐CoV‐2) infection is creating serious challenges for health laboratories that seek to identify viral infections as early as possible, optimally at the earliest appearance of symptom. Indeed, there is urgent need to develop and deploy robust diagnostic methodologies not only to use in health laboratory environments but also directly in places where humans circulate and spread the virus such as airports, trains, boats, and any public aggregation places. The success of a reliable and sensitive asymptomatic diagnosis relies on the identification and measurement of informative biomarkers from human host and virus in a rapid, sensitive, and inexpensive manner. The objective of this article is to describe an innovative multidisciplinary approach to develop an efficient, inexpensive, and easy‐to‐use portable instrument (bCUBE(®) by Hyris Ltd) that can be employed as a surveillance system for the emergency caused by SARS‐CoV‐2. A solution for Coronavirus testing, compliant with CDC guidelines, is scheduled to be released in the next weeks. In addition, we will describe a workflow and path of an integrated multi‐omic approach that will lead to host and pathogen biomarker discovery in order to train the instrument to provide reliable results based on a specific biomarker's fingerprint of SARS‐CoV‐2 infection.

positive: Analysis of clinical characteristics and laboratory findings of 95 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a retrospective analysis BACKGROUND: Since December 2019, 2019 novel coronavirus pneumonia emerged in Wuhan city and rapidly spread throughout China and even the world. We sought to analyse the clinical characteristics and laboratory findings of some cases with 2019 novel coronavirus pneumonia . METHODS: In this retrospective study, we extracted the data on 95 patients with laboratory-confirmed 2019 novel coronavirus pneumonia in Wuhan Xinzhou District People's Hospital from January 16th to February 25th, 2020. Cases were confirmed by real-time RT-PCR and abnormal radiologic findings. Outcomes were followed up until March 2th, 2020. RESULTS: Higher temperature, blood leukocyte count, neutrophil count, neutrophil percentage, C-reactive protein level, D-dimer level, alanine aminotransferase activity, aspartate aminotransferase activity, α - hydroxybutyrate dehydrogenase activity, lactate dehydrogenase activity and creatine kinase activity were related to severe 2019 novel coronavirus pneumonia and composite endpoint, and so were lower lymphocyte count, lymphocyte percentage and total protein level. Age below 40 or above 60 years old, male, higher Creatinine level, and lower platelet count also seemed related to severe 2019 novel coronavirus pneumonia and composite endpoint, however the P values were greater than 0.05, which mean under the same condition studies of larger samples are needed in the future. CONCLUSION: Multiple factors were related to severe 2019 novel coronavirus pneumonia and composite endpoint, and more related studies are needed in the future.

positive: Characteristics and prognostic factors of disease severity in patients with COVID-19: The Beijing experience COVID-19 has become one of the worst infectious disease outbreaks of recent times, with over 2.1 million cases and 120,000 deaths so far. Our study investigated the demographic, clinical, laboratory and imaging features of 63 patients with COVID-19 in Beijing. Patients were classified into four groups, mild, moderate, severe and critically ill. The mean age of our patients was 47 years of age (range 3-85) and there was a slight male predominance (58.7%). Thirty percent of our patients had severe or critically ill disease, but only 20% of severe and 33% of critically ill patients had been to Wuhan. Fever was the most common presentation (84.1%), but cough was present in only slightly over half of the patients. We found that lymphocyte and eosinophils count were significantly decreased in patients with severe disease (p = 0.001 and p = 0.000, respectively). Eosinopenia was a feature of higher levels of severity. Peripheral CD4+, CD8+ T lymphocytes, and B lymphocytes were significantly decreased in severe and critically ill patients, but there was only a non-statistically significant downward trend in NK cell numbers with severity. Of note is that liver function tests including AST, ALT, GGT and LDH were elevated, and albumin was decreased. The inflammatory markers CRP, ESR and ferritin were elevated in patients with severe disease or worse. IL-6 levels were also higher, indicating that the presence of a hyperimmune inflammatory state portends higher morbidity and mortality. In a binary logistic regression model, C-reactive protein level (OR 1.073, [CI, 1.013-1.136]; p = 0.017), CD8 T lymphocyte counts (OR 0.989, [CI, 0.979-1.000]; p = 0.043), and D-dimer (OR 5.313, [CI, 0.325-86.816]; p = 0.241) were independent predictors of disease severity.

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

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

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

positive: [Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia]. Objective: To analyze the clinical characteristics of 2019 novel coronavirus (2019-nCoV) pneumonia and to investigate the correlation between serum inflammatory cytokines and severity of the disease. Methods: 29 patients with 2019-ncov admitted to the isolation ward of Tongji hospital affiliated to Tongji medical college of Huazhong University of Science and Technology in January 2020 were selected as the study subjects. Clinical data were collected and the general information, clinical symptoms, blood test and CT imaging characteristics were analyzed. According to the relevant diagnostic criteria, the patients were divided into three groups: mild (15 cases), severe (9 cases) and critical (5 cases). The expression levels of inflammatory cytokines and other markers in the serum of each group were detected, and the changes of these indicators of the three groups were compared and analyzed, as well as their relationship with the clinical classification of the disease. Results: (1) The main symptoms of 2019-nCoV pneumonia was fever (28/29) with or without respiratory and other systemic symptoms. Two patients died with underlying disease and co-bacterial infection, respectively. (2) The blood test of the patients showed normal or decreased white blood cell count (23/29), decreased lymphocyte count (20/29), increased hypersensitive C reactive protein (hs-CRP) (27/29), and normal procalcitonin. In most patients,serum lactate dehydrogenase (LDH) was significantly increased (20/29), while albumin was decreased(15/29). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Tbil), serum creatinine (Scr) and other items showed no significant changes. (3) CT findings of typical cases were single or multiple patchy ground glass shadows accompanied by septal thickening. When the disease progresses, the lesion increases and the scope expands, and the ground glass shadow coexists with the solid shadow or the stripe shadow. (4) There were statistically significant differences in the expression levels of interleukin-2 receptor (IL-2R) and IL-6 in the serum of the three groups (P<0.05), among which the critical group was higher than the severe group and the severe group was higher than the mildgroup. However, there were no statistically significant differences in serum levels of tumor necrosis factor-alpha (TNF-α), IL-1, IL-8, IL-10, hs-CRP, lymphocyte count and LDH among the three groups (P>0.05). Conclusion: The clinical characteristics of 2019-nCoV pneumonia are similar to those of common viral pneumonia. High resolution CT is of great value in the differential diagnosis of this disease. The increased expression of IL-2R and IL-6 in serum is expected to predict the severity of the 2019-nCoV pneumonia and the prognosis of patients.

positive: Diabetes is a risk factor for the progression and prognosis of COVID-19 BACKGOUND: To figure out whether diabetes is a risk factor influencing the progression and prognosis of 2019 novel coronavirus disease (COVID-19). METHODS: A total of 174 consecutive patients confirmed with COVID-19 were studied. Demographic data, medical history, symptoms and signs, laboratory findings, chest computed tomography (CT) as well the treatment measures were collected and analysed. RESULTS: We found that COVID-19 patients without other comorbidities but with diabetes (n = 24) were at higher risk of severe pneumonia, release of tissue injury-related enzymes, excessive uncontrolled inflammation responses and hypercoagulable state associated with dysregulation of glucose metabolism. Furthermore, serum levels of inflammation-related biomarkers such as IL-6, C-reactive protein, serum ferritin and coagulation index, D-dimer, were significantly higher (P < .01) in diabetic patients compared with those without, suggesting that patients with diabetes are more susceptible to an inflammatory storm eventually leading to rapid deterioration of COVID-19. CONCLUSIONS: Our data support the notion that diabetes should be considered as a risk factor for a rapid progression and bad prognosis of COVID-19. More intensive attention should be paid to patients with diabetes, in case of rapid deterioration.

positive: The Acute Respiratory Distress Syndrome Biomarker Pipeline: Crippling Gaps between Discovery and Clinical Utility Recent innovations in translational research have ushered an exponential increase in the discovery of novel biomarkers, thereby elevating the hope for deeper insights into “personalized” medicine approaches to disease phenotyping and care. However, a critical gap exists between the fast pace of biomarker discovery and the successful translation to clinical use. This gap underscores the fundamental biomarker conundrum across various acute and chronic disorders: how does a biomarker address a specific unmet need? Additionally, the gap highlights the need to shift the paradigm from a focus on biomarker discovery to greater translational impact and the need for a more streamlined drug approval process. The unmet need for biomarkers in acute respiratory distress syndrome (ARDS) is for reliable and validated biomarkers that minimize heterogeneity and allow for stratification of subject selection for enrollment in clinical trials of tailored therapies. This unmet need is particularly highlighted by the ongoing SARS-CoV-2/COVID-19 pandemic. The unprecedented numbers of COVID-19-induced ARDS cases has strained health care systems across the world and exposed the need for biomarkers that would accelerate drug development and the successful phenotyping of COVID-19-infected patients at risk for development of ARDS and ARDS mortality. Accordingly, this review discusses the current state of ARDS biomarkers in the context of the drug development pipeline and highlight gaps between biomarker discovery and clinical implementation while proposing potential paths forward. We discuss potential ARDS biomarkers by category and by context of use, highlighting progress in the development continuum. We conclude by discussing challenges to successful translation of biomarker candidates to clinical impact and proposing possible novel strategies.

positive: Clinical analysis of risk factors for severe patients with novel coronavirus pneumonia/ 中华传染病杂志 Objective To analyze the clinical features of patients with coronavirus disease 2019 (COVID-19) in Shanghai and to investigate the risk factors for disease progression to severe cases. Methods The clinical data of 292 adult patients with COVID-19 hospitalized in Shanghai Public Health Clinical Center from January 20, 2020 to February 10, 2020 were retrospectively analyzed, including 21 severe patients and 271 mild patients. The demographic characteristics, epidemiological history, history of underlying diseases and laboratory examinations were compared between the two groups. Measurement data were compared using t test or Mann-Whitney U test. The count data were compared using hi-square test. The binary logistic regression equation was used to analyze the risk factors for the progression of patients to severe cases. Results Among the 292 patients, 21 were severe cases with the rate of 7.2% (21/292). One patient died, and the mortality rate was 4.8% in severe patients. The severe patients aged (65.0±15.7) years old, 19 (90.5%) were male, 11 (52.4%) had underlying diseases, 7 (33.3%) had close relatives diagnosed with COVID-19. The mild patients aged (48.7±15.7) years old, 135 (49.8%) were male, 74 (27.3%) had underlying diseases, 36 (13.3%) had close relatives diagnosed with COVID-19. The differences between two groups were all significant statistically ( t =-4.730, χ 2 =12.930, 5.938 and 4.744, respectively, all P <0.05). Compared with the mild patients, the levels of absolute numbers of neutrophils, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, creatinine, serum cystatin C, C reactive protein (CRP), procalcitonin , D -dimer, pro-B-type natriuretic peptide (proBNP), serum myoglobin, creatine kinase (CK), creatine kinase isoenzyme (CK-MB), serum troponin I (cTnI) in severe patients were all significantly higher ( U =2 091.5, 1 928.0, 1 215.5, 729.0, 1 580.5, 1 375.5, 917.5, 789.5, 1 209.0, 1 434.0, 638.0, 964.5, 1 258.0 and 1 747.5, respectively, all P <0.05), while the levels of lymphocyte count, albumin, transferrin, CD3 + T lymphocyte count, CD8 + T lymphocyte count and CD4 + T lymphocyte count in severe patients were all significantly lower ( U =1 263.5, t =4.716, U =1 214.0, 962.0, 1 167.5 and 988.0, respectively, all P <0.05). Further logistic regression analysis showed that the albumin (odds ratio ( OR )=0.806, 95% CI 0.675-0.961), CRP ( OR =1.016, 95% CI 1.000-1.032), serum myoglobin ( OR =1.010, 95% CI 1.004-1.016), CD3 + T lymphocyte count ( OR =0.996, 95% CI 0.991-1.000) and CD8 + T lymphocyte count ( OR =1.006, 95% CI 1.001-1.010) at admission were independent risk factors for the progression of COVID-19 patients to severe illness (all P <0.05). Conclusions Severe cases of patients with COVID-19 in Shanghai are predominantly elderly men with underlying diseases. Albumin, CRP, serum myoglobin, CD3 + T lymphocyte count and CD8 + T lymphocyte count could be used as early warning indicators for severe cases, which deserve more clinical attention.

positive: C-reactive protein, procalcitonin, D-dimer, and ferritin in severe coronavirus disease-2019: a meta-analysis BACKGROUND: Patients critically ill with coronavirus disease-2019 (COVID-19) feature hyperinflammation, and the associated biomarkers may be beneficial for risk stratification. We aimed to investigate the association between several biomarkers, including serum C-reactive protein (CRP), procalcitonin (PCT), D-dimer, and serum ferritin, and COVID-19 severity. METHODS: We performed a comprehensive systematic literature search through electronic databases. The outcome of interest for this study was the composite poor outcome, which comprises mortality, acute respiratory distress syndrome, need for care in an intensive care unit, and severe COVID-19. RESULTS: A total of 5350 patients were pooled from 25 studies. Elevated CRP was associated with an increased composite poor outcome [risk ratio (RR) 1.84 (1.45, 2.33), p < 0.001; I(2): 96%] and its severe COVID-19 (RR 1.41; I(2): 93%) subgroup. A CRP ⩾10 mg/L has a 51% sensitivity, 88% specificity, likelihood ratio (LR) + of 4.1, LR- of 0.5, and an area under curve (AUC) of 0.84. An elevated PCT was associated with an increased composite poor outcome [RR 3.92 (2.42, 6.35), p < 0.001; I(2): 85%] and its mortality (RR 6.26; I(2): 96%) and severe COVID-19 (RR 3.93; I(2): 63%) subgroups. A PCT ⩾0.5 ng/ml has an 88% sensitivity, 68% specificity, LR+ of 2.7, LR- of 0.2, and an AUC of 0.88. An elevated D-dimer was associated with an increased composite poor outcome [RR 2.93 (2.14, 4.01), p < 0.001; I(2): 77%], including its mortality (RR 4.15; I(2): 83%) and severe COVID-19 (RR 2.42; I(2): 58%) subgroups. A D-dimer >0.5 mg/L has a 58% sensitivity, 69% specificity, LR+ of 1.8, LR- of 0.6, and an AUC of 0.69. Patients with a composite poor outcome had a higher serum ferritin with a standardized mean difference of 0.90 (0.64, 1.15), p < 0.0001; I(2): 76%. CONCLUSION: This meta-analysis showed that an elevated serum CRP, PCT, D-dimer, and ferritin were associated with a poor outcome in COVID-19. The reviews of this paper are available via the supplemental material section.

positive: Clinical characteristics and co-infections of 354 hospitalized patients with COVID-19 in Wuhan, China: a retrospective cohort study From December 2019, a novel coronavirus, SARS-CoV-2, caused an outbreak of pneumonia in Wuhan city and rapidly spread throughout China and globally. However, the clinical characteristics and co-infection with other respiratory pathogens of patients with COVID-19 and the factors associated with severity of COVID-19 are still limited. In this retrospective cohort study, we included 354 inpatients with COVID-19 admitted to Renmin Hospital of Wuhan University from February 4, 2020 to February 28, 2020. We found levels of interleukin-6, interleukin-10, C-reactive protein, D-dimer, white blood cell count and neutrophil count were clearly elevated in males and critical cases compared with females and severe and mild cases, respectively. However, lymphopenia was more severe in males than females and levels of tumor necrosis factor alpha were reduced significantly in critical cases than severe and mild cases. 23.5% of severe cases and 24.4% of critical cases were co-infected with other respiratory pathogens. Additionally, stepwise multivariable regression analysis suggested that co-infection, lymphocyte count and levels of D-dimer were associated with severity of COVID-19.These findings provide crucial clues for further identification of the mechanisms, characteristics and treatments of patients with COVID-19.

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: Validation of reported risk factors for disease classification and prognosis in COVID-19: a descriptive and retrospective study Risk indicators viral load (ORF1ab Ct), lymphocyte percentage (LYM%), C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT) and lactic acid (LA) in COVID-19 patients have been proposed in recent studies. However, the predictive effects of those indicators on disease classification and prognosis remains largely unknown. We dynamically measured those reported indicators in 132 cases of COVID-19 patients including the moderate-cured (moderated and cured), severe-cured (severe and cured) and critically ill (died). Our data showed that CRP, PCT, IL-6, LYM%, lactic acid and viral load could predict prognosis and guide classification of COVID-19 patients in different degrees. CRP, IL-6 and LYM% were more effective than other three factors in predicting prognosis. For disease classification, CRP and LYM% were sensitive in identifying the types between critically ill and severe (or moderate). Notably, among the investigated factors, LYM% was the only one that could distinguish between the severe and moderate types. Collectively, we concluded that LYM% was the most sensitive and reliable predictor for disease typing and prognosis. During the COVID-19 pandemic, the precise classification and prognosis prediction are critical for saving the insufficient medical resources, stratified treatment and improving the survival rate of critically ill patients. We recommend that LYM% be used independently or in combination with other indicators in the management of COVID-19.

positive: Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis Abstract Background Many studies on COVID-19 have reported diabetes to be associated with severe disease and mortality, however, the data is conflicting. The objectives of this meta-analysis were to explore the relationship between diabetes and COVID-19 mortality and severity, and to determine the prevalence of diabetes in patients with COVID-19. Methods We searched the PubMed for case-control studies in English, published between Jan 1 and Apr 22, 2020, that had data on diabetes in patients with COVID-19. The frequency of diabetes was compared between patients with and without the composite endpoint of mortality or severity. Random effects model was used with odds ratio as the effect size. We also determined the pooled prevalence of diabetes in patients with COVID-19. Heterogeneity and publication bias were taken care by meta-regression, sub-group analyses, and trim and fill methods. Results We included 33 studies (16,003 patients) and found diabetes to be significantly associated with mortality of COVID-19 with a pooled odds ratio of 1.90 (95% CI: 1.37–2.64; p < 0.01). Diabetes was also associated with severe COVID-19 with a pooled odds ratio of 2.75 (95% CI: 2.09–3.62; p < 0.01). The combined corrected pooled odds ratio of mortality or severity was 2.16 (95% CI: 1.74–2.68; p < 0.01). The pooled prevalence of diabetes in patients with COVID-19 was 9.8% (95% CI: 8.7%–10.9%) (after adjusting for heterogeneity). Conclusions Diabetes in patients with COVID-19 is associated with a two-fold increase in mortality as well as severity of COVID-19, as compared to non-diabetics. Further studies on the pathogenic mechanisms and therapeutic implications need to be done.

positive: [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.

positive: Plasma albumin levels predict risk for nonsurvivors in critically ill patients with COVID-19 Aim: We aimed to explore the biomarkers for disease progression or the risk of nonsurvivors. Materials & methods: This study included 134 hospitalized patients with confirmed COVID-19 infection. The outcome of moderate versus severe versus critically ill patients and survivors versus nonsurvivors were compared. Results: An increase in the severity of COVID-19 pneumonia was positively associated with lower levels of platelets and albumin (all p < 0.05). In the critical group, the plasma levels of albumin continued to have a significant association for the risk of nonsurvivors (p < 0.05), even after adjusting for confounding factors. Conclusion: Albumin levels could be used as an independent predictor of the risk of nonsurvivors in critically ill patients with COVID-19.

positive: Acute Myocardial Injury of Patients with Coronavirus Disease 2019 Background: Since the outbreak of the Coronavirus Disease 2019 (COVID-19) in China, respiratory manifestations of the disease have been observed. However, as a fatal comorbidity, acute myocardial injury (AMI) in COVID-19 patients has not been previously investigated in detail. We investigated the clinical characteristics of COVID-19 patients with AMI and determined the risk factors for AMI in them. Methods: We analyzed data from 53 consecutive laboratory-confirmed and hospitalized COVID-19 patients (28 men, 25 women; age, 19-81 years). We collected information on epidemiological and demographic characteristics, clinical features, routine laboratory tests (including cardiac injury biomarkers), echocardiography, electrocardiography, imaging findings, management methods, and clinical outcomes. Results: Cardiac complications were found in 42 of the 53 (79.25%) patients: tachycardia (n=15), electrocardiography abnormities (n=11), diastolic dysfunction (n=20), elevated myocardial enzymes (n=30), and AMI (n=6). All the six AMI patients were aged >60 years; five of them had two or more underlying comorbidities (hypertension, diabetes, cardiovascular diseases, and chronic obstructive pulmonary disease). Novel coronavirus pneumonia (NCP) severity was higher in the AMI patients than in patients with non-definite AMI (p<0.001). All the AMI patients required care in intensive care unit; of them, three died, two remain hospitalized. Multivariate analyses showed that C-reactive protein (CRP) levels, NCP severity, and underlying comorbidities were the risk factors for cardiac abnormalities in COVID-19 patients. Conclusions: Cardiac complications are common in COVID-19 patients. Elevated CRP levels, underlying comorbidities, and NCP severity are the main risk factors for cardiac complications in COVID-19 patients.

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

positive: Clinical features and outcomes of 221 patients with COVID-19 in Wuhan, China Rationale: In late December 2019, an outbreak of acute respiratory illness, now officially named as COVID-19, or coronavirus disease 2019, emerged in Wuhan, China, now spreading across the whole country and world. More data were needed to understand the clinical characteristics of the disease. Objectives: To study the epidemiology, clinical features and outcomes of patients with COVID-19. Methods: we performed a single center, retrospective case series study in 221 patients with laboratory confirmed SARS-CoV-2 pneumonia at a university hospital. Measurements and Main Results: The median age was 55.0 years and 48.9% were male and only 8 (3.6%) patients had a history of exposure to the Huanan Seafood Market. Compared to the non-severe pneumonia patients, the median age of the severe patients was significantly older, and they were more likely to have chronic comorbidities. Most common symptoms in severe patients were high fever, anorexia and dyspnea. On admission, 33.0% patients showed leukopenia and 73.8% showed lymphopenia. In addition, the severe patients suffered a higher rate of co-infections with bacteria or fungus and they were more likely to developing complications. As of February 15, 2020, 19.0% patients had been discharged and 5.4% patients died. 80% of severe cases received ICU care, and 52.3% of them transferred to the general wards due to relieved symptoms, and the mortality rate of severe patients in ICU was 20.5%. Conclusions: The COVID-19 epidemic spreads rapidly by human-to-human transmission. Patients with elder age, chronic comorbidities, blood leukocyte/lymphocyte count, procalcitonin level, co-infection and severe complications might increase the risk of poor clinical outcomes. Keywords: coronavirus disease 2019; clinical features; outcomes; severe patients

positive: Clinical Characteristics and Short-Term Outcomes of Severe Patients with COVID-19 in Wuhan, China Objective. A novel pneumonia (COVID-19) which is sweeping the globe was started in December, 2019, in Wuhan, China. Most deaths occurred in severe and critically cases, but information on prognostic risk factors for severe ill patients is incomplete. Further research is urgently needed to guide clinicians, so we prospectively evaluate the clinical outcomes of 114 severe ill patients with COVID-19 for short-term in the Union Hospital in Wuhan, China. Methods. In this single-centered, prospective and observational study, we enrolled 114 severe ill patients with confirmed COVID-19 from Jan 23, 2020 to February 22, 2020. Epidemiological, demographic and laboratory information were collected at baseline, data on treatment and outcome were collected until the day of death or discharge or for the first 28 days after severe ill diagnosis, whichever was shorter. Univariate and multivariate Cox proportional hazard models were used to determine hazard ratios (HRs) and 95% confidence intervals (CIs) of poor outcome. Results. Among enrolled 114 patients, 94 (82.5%) had good outcome while 20 (17.5%) had poor outcome. No significant differences were showed in age, gender and the prevalence of coexisting disorders between outcome groups. Results of multivariate Cox analyses indicated that higher levels of oxygen saturation (HR, 0.123; 95% CI, 0.041-0.369), albumin (HR, 0.060; 95% CI, 0.008-0.460) and arterial partial pressure of oxygen (HR, 0.321; 95% CI, 0.106-0.973) were associated with decreased risk of developing poor outcome within 28 days. In the other hand, higher levels of leucocytes (HR, 5.575; 95% CI, 2.080-14.943), neutrophils (HR, 2.566; 95% CI, 1.022-6.443), total bilirubin (HR, 6.171; 95% CI, 2.458-15.496), globulin (HR, 2.526; 95% CI, 1.027-6.211), blood urea nitrogen (HR, 5.640; 95% CI, 2.193-14.509), creatine kinase-MB (HR, 3.032; 95% CI, 1.203-7.644), lactate dehydrogenase (HR, 4.607; 95% CI, 1.057-20.090), hypersensitive cardiac troponin I (HR, 5.023; 95% CI, 1.921-13.136), lactate concentration (HR,15.721; 95% CI, 2.099-117.777), Interleukin-10 (HR, 3.551; 95% CI, 1.280-9.857) and C-reactive protein (HR, 5.275; 95% CI, 1.517-18.344) were associated with increased risk of poor outcome development. We also found that traditional Chinese medicine can significantly improve the patient's condition, which is conducive to the transformation from severe to mild. Conclusion. In summary, we firstly reported this single-centered, prospective and observational study for short-term outcome in severe patients with COVID-19. We found that cytokine storm and uncontrolled inflammation responses, liver, kidney, cardiac dysfunction may play important roles in final outcome of severe ill patients with COVID-19. Our study will provide clinicians to be benefit to rapidly estimate the likelihood risk of short-term poor outcome for severe patients.

positive: Predicting Illness Severity and Short-Term Outcomes of COVID-19: A Retrospective Cohort Study in China Among 417 COVID-19 patients in Shenzhen, demographic characteristics, clinical manifestations and baseline laboratory tests showed significant differences between mild-moderate cohort and severe-critical cohort.Based on these differences, a convenient mathematical model was established to predict the illness severity of COVID-19. The model includes four parameters: age, BMI, CD4(+) lymphocytes and IL-6 levels. The AUC of the model is 0.911.The high risk factors for developing to severe COVID-19 are: age ≥ 55 years, BMI > 27 kg / m(2), IL-6 ≥ 20 pg / ml, CD4(+) T cell ≤ 400 count / μ L.Among 249 discharged COVID-19 patients, those who recovered after 20 days had a lower count of platelet, a higher level of estimated glomerular filtration rate, and higher level of interleukin-6 and myoglobin than those who recovered within 20 days.

positive: Inflammation Profiling of Critically Ill Coronavirus Disease 2019 Patients OBJECTIVES: Coronavirus disease 2019 is caused by severe acute respiratory syndrome-coronavirus-2 infection to which there is no community immunity. Patients admitted to ICUs have high mortality, with only supportive therapies available. Our aim was to profile plasma inflammatory analytes to help understand the host response to coronavirus disease 2019. DESIGN: Daily blood inflammation profiling with immunoassays. SETTING: Tertiary care ICU and academic laboratory. SUBJECTS: All patients admitted to the ICU suspected of being infected with severe acute respiratory syndrome-coronavirus-2, using standardized hospital screening methodologies, had daily blood samples collected until either testing was confirmed negative on ICU day 3 (coronavirus disease 2019 negative), or until ICU day 7 if the patient was positive (coronavirus disease 2019 positive). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Age- and sex-matched healthy controls and ICU patients that were either coronavirus disease 2019 positive or coronavirus disease 2019 negative were enrolled. Cohorts were well-balanced with the exception that coronavirus disease 2019 positive patients were more likely than coronavirus disease 2019 negative patients to suffer bilateral pneumonia. Mortality rate for coronavirus disease 2019 positive ICU patients was 40%. We measured 57 inflammatory analytes and then analyzed with both conventional statistics and machine learning. Twenty inflammatory analytes were different between coronavirus disease 2019 positive patients and healthy controls (p < 0.01). Compared with coronavirus disease 2019 negative patients, coronavirus disease 2019 positive patients had 17 elevated inflammatory analytes on one or more of their ICU days 1–3 (p < 0.01), with feature classification identifying the top six analytes between cohorts as tumor necrosis factor, granzyme B, heat shock protein 70, interleukin-18, interferon-gamma-inducible protein 10, and elastase 2. While tumor necrosis factor, granzyme B, heat shock protein 70, and interleukin-18 were elevated for all seven ICU days, interferon-gamma-inducible protein 10 transiently elevated on ICU days 2 and 3 and elastase 2 increased over ICU days 2–7. Inflammation profiling predicted coronavirus disease 2019 status with 98% accuracy, whereas elevated heat shock protein 70 was strongly associated with mortality. CONCLUSIONS: While many inflammatory analytes were elevated in coronavirus disease 2019 positive ICU patients, relative to healthy controls, the top six analytes distinguishing coronavirus disease 2019 positive ICU patients from coronavirus disease 2019 negative ICU patients were tumor necrosis factor, granzyme B, heat shock protein 70, interleukin-18, interferon-gamma-inducible protein 10, and elastase 2.

positive: Serum amyloid A is a predictor for prognosis of COVID‐19

positive: 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

positive: [Value of neutrophil-to-lymphocyte ratio in the classification diagnosis of coronavirus disease 2019]. OBJECTIVE To investigate the clinical significance of neutrophil-to-lymphocyte ratio (NLR) in classification of patients with coronavirus disease 2019 (COVID-19). METHODS A retrospective analysis was performed on 72 patients with COVID-19 admitted to the critical ward of Cancer Center of Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology in Wuhan from February to March in 2020. The patients were divided into two groups: moderate type (non-severe group) and severe/critical type (severe group). The results of white blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LYM), interleukin-6 (IL-6) and D-dimer were collected at the 2nd day after admission from the two groups, and the NLR was calculated. The diagnostic value of WBC, NEU, LYM, IL-6, D-dimer and NLR on COVID-19 classification was evaluated by the receiver operating characteristic (ROC) curve. RESULTS A total of 72 COVID-19 patients were enrolled, among whom 52 were moderate, 17 were severe, and 3 were critical. The most common clinical manifestations of patients were fever (70.8%), cough (36.1%), chest tightness and breathlessness (37.5%), diarrhea (15.3%), fatigue (15.3%), vomiting and nausea (11.1%), occasionally accompanied by acute dyspnea (2.8%), and only one patient had no clinical symptom (1.4%). The levels of WBC, NEU, IL-6, D-dimer and NLR in the severe group were significantly higher than those in the non-severe group [WBC (×109/L): 7.81±3.65 vs. 5.34±1.69, NEU (×109/L): 5.83±3.13 vs. 3.24±1.53, IL-6 (ng/L): 133.63 (71.09, 249.61) vs. 28.05 (6.41, 101.24), D-dimer (mg/L): 0.86 (0.31, 2.56) vs. 0.33 (0.20, 0.71), NLR: 6.14±4.75 vs. 2.66±1.93, all P < 0.05], and the level of LYM was significantly lower than that in the non-severe group (×109/L: 1.09±0.56 vs. 1.49±0.74, P < 0.05). The results of ROC curve analysis showed that the areas under ROC curve (AUC) of WBC, NEU, LYM, IL-6, D-dimer and NLR for COVID-19 classification were 0.790 [95% confidence interval (95%CI) was 0.684-0.897), 0.869 (95%CI was 0.789-0.949), 0.719 (95%CI was 0.592-0.847), 0.790 (95%CI was 0.682-0.898), 0.676 (95%CI was 0.526-0.827), and 0.888 (95%CI was 0.814-0.963) respectively. The AUC of NLR was the highest, which was of high diagnostic value; when the optimum cut-off value of NLR was 3.00, the sensitivity was 100%, and the specificity was 73.1%. CONCLUSIONS NLR can be used as a biomarker to predict classification of COVID-19 patients independently, which can provide a theoretical basis for the classification management of COVID-19 patients.

positive: Laboratory characteristics of patients infected with the novel SARS-CoV-2 virus A subgroup of COVID-19 patients develop very severe disease with requirement for ICU treatment, ventilation, and ECMO therapy. Laboratory tests indicate that the immune and clotting system show marked alterations with hyper-activation, hyper-inflammation, cytokine storm development. Furthermore, organ-specific biomarkers demonstrate the involvement of cardiac muscle, kidney, and liver dysfunction in many patients. In this article the use of laboratory biomarkers is discussed with regard to their use for diagnosis, disease progression, and risk assessment.

positive: Epidemiology, virology, and clinical features of severe acute respiratory syndrome -coronavirus-2 (SARS-CoV-2; Coronavirus Disease-19) A cluster of severe pneumonia of unknown etiology in Wuhan City, Hubei province in China emerged in December 2019. A novel coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was isolated from lower respiratory tract sample as the causative agent. The current outbreak of infections with SARS-CoV-2 is termed Coronavirus Disease 2019 (COVID-19) by the World Health Organization (WHO). COVID-19 rapidly spread into at least 114 countries and killed more than 4,000 people by March 11 2020. WHO officially declared COVID-19 a pandemic on March 11, 2020. There have been two novel coronavirus outbreaks in the past two decades. The 2002-2003 outbreak of severe acute respiratory syndrome (SARS) in 2002-2003 caused by SARS-CoV had a case fatality rate of around 10% (8,098 confirmed cases and 774 death), while Middle East respiratory syndrome (MERS) caused by MERS-CoV killed 861 people out of a total 2,502 confirmed cases between 2012 and 2019. The purpose of this review is to summarize known-to-date information about SARS-CoV-2, transmission of SARS-CoV-2, and clinical features.

positive: Clinical features and laboratory inspection of novel coronavirus pneumonia (COVID-19) in Xiangyang, Hubei Background: Since December 2019, a novel coronavirus pneumonia (COVID-19) rapidly spread in China, reached multiple continents currently.We aimed to reveal the infectious characteristics of COVID-19 that provide more information for the research of novel coronavirus. Methods: We performed a retrospective study on the clinical characteristics of 128 COVID-19 cases with laboratory-confirmed from Xiangyang No 1 Hospitalad during January 2020 to 16 February 2020. Results: Female patients account for 53.1%. The aged below 20 years that accounts for 1.6% of overall patients. The aged in 21~50, 51~65, over 66 years were accounts for 44.5%, 35.1%,18.8%, respectively. In the difference age spectrum, all severe groups compared with non-severe groups were difference significantly ( P < 0.01 ). Fever ( 89.8% ) and Cough ( 67.2% ) were common clinical symptoms. The rate of patients with sore throats (14.1%) was rare. The rate of chest computed tomography scan showing ground glass opacity in overall, non-severe, severe groups were 63.3%, 60.7%, 76.2%, respectively. White blood cell counts in the normal range of overall patients, but severe group patients were increased significantly ( P < 0.01). Lymphocytes of overall patients were decreased. Alanine transaminase (ALT) and aspartate transaminase (AST) in the normal range of overall patients, but its were elevated in the severe group. Creatinine (CR) and blood urea nitrogen (BUN) of overall patients in the normal range. C-reactive protein (CRP) level of all patients were increased markedly, but it in the severe group was significantly higher than that in the non-severe group ( P < 0.01 ). Conclusions: Our data provide more information that advanced age, lower lymphocytes levels at the diagnosed COVID-19 patients may be a risk factor for unfavourable prognosis. The white blood cells and C-reactive protein level elevated in severe COVID-19 patients may be accompanying bacterial infection. 2019-nCov may be carries a risk factor of impaired liver and kidney function.

positive: Myocardial injury characterized by elevated cardiac troponin and in‐hospital mortality of COVID‐19: an insight from a meta‐analysis Elevation of high‐sensitivity cardiac troponin (hs‐cTn) is a surrogate of myocardial injury, which appears to be a common complication of coronavirus disease 2019 (COVID‐19). In this study, a meta‐analysis was performed to clarify the association between myocardial injury assessed by hs‐cTn levels and in‐hospital mortality in patients with COVID‐19. All existing studies on myocardial injury in patients with COVID‐19 were retrieved from PubMed and EMBASE through April 13, 2020. In cases where overlap of the study population or enrollment period was found in articles published from the same hospitals, the article with the largest number of patients was only included in the analysis. The pooled odds ratio was calculated using inverse variance weighted random‐effects models. Six observational studies which included a total of 1,231 patients met the search criteria. The percentage of patients with hs‐cTn levels varied across the studies (13‐41%). Elevated hs‐cTn levels were significantly associated with an increase in in‐hospital mortality (pooled odds ratio, 22.7; 95% confidence interval, 13.6‐38.1; P<0.001) with a moderate heterogeneity (I (2)=28%), suggesting that elevated hs‐cTn levels might be used as a reliable marker of disease severity early in the course of COVID‐19. This article is protected by copyright. All rights reserved.

positive: Higher plasma levels of chemokine CCL19 are associated with poor SARS-CoV-2 acute respiratory distress syndrome (ARDS) outcomes. COVID19 pandemic has so far caused over three hundred thousand deaths worldwide, primarily due to complications from SARS-CoV-2-associated acute respiratory distress syndrome (ARDS). While an ARDS-driven hyperinflammatory phenotype is associated with higher mortality in non-COVID patients, there is little information on how cytokines and chemokines expressions correlate with clinical outcomes in COVID19 patients. We prospectively enrolled a cohort of 41 patients with acute respiratory distress syndrome on mechanical ventilation. Patients’ blood was obtained at enrollment and outcome measures were liberation from mechanical ventilation and hospital-free days. We determined the expression levels of 44 circulating cytokines/chemokines and found 13 of them associated with worse outcomes. After correcting for multiple comparisons/false discovery rate, only one chemokine (CCL19) remained significantly associated with outcomes (p=0.009). Although not described in association with COVID19, this chemokine was previously found elevated in an animal model of SARS-CoV. Moreover, CCL19 seems to be relevant for bronchus-associated lymphoid tissue (BALT) maintenance and for lung immunity to influenza virus. While this finding requires corroboration, CCL19 determination could facilitate early identification of COVID19-ARDS patients at higher risk of death and be novel target for immunotherapy in this setting.

positive: Serum Amyloid A is a biomarker of severe Coronavirus Disease and poor prognosis 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.

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

positive: Coronavirus disease (COVID-19): Rheumatological Prospects/Relevance In December 2019, an outbreak of a novel infection under the working name 2019-nCoV was registered in Wuhan (the Hubei Province located in China's central region), which has quickly spread throughout almost the entire world and become pandemic. The World Health Organization (WHO) proposed a new name coronavirus disease (COVID-19) for this disease, whereas the International Committee on Virus Taxonomy renamed 2019-nCov as SARS-Cov-2 (Severe Acute Respiratory Syndrome Coronavirus-2). The development of the COVID-19 pandemic is not only of great social importance, but also draws the attention of a medical community to the fundamentally new clinical and fundamental problems of the immunopathology of human diseases that are yet to be formulated. The unique experience gained in rheumatology from studies of the pathogenetic mechanisms and pharmacotherapy of immune-mediated inflammatory rheumatic diseases (IMIRDs) can be of great importance for deciphering the nature of the pathological processes that underlie the severe, potentially fatal complications of COVID-19, and may assist in improving their therapy. As for prospects in patients with IMIRDs, although the development of COVID-19 in the presence of IMIRDs has not yet fortunately been described, infection with SARS-CoV-2, like other viruses, can be assumed to cause an exacerbation of the pathological process, whereas severe immune system pathology and comorbidities can worsen the course of infection. Since, according to the current concepts, it is the «hyperimmune» response, and not just the effect only of the virus itself, that underlies lung damage and deaths from COVID-19, special attention is drawn to the effects of antirheumatic therapy that includes glucocorticoids, disease-modifying anti-rheumatic drugs (DMARDs), biological agents, and targeted DMARDs, which can have a multidirectional effect on the course of COVID-19. There are significant theoretical prerequisites for the repurposing of some drugs widely used in rheumatology for the treatment of COVID-19 and its complications. Consideration is given to the prospects of studying the immunopathology of COVID-19 and to the theoretical justifications for the use of antimalarial 4-aminoquinolines, anti-cytokine monoclonal antibodies (mAbs), and Janus kinase inhibitors for the prevention of complications and for the treatment of COVID-19.

positive: Valor pronóstico de biomarcadores cardíacos en la enfermedad por COVID-19 Resumen Introducción: en la enfermedad por COVID-19 se ha establecido que los pacientes con enfermedad cardiometabólica de base, tienen mayor riesgo de presentar desenlaces adversos. Esto ha incrementado el interés en estudiar variables cardiovasculares relevantes, para plantear su correlación con los desenlaces clínicos en esta población. Objetivo: describir el valor pronóstico de los biomarcadores cardíacos en la enfermedad por COVID-19. Métodos: revisión no sistemática de la literatura en bases de datos como PubMed, Google Scholar, Clinical Key, SciELO, entre otras, utilizando palabras clave, términos planos y términos MeSh. Resultados: se eligieron 22 bibliografías, entre ellas artículos de revisión de tema, revisiones sistemáticas, metaanálisis, estudios observacionales y artículos originales publicados hasta la fecha (mayo 13 de 2020), que en la mayoría describen la alteración de biomarcadores cardiacos y su relación con la evolución clínica de los pacientes con COVID-19. Discusión: se encontró que la troponina y el péptido natriurético se comportan como factores de riesgo independientes para compromiso clínico severo, requerimiento de soporte ventilatorio o hemodinámico, estancia en la UCI, y aumento de la mortalidad. Conclusiones: es razonable plantear el uso de estos biomarcadores en la estratificación del riesgo en pacientes con COVID-19 y enfermedad cardiovascular establecida. Abstract Introduction: It has been established that patients with an underlying cardiometabolic disease and COVID-19 infections, have a higher risk of an adverse outcome. This has led to an increase in the interest of studying relevant cardiovascular variables, in order to establish their association with clinical outcomes in this population. Objective: To describe the prognostic value of cardiac biomarkers in disease caused by COVID-19. Methods: A non-systematic review of the literature was carried out in data bases that included PubMed, Google Scholar, Clinical Key, SciELO, using the keywords, plain terms, and MeSH terms. Results: A total of 22 articles were chosen. They consisted of review articles on the subject, systematic reviews, meta-analyses, observational studies, and original articles published up until 13 May 2020. The majority of them described the changes in cardiac biomarkers and their relationship with the clinical outcome of patients COVID-19. Discussion: It was found that Troponin and Natriuretic Peptide behaved as independent risk factors for severe clinical compromise, requiring ventilatory or haemodynamic support, admission to ICU, and an increase in mortality. Conclusions: It is reasonable to recommend the use of these biomarkers in the stratification of risk in patients with COVID-19 and an established cardiovascular disease.

positive: Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID‐19 The role of clinical laboratory data in the differential diagnosis of the severe forms of COVID‐19 has not been definitely established. The aim of this study was to look for the warning index in severe COVID‐19 patients. We investigated 43 adult patients with COVID‐19. The patients were classified into mild group (28 patients) and severe group (15 patients). A comparison of the hematological parameters between the mild and severe groups showed significant differences in interleukin‐6 (IL‐6), d‐dimer (d‐D), glucose, thrombin time, fibrinogen, and C‐reactive protein (P < .05). The optimal threshold and area under the receiver operator characteristic curve (ROC) of IL‐6 were 24.3 and 0.795 µg/L, respectively, while those of d‐D were 0.28 and 0.750 µg/L, respectively. The area under the ROC curve of IL‐6 combined with d‐D was 0.840. The specificity of predicting the severity of COVID‐19 during IL‐6 and d‐D tandem testing was up to 93.3%, while the sensitivity of IL‐6 and d‐D by parallel test in the severe COVID‐19 was 96.4%. IL‐6 and d‐D were closely related to the occurrence of severe COVID‐19 in the adult patients, and their combined detection had the highest specificity and sensitivity for early prediction of the severity of COVID‐19 patients, which has important clinical value.

positive: D-dimer as a biomarker for disease severity and mortality in COVID-19 patients: a case control study BACKGROUND: Over 5,488,000 cases of coronavirus disease-19 (COVID-19) have been reported since December 2019. We aim to explore risk factors associated with mortality in COVID-19 patients and assess the use of D-dimer as a biomarker for disease severity and clinical outcome. METHODS: We retrospectively analyzed the clinical, laboratory, and radiological characteristics of 248 consecutive cases of COVID-19 in Renmin Hospital of Wuhan University, Wuhan, China from January 28 to March 08, 2020. Univariable and multivariable logistic regression methods were used to explore risk factors associated with in-hospital mortality. Correlations of D-dimer upon admission with disease severity and in-hospital mortality were analyzed. Receiver operating characteristic curve was used to determine the optimal cutoff level for D-dimer that discriminated those survivors versus non-survivors during hospitalization. RESULTS: Multivariable regression that showed D-dimer > 2.0 mg/L at admission was the only variable associated with increased odds of mortality [OR 10.17 (95% CI 1.10–94.38), P = 0.041]. D-dimer elevation (≥ 0.50 mg/L) was seen in 74.6% (185/248) of the patients. Pulmonary embolism and deep vein thrombosis were ruled out in patients with high probability of thrombosis. D-dimer levels significantly increased with increasing severity of COVID-19 as determined by clinical staging (Kendall’s tau-b = 0.374, P = 0.000) and chest CT staging (Kendall’s tau-b = 0.378, P = 0.000). In-hospital mortality rate was 6.9%. Median D-dimer level in non-survivors (n = 17) was significantly higher than in survivors (n = 231) [6.21 (3.79–16.01) mg/L versus 1.02 (0.47–2.66) mg/L, P = 0.000]. D-dimer level of > 2.14 mg/L predicted in-hospital mortality with a sensitivity of 88.2% and specificity of 71.3% (AUC 0.85; 95% CI = 0.77–0.92). CONCLUSIONS: D-dimer is commonly elevated in patients with COVID-19. D-dimer levels correlate with disease severity and are a reliable prognostic marker for in-hospital mortality in patients admitted for COVID-19.

positive: [Venous thrombotic risk related to SARS-CoV-2 : prevalence, recommendations and perspectives]. Since the SARS-CoV-2 pandemic outbreak, growing evidence suggests that patients suffering from COVID-19 are at increased risk of thrombotic events. The sepsis-related activation of the coagulation combined with a high prevalence of common thrombotic risk factors could contribute to this prothrombotic state. Coagulation biomarkers could help in the identification of patients at risk of complications and mortality. The incidence of venous thromboembolic events appears to be increased, especially in severe COVID-19 patients. Based on that knowledge, several societies have provided recommendation on the prevention of venous thromboembolism. In this narrative review, we summarize available epidemiologic data on venous thromboembolism and recommendations on thromboprophylaxis in COVID-19.

positive: The potential role of IL-6 in monitoring severe case of coronavirus disease 2019 Abstract. Background: The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan City, China spreads rapidly since December, 2019. Most patients show mild symptoms, but some of them develop into severe disease. There is currently no specific medication. The purpose of this study is to to explore changes of markers in peripheral blood of severe COVID-19 patients, which may be of value in disease monitoring. Methods Clinical data of patients with nonsevere and severe type COVID-19 diagnosed by laboratory test in our institution were collected. The relationship between peripheral blood cells and cytokines, clinical manifestation and outcome was analyzed. Results A total of 69 severe type COVID-19 patients were included. On admission, the median age of severe cases was 56-year old, with 52.17% female patient. The most common symptoms were fever (79.72%), cough (63.77%), shortness of breath (57.97%) and fatigue (50.72%). Diarrhea is less common. The most common comorbidity is hypertension. Upon admission, the proportion of bilateral pulmonary involvement and interstitial abnormalities evidenced by chest computed tomography (CT) imaging in severe cases was 60.87% and 27.54%, respectively. Compared with patients with nonsevere disease, those with severe disease showed obvious lymphocytopenia. Elevated level of lactate dehydrogenase (LDH), C-reactive protein (CRP), ferritin and D-dimer was found in most cases. Two patients (2.9%) needed transfer to the intensive care unit. Baseline immunological parameters and most of the inflammatory parameters were basically within the normal range. However, baseline interleukin-6 (IL-6) was significantly increased in severe type, which was closely related to the maximal body temperature during hospitalization and to CT findings. Baseline IL-6 was also significantly related to the increase of baseline level of CRP, LDH, ferritin and D-dimer. The increase of baseline IL-6 level suggests that it may positively correlate with the severity of COVID-19. Among the 30 severe type patients whose IL-6 was assessed before and after treatment, significant decrease in IL-6 and improved CT assessment was found in 25 patients after treatment. Whereas the IL-6 level was further increased in 3 cases, which was closely related to disease progression. It is suggested that IL-6 may be used as a marker for disease monitoring in severe COVID-19 patients. Conclusions On admission, the baseline level of IL-6, CRP, LDH and ferritin was closely related to the severity of COVID-19, and the elevated IL-6 was significantly related to the clinical manifestation of severe type patients. The decrease of IL-6 was closely related to treatment effectiveness, while the increase of IL-6 indicated disease exacerbation. Collectively, the dynamic change of IL-6 level can be used as a marker for disease monitoring in patients with severe COVID-19.

positive: Protein based biomarkers for non-invasive Covid-19 detection COVID-19 has become a substantial lethal disease worldwide, and early diagnosis is a significant concern for this virus. Currently, RT-PCR is being used worldwide for the detection of this virus with human to human transmission. Furthermore, the recent develop biosensor leading to others diagnosis approach but being invasive are painful and time taking. Another possibility can be protein-based biomarkers as an application of biosensors for detection and early diagnostics. Considering the other approach, that is, microfluidics-based biosensor, though being a non-invasive method, will be restricting virus transmission. This review commences with the recent develop biosensor for Covid-19 detection and listing down the available biomarkers with their secretion range comparison of normal to COVID-19 patients through clinical analysis in china and concludes with the future approach for the diagnosis.

positive: C-reactive protein: A promising biomarker for poor prognosis in COVID-19 infection BACKGROUND: The novel coronavirus disease 2019 (COVID-19) first broke out in Wuhan, China, spread over 227 countries and caused approximately 0.3 million death worldwide. Several biomolecules have been explored for possible biomarkers for prognosis outcome. Although increased C reactive protein (CRP) is associated with death due to COVID-19 infections, results from different populations remain inconsistent. For a conclusive result, the present meta-analysis was performed. METHODS: We conducted a literature search in PubMed and Scopus database for the association of CRP concentration with COVID-19 disease outcomes. A total of 16 eligible studies were enrolled in the present analysis comprising of 1896 survivors and 849 non-survivors cases. Concentrations of CRP were compared and analyzed by a meta-analysis. RESULTS: Egger's regression analysis (intercept = 0.04, P = 0.98, 95%CI = -5.48 to 5.58) and funnel plot revealed an absence of publication bias in the included studies. Due to the presence of significant heterogeneity across the studies (Q = 252.03, Pheterogeneity = 0.000, I2 = 93.65) random model was used for the analysis of the present study. The results of the meta-analysis demonstrated a significant role of CRP in COVID-19 infection outcome (Standard difference in means = 1.371, P = 0.000). CONCLUSIONS: Concentrations of CRP remained high in patients who died of COVID-19 infection and could be a promising biomarker for assessing disease lethality.

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

positive: The values of coagulation function in COVID-19 patients Objective: To investigate the blood coagulation function in COVID-19 patients, and the correlation between coagulopathy and disease severity. Methods: We retrospectively collected 147 clinically diagnosed COVID-19 patients at Wuhan Leishenshan Hospital of Hubei, China. We analyzed the coagulation function in COVID-19 patients through the data including thrombin-antithrombin complex (TAT), 2-plasmininhibitor-plasmin Complex (PIC), thrombomodulin (TM), t-PA/PAI-1 Complex (t-PAIC), prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), D-Dimer (DD), and platelet (PLT). Result: The levels of TAT, PIC, TM, t-PAIC, PT, INR, FIB, and DD in COVID-19 patients were higher than health controls (p<0.05), and also higher in the patients with thrombotic disease than without thrombotic disease (p<0.05). What's more, the patients with thrombotic disease had a higher case-fatality (p<0.05). TAT, PIC, TM, t-PAIC, PT, INR, APTT, FIB, DD, and PLT were also found correlated with disease severity. Meanwhile, we found that there were significant difference in TAT, TM, t-PAIC, PT, INR, APTT, DD, and PLT in the death and survival group. Further using univariate and multivariate logistic regression analysis also found that t-PAIC and DD were independent risk factors for death in patients and are excellent predicting the mortality risk of COVID-19. Conclusion: The coagulation systems in COVID-19 patients are inordinate, and dynamic monitoring of them, might be a key in the control of COVID-19 death.

positive: Biomarkers of biological age as predictors of COVID-19 disease severity

positive: Viable circulating endothelial cells and their progenitors are increased in Covid-19 patients During the course of Covid-19, the disease caused by the new Coronavirus SARS-CoV-2, thrombotic phenomena and/or diffuse vascular damage are frequent, and viral elements have been observed within endothelial cells. Circulating endothelial cells (CECs) and their progenitors (CEPs) are increased in cardiovascular, thrombotic, infectious and cancer diseases. Using a validated flow cytometry procedure, we found that viable CEPs/mL were significantly increased in Covid-19 patients compared to healthy controls. This increase was observed in patients with mild symptoms and not further augmented in patients with severe symptoms. In patients who recovered, CEPs decreased, but were in a range still significantly higher than normal controls. Regarding mature CECs, in Covid-19 patients their absolute number was similar to those observed in healthy controls, but the viable/apoptotic CEC ratio was significantly different. Both mild and severe Covid-19 patients had significantly more viable CECs compared to healthy controls. Patients who recovered had significantly less CECs/mL when compared to controls as well as to mild and severe Covid-19 patients. A positive correlation was found between the copies of SARS-CoV-2 RNA in the cellular fraction and apoptotic CEPs/mL in severe Covid-19 patients. These findings suggest that CECs and CEPs might be investigated as candidate biomarkers of endothelial damage in Covid-19 patients.

positive: Clinical decision support tool and rapid point-of-care platform for determining disease severity in patients with COVID-19. SARS-CoV-2 is the virus that causes coronavirus disease (COVID-19) which has reached pandemic levels resulting in significant morbidity and mortality affecting every inhabited continent. The large number of patients requiring intensive care threatens to overwhelm healthcare systems globally. Likewise, there is a compelling need for a COVID-19 disease severity test to prioritize care and resources for patients at elevated risk of mortality. Here, an integrated point-of-care COVID-19 Severity Score and clinical decision support system is presented using biomarker measurements of C-reactive protein (CRP), N-terminus pro B type natriuretic peptide (NT-proBNP), myoglobin (MYO), D-dimer, procalcitonin (PCT), creatine kinase-myocardial band (CK-MB), and cardiac troponin I (cTnI). The COVID-19 Severity Score combines multiplex biomarker measurements and risk factors in a statistical learning algorithm to predict mortality. The COVID-19 Severity Score was trained and evaluated using data from 160 hospitalized COVID-19 patients from Wuhan, China. Our analysis finds that COVID-19 Severity Scores were significantly higher for the group that died versus the group that was discharged with median (interquartile range) scores of 59 (40-83) and 9 (6-17), respectively, and area under the curve of 0.94 (95% CI 0.89-0.99). Although this analysis represents patients with cardiac comorbidities (hypertension), the inclusion of biomarkers from other pathophysiologies implicated in COVID-19 (e.g., D-dimer for thrombotic events, CRP for infection or inflammation, and PCT for bacterial co-infection and sepsis) may improve future predictions for a more general population. These promising initial models pave the way for a point-of-care COVID-19 Severity Score system to impact patient care after further validation with externally collected clinical data. Clinical decision support tools for COVID-19 have strong potential to empower healthcare providers to save lives by prioritizing critical care in patients at high risk for adverse outcomes.

positive: The Risk of Children Hospitalized With Severe COVID-19 in Wuhan. BACKGROUND Novel coronavirus disease (COVID-19) is spreading globally. Little is known about the risk factors for the clinical outcomes of COVID-19 in children. METHODS A retrospective case-control study was taken in children with severe acute respiratory syndrome coronary virus-2 infection in Wuhan Children's Hospital. Risk factors associated with the development of COVID-19 and progression were collected and analyzed. RESULTS Eight out of 260 children diagnosed with severe COVID-19 pneumonia were included in the study. Thirty-five children with COVID-19 infection matched for age, sex and date of admission, and who classified as non-severe type, were randomly selected from the hospital admissions. For cases with severe pneumonia caused by COVID-19, the most common symptoms were dyspnea (87.5%), fever (62.5%) and cough (62.5%). In laboratory, white blood cells count was significantly higher in severe children than non-severe children. Levels of inflammation bio-makers such as hsCRP, IL-6, IL-10 and D-dimer elevated in severe children compared with non-severe children on admission. The level of total bilirubin and uric acid clearly elevated in severe children compared with non-severe children on admission. All of severe children displayed the lesions on chest CT, more lung segments were involved in severe children than in non-severe children, which was only risk factor associated with severe COVID-19 pneumonia in multivariable analysis. CONCLUSIONS More than 3 lung segments involved were associated with greater risk of development of severe COVID-19 in children. Moreover, the possible risk of the elevation of IL-6, high total bilirubin and D-dimer with univariable analysis could identify patients to be severe earlier.

positive: Epidemiology, virology, and clinical features of severe acute respiratory syndrome -coronavirus-2 (SARS-CoV-2; Coronavirus Disease-19) A cluster of severe pneumonia of unknown etiology in Wuhan City, Hubei province in China emerged in December 2019. A novel coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was isolated from lower respiratory tract sample as the causative agent. The current outbreak of infections with SARS-CoV-2 is termed Coronavirus Disease 2019 (COVID-19) by the World Health Organization (WHO). COVID-19 rapidly spread into at least 114 countries and killed more than 4,000 people by March 11 2020. WHO officially declared COVID-19 a pandemic on March 11, 2020. There have been 2 novel coronavirus outbreaks in the past 2 decades. The outbreak of severe acute respiratory syndrome (SARS) in 2002–2003 caused by SARS-CoV had a case fatality rate of around 10% (8,098 confirmed cases and 774 deaths), while Middle East respiratory syndrome (MERS) caused by MERS-CoV killed 861 people out of a total 2,502 confirmed cases between 2012 and 2019. The purpose of this review is to summarize known-to-date information about SARS-CoV-2, transmission of SARS-CoV-2, and clinical features.

positive: A review of cardiac manifestations and predictors of outcome in patients with COVID – 19 Abstract Coronavirus disease (COVID-19) pandemic has so far involved 184 countries and more than 2.79 million patients worldwide. Over the past three months, it has attributed to more than 196, 000 deaths, with more than 50, 000 deaths in the United States alone. Pulmonary manifestations are predominant and have been well identified. Cardiac involvement is also common. Acute cardiac injury, the most common cardiac manifestation of this disease can be seen in patients even without prior cardiac comorbidities. Established cardiovascular risk factors such as diabetes mellitus, hypertension, and coronary artery disease predispose to cardiac injury, the severity of illness and mortality. Non-ischemic myocardial injury secondary to cytokine storm is thought to be the predominant mechanism of acute cardiac injury associated with COVID-19. Multiple mechanisms and processes contribute to cardiac injury resulting in a poor outcome. Some of these are not clearly understood. Clinical and diagnostic details of cardiovascular involvement in these patients are mostly limited to biochemical markers. Multiple therapeutic agents have been tried with questionable efficacy and without clinical evidence. Interactions of comorbidities, cardiovascular drugs, the cardiac effect of therapeutic agents on the illness continue to be under investigation. With an increasing number of patients, newer promising therapies, and ongoing clinical trials, the exact mechanisms and extent to which these risk factors contribute to outcomes will be clearer in the future.

positive: Clinical and laboratory predictors of in-hospital mortality in patients with COVID-19: a cohort study in Wuhan, China BACKGROUND: This study aimed to develop mortality-prediction models for patients with Coronavirus disease 2019 (COVID-19). METHODS: The training cohort were consecutive patients with COVID-19 in the First People’s Hospital of Jiangxia District in Wuhan from January 7, 2020 to February 11, 2020. We selected baseline clinical and laboratory data through the stepwise Akaike information criterion and ensemble XGBoost model to build mortality-prediction models. We then validated these models by randomly collecting COVID-19 patients in the Infection department of Union Hospital in Wuhan from January 1, 2020, to February 20, 2020. RESULTS: 296 patients with COVID-19 were enrolled in the training cohort, 19 of whom died during hospitalization and 277 were discharged from the hospital. The clinical model developed with age, history of hypertension and coronary heart disease showed AUC of 0.88 (95% CI, 0.80-0.95); threshold, -2.6551; sensitivity, 92.31%; specificity, 77.44% and negative predictive value (NPV), 99.34%. The laboratory model developed with age, high-sensitivity C-reactive protein (hsCRP), peripheral capillary oxygen saturation (SpO2), neutrophil and lymphocyte count, D-dimer, aspartate aminotransferase (AST) and glomerular filtration rate (GFR) had a significantly stronger discriminatory power than the clinical model (p=0.0157), with AUC of 0.98 (95% CI, 0.92-0.99); threshold, -2.998; sensitivity, 100.00%; specificity, 92.82% and NPV, 100.00%. In the subsequent validation cohort (N=44), the AUCs (95% CI) were 0.83 (0.68, 0.93) and 0.88 (0.75, 0.96) for clinical model and laboratory model, respectively. CONCLUSIONS: We developed two predictive models for the in-hospital mortality of patients with COVID-19 in Wuhan and validated in patients from another center.

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

positive: Prognosis of COVID-19: Changes in laboratory parameters. INTRODUCTION Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome - Coronavirus 2 (SARS-CoV-2) emerged in China and has become a global threat. Comparison of hematological parameters between mild and severe cases of SARS-CoV 2 is so far limited, but significant differences in parameters such as interleukin-6, d-dimers, glucose, fibrinogen and C-reactive protein have been already reported. PURPOSE In this study we analyzed the changes observed in easily measured blood biomarkers in the patients and provided evidence of how these markers can be used as prognostic factors of the disease. METHODS Demographic characteristics, detailed medical history, and laboratory findings of all enrolled SARS-CoV 2 infection positive patients who were referred to Patras University Hospital from the period of March 4th 2020 (when first confirmed case in Greece appeared in our hospital) until April 4th 2020 were extracted from electronic medical records and analyzed. RESULTS We provided evidence that some very common laboratory values can be used as independent predictive factors in SARS-CoV 2 infection. Despite the retrospective nature of this study and the small number of subjects analyzed, we showed that NLR, LDH, d-dimers, CRP, fibrinogen and ferritin can be used early at the patient's first visit for SARS-CoV 2 infection symptoms and can predict the severity of infection. CONCLUSION More studies are warranted to further objectively confirm the clinical value of prognostic factors related to SARS-CoV 2 and establish an easy-to-get panel of laboratory findings for evaluating the disease severity.

positive: Burden and prevalence of prognostic factors for severe covid-19 disease in Sweden Objectives: Describe the burden and prevalence of prognostic factors of severe COVID-19 disease at national and county level in Sweden. Design: Cross sectional study Setting: Sweden Participants: 9,624,428 individuals living in Sweden on 31st December 2014 and alive on 1st January 2016 Main outcome measures: Burden and prevalence of prognostic factors for severe COVID-19 based on the guidelines from the World Health Organization and European Centre for Disease Prevention and Control, which are age 70 years and older, cardiovascular disease, cancer, chronic obstructive pulmonary disease, severe asthma, and diabetes. Prognostic factors were identified based on records for three years before 1st January 2016 from the Swedish National Inpatient and Outpatient Specialist Care Register, Prescribed Drug Register, and Cancer Register. Results: 22.1% of the study population had at least one prognostic factor for severe COVID-19 (2,131,319 individuals), and 1.6% had at least three factors (154,746 individuals). The prevalence of underlying medical conditions in the whole study population ranged from 0.8% with chronic obstructive pulmonary disease (78,516 individuals) to 7.4% with cardiovascular disease (708,090 individuals), and the county specific prevalence of at least one prognostic factor ranged from 19.2% in Stockholm (416,988 individuals) to 25.9% in Kalmar (60,005 individuals). Conclusions: The prevalence of prognostic factors for severe COVID-19 disease will aid authorities in optimally planning healthcare resources during the ongoing pandemic. Results can also be applied to underlying assumptions of disease burden in modelling efforts to support COVID-19 planning. This information is crucial when deciding appropriate strategies to mitigate the pandemic and reduce both the direct mortality burden from the disease itself, and the indirect mortality burden from potentially overwhelmed health systems.

positive: Focus on Receptors for Coronaviruses with Special Reference to Angiotensin-converting Enzyme 2 as a Potential Drug Target - A Perspective Coronaviruses (CoVs) possess an enveloped, single, positive-stranded RNA genome which encodes for four membrane proteins, namely spike (S), envelope (E), membrane (M) and nucleocapsid (N) proteins 3-5 [1]. With regard to pathogenicity, S proteins are essential for viral entry into host cells [2, 3]. SARS-CoV binds to the angiotensin-converting enzyme (ACE)2 which is present on nonimmune cells, such as respiratory and intestinal epithelial cells, endothelial cells, kidney cells (renal tubules) and cerebral neurons and immune cells, such as alveolar monocytes/macrophages [4-6]. Of note, CD209L or liver/lymph node special intercellular adhesion molecule-3-grabbing non-integrin (SIGN) and dendritic cell (DC)-SIGN are alternative receptors for SARS-CoV but with lower affinity [7]. In the case of MERS-CoV, S proteins bind to the host cell receptor dipeptidyl peptidase 4 (DPP4 or CD26) which is broadly expressed on intestinal, alveolar, renal, hepatic and prostate cells as well as on activated leukocytes [8]. Then, viruses replicate in target cells with release of mature virions, which, in turn, invade new target cells [9]. Evidence has been provided that SARSCoV proteins are cleaved into two subunits, S1 and S2, respectively, and the amino acids 318-510 of the S1 represent the receptor-binding domain (RBD) which binds to ACE2 [10, 11]. Quite importantly, in the context of RBD there is the receptor-binding motif (RBM) (amino acids 424- 494), which accounts for complete binding to ACE2 [11]. Moreover, by means of two residues at positions 479 and 487 RBD allows virus progression and tropism [10, 11]. In the case of MERSCoV, its RBM binds to DPP4 with residues 484-567, thus, suggesting that its RBD differs from that of SARS-CoV [12, 13]. In a very recent paper, Wan and associates [14] have investigated the receptor recognition by COVID-19 (a new term to indicate the 2019-nCoV in Wuhan) on the bases of structural studies. In this respect, the sequence of COVID-19 RBM is similar to that of SARSCoV, thus, implicating that ACE2 may represent the binding receptors for COVID-19. Furthermore, gln493 residue of COVID-19 RBM seems to allow interaction with human ACE2, thus, suggesting the ability of this virus to infect human cells. According, to Wan and associates structural analysis [14], COVID-19 binds to human ACE2 with a lesser efficiency than human SARS-CoV (2002) but with higher affinity than human SARS-CoV (2003). Furthermore, same authors predicted that a single mutation at the 501 position may enhance the COVID-19 RBD binding capacity to human ACE2 and this evolution should be monitored in infected patients [14]. These predictive findings by Wan and associates [14] are confirmed by two contemporary studies by Letko and Muster [15] and Peng and associates [16]. In particular, the report by Peng and associates [16], points out the possible origin of COVID-19 from bats [16]. From a pathogenic point of view, evidence has been provided that binding of S2 to ACE2 receptor leads to its down-regulation with subsequent lung damage in the course of SARS-CoV infection [17]. Down-regulation of ACE2 causes excessive production of angiotensin (ANG) II by the related enzyme ACE with stimulation of ANG type 1a receptor (AT1R) and enhanced lung vascular permeability [18]. In particular, same authors have reported that recombinant ACE2 could attenuate severe acute lung injury in mice [18]. Moreover, Battle and associates [19] also proposed to use already available recombinant ACE2 for intercepting COVID-19 and attenuating infection. In the previous paragraphs, the presence of ACE2 on immune cells has been pointed out and, by analogy to epithelial cells, this receptor may also be down-regulated following viral entry. Therefore, in CoV-infected animal models and in infected humans further investigations are required to clarify a possible reduced expression of ACE2 on immune cells. In fact, in the course of SARS-CoV infection, a number of immune disorders have been detected. Three reports have demonstrated the ability of CoV to inhibit interferon (IFN)-ï¢ production in the course of SARS acting as IFN antagonist [20-22]. In senescent Balb/c mice, depletion of T lymphocytes is associated to more severe interstitial pneumonitis and delayed clearance of SARS-CoV, thus, suggesting a protective role played by these cells [23]. In this connection, both SARS-CoV and MERS-CoV have been shown to induce T cell apoptosis, thus, aggravating the clinical course of disease [24, 25]. Quite interestingly, memory CD8+ T cells specific for SARS-CoV M and N proteins have been detected up to 11 years post-infection [26]. As far as humoral immune responsiveness is concerned, evidence has been provided that S1 subunit from MERS-CoV is highly immunogenic in mice [27]. Moreover, monoclonal antibodies have been shown to be highly neutralizing against MERS-CoV replication and endowed with post exposure effectiveness in susceptible mice [28, 29]. Human neutralizing antibodies have also been isolated from a recovered patient, thus, suggesting the role of humoral immunity in the control of the persistence of CoV in the host [30]. In particular, IgG response occurs early in infection and its prolonged production may serve for virus clearance during recovery also in view of the absence of viremia in convalescent sera from SARS patients [31]. According to current literature, severity of COVID-19 infection correlates with lymphopenia and patients who died from COVID-19 had lower lymphocyte counts when compared to survivors [32, 33]. These data suggest that lymphocyte-mediated anti-viral activity is poorly effective against COVID-19. Despite lymphopenia, evidence for an exaggerate release of proinflammatory cytokines [interleukin (IL)-1 and IL-6] has been reported in the course acute respiratory syndrome in COVID19 infected patients, thus, aggravating the clinical course of disease [34]. As recently reported, during COVID-19 pandemic in both Italy and China higher frequency of fatalities have been observed in the frail elderly population with previous comorbidities [35]. It is well known that decline of immunity occurs in ageing and, therefore, COVID-19 may gain easier access to the respiratory tract in frail elderly patients [36]. There is evidence that ACE2 protects from severe acute lung failure and operates as a negative regulator of the renin-angiotensin system (RAS) [18, 37]. It is well known that ANG II via activation of the AT1R promotes detrimental effects on the host, such as, vasoconstriction, reactive oxygen species generation, inflammation and matrix remodelling [38]. ACE2 counterbalances the noxious effects exhibited by ANG II and AT1R via activation of AT2R which arrests cell growth, inflammation and fibrosis [39]. In this framework, Gurwitz [40] proposed to use AT1R blockers, such as losartan, as a potential treatment of COVID-19 infection. In fact, losartan as well as olmesartan, used for treating hypertension in patients, were able to increase ACE2 expression after 28 days treatment of rats with myocardial infarction [41]. Then, Gurwitz suggests to evaluate severity of symptoms in COVID-19 infected patients under previous chronic treatment with AT1R blockers in comparison to COVID-19 infected patients who did not take AT1R blockers [40]. Quite interestingly, 75% of aged COVID-19 infected patients admitted to Italian hospitals had hypertension [unpublished data]. However, the putative effects of ACE-2 down-regulation on the cardiovascular system in the course of COVID-19 pandemic need more intensive studies. Taken together, these evidences suggest that CoV-induced down-regulation of ACE2 activates RAS with collateral damage to organs, such as lungs, in the course of SARS-related pneumonia. Then, putative therapeutic measures aimed at increasing ACE2 levels on respiratory epithelial cells should be taken into serious consideration. Quite interestingly, over the past few years, three key papers have demonstrated the ability of a polyphenol, resveratrol (RES), to experimentally deactivate the RAS system in maternal and post-weaning high fat diet, arterial ageing and high fat diet, respectively [42-44]. In all these experimental models, RES led to an increase of ACE2 with reduction of organ damage, such as liver steatosis and aorta media thickness and decrease of adipose tissue mass, respectively. As far as the mechanism of action of RES is concerned, this polyphenol is able to activate sirtuin (Sirt)1 [45-47]. In turn, Sirt1 down-regulates AT1R expression via ACE2 up-regulation [43, 48]. Of importance, Lin and associates [48] have demonstrated the ability of RES to in vitro inhibit MERS-CoV infection of Vero E6 cells, thus, prolonging cell survival in virtue of an anti-apoptotic mechanism. These findings suggest a direct antiviral effect exerted by RES. It would be very interestingly to evaluate the direct effects of RES on COVID-19, in vitro. The data above discussed strongly suggest, that RES, as an activators of ACE2, should be investigated in animal models of CoV-induced severe pneumonia, also taking into account the antioxidant, anti-inflammatory and immunomodulating effects exerted by polyphenols [49]. Then, successful animal studies may pave the way for RES-based human trials in COVID-infected patients. Note added in proof During the reviewing process of this perspective other related papers have been published. Hanff and associates [50] have discussed the possible association between COVID-19-associated cardiovascular mortality and dysregulation of the Renin Angiotensin System (RAS). From a pharmacologic point of view, RAS inhibition leads to upregulation of ACE2, thus, attenuating acute respiratory syndrome and myocarditis in COVID-19-infected patients. Conversely, increase in ACE2 expression may facilitate the access into the host of COVID-19, thus, aggravating the clinical picture. Such a dilemma would be solved byclinical trials based on RAS blockade or initiation and monitoring related effects. Contemporarily, Danser and associates [51] claim that there is no evidence to stop RAS blockers in the course of COVID-19 infection. In fact, there are no available data which support that ACE inhibitors or ANG II type I receptor blockers increase COVID-19 infection via its binding to ACE2. Finally, Kuster and associates [52] write that there are no data on the strict relationship between ACE2 activity and SARS-CoV2 mortality. Moreover, in the SARSCoV2, cells expressing ACE2 were not attacked by the virus, while cells lacking ACE2 were bound by the SARS-CoV2 virus [53]. These findings suggest that also in the case of RES effects on COVID-19 infection, the dual role of ACE2 should be taken into serious consideration.

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

positive: Alterations of the Gut Microbiota in Patients with COVID-19 or H1N1 Influenza BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging serious global health problem. Gastrointestinal symptoms are common in COVID-19 patients, and SARS-CoV-2 RNA has been detected in stool specimens. However, the relationship between the gut microbiome and disease remains to be established. METHODS: We conducted a cross-sectional study of 30 COVID-19 patients, 24 influenza A (H1N1) patients, and 30 matched healthy controls (HC) to identify differences in the gut microbiota by 16S ribosomal RNA (rRNA) gene V3-V4 region sequencing. RESULTS: Compared with HC, COVID-19 patients had significantly reduced bacterial diversity, a significantly higher relative abundance of opportunistic pathogens, such as Streptococcus, Rothia, Veillonella and Actinomyces, and a lower relative abundance of beneficial symbionts. Five biomarkers showed high accuracy for distinguishing COVID-19 patients from HC with an area under the curve (AUC) up to 0.89. Patients with H1N1 displayed lower diversity and different overall microbial composition compared with COVID-19 patients. Seven biomarkers were selected to distinguish the two cohorts with an AUC of 0.94. CONCLUSION: The gut microbial signature of patients with COVID-19 was different from that of H1N1 patients and HC. Our study suggests the potential value of the gut microbiota as a diagnostic biomarker and therapeutic target for COVID-19, but further validation is needed.

positive: [Analysis of the clinical characteristics and early warning model construction of severe/critical coronavirus disease 2019 patients] OBJECTIVE: To analyze the clinical characteristics of critical patients with coronavirus disease 2019 (COVID-19), build an early warning model for severe/critical type, and aim at providing reference for the prediction of severe/critical COVID-19. METHODS: The clinical data of COVID-19 patients treated in the Second People' Hospital of Fuyang City from January 20th to February 18th in 2020 were retrospective analyzed, including the demographic and epidemiological date, vital signs and hematology indexes, etc. on admission. Patients were divided into the normal type (set as normal group) and severe/critical type (set as severe group) according to the COVID-19 treatment plan classification standard published by National Health Commission of the People's Republic of China. The differences between two groups were compared, and the variables with statistical significance were incorporated in the multivariate binary unconditional Logistic regression analysis to screen the risk factors of severe/critical type. Risk factors were summarized to establish an early warning model, and the receiver operating characteristic (ROC) curve was carried out to evaluate the significance of the early warning model in the screening of critically COVID-19. RESULTS: A total of 155 patients with COVID-19 were admitted, including 125 patients of normal type and 30 patients of severe/critical type. (1) Compared with normal group, patients in severe group were older, and with higher proportion of basic diseases, higher body mass index (BMI), higher incidence of tachypnea, persistent high fever, peripheral blood oxygen saturation (SpO2) < 0.95, while the white blood cell count (WBC), CD4+T lymphocyte, CD8+T lymphocyte, lymphocyte count (LYM) were decreased obviously, the levels of interleukin-6 (IL-6), C-reactive protein (CRP) and serum amyloid a protein (SAA), and CT showed higher incidence of multi-pulmonary lobe lesions. There were no significant differences of gender, travel history from Wuhan, smoking history, shock index (SI) and CD4+/CD8+ ratio between the two groups. (2) Multivariate Logistic regression analysis showed that age ≥ 60 years old [odds ratio (OR) = 1.620, P = 0.031], combined with underlying diseases (OR = 1.521, P = 0.044), persistent high fever (OR = 2.469, P = 0.014), WBC < 2.0×109/L and/or LYM < 0.4×109/L (OR = 3.079, P = 0.006), pulmonary multilobar lesions (OR = 1.367, P = 0.047), and IL-6 ≥ 30 ng/L (OR = 2.426, P = 0.010) were the risk factors of severe/critical COVID-19. (3) The OR value corresponding to each risk factors were scored by rounding. Two points were scored for age ≥ 60 years old, with underlying diseases, persistent high fever and IL-6 ≥ 30 ng/L, 3 points for WBC < 2.0×109/L and/or LYM < 0.4×109/L, 1 point for pulmonary multilobar lesions, and totally calculated as early warning model scores. The early warning model score of the severe group was significantly higher than that of the normal group (9.33±2.79 vs. 5.04±2.38, t = 9.010, P = 0.001). (4) The ROC curve analysis showed the area under ROC curve (AUC) of early warning model on the early screening of severe/critical patients in COVID-19 was 0.944, and 95% confidence interval (95%CI) was 0.903-0.985; and the sensitivity and specificity were 93.3% and 72.0% respectively while the cut-off was 6.5. CONCLUSIONS: There are many differences between severe/critical and mild COVID-19 patients. The establishment of early warning model could help to screen severe/critical patients at an early stage, with certain significance for guiding treatment.

positive: Correlation between the variables collected at admission and progression to severe cases during hospitalization among patients with COVID‐19 in Chongqing Mortality is high among severe patients with 2019 novel coronavirus‐infected disease (COVID‐19). Early prediction of progression to severe cases is needed. We retrospectively collected patients with COVID‐19 in two hospital of Chongqing from 1st January to 29th February 2020. At admission, we collected the demographics and laboratory tests to predict whether the patient would progress to severe cases in hospitalization. Severe case was confirmed when one of the following criteria occurred: (a) dyspnea, respiratory rate ≥30 breaths/min, (b) blood oxygen saturation ≤93%, and (c) PaO(2)/FiO(2) ≤ 300 mm Hg. At admission, 348 mild cases were enrolled in this study. Of them, 20 (5.7%) patients progressed to severe cases after median 4.0 days (interquartile range: 2.3‐6.0). Pulmonary inflammation index, platelet counts, sodium, C‐reactive protein, prealbumin, and PaCO(2) showed good distinguishing power to predict progression to severe cases (each area under the curve of receiver operating characteristics [AUC] ≥ 0.8). Age, heart rate, chlorine, alanine aminotransferase, aspartate aminotransferase, procalcitonin, creatine kinase, pH, CD3 counts, and CD4 counts showed moderate distinguishing power (each AUC between 0.7‐0.8). And potassium, creatinine, temperature, and D‐dimer showed mild distinguishing power (each AUC between 0.6‐0.7). In addition, higher C‐reactive protein was associated with shorter time to progress to severe cases (r = −0.62). Several easily obtained variables at admission are associated with progression to severe cases during hospitalization. These variables provide a reference for the medical staffs when they manage the patients with COVID‐19.

positive: Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Summary Background In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding National Key R&D Program of China.

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: Prognostic value of C-reactive protein in patients with COVID-19 Background Elevated serum C-reactive protein (CRP) level was observed in most patients with COVID-19. Methods Data of COVID-19 patients with clinical outcome in a designated hospital in Wuhan, China, were retrospectively collected and analyzed from Jan 30 to Feb 20, 2020. The prognostic value of admission CRP was evaluated in patients with COVID-19. Results Out of 298 patients enrolled, 84 died and 214 recovered. Most non-survivors tended to be males, old aged, or with chronic diseases. Compared to survivors, non-survivors showed significantly higher white blood cell and neutrophil count, neutrophil to lymphocyte ratio (NLR), systemic immune-inflammation index (SII, defined by platelet count multiply by NLR), CRP, procalcitonin, and D-dimer, and lower red blood cell, lymphocyte, and platelet count. Age, neutrophil count, platelet count, and CRP were identified as independent predictors of adverse outcome. The area under the receiver operating characteristic (ROC) curve (AUC) of CRP (0.896) was significantly higher than that of age (0.833), neutrophil count (0.820), and platelet count (0.678) in outcome prediction (all p<0.05). With a cut-off value of 41.4, CRP exhibited sensitivity 90.5%, specificity 77.6%, positive predictive value 61.3%, and negative predictive value 95.4%. Subgroup analysis revealed that CRP remained robust accuracy in adverse outcome prediction in patients with different disease severity (AUC 0.832, z=10.23, p<0.001; AUC 0.989, z=44.04, p<0.001). CRP was also an independent discriminator of severe/critical illness on admission (AUC 0.783, z=10.69, p<0.001). Conclusions In patients with COVID-19, admission CRP correlated with disease severity and tended to be a good predictor of adverse outcome.

positive: The Association of Lymphocyte count and levels of CRP, D-Dimer, and LDH with severe coronavirus disease 2019 (COVID-19): A Meta-Analysis The rapid progression of Coronavirus disease 2019 (COVID-19) and its increasing burden on health systems necessitate the identification of parameters of severe infection to help in monitoring, prognoses and development of treatment algorithms. This review aims to investigate the association of lymphocyte count, CRP, LDH, and D-Dimer with the severe form of COVID-19. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases of MEDLINE/PubMed, WHO-Virtual Health Library (VHL), and ScienceDirect were used for the systematic search. Random effects model was used to estimate the pooled standardized mean differences (SMD) with the corresponding 95% confidence interval (CI), using OpenMeta Analyst software. A total of 11 studies, with 2437 COVID-19 patients, which fulfilled the eligibility criteria were included in the meta-analysis. The analysis revealed that lymphocyte count was significantly lower in patients with the severe form of COVID-19 (SMD = - 1.025, P value <.001). Also, the analysis of SMD showed that patients with severe COVID-19 have a significantly higher serum levels of CRP (SMD = 3.363, P value <.001), D-Dimer (SMD = 1.073, P value <.001), and LDH (SMD = 3.345, P value <.001). Low lymphocyte count and high levels of CRP, LDH, and D-Dimer are associated with severe COVID-19. These laboratory markers could be used as clinical indicators of worsening illness and poor prognosis of COVID-19.

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

positive: Clinical and Immune Features of Hospitalized Pediatric Patients With Coronavirus Disease 2019 (COVID-19) in Wuhan, China IMPORTANCE: The epidemiologic and clinical characteristics of pediatric patients with coronavirus disease 2019 (COVID-19) have been reported, but information on immune features associated with disease severity is scarce. OBJECTIVE: To delineate and compare the immunologic features of mild and moderate COVID-19 in pediatric patients. DESIGN, SETTING, AND PARTICIPANTS: This single-center case series included 157 pediatric patients admitted to Wuhan Children’s Hospital with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data were collected from January 25 to April 18, 2020. EXPOSURES: Documented SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES: Clinical and immunologic characteristics were collected and analyzed. Outcomes were observed until April 18, 2020. RESULTS: Of the 157 pediatric patients with COVID-19, 60 (38.2%) had mild clinical type with pneumonia, 88 (56.1%) had moderate cases, 6 (3.8%) had severe cases, and 3 (1.9%) were critically ill. The 148 children with mild or moderate disease had a median (interquartile range [IQR]) age of 84 (18-123) months, and 88 (59.5%) were girls. The most common laboratory abnormalities were increased levels of alanine aminotransferase (ALT) (median [IQR], 16.0 [12.0-26.0] U/L), aspartate aminotransferase (AST) (median [IQR], 30.0 [23.0-41.8] U/L), creatine kinase MB (CK-MB) activity (median [IQR], 24.0 [18.0-34.0] U/L), and lactate dehydrogenase (LDH) (median [IQR], 243.0 [203.0-297.0] U/L), which are associated with liver and myocardial injury. Compared with mild cases, levels of inflammatory cytokines including interleukin 6, tumor necrosis factor α, and interferon γ were unchanged, whereas the level of immune suppressive interleukin 10 was markedly increased in moderate cases compared with mild cases (median [IQR], 3.96 [3.34-5.29] pg/mL vs 3.58 [3.10-4.36] pg/mL; P = .048). There was no statistically significant difference in absolute number of lymphocytes (including T cells and B cells) between mild and moderate cases, but moderate cases were associated with a decrease in neutrophil levels compared with mild cases (median [IQR], 2310/μL [1680/μL-3510/μL] vs 3120/μL [2040/μL-4170/μL]; P = .01). Immunoglobin G and the neutrophil to lymphocyte ratio were negatively associated with biochemical indices related to liver and myocardial injury (immunoglobulin G, ALT: r, −0.3579; AST: r, −0.5280; CK-MB activity: r, −0.4786; LDH: r, −0.4984; and neutrophil to lymphocyte ratio, ALT: r, −0.1893; AST: r, −0.3912; CK-MB activity: r, −0.3428; LDH: r, −0.3234), while counts of lymphocytes, CD4(+) T cells, and interleukin 10 showed positive associations (lymphocytes, ALT: r, 0.2055; AST: r, 0.3615; CK-MB activity: r, 0.338; LDH: r, 0.3309; CD4(+) T cells, AST: r, 0.4701; CK-MB activity: r, 0.4151; LDH: r, 0.4418; interleukin 10, ALT: r, 0.2595; AST: r, 0.3386; CK-MB activity: r, 0.3948; LDH: r, 0.3794). CONCLUSIONS AND RELEVANCE: In this case series, systemic inflammation rarely occurred in pediatric patients with COVID-19, in contrast with the lymphopenia and aggravated inflammatory responses frequently observed in adults with COVID-19. Gaining a deeper understanding of the role of neutrophils, CD4(+) T cells, and B cells in the pathogenesis of SARS-CoV-2 infection could be important for the clinical management of COVID-19.

positive: Longitudinal hematologic and immunologic variations associated with the progression of COVID-19 patients in China Background Crucial roles of hematologic and immunologic responses in progression of COVID-19 remains largely unclear. Objective We sought to address the dynamic changes of hematologic and immunologic biomarkers and their associations with severity and outcomes of the disease. Methods A retrospective study including 548 COVID-19 patients with clarified outcome (discharged or deceased) from a national cohort in China was performed. Cross-sectional and longitudinal variations were compared and the associations with different severity and outcomes were analyzed. Results On admission, the counts of lymphocytes, T cell subsets, eosinophils and platelets decreased markedly, especially in severe/critical and fatal patients. Increased neutrophil count and neutrophils-to-lymphocytes ratio were predominant in severe/critical cases or non-survivors. During hospitalization, eosinophils, lymphocytes and platelets were shown an increasing trend in survivors, but maintained lower levels or dropped significantly afterwards in non-survivors. Non-survivors kept high level or showed an upward trend for neutrophils, IL-6, procalcitonin, D-dimer, amyloid A protein and C-reactive protein, which were kept stable or shown downward trend in survivors. Positive correlation between CD8+ T cell and lymphocytes count was found in survivors but not in non-survivors. A multivariate Cox regression model suggested that restored levels of lymphocytes, eosinophils and platelets could serve as the predictors for the recovery, while progressive increases in neutrophils, basophils and IL-6 were associated with fatal outcome. Conclusions Hematologic and immunologic impairment showed a significantly different profile between survivors and non-survivors in COVID-19 patients with different severity. The longitudinal variations of these biomarkers could serve to predict recovery or fatal outcome.

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

positive: Neutrophil to lymphocyte ratio as prognostic and predictive factor in patients with coronavirus disease 2019: A retrospective cross-sectional study This retrospective study was designed to explore whether neutrophil to lymphocyte ratio (NLR) is a prognostic factor in patients with coronavirus disease 2019 (COVID-19). A cohort of patients with COVID-19 admitted to the Tongren Hospital of Wuhan University from 11 January 2020 to 3 March 2020 was retrospectively analyzed. Patients with hematologic malignancy were excluded. The NLR was calculated by dividing the neutrophil count by the lymphocyte count. NLR values were measured at the time of admission. The primary outcome was all-cause in-hospital mortality. A multivariate logistic analysis was performed. A total of 1004 patients with COVID-19 were included in this study. The mortality rate was 4.0% (40 cases). The median age of nonsurvivors (68 years) was significantly older than survivors (62 years). Male sex was more predominant in nonsurvival group (27; 67.5%) than in the survival group (466; 48.3%). NLR value of nonsurvival group (median: 49.06; interquartile range [IQR]: 25.71-69.70) was higher than that of survival group (median: 4.11; IQR: 2.44-8.12; P < .001). In multivariate logistic regression analysis, after adjusting for confounding factors, NLR more than 11.75 was significantly correlated with all-cause in-hospital mortality (odds ratio = 44.351; 95% confidence interval = 4.627-425.088). These results suggest that the NLR at hospital admission is associated with in-hospital mortality among patients with COVID-19. Therefore, the NLR appears to be a significant prognostic biomarker of outcomes in critically ill patients with COVID-19. However, further investigation is needed to validate this relationship with data collected prospectively.

positive: Association of inflammatory markers with the severity of COVID-19 Background: The ongoing worldwide epidemic of Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed a huge threat to global public health. However, with regard to the effects of inflammatory markers on the severity of COVID-19, studies have reported associations that vary in strength and direction. Aims: In the meta-analysis, we aimed to provide an overview of the association of inflammatory markers with severity of COVID-19. Methods: The following databases were searched: PubMed, Embase, Cochrane Library, Wanfang database and CNKI (China National Knowledge Infrastructure) database until March 20, 2020. Weighted mean difference (WMD) and 95% confidence intervals (CIs) were pooled using random or fixed-effects models. Results: A total of 16 studies were included in our analysis comprising of 3962 patients with COVID-19. Random-effects results demonstrated that patients with COVID-19 in non-severe group had lower levels for CRP (WMD = -41.78 mg/l, 95% CI = [-52.43, -31.13], P < 0.001), PCT (WMD = -0.13 ng/ml, 95% CI = [-0.20, -0.05], P < 0.001), IL-6 (WMD = -21.32 ng/l, 95% CI = [-28.34, -14.31], P < 0.001), ESR (WMD = -8.40 mm/h, 95% CI = [-14.32, -2.48], P = 0.005), SAA (WMD = -43.35 μg/ml, 95% CI = [-80.85, -5.85], P = 0.020) and serum ferritin (WMD = -398.80 mg/l, 95% CI = [-625.89, -171.71], P < 0.001), compared with those in severe group. Moreover, survivors had lower level for IL-6 than non-survivors with COVID-19 (WMD = -4.80 ng/ml, 95% CI = [-5.87, -3.73], P < 0.001). These results were consistent through sensitivity analysis and publication bias assessment. Conclusions: The meta-analysis highlights the association of inflammatory markers with the severity of COVID-19. Measurement of inflammatory markers might help clinicians to monitor and evaluate the severity and prognosis of COVID-19.

positive: Clinical Characteristics of COVID‐19 in patients with pre‐existing ILD: A retrospective study in a single center in Wuhan, China BACKGROUND: Since the outbreak of 2019 novel coronavirus (SARS‐CoV‐2) pneumonia, many patients with underlying disease, such as interstitial lung disease (ILD), were admitted to Tongji hospital in Wuhan, China. To date, no data have ever been reported to reflect the clinical features of Corona Virus Disease 2019 (COVID‐19) among these patients with pre‐existing ILD. METHODS: We analyzed the incidence and severity of COVID‐19 patients with ILD among 3201 COVID‐19 inpatients, and compared two independent cohorts of COVID‐19 patients with pre‐existing ILD (n=28) and non‐ILD COVID‐19 patients (n=130). RESULTS: Among those 3201 COVID‐19 inpatients, 28 of whom were COVID‐19 with ILD (0.88%). Fever was the predominant symptom both in COVID‐19 with ILD (81.54%) and non‐ILD COVID‐19 patients (72.22%). However, COVID‐19 patients with ILD were more likely to have cough, sputum, fatigue, dyspnea, and diarrhea. Very significantly higher number of neutrophils, monocytes, IL‐8, IL‐10, IL‐1β and D‐Dimer was characterized in COVID‐19 with ILD as compared to those of non‐ILD COVID‐19 patients. Furthermore, logistic regression models showed neutrophils counts, pro‐inflammatory cytokines (TNF‐α, IL6, IL1β, IL2R), and coagulation dysfunction biomarkers (D‐Dimer, PT, Fbg) were significantly associated with the poor clinical outcomes of COVID‐19. CONCLUSION: ILD patients could be less vulnerable to SARS‐CoV‐2. However, ILD patients tend to severity condition after being infected with SARS‐CoV‐2. The prognosis of COVID‐19 patients with per‐existing ILD is significantly worse than that of non‐ILD patients. And more, aggravated inflammatory responses and coagulation dysfunction appear to be the critical mechanisms in the COVID‐19 patients with ILD. This article is protected by copyright. All rights reserved.

positive: Low levels of the prognostic biomarker suPAR are predictive of mild outcome in patients with symptoms of COVID-19 - a prospective cohort study OBJECTIVE To examine if baseline soluble urokinase plasminogen activator receptor (suPAR) can predict whether patients with COVID-19 symptoms will need mechanical ventilation during a 14-day follow-up. Furthermore, to examine differences in demographics, clinical signs, and biomarkers in patients tested either positive or negative for SARS-CoV-2. DESIGN Prospective cohort study including patients presenting with symptoms of COVID-19. SETTING Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark. PARTICIPANTS 407 patients presenting with symptoms of COVID-19 were included from the Emergency Department (ED). Patients were included from March 19 to April 3 and follow-up data was collected until April 17, 2020. MAIN OUTCOME MEASURES Primary outcomes were respiratory failure in patients presenting with symptoms of COVID-19 and in those with a positive SARS-CoV-2 RT-PCR test, respectively. Furthermore, we analysed differences between patients testing positive and negative for SARS-CoV-2, and disease severity outcomes in SARS-CoV-2 positive patients according to baseline suPAR. BACKGROUND Patients admitted to ED with clinical signs or symptoms of COVID-19 infection need a safe and quick triage, in order to determine if an in-hospital stay is necessary or if the patient can safely be isolated in their own home with relevant precautions. suPAR is a biomarker previously shown to be associated with adverse outcomes in acute medical patients. We aimed to examine if suPAR at baseline presentation is predictive of respiratory failure in patients presenting with symptoms of COVID-19. Furthermore, we examined demographic, clinical, and biochemical differences between SARS-CoV-2-positive and negative patients. RESULTS Among the 407 symptomatic patients, the median (interquartile range) age was 64 years (47-77), 58% were women, and median suPAR was 4.2 ng/ml (2.7-6.4). suPAR level below 4.75 ng/ml at admission ruled out respiratory failure during follow-up with an area under the curve (95% CI) of 0.89 (0.85-0.94) and a negative predictive value of 99.5%. Of the 407 symptomatic patients, 117 (28.8%) had a positive RT-PCR test for SARS-CoV-2 and presented with significant differences in vital signs, cell counts, and biomarkers compared to SARS-CoV-2 negative patients. In SARS-CoV-2 positive patients eligible for mechanical ventilation (N=87), 26 (30%) developed respiratory failure. Best baseline predictors of respiratory failure were suPAR with an area under the curve (95% CI) of 0.88 (0.80-0.95), EWS 0.84 (0.75-0.93), lactate dehydrogenase 0.82 (0.71-0.93), and C-reactive protein 0.80 (0.70-0.89). CONCLUSION SARS-CoV-2 affects several patient parameters underpinning the severe impact of the infection. A low suPAR level (<4.75 ng/ml) at baseline is a useful biomarker for aiding clinical decisions including discharge of patients presenting with symptoms of COVID-19.

positive: Exploring diseases/traits and blood proteins causally related to expression of ACE2, the putative receptor of 2019-nCov: A Mendelian Randomization analysis The novel coronavirus 2019-nCoV has caused major outbreaks in many parts of the world. A better understanding of the pathophysiology of COVID-19 is urgently needed. Clinically, it is important to identify who may be susceptible to infection and identify treatments for the disease. There is good evidence that ACE2 is a receptor for 2019-nCoV, and studies also suggested that high expression of ACE2 may increase susceptibility to infection. Here we conducted a phenome-wide Mendelian randomization (MR) study to prioritize diseases/traits and blood proteins that may be causally linked to ACE2 expression in the lung. Expression data was based on GTEx. We also explored drug candidates whose targets overlapped with the top-ranked proteins in MR analysis, as these drugs could potentially alter ACE2 expression and may be clinically relevant. Notably, MR is much less vulnerable to confounding and reverse causality compared to observational studies. The most consistent finding was a tentative causal association between diabetes-related traits and increased ACE2 expression. Based on one of the largest GWAS on type II diabetes (T2DM) to date (N=898,130), we found that T2DM is causally linked to raised ACE2 expression (beta=0.1835, 95% CI 0.0853-0.2817; p=2.49E-4; GSMR method). Significant associations (at nominal level; p<0.05) was also observed across multiple datasets, with different analytic methods, and for both type I and II diabetes. Other diseases/traits having nominal significant associations with increased ACE2 included inflammatory bowel disease, (ER+) breast and lung cancers, asthma, smoking and elevated ALT, among others. We also uncovered a number of plasma/serum proteins potentially linked to altered ACE2 expression, and the top enriched pathways included cytokine-cytokine-receptor interaction, VEGF signaling, JAK-STAT signaling etc. We also explored drugs that target some of the top-ranked proteins in the MR analysis. In conclusion, the current MR analysis reveals diseases/traits and blood proteins that may causally affect ACE2 expression, which in turn may influence susceptibility to the infection. The proteome-wide MR analysis may shed light on the molecular mechanisms underlying ACE2 expression, and may help guide drug repositioning in the future. Nevertheless, we stress that further studies are required to verify our findings due to various limitations and the exploratory nature of some analyses.

positive: Clinical and pathological investigation of patients with severe COVID-19 BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), has become a pandemic. This study addresses the clinical and immunopathological characteristics of severe COVID-19. METHODS: Sixty-nine patients with COVID-19 were classified into severe and nonsevere groups to analyze their clinical and laboratory characteristics. A panel of blood cytokines was quantified over time. Biopsy specimens from 2 deceased cases were obtained for immunopathological, ultrastructural, and in situ hybridization examinations. RESULTS: Circulating cytokines, including IL-8, IL-6, TNF-α, IP10, MCP1, and RANTES, were significantly elevated in patients with severe COVID-19. Dynamic IL-6 and IL-8 were associated with disease progression. SARS-CoV-2 was demonstrated to infect type II and type I pneumocytes and endothelial cells, leading to severe lung damage through cell pyroptosis and apoptosis. In severe cases, lymphopenia, neutrophilia, depletion of CD4+ and CD8+ T lymphocytes, and massive macrophage and neutrophil infiltrates were observed in both blood and lung tissues. CONCLUSIONS: A panel of circulating cytokines could be used to predict disease deterioration and inform clinical interventions. Severe pulmonary damage was predominantly attributed to both cytopathy caused by SARS-CoV-2 and immunopathologic damage. Strategies that prohibit pulmonary recruitment and overactivation of inflammatory cells by suppressing cytokine storm might improve the outcomes of patients with severe COVID-19.

positive: Prognosis of COVID-19: Changes in laboratory parameters INTRODUCTION: Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome - Coronavirus 2 (SARS-CoV-2) emerged in China and has become a global threat Comparison of hematological parameters between mild and severe cases of SARS-CoV 2 is so far limited, but significant differences in parameters such as interleukin-6, d-dimers, glucose, fibrinogen and C-reactive protein have been already reported PURPOSE: In this study we analyzed the changes observed in easily measured blood biomarkers in the patients and provided evidence of how these markers can be used as prognostic factors of the disease METHODS: Demographic characteristics, detailed medical history, and laboratory findings of all enrolled SARS-CoV 2 infection positive patients who were referred to Patras University Hospital from the period of March 4th 2020 (when first confirmed case in Greece appeared in our hospital) until April 4th 2020 were extracted from electronic medical records and analyzed RESULTS: We provided evidence that some very common laboratory values can be used as independent predictive factors in SARS-CoV 2 infection Despite the retrospective nature of this study and the small number of subjects analyzed, we showed that NLR, LDH, d-dimers, CRP, fibrinogen and ferritin can be used early at the patient's first visit for SARS-CoV 2 infection symptoms and can predict the severity of infection CONCLUSION: More studies are warranted to further objectively confirm the clinical value of prognostic factors related to SARS-CoV 2 and establish an easy-to-get panel of laboratory findings for evaluating the disease severity

positive: Association of inflammatory markers with the severity of COVID-19: a meta-analysis Abstract Objectives Studies reported associations of inflammatory markers with the severity of COVID-19, but conclusions were inconsistent. We aimed to provide an overview of the association of inflammatory markers with severity of COVID-19. Methods We searched PubMed, Embase, Cochrane Library, Wanfang and China National Knowledge Infrastructure (CNKI) database until March 20, 2020. Weighted mean difference (WMD) and 95% confidence intervals (CIs) were pooled using random or fixed-effects models. Results A total of 16 studies comprising of 3962 patients with COVID-19 were included in our analysis. Random-effect results demonstrated that patients with COVID-19 in nonsevere group had lower levels for CRP (WMD = -41.78 mg/l, 95% CI = [-52.43, -31.13], P < 0.001), PCT (WMD = -0.13 ng/ml, 95% CI = [-0.20, -0.05], P < 0.001), IL-6 (WMD = -21.32 ng/l, 95% CI = [-28.34, -14.31], P < 0.001), ESR (WMD = −8 mm/h, 95% CI = [-14, -2], P = 0.005), SAA (WMD = -43.35 μg/ml, 95% CI = [-80.85, -5.85], P = 0.020) and serum ferritin (WMD = -398.80 mg/l, 95% CI = [-625.89, -171.71], P < 0.001), compared with those in severe group. Moreover, survivors had a lower level for IL-6 than non-survivors (WMD = -4.80 ng/ml, 95% CI = [-5.87, -3.73], P < 0.001). These results were consistent through sensitivity analysis and publication bias assessment. Conclusions The meta-analysis highlights the association of inflammatory markers with the severity of COVID-19. Measurement of inflammatory markers might assist clinicians to monitor and evaluate the severity and prognosis of COVID-19.

positive: Clinical value of immune-inflammatory parameters to assess the severity of coronavirus disease 2019 OBJECTIVE: To explore the clinical value of immune-inflammatory markers to assess the severity of coronavirus disease 2019 (COVID-19). METHODS: 127 consecutive hospitalized patients with confirmed COVID-19 were enrolled in this study, and classified into non-severe and severe groups. Demographics, symptoms, underlying diseases and laboratory data were collected and assessed for predictive value. RESULTS: Of 127 COVID-19 patients, 16 cases (12.60%) were classified into the severe group. High level of interleukin-6 (IL-6), C-reaction protein (CRP) and hypertension were independent risk factors for the severity of COVID-19. The risk model based on IL-6, CRP and hypertension had the highest area under the receiver operator characteristic curve (AUROC). Additionally, the baseline IL-6 was positively correlated with other immune-inflammatory parameters and the dynamic change of IL-6 in the severe cases were parallel to the amelioration of the disease. CONCLUSION: Our study showed that high level of IL-6, CRP and hypertension were independent risk factors for assessing the severity of COVID-19. The risk model established upon IL-6, CRP and hypertension had the highest predictability in this study. Besides, IL-6 played a pivotal role in the severity of COVID-19 and had a potential value for monitoring the process of severe cases.

positive: Elevated troponin in patients with Coronavirus Disease 2019 (COVID-19): possible mechanisms Abstract Coronavirus disease 2019 (COVID-19) is a pandemic that has affected more than 1.8 million people worldwide, overwhelmed health care systems due to the high proportion of critical presentations, and resulted in over 100,000 deaths. Since the first data analyses in China, elevated cardiac troponin has been noted in a substantial proportion of patients, implicating myocardial injury as a possible pathogenic mechanism contributing to severe illness and mortality. Accordingly, high troponin levels are associated with increased mortality in patients with COVID-19. This brief review explores the available evidence regarding the association between COVID-19 and myocardial injury.

positive: Eosinopenia and elevated C-reactive protein facilitate triage of COVID-19 patients in fever clinic: a retrospective case-control study Abstract Background Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a pandemic affecting over 200 countries. Many cities have established designated fever clinics to triage suspected COVID-19 patients from other patients with similar symptoms. However, given the limited availability of the nucleic acid test as well as long waiting time for both the test and radiographic examination, the quarantine or therapeutic decisions for a large number of mixed patients were often not made in time. We aimed to identify simple and quickly available laboratory biomarkers to facilitate effective triage at the fever clinics for sorting suspected COVID-19 patients from those with COVID-19-like symptoms. Methods We collected clinical, etiological, and laboratory data of 989 patients who visited the Fever Clinic at Wuhan Union Hospital, Wuhan, China, from Jan 31 to Feb 21. Based on polymerase chain reaction (PCR) nucleic acid testing for SARS-CoV-2 infection, they were divided into two groups: SARS-CoV-2-positive patients as cases and SARS-CoV-2-negative patients as controls. We compared the clinical features and laboratory findings of the two groups, and analyzed the diagnostic performance of several laboratory parameters in predicting SARS-CoV-2 infection and made relevant comparisons to the China diagnosis guideline of having a normal or decreased number of leukocytes (≤9•5 109/L) or lymphopenia (<1•1 109/L). Findings Normal or decreased number of leukocytes (≤9•5 109/L), lymphopenia (<1•1 109/L), eosinopenia (<0•02 109/L), and elevated hs-CRP (≥4 mg/L) were presented in 95•0%, 52•2%, 74•7% and 86•7% of COVID-19 patients, much higher than 87•2%, 28•8%, 31•3% and 45•2% of the controls, respectively. The eosinopenia produced a sensitivity of 74•7% and specificity of 68•7% for separating the two groups with the area under the curve (AUC) of 0•717. The combination of eosinopenia and elevated hs-CRP yielded a sensitivity of 67•9% and specificity of 78•2% (AUC=0•730). The addition of eosinopenia alone or the combination of eosinopenia and elevated hs-CRP into the guideline-recommended diagnostic parameters for COVID-19 improved the predictive capacity with higher than zero of both net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Interpretation The combination of eosinopenia and elevated hs-CRP can effectively triage suspected COVID-19 patients from other patients attending the fever clinic with COVID-19-like initial symptoms. This finding would be particularly useful for designing triage strategies in an epidemic region having a large number of patients with COVID-19 and other respiratory diseases while limited medical resources for nucleic acid tests and radiographic examination. Funding This work was supported by the National Natural Science Foundation of China (NSFC) and the Major Scientific and Technological Innovation Projects of Hubei Province (MSTIP).

positive: Lactate dehydrogenase levels predict coronavirus disease 2019 (COVID-19) severity and mortality: A pooled analysis Coronavirus disease 2019 (COVID-19) infection has now reached a pandemic state, affecting more than a million patients worldwide. Predictors of disease outcomes in these patients need to be urgently assessed to decrease morbidity and societal burden. Lactate dehydrogenase (LDH) has been associated with worse outcomes in patients with viral infections. In this pooled analysis of 9 published studies (n = 1532 COVID-19 patients), we evaluated the association between elevated LDH levels measured at earliest time point in hospitalization and disease outcomes in patients with COVID-19. Elevated LDH levels were associated with a ~6-fold increase in odds of developing severe disease and a ~16-fold increase in odds of mortality in patients with COVID-19. Larger studies are needed to confirm these findings.

positive: Development and validation of chest CT-based imaging biomarkers for early stage COVID-19 screening Coronavirus Disease 2019 (COVID-19) is currently a global pandemic, and the early screening of COVID-19 is one of the key factors for COVID-19 control and treatment. Here, we developed and validated chest CT-based imaging biomarkers for COVID-19 patient screening. We identified the vasculature-like signals from CT images and found that, compared to healthy and community acquired pneumonia (CAP) patients, the COVID-19 patients revealed significantly higher abundance of these signals. Furthermore, unsupervised feature learning leads to the discovery of clinical-relevant imaging biomarkers from the vasculature-like signals for accurate and sensitive COVID-19 screening that has been double-blindly validated in an independent hospital (sensitivity: 0.941, specificity: 0.904, AUC: 0.952). Our findings could open a new avenue to assist screening of COVID-19 patients.

positive: Proteomic and Metabolomic Characterization of COVID-19 Patient Sera Severe COVID-19 patients account for most of the mortality of this disease. Early detection and effective treatment of severe patients remain major challenges. Here, we performed proteomic and metabolomic profiling of sera from 46 COVID-19 and 53 control individuals. We then trained a machine learning model using proteomic and metabolomic measurements from a training cohort of 18 non-severe and 13 severe patients. The model correctly classified severe patients with an accuracy of 93.5%, and was further validated using ten independent patients, seven of which were correctly classified. We identified molecular changes in the sera of COVID-19 patients implicating dysregulation of macrophage, platelet degranulation and complement system pathways, and massive metabolic suppression. This study shows that it is possible to predict progression to severe COVID-19 disease using serum protein and metabolite biomarkers. Our data also uncovered molecular pathophysiology of COVID-19 with potential for developing anti-viral therapies.

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

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

positive: The hemocyte counts as a potential biomarker for predicting disease progression in COVID-19: a retrospective study. Objectives In December 2019, there was an outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, and since then, the disease has been increasingly spread throughout the world. Unfortunately, the information about early prediction factors for disease progression is relatively limited. Therefore, there is an urgent need to investigate the risk factors of developing severe disease. The objective of the study was to reveal the risk factors of developing severe disease by comparing the differences in the hemocyte count and dynamic profiles in patients with severe and non-severe COVID-19. Methods In this retrospectively analyzed cohort, 141 confirmed COVID-19 patients were enrolled in Taizhou Public Health Medical Center, Taizhou Hospital, Zhejiang Province, China, from January 17, 2020 to February 26, 2020. Clinical characteristics and hemocyte counts of severe and non-severe COVID patients were collected. The differences in the hemocyte counts and dynamic profiles in patients with severe and non-severe COVID-19 were compared. Multivariate Cox regression analysis was performed to identify potential biomarkers for predicting disease progression. A concordance index (C-index), calibration curve, decision curve and the clinical impact curve were calculated to assess the predictive accuracy. Results The data showed that the white blood cell count, neutrophil count and platelet count were normal on the day of hospital admission in most COVID-19 patients (87.9%, 85.1% and 88.7%, respectively). A total of 82.8% of severe patients had lymphopenia after the onset of symptoms, and as the disease progressed, there was marked lymphopenia. Multivariate Cox analysis showed that the neutrophil count (hazard ratio [HR] = 4.441, 95% CI = 1.954-10.090, p = 0.000), lymphocyte count (HR = 0.255, 95% CI = 0.097-0.669, p = 0.006) and platelet count (HR = 0.244, 95% CI = 0.111-0.537, p = 0.000) were independent risk factors for disease progression. The C-index (0.821 [95% CI, 0.746-0.896]), calibration curve, decision curve and the clinical impact curve showed that the nomogram can be used to predict the disease progression in COVID-19 patients accurately. In addition, the data involving the neutrophil count, lymphocyte count and platelet count (NLP score) have something to do with improving risk stratification and management of COVID-19 patients. Conclusions We designed a clinically predictive tool which is easy to use for assessing the progression risk of COVID-19, and the NLP score could be used to facilitate patient stratification management.

positive: Serum protein profiling reveals a landscape of inflammation and immune signaling in early-stage COVID-19 infection Coronavirus disease 2019 (COVID-19) is a highly contagious infection and threating the human lives in the world. The elevation of cytokines in blood is crucial to induce cytokine storm and immunosuppression in the transition of severity in COVID-19 patients. However, the comprehensive changes of serum proteins in COVID-19 patients throughout the SARS-CoV-2 infection is unknown. In this work, we developed a high-density antibody microarray and performed an in-depth proteomics analysis of serum samples collected from early COVID-19 (n=15) and influenza (n=13) patients. We identified a large set of differentially expressed proteins (n=125) that participate in a landscape of inflammation and immune signaling related to the SARS-CoV-2 infection. Furthermore, the significant correlations of neutrophil and lymphocyte with the CCL2 and CXCL10 mediated cytokine signaling pathways was identified. These information are valuable for the understanding of COVID-19 pathogenesis, identification of biomarkers and development of the optimal anti-inflammation therapy.

positive: Association between chest CT features and clinical course of Coronavirus Disease 2019 Abstract Purpose This retrospective study aims to illustrate the radiographic characteristics of Coronavirus Disease 2019 and the correlation with the clinical course. Methods 195 hospitalized patients confirmed as Coronavirus Disease 2019 at First Hospital of Changsha, Hunan Province from December 31, 2019 to February 20, 2020 were enrolled. Chest computed tomography scan, clinical data and laboratory tests results were collected accordingly. Variable characteristics were recorded, radiographic evolution and outcome were analyzed along with the time course. Representative laboratory tests results were analyzed based on the image findings. Results Majority of the patients showed bilateral (73.8%), multiple lobes involvements (75.9%), peripheral distribution (83.1%), ground-glass opacification (41.0%), increased vascular margins (63.1%), long axis parallelism (55.9%), patchy ground-glass opacities beneath the pleura (51.3%) and consolidation (45.6%). According to the repeated radiology analysis, patients of improving/stable group tended to have younger age compared with worsening group (45.3 ± 15.0 VS. 59.3 ± 13.5, P = 0.001). Based on the laboratory test results, patients with positive image findings shared elder age, 46.0 (35.0–60.0)VS.31.0 (12.0–37.0) P < 0.001, and higher chance developing fever(P < 0.05); higher level of lymphocytes, C-reactive protein, erythrocyte sedimentation rate and lactate dehydrogenase; lower level of white blood cells, neutrophil and albumin(P < 0.001). Conclusions There are several specific image changes along with the disease progression may be helpful in early recognition and differential diagnosis of Coronavirus Disease 2019. Comprehensive assessments of both imaging feature and laboratory test results may offer an intact knowledge of Coronavirus Disease 2019.

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: Low testosterone levels predict clinical adverse outcomes in SARS‐CoV‐2 pneumonia patients BACKGROUND: The pandemic of new severe acute respiratory syndrome (SARS) due to coronavirus (CoV) 2 (SARS‐CoV‐2) has stressed the importance of effective diagnostic and prognostic biomarkers of clinical worsening and mortality. Epidemiological data showing a differential impact of SARS‐CoV‐2 infection on women and men have suggested a potential role for testosterone (T) in determining gender disparity in the SARS‐CoV‐2 clinical outcomes. OBJECTIVES: To estimate the association between T level and SARS‐CoV‐2 clinical outcomes (defined as conditions requiring transfer to higher or lower intensity of care or death) in a cohort of patients admitted in the respiratory intensive care unit (RICU). MATERIALS AND METHODS: A consecutive series of 31 male patients affected by SARS‐CoV‐2 pneumonia and recovered in the respiratory intensive care unit (RICU) of the “Carlo Poma” Hospital in Mantua were analyzed. Several biochemical risk factors (ie, blood count and leukocyte formula, C‐reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), ferritin, D‐dimer, fibrinogen, interleukin 6 (IL‐6)) as well as total testosterone (TT), calculated free T (cFT), sex hormone–binding globulin (SHBG), and luteinizing hormone (LH) were determined. RESULTS: Lower TT and cFT were found in the transferred to ICU/deceased in RICU group vs groups of patients transferred to IM or maintained in the RICU in stable condition. Both TT and cFT showed a negative significant correlation with biochemical risk factors (ie, the neutrophil count, LDH, and PCT) but a positive association with the lymphocyte count. Likewise, TT was also negatively associated with CRP and ferritin levels. A steep increase in both ICU transfer and mortality risk was observed in men with TT < 5 nmol/L or cFT < 100 pmol/L. DISCUSSION AND CONCLUSION: Our study demonstrates for the first time that lower baseline levels of TT and cFT levels predict poor prognosis and mortality in SARS‐CoV‐2‐infected men admitted to RICU.

positive: Hemostatic laboratory derangements in COVID-19 with a focus on platelet count Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease in 2019 (COVID-19) which rapidly evolved from an outbreak in Wuhan, China into a pandemic that has resulted in over millions of infections and over hundreds of thousands of mortalities worldwide. Various coagulopathies have been reported in association with COVID-19, including disseminated intravascular coagulation (DIC), sepsis-induced coagulopathy (SIC), local microthrombi, venous thromboembolism (VTE), arterial thrombotic complications, and thrombo-inflammation. There is a plethora of publications and conflicting data on hematological and hemostatic derangements in COVID-19 with some data suggesting the link to disease progress, severity and/or mortality. There is also growing evidence of potentially useful clinical biomarkers to predict COVID-19 progression and disease outcomes. Of those, a link between thrombocytopenia and COVID-19 severity or mortality was suggested. In this opinion report, we examine the published evidence of hematological and hemostatic laboratory derangements in COVID-19 and the interrelated SARS-CoV-2 induced inflammation, with a focussed discussion on platelet count alterations. We explore whether thrombocytopenia could be a potential disease biomarker and we provide recommendations for future studies in this regard.

positive: Cardiac troponin I in patients with coronavirus disease 2019 (COVID-19): Evidence from a meta-analysis()

positive: T-Cell Subset Counts in Peripheral Blood Can Be Used as Discriminatory Biomarkers for Diagnosis and Severity Prediction of Coronavirus Disease 2019 This study evaluated the significance of lymphocyte subset detection in peripheral blood in the diagnosis and prognosis of coronavirus disease 2019 (COVID-19). Our results revealed that CD3+ T cells, CD4+ T cells, CD8+ T cells, and natural killer cells were significantly decreased in patients with COVID-19. These patients had a relatively slight decrease in CD4+ T cells but a severe decrease in CD8+ T cells. The significantly elevated CD4/CD8 ratio was observed in COVID-19 patients. T-cell subset counts were related to the severity and prognosis of COVID-19, suggesting that the counts of CD8+ T and CD4+ T cells can be used as diagnostic markers of COVID-19 and predictors of disease severity.

positive: AI-Driven CT-based quantification, staging and short-term outcome prediction of COVID-19 pneumonia Chest computed tomography (CT) is widely used for the management of Coronavirus disease 2019 (COVID-19) 49 pneumonia because of its availability and rapidity. The standard of reference for confirming COVID-19 relies on microbiological tests but these tests might not be available in an emergency setting and their results are not immediately available, contrary to CT. In addition to its role for early diagnosis, CT has a prognostic role by allowing visually evaluating the extent of COVID-19 lung abnormalities. The objective of this study is to address prediction of short-term outcomes, especially need for mechanical ventilation. In this multi-centric study, we propose an end-to-end artificial intelligence solution for automatic quantification and prognosis assessment by combining automatic CT delineation of lung disease meeting the performance of experts and data-driven identification of biomarkers for its prognosis. AI-driven combination of variables with CT-based biomarkers offers perspectives for optimal patient management given the shortage of intensive care beds and ventilators.

positive: 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.

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: Comparative analysis of laboratory indexes of severe and non-severe patients infected with COVID-19 BACKGROUND: The pandemic coronavirus disease 2019 (COVID-19) has threaten the global health. The characteristics of laboratory findings of coronavirus are of great significance for clinical diagnosis and treatment. We found indicators that may most effectively predict a non-severe COVID-19 patient develop into a severe patient. METHODS: We conducted a meta-analysis to compare the laboratory findings of severe patients with non-severe patients with COVID-19 from searched articles. RESULTS: Through the analysis of laboratory examination information of patients with COVID-19 from 35 articles (5912 patients), we demonstrated that severe cases possessed higher levels of leukocyte (1.20-fold), neutrophil (1.33-fold), CRP (3.04-fold), PCT (2.00-fold), ESR (1.44-fold), AST (1.40-fold), ALT (1.34-fold), LDH (1.54-fold), CK (1.44-fold), CK-MB (1.39-fold), total bilirubin (1.14-fold), urea (1.28-fold), creatine (1.09-fold), PT (1.03-fold) and D-dimer (2.74-fold), as well as lower levels of lymphocytes (1.44-fold), eosinophil (2.00-fold), monocyte (1.08-fold), Hemoglobin (1.53-fold), PLT (1.15-fold), albumin (1.15-fold), and APTT (1.02-fold). Lymphocyte subsets and series of inflammatory cytokines were also different in severe cases with the non-severe ones, including lower levels of CD4 T cells (2.10-fold) and CD8 T cells (2.00-fold), higher levels of IL-1ß (1.02-fold), IL-6 (1.93-fold) and IL-10 (1.55-fold). CONCLUSIONS: Some certain laboratory inspections could predict the progress of the COVID-19 changes, especially lymphocytes, CRP, PCT, ALT, AST, LDH, D-dimer, CD4 T cells and IL6, which provide valuable signals for preventing the deterioration of the disease.

positive: COVID-19 severity is associated with immunopathology and multi-organ damage COVID-19 is characterised by dysregulated immune responses, metabolic dysfunction and adverse effects on the function of multiple organs. To understand how host responses contribute to COVID-19 pathophysiology, we used a multi-omics approach to identify molecular markers in peripheral blood and plasma samples that distinguish COVID-19 patients experiencing a range of disease severities. A large number of expressed genes, proteins, metabolites and extracellular RNAs (exRNAs) were identified that exhibited strong associations with various clinical parameters. Multiple sets of tissue-specific proteins and exRNAs varied significantly in both mild and severe patients, indicative of multi-organ damage. The continuous activation of IFN-I signalling and neutrophils, as well as a high level of inflammatory cytokines, were observed in severe disease patients. In contrast, COVID-19 in mild patients was characterised by robust T cell responses. Finally, we show that some of expressed genes, proteins and exRNAs can be used as biomarkers to predict the clinical outcomes of SARS-CoV-2 infection. These data refine our understanding of the pathophysiology and clinical progress of COVID-19 and will help guide future studies in this area.

positive: Can we predict the severity of coronavirus disease 2019 with a routine blood test? INTRODUCTION: The ongoing worldwide pandemic of coronavirus disease 2019 (COVID19) has posed a huge threat to global public health. However, the issue as to whether routine blood tests could be used to monitor and predict the severity and prognosis of COVID19 has not been comprehensively investigated so far. OBJECTIVES: This study aimed to provide an overview of the association of markers in the routine blood test with the severity of COVID19. METHODS: PubMed, Embase, Cochrane Library, Wanfang, and China National Knowledge Infrastructure (CNKI) databases were searched to identify studies reporting data on markers in the routine blood test and the severity of COVID19, published until March 20, 2020. The STATA software was used for metaanalysis. RESULTS: A total of 15 studies with 3090 patients with COVID19 were included in this analysis. Patients in the nonsevere group, compared with those in the severe group, had lower counts of white blood cells (weighted mean difference [WMD], -0.85 [×109/l]; 95% CI, -1.54 to -0.16; P = 0.02) and neutrophils (WMD, -1.57 [×109/l]; 95% CI, -2.6 to -0.54; P = 0.003), greater counts of lymphocytes (WMD, 0.29 [×109/l]; 95% CI, 0.22-0.36; P <0.001) and platelets (WMD, 19.05 [×109/l]; 95% CI, 3.04-35.06; P = 0.02), and a lower neutrophiltolymphocyte (NLR) ratio (WMD, -2.48; 95% CI, -3.81 to -1.15; P <0.001). There was no difference in the monocyte count (WMD, 0.01 [×109/l]; 95% CI, -0.01 to 0.03; P = 0.029) between these 2 groups. Sensitivity analysis and metaanalysis based on standard mean difference did not change the conclusions regarding neutrophils, lymphocytes, and NLR, but yielded inconsistent results for white blood cells and platelets. CONCLUSIONS: Severe patients had more neutrophils, higher NLR level, and fewer lymphocytes than non-severe patients with COVID-19. Measurement of these markers might assist clinicians to monitor and predict the severity and prognosis of COVID-19.

positive: A Precision Medicine Approach to SARS-CoV-2 Pandemic Management PURPOSE OF REVIEW: Precision medicine (PM) represents a new paradigm in disease diagnosis, prevention, and treatment. To apply PM premises in an emerging coronavirus pandemic acquires potentially greater relevance in order to allow the selection of specific preventive measures as well as biomarkers that will be useful in disease management. RECENT FINDINGS: The identification of the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as the responsible for the coronavirus disease 2019 (COVID-19) pandemic had led to a plethora of strategies to contain viral dissemination, affecting life styles and personal behaviors. Viral genomic sequencing has shown that SARS-CoV-2 spike protein utilizes angiotensin-converting enzyme 2 (ACE2) found on ciliated epithelial cells of the human lungs as its specific receptor. Neutralizing antibodies to the receptor-binding domain of the spike protein were detected in patients recovered from COVID-19; however, both T cells and NK cells were reduced in severe cases. Excessive and uncontrolled releases of pro-inflammatory cytokines such as IL-1B, IL-1RA, IL-7, IL-8, IL-9, IL-10, fibroblast growth factor (FGF), granulocyte–macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor (TNFα) were increased in severe patients. These cytokines might be useful biomarkers of disease worsening and potential targets for new biological therapies currently under investigation. SUMMARY: Present knowledge and recent developments in PM approach to COVID-19 disease prevention, evaluation, and management are pointed out. Better understanding of pathogenic pathways together with an accurate phenotype classification of patients presented with SARS-CoV-2 infection and symptoms might contribute to a more accurate definition of biomarkers and other diagnostic tools, which may lead to more precise mitigation strategies, personalized pharmacologic options, as well as new biological therapy developments.

positive: [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.

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

positive: IL-6 combined with CD8+ T cell count early predict in-hospital mortality for patients with COVID-19. BACKGROUND The numbers of fatal cases of Coronavirus Disease 2019 (COVID-19) continue to increase rapidly around the world. We aim to retrospectively investigate potential roles of factors, mainly immunologic parameters, in early predicting outcomes of patients with COVID-19. METHODS A total of 1,018 patients confirmed COVID-19 were enrolled in our retrospective study from two centers. The data of clinical features, laboratory tests, immunological tests, radiological findings, and outcomes were collected. Univariate and multivariable logistic regression analysis were performed to evaluate factors associated with in-hospital mortality. Receiver operator characteristic (ROC) curves and survival curves were plotted to evaluate the clinical usefulness. RESULTS Compared to the survival patients, the counts of all T lymphocytes subsets were markedly lower in non-survivors(P < 0.001), especially in CD8+ T cells (96.89 vs 203.98 cells/μl, P < 0.001) . Among all tested cytokines, IL-6 elevated most significantly with an upward trend of more than ten times (56.16 vs 5.36 pg/mL, P < 0.001). By a multivariable logistic regression analysis, two immunological indicators were found to be associated with in-hospital mortality, including IL-6 > 20 pg/mL (OR = 9.781; 95%CI, 6.304-15.174; P < 0.001) and CD8+ T cell count < 165 cells/μl (OR = 5.930; 95%CI, 3.677-9.562; P < 0.001), after adjusting confounding factors (age, gender, and underlying diseases). All the patients were divided into four groups according to levels of IL-6 and CD8+ T cells. The group with IL-6 > 20 pg/mL and CD8+ T cell count < 165 cells/μl had more old and male patients, as well as more proportion of patients with comorbidities, ventilation, ICU admission, shock, and death than those of any other group (P < 0.001). Furthermore, the ROC curve of the model combining IL-6 (>20 pg/mL) and CD8+ T cell count(<165 cells/μl) displayed more favorable discrimination than that of CURB-65 score (area under curve (AUC) = 0.907 vs 0.843, P < 0.001). Hosmer-Lemeshow test showed a good fitting of the model with no statistical significance (P = 0.581). CONCLUSIONS We firstly identify two reliable prognostic indicators, IL-6 (>20 pg/mL) and CD8+ T cell count (<165 cells/μl), which can accurately stratify patients into risk categories and predict mortality of patients with COVID-19. Those two indicators combined may guide clinicians to evaluate patient prognosis and make appropriate decisions.

positive: Clinical Analysis of 25 Novel Coronavirus Infections in Children BACKGROUND: To describe the characteristics of clinical manifestations of children with 2019 novel coronavirus (2019-nCoV) infection in Chongqing. METHODS: All 25 children with laboratory-confirmed 2019-nCoV infection by real-time reverse transcription-PCR (RNA-PCR) were admitted from the 4 designated treatment hospitals of 2019-nCoV in Chongqing from January 19 to March 12, 2020. Clinical data and epidemiological history of these patients were retrospectively collected and analyzed. RESULTS: The diagnosis was confirmed through RNA-PCR testing. Among the 25 cases, 14 were males and 11 were females. The median age was 11.0 (6.3-14.5) years (range 0.6-17.0 years). All children were related to a family cluster outbreak, and 7 children (28%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 8 (32%) asymptomatic, 4 (16%) very mild cases and 13 (52%) common cases. No severe or critical cases were identified. The most common symptoms were cough (13 cases, 52%) and fever (6 cases, 24%). The duration time of clinical symptoms was 13.0 (8.0-25.0) days. In the 25 cases, on admission, 21 cases (84%) had normal white blood cell counts, while only 2 cases (8%) more than 10 × 10/L and 2 cases (8%) less than 4 × 10/L, respectively; 22 cases(88%) had normal CD4+ T lymphocyte counts, while in the remaining 3 cases(8%) this increased mildly; 23 cases had normal CD8+ T lymphocyte counts, while in the remaining 2 cases (8%) CD8+ T lymphocyte counts were mildly increased as well. All Lymphocyte counts were normal. There were no statistical differences of lab results between the groups of asymptomatic cases, mild cases and common cases. There were only 13 cases with abnormal CT imaging, most of which were located in the subpleural area of the bottom of the lung. All patients were treated with interferon, 6 cases combined with Ribavirin, and 12 cases combined with lopinavir or ritonavir. The days from onset to RNA turning negative was 15.20 ± 6.54 days. There was no significant difference of RNA turning negative between the groups of interferon, interferon plus ribavirin and interferon plus lopinavir or ritonavir treatment. All the cases recovered and were discharged from hospital. CONCLUSIONS: The morbidity of 2019-nCoV infection in children is lower than in adults and the clinical manifestations and inflammatory biomarkers in children are nonspecific and milder than that in adults. RNA-PCR test is still the most reliable diagnostic method, especially for asymptomatic patients.

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

positive: Lymphopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A systemic review and meta-analysis Abstract Objectives Coronavirus Disease 2019 (COVID-19) is a new respiratory and systemic disease which needs quick identification of potential critical patients. This meta-analysis aimed to explore the relationship between lymphocyte count and the severity of COVID-19. Methods Comprehensive systematic literature search was carried out to find studies published from December 2019 to 22 March 2020 from five Databases. The language of literatures included English and Chinese. Mean difference (MD) of lymphocyte count in COVID-19 patients with or without severe disease and odds ratio (OR) of lymphopenia for severe form of COVID-19 was evaluated with this meta-analysis. Results Overall 13 case-series with a total of 2282 cases were included in the study. The pooled analysis showed that lymphocyte count was significantly lower in severe COVID-19 patients (MD -0.31×109/L; 95%CI: -0.42 to -0.19×109/L). The presence of lymphopenia was associated with nearly threefold increased risk of severe COVID-19 (Random effects model, OR=2.99, 95% CI: 1.31-6.82). Conclusions Lymphopenia is a prominent part of severe COVID-19 and a lymphocyte count of less than 1.5×109/L may be useful in predicting the severity clinical outcomes.

positive: Association of cardiac biomarkers and comorbidities with increased mortality, severity, and cardiac injury in COVID-19 patients: A meta-regression and decision tree analysis BACKGROUND: Coronavirus disease-2019 (COVID-19) has a deleterious effect on several systems, including the cardiovascular system. We aim to systematically explore the association of COVID-19 severity and mortality rate with the history of cardiovascular diseases and/or other comorbidities and cardiac injury laboratory markers. METHODS: The standardized mean difference (SMD) or odds ratio (OR) and 95% confidence intervals (CIs) were applied to estimate pooled results from the 56 studies. The prognostic performance of cardiac markers for predicting adverse outcomes and to select the best cutoff threshold was estimated by receiver operating characteristic curve analysis. Decision tree analysis by combining cardiac markers with demographic and clinical features was applied to predict mortality and severity in patients with COVID-19. RESULTS: A meta-analysis of 17 794 patients showed patients with high cardiac troponin I (OR = 5.22, 95% CI = 3.73-7.31, P < .001) and aspartate aminotransferase (AST) levels (OR = 3.64, 95% CI = 2.84-4.66, P < .001) were more likely to develop adverse outcomes. High troponin I more than 13.75 ng/L combined with either advanced age more than 60 years or elevated AST level more than 27.72 U/L was the best model to predict poor outcomes. CONCLUSIONS: COVID-19 severity and mortality are complicated by myocardial injury. Assessment of cardiac injury biomarkers may improve the identification of those patients at the highest risk and potentially lead to improved therapeutic approaches.

positive: Risk factors for severe corona virus disease 2019 (COVID-19) patients : a systematic review and meta analysis Importance: With the increasing number of infections for COVID-19, the global health resources are deficient. At present, we don't have specific medicines or vaccines against novel coronavirus pneumonia (NCP) and our assessment of risk factors for patients with severe pneumonia was limited. In order to maximize the use of limited medical resources, we should distinguish between mild and severe patients as early as possible. Objective: To systematically review the evidence of risk factors for severe corona virus disease 2019 (COVID-19) patients. Evidence Review: We conducted a comprehensive search for primary literature in both Chinese and English electronic bibliographic data bases including China National Knowledge Infrastructure (CNKI), Wanfang, Weipu, Chinese Biomedicine Literature Database (CBM-SinoMed), MEDLINE (via PubMed), EMBASE, Cochrane Central Register, and Web of science. The American agency for health research and quality (AHRQ) tool were used for assessing risk of bias. Mata-analysis was undertaken using STATA version 15.0. Results: 20 articles (N=4062 participants) were eligible for this systematic review and meta-analysis. First in this review and meta-analysis, we found that elderly male patients with a high body mass index, high breathing rate and a combination of underlying diseases (such as hypertension, diabetes, cardiovascular disease, and chronic obstructive pulmonary disease) were more likely to develop into critically ill patients. second, compared with ordinary patients, severe patients had more significant symptom such as fever and dyspnea. Besides, the laboratory test results of severe patients had more abnormal than non-severe patients, such as the elevated levels of white-cell counts, liver enzymes, lactate dehydrogenase, creatine kinase, c-reactive protein and procalcitonin, etc, while the decreased levels of lymphocytes and albumin, etc. Interpretation: This is the first systematic review investigating the risk factors for severe corona virus disease 2019 (COVID-19) patients. The findings are presented and discussed by different clinical characteristics. Therefore, our review may provide guidance for clinical decision-making and optimizes resource allocation.

positive: Lymphopenic community acquired pneumonia as signature of severe COVID-19 infection

positive: Biomarker variation in patients successfully treated with tocilizumab for severe coronavirus disease 2019 (COVID-19): results of a multidisciplinary collaboration. OBJECTIVES Acute respiratory distress syndrome (ARDS) related to SARS-CoV-2 is likely due to a cytokine storm characterised by a major release of pro-inflammatory cytokines, including interleukin-6 (IL-6). Blocking excessive IL-6 production might be the key to the COVID-19-ARDS treatment. Beneficial effects of IL-6 blockade using a humanised anti-IL-6 receptor antibody, tocilizumab (TCZ) were previously reported in patients with COVID-19 related ARDS. The aim of the study was to study the variation over time of several biomarkers, demonstrated to be predictors of poor prognostic, in subjects successfully treated with TCZ for severe COVID-19. METHODS Retrospective analysis of a case series of patients with COVID-19-ARDS, evidenced by RT-PCR and lung CT-scan. Patients with increasing O2 requirements, within the window of opportunity for TCZ treatment (Day 7 to Day 17 after onset of symptoms) were treated with TCZ (2 infusions of 8 mg/kg). Demographic, biological and clinical data were collected from the patients' files. Serum levels of CRP, ferritin, fibrinogen, lymphocytes, platelets, creatinine, D-dimer and liver enzymes were assayed at the time of the first TCZ administration, then every two days for 8 days. RESULTS 40 patients were treated with TCZ. Most of them had several comorbidities, and all had multiple biological abnormalities (lymphopenia, increased CRP, ferritin, fibrinogen, D-dimer, liver enzymes). 30 patients (75%) benefited from TCZ and 10 patients died. In the survivors, following TCZ administration CRP decreased dramatically as early as day 4 (-86.7%, p<0.0001) and returned to normal at day 6. Fibrinogen and lymphocyte count returned to normal values at day 6. Ferritin also decreased significantly. No significant change was observed for D-dimer (p=0.68) and other studied biomarkers (haemoglobin, leucocyte count, AST). CONCLUSIONS In patients with COVID-19 acute respiratory distress syndrome, treatment with TCZ resulted in favourable evolution in 75% of the cases. Biomarkers of inflammation (CRP, ferritin, fibrinogen) decreased dramatically as early as the 4th day after TCZ injection. Lymphopenia, a predictor of poor prognostic, was reversed 6 days after TCZ injection.

positive: Therapeutic effects of dipyridamole on COVID-19 patients with coagulation dysfunction The human coronavirus HCoV-19 infection can cause acute respiratory distress syndrome (ARDS), hypercoagulability, hypertension, extrapulmonary multiorgan dysfunction. Effective antiviral and anti-coagulation agents with safe clinical profiles are urgently needed to improve the overall prognosis. We screened an FDA approved drug library and found that an anticoagulant agent dipyridamole (DIP) suppressed HCoV-19 replication at an EC50 of 100 nM in vitro. It also elicited potent type I interferon responses and ameliorated lung pathology in a viral pneumonia model. In analysis of twelve HCoV-19 infected patients with prophylactic anti-coagulation therapy, we found that DIP supplementation was associated with significantly increased platelet and lymphocyte counts and decreased D-dimer levels in comparison to control patients. Two weeks after initiation of DIP treatment, 3 of the 6 severe cases (60%) and all 4 of the mild cases (100%) were discharged from the hospital. One critically ill patient with extremely high levels of D-dimer and lymphopenia at the time of receiving DIP passed away. All other patients were in clinical remission. In summary, HCoV-19 infected patients could potentially benefit from DIP adjunctive therapy by reducing viral replication, suppressing hypercoagulability and enhancing immune recovery. Larger scale clinical trials of DIP are needed to validate these therapeutic effects.

positive: Evaluation of variation in D-dimer levels among COVID-19 and bacterial pneumonia: a retrospective analysis In the recent outbreak of novel coronavirus infection worldwide, the risk of thrombosis and bleeding should be concerned. We aimed to observe the dynamic changes of D-dimer levels during disease progression to evaluate their value for thrombosis. In this study, we report the clinical and laboratory results of 57 patients with confirmed COVID-19 pneumonia and 46 patients with confirmed community-acquired bacterial pneumonia (CAP). And their concentrations of D-dimer, infection-related biomarkers, and conventional coagulation were retrospectively analyzed. The Padua prediction score is used to identify patients at high risk for venous thromboembolism (VTE). The results found that, on admission, both in COVID-19 patients and CAP patients, D-dimer levels were significantly increased, and compared with CAP patients, D-dimer levels were higher in COVID-19 patients (P < 0.05). Besides, we found that in COVID-19 patients, D-dimer were related with markers of inflammation, especially with hsCRP (R = 0.426, P < 0.05). However, there was low correlation between VTE score and D-dimer levels (Spearman’s R = 0.264, P > 0.05) weakened the role of D-dimer in the prediction of thrombosis. After treatments, D-dimer levels decreased which was synchronous with hsCRP levels in patients with good clinical prognosis, but there were still some patients with anomalous increasing D-dimer levels after therapy. In conclusion, elevated baseline D-dimer levels are associated with inflammation but not with VTE score in COVID-19 patients, suggesting that it is unreasonable to judge whether anticoagulation is needed only according to D-dimer levels. However, the abnormal changes of D-dimer and inflammatory factors suggest that anticoagulant therapy might be needed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11239-020-02171-y) contains supplementary material, which is available to authorized users.

positive: Anemia and iron metabolism in COVID-19: A systematic review and meta-analysis Iron metabolism and anemia may play an important role in multiple organ dysfunction syndrome in Coronavirus disease 2019 (COVID-19). If confirmed, this has important implications for the more than 1.62 billion people estimated to have anemia globally. We conducted a systematic review and meta-analysis to evaluate biomarkers of anemia and iron metabolism (hemoglobin, ferritin, transferrin, soluble transferrin receptor, hepcidin, haptoglobin, unsaturated iron-binding capacity, erythropoietin, free erythrocyte protoporphyrine, and prevalence of anemia) in patients diagnosed with COVID-19, and explore their prognostic value. Six bibliographic databases were searched up to May 5th 2020. We included 56 unique studies, with data from 14,044 COVID-19 patients (59 years median age). Pooled mean hemoglobin and ferritin levels in COVID-19 patients across all ages were 130.41 g/L (95% Confidence Interval (CI), 128.42; 132.39) and 673.91 ng/mL (95% CI, 420.98; 926.84), respectively. Hemoglobin levels decreased with advancing age and increasing percentage of comorbid and critically ill patients, while levels of ferritin increased with increasing male proportion and mean hemoglobin levels. Compared to moderate cases, severe cases had lower pooled mean hemoglobin [weighted mean difference (WMD), -4.21 (95% CI -6.63; -1.78)] and higher ferritin [WMD, -730.55 ng/mL (95% CI 413.24; 1047.85)]. A significant difference in mean ferritin level of 1027.23 ng/mL (95% CI 819.53; 1234.94) was found between survivors and non-survivors, but not in hemoglobin levels. No studies provided information on anemia or other biomarkers of interest. Future studies should explore the impact of iron metabolism and anemia and in the pathophysiology, prognosis, and treatment of COVID-19.

positive: Cardiac biomarker-based risk stratification algorithm in patients with severe COVID-19 BACKGROUND AND AIMS: Cardiac biomarkers like cardiac troponins and natriuretic peptides are elevated in a substantial proportion of patients with coronavirus disease 2019 (COVID-19). We propose an algorithmic approach using cardiac biomarkers to triage, risk-stratify and prognosticate patients with severe COVID-19. METHODS: We systematically searched the PubMed and Google Scholar databases until May 31st, 2020, and accessed the available data on the role of cardiac biomarkers in patients with COVID-19. RESULTS: COVID-19 is associated with acute cardiac injury in around 7-28% of patients, significantly increasing its associated complications and mortality. Patients with underlying cardiovascular disease are more prone to develop acute cardiac injury as a result of COVID-19. The use of cardiac biomarkers may aid in differentiating the cardiac cause of dyspnea in patients with severe COVID-19. Cardiac biomarkers may also aid in triaging, risk-stratification, clinical decision-making, and prognostication of patients with COVID-19. However, there are concerns that routine testing in all patients with COVID-19 irrespective of severity, may result in unnecessary downstream investigations which may be misleading. In this brief review, using an algorithmic approach, we have tried to rationalize the use of cardiac biomarkers among patients with severe COVID-19. This approach is also likely to lessen the infection exposure risk to the cardiovascular team attending patients with severe COVID-19. CONCLUSION: It appears beneficial to triage, risk-stratify, and prognosticate patients with COVID-19 based on the evidence of myocardial injury and the presence of underlying cardiovascular disease. Future research studies are, however, needed to validate these proposed benefits.

positive: Cardiovascular factors predicting poor outcome in COVID – 19 patients

positive: Kardiale Biomarker und COVID-19-Phänotypen und Interpretation./ [Cardiac biomarkers and COVID-19 - Phenotypes and Interpretation] Current pandemic caused by SARS-CoV-2 inducing viral COVID-19 pneumonia, is categorized in 3 stages. Some biomarkers could be assigned to one of these stages, showing a correlation to mortality in COVID-19 patients. Laboratory findings in COVID-19, especially when serially evaluated, may represent individual disease severity and prognosis. These may help planning and controlling therapeutic interventions. Biomarkers for myocardial injury (high sensitive cardiac troponin, hsTn) or hemodynamic stress (NTproBNP) may occur in COVID-19 pneumonia such as in other pneumonias, correlating with severity and prognosis of the underlying disease. In hospitalized COVID-19 patients' mild increases of hsTn or NTproBNP may be explained by cardiovascular comorbidities and direct or indirect cardiac damage or stress caused by or during COVID-19 pneumonia. In case of suspected NSTE-ACS and COVID-19, indications for echocardiography or reperfusion strategy should be carefully considered against the risk of contamination.

positive: Evaluation of antibody responses against SARS coronaviral nucleocapsid or spike proteins by immunoblotting or ELISA Severe acute respiratory syndrome (SARS)‐CoV is a newly emerging virus that causes SARS with high mortality rate in infected people. To study the humoral responses against SARS‐CoV, we evaluated nucleocapsid (N) and spike (S) proteins‐specific antibodies in patients' sera by Western blotting and enzyme‐linked immunosorbent assay (ELISA). Recombinant N and S proteins of SARS‐CoV were purified from transformed E. coli. Serum specimens from 40 SARS‐CoV‐infected patients in the convalescent phase were analyzed by Western blotting using the purified antigens. Serial serum specimens from 12 RT‐PCR‐confirmed SARS patients were assayed by ELISA using the recombinant N protein as coated antigen. By Western blotting, 97.5% of the SARS patients were positive for N protein‐specific antibodies whereas only 47.5% of the samples were positive for S protein‐specific antibodies. Using N protein‐based ELISA, 10 out of the 12 patients were positive for N protein‐specific antibodies and 6 of them showed seroconversion at mean of 16 days after onset of fever. Immunoblotting was useful for detecting the humoral immune response after SARS‐CoV infection. Antibodies against SARS‐CoV N protein appear at the early stage of infection, therefore, N protein‐based ELISA could serve as a simple, sensitive, and specific test for diagnosing SARS‐CoV infection. J. Med. Virol. 73:338–346, 2004. © 2004 Wiley‐Liss, Inc.

positive: The clinical implication of dynamic neutrophil to lymphocyte ratio and D-dimer in COVID-19: A retrospective study in Suzhou China Abstract Objective To investigate the clinical features of COVID-19 cases in Suzhou China. Biomarkers were screened out of hematological parameters for risk stratification. Method Confirmed COVID-19 adult patients in Suzhou were included. The patient data was collected, and the results of laboratory examinations were compared between the mild/moderate and severe COVID-19 groups. A ROC was calculated to compare the diagnostic performance of candidate indexes, and dynamic levels of hematological indexes were compared between the two groups. Result 75 patients were enrolled, with a mean age of 46.6 ± 14 years, and 45 patients were male. All patients were classified into two groups: the mild/moderate group and the severe group. WBC, neutrophil to lymphocyte ratio (NLR), D-dimer, and fibrinogen levels of the severe group were significantly higher (P < 0.05) than the mild/moderate, and the lymphocyte was lower. The ROC test showed that the hematological parameters had a larger AUC than that of inflammatory factors. There was a significant difference in lymphocyte and fibrinogen levels between the two groups on day 1 (P < 0.05). However, NLR of the severe group was higher than the mild/moderate on days 1, 4 and 14 (P < 0.01), and so was D-dimer on days 1, 7 and 14 (P < 0.05). Conclusion The common COVID-19 abnormal hematological indexes on admission included hyperfibrinogenemia, lymphopenia, the elevation of D-dimer, and leukopenia, which were significantly different between the mild/moderate and severe COVID-19 groups. Furthermore, the dynamic change of NLR and D-dimer level can distinguish severe COVID-19 cases from the mild/moderate.

positive: 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.

positive: CT characteristics of patients infected with 2019 novel coronavirus: association with clinical type AIM: To summarise the features of chest computed tomography (CT) of a series of patients infected with 2019 novel coronavirus (2019-nCov) to speed up recognition and have a better understanding of COVID-19 disease. MATERIALS AND METHODS: The clinical information and chest CT images of 93 patients infected with 2019-nCov from multiple centres were reviewed. RESULTS: Of the 93 cases, abnormalities in 91 cases were located at the subpleural level, presenting with ground-glass opacity (GGO; n=69, 74.2%) and consolidation (n=56, 60.2%) in multiple lobes. Other CT features included vascular dilatation (n=83, 89.2%), interlobular septal thickening (n=29, 31.2%), bronchodilatation (n=44, 47.3%), the crazy-paving sign (n=34, 36.6%), the sieve-hole sign (n=12, 12.9%), pleural thickening (n=21, 22.6%), and pleural effusion (n=8, 8.6%). Multiple lobe involvement, including the presence of consolidation, the crazy-paving sign, interlobular septal thickening, pleural thickening and pleural effusion, was more common in critical patients with heavy/critical infection (p<0.05), whereas the presence of GGO, involvement of one or two lobes, and the halo sign were more common in patients with mild/common-type infections (p<0.05). Moreover, older age, higher body temperature, complaints of chest tightness and breathlessness, and lymphopenia was associated with heavy/critical infections. CONCLUSION: The CT and clinical appearances of COVID-19 are variable and reflect the severity of COVID-19 to some extent.

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

positive: COVID-19 and the clinical hematology laboratory The ongoing COVID-19 pandemic originated in Wuhan, Hubei Province, China, in December 2019. The etiologic agent is a novel coronavirus of presumed zoonotic origin with structural similarity to the viruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Like SARS and MERS, COVID-19 infection manifests most frequently with lower respiratory symptoms. A minority of patients progress to acute respiratory distress syndrome/ diffuse alveolar damage. In addition to its central role in the diagnosis of COVID-19 infection, the clinical laboratory provides critical information to clinicians regarding prognosis, disease course, and response to therapy. The purpose of this review is to (a) provide background context about the origins and course of the pandemic, (b) discuss the laboratory's role in the diagnosis of COVID-19 infection, (c) summarize the current state of biomarker analysis in COVID-19 infection, with an emphasis on markers derived from the hematology laboratory, (d) comment on the impact of COVID-19 on hematology laboratory safety, and (e) describe the impact the pandemic has had on organized national and international educational activities worldwide.

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: Clinical features and outcomes of 2019 novel coronavirus-infected patients with cardiac injury Aims To explore the epidemiological and clinical features of 2019 novel coronavirus(2019-nCoV)-infected patients with cardiac injury . Methods and results Data were collected from patients medical records, and we defined cardiac injury according to cardiac biomarker troponin I level > 0.03>ug/L. Among the 291 patients, 15 (5.2%) showed evidence of cardiac injury. Of 16 hospitalized patients with cardiac injury, the median age was 62 years, and 11/15 (73.3%) were men. Underlying cardiovascular diseases in some patients were hypertension (n=7, 46.6%), coronary heart disease (n=3, 20%) and diabetes (n=3, 20%). The most common symptoms at illness onset in patients with cardiac injury were fever (n=11, 73.3%), cough (n=7, 46.7%), headache or fatigue (n=5, 33.3%) and dyspnoea (n=4, 26.6%). These patients had higher systolic pressures, and lower lymphocyte counts and platelet counts, compared with patients without cardiac injury, respectively. Bilateral infiltrates on chest X-ray and elevated C-reactive protein occurred in all patients with cardiac injury. Compared with patients without cardiac injury, patients with cardiac injury were more likely to develop acute respiratory distress syndrome (73.3%), and receive mechanical ventilation (53.4%), continuous renal replacement therapy (33.3%), extracorporeal membrane oxygenation (26.7%) and vasopressor therapy (26.7%) and be admitted to the intensive care unit (73.3%). One patient died during the study. Conclusion Cardiac injury is a common condition among patients infected with 2019-nCoV.Compared with patients without cardiac injury, the clinical outcomes of patients with cardiac injury are relatively worse. Keywords: 2019-nCoV, Cardiac injury, Clinical features

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: Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19 BACKGROUND: The inflammatory response plays a critical role in coronavirus disease 2019 (COVID-19), and inflammatory cytokine storm increases the severity of COVID-19. OBJECTIVE: To investigate the ability of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT) to predict mild and severe cases of COVID-19. STUDY DESIGN: This retrospective cohort study included 140 patients diagnosed with COVID-19 from January 18, 2020, to March 12, 2020. The study population was divided into two groups according to disease severity: a mild group (MG) (n = 107) and a severe group (SG) (n = 33). Data on demographic characteristics, baseline clinical characteristics, and the levels of IL-6, CRP, and PCT on admission were collected. RESULTS: Among the 140 patients, the levels of IL-6, CRP, and PCT increased in 95 (67.9 %), 91 (65.0 %), and 8 (5.7 %) patients on admission, respectively. The proportion of patients with increased IL-6, CRP, and PCT levels was significantly higher in the SG than in the MG. Cox proportional hazard model showed that IL-6 and CRP could be used as independent factors to predict the severity of COVID-19. Furthermore, patients with IL-6 > 32.1 pg/mL or CRP > 41.8 mg/L were more likely to have severe complications. CONCLUSION: The serum levels of IL-6 and CRP can effectively assess disease severity and predict outcome in patients with COVID-19.

positive: Clinical characteristics of 25 death cases infected with COVID-19 pneumonia: a retrospective review of medical records in a single medical center, Wuhan, China Summary Background The pneumonia caused by the 2019 novel coronavirus (SARS-CoV-2) is a highly infectious disease, which was occurred in Wuhan, Hubei Province, China in December 2019. As of February 13, 2020, a total of 59883 cases of COVID-19 in China have been confirmed and 1368 patients have died from the disease. However, the clinical characteristics of the dyed patients were still not clearly clarified. This study aims to summarize the clinical characteristics of death cases with COVID-19 and to identify critically ill patients of COVID-19 early and reduce their mortality. Methods The clinical records, laboratory findings and radiologic assessments included chest X-ray or computed tomography were extracted from electronic medical records of 25 died patients with COVID-19 in Renmin Hospital of Wuhan University from Jan 14 to Feb 13, 2020. Two experienced clinicians reviewed and abstracted the data. Findings The mean age of the dead was 71.48 years, the average course of the disease was 10.56 days, all patients eventually died of respiratory failure. All of those who died had underlying diseases, the most common of which was hypertension (16/25, 64%), followed by diabetes (10/25, 40%), heart diseases (8/25, 32%), kidney diseases (5/25, 20%), cerebral infarction (4/25, 16%), chronic obstructive pulmonary disease (COPD, 2/25, 8%), malignant tumors (2/25, 8%) and acute pancreatitis (1/25, 4%). The most common organ damage outside the lungs was the heart, followed by kidney and liver. In the patients' last examination before death, white blood cell and neutrophil counts were elevated in 17 patients (17/25, 68%) and 18 patients (18/25, 72%), lymphocyte counts were decreased in 22 patients (22/25, 88%). Most patients' PCT, CRP and SAA levels were elevated, the percentages were 90.5% (19/21), 85% (19/20) and 100% (21/21) respectively. The levels of the last test of neutrophils (15/16, 93.8%), PCT (11/11, 100%), CRP (11/13, 84.6%), cTnI (8/9, 88.9%), D-Dimer (11/12, 91.6%) and LDH (9/9, 100%) were increased as compared to the first test, while the levels of lymphocytes were decreased (14/16, 87.5%). Interpretation The age and underlying diseases (hypertension, diabetes, etc.) were the most important risk factors for death of COVID-19 pneumonia. Bacterial infections may play an important role in promoting the death of patients. Malnutrition was common to severe patients. Multiple organ dysfunction can be observed, the most common organ damage was lung, followed by heart, kidney and liver. The rising of neutrophils, SAA, PCT, CRP, cTnI, D-Dimer and LDH levels can be used as indicators of disease progression, as well as the decline of lymphocytes counts.

positive: Clinical Characteristics of Patients with Severe Pneumonia Caused by the 2019 Novel Coronavirus in Wuhan, China Abstract Background: A new virus broke out in Wuhan, Hubei, China, and was later named 2019 novel coronavirus (2019-nCoV). The clinical characteristics of severe pneumonia caused by 2019-nCoV are still not clear. Objectives: The aim of this study was to explore the clinical characteristics and risk factors of the severe pneumonia caused by the 2019-nCoV in Wuhan, China. Method: The study included patients hospitalized at the central hospital of Wuhan who had been diagnosed with a pneumonia caused by the novel coronavirus. Clinical features, chronic co-morbidities, demographic data, laboratory examinations, and chest computed tomography (CT) scans were reviewed through electronic medical records. SPSS was used for data analysis to explore the clinical characteristics and risk factors of the patients with the severe pneumonia. Results: A total of 110 patients diagnosed with 2019 novel coronavirus pneumonia were included in the study, including 38 with severe pneumonia and 72 with non-severe pneumonia. Statistical analysis showed that advanced age, an increase of D-dimer, and a decrease of lymphocytes were characteristics of the patients with severe pneumonia. Moreover, in the early stage of the disease, chest CT scans of patients with the severe pneumonia showed the illness can progress rapidly. Conclusions: Advanced age, lymphocyte decline, and D-dimer elevation are important characteristics of patients with severe pneumonia. Clinicians should focus on these characteristics to identify high-risk patients at an early stage.

positive: Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP) Background: To explore the cellular immunity and cytokines status of NCP patients and to predict the correlation between the cellular immunity levels, cytokines and the severity of patients. Methods: 123 NCP patients were divided into mild and severe groups. Peripheral blood was collected, lymphocyte subsets and cytokines were detected. Correlation analysis was performed on the lymphocyte subsets and cytokines, and the differences between the indexes of the two groups were analyzed. Results: 102 mild and 21 severe patients were included. Lymphocyte subsets were reduced in two groups. The proportion of CD8 + T reduction in the mild and severe group was 28.43% and 61.9%, respectively; The proportion of B cell reduction was 25.49% and 28.57%; The proportion of NK cell reduction was 34.31% and 47.62%; The detection value of IL-6 was 0 in 55.88% of the mild group, mild group has a significantly lower proportion of patients with IL-6 higher than normal than severe group; There was no significant linear correlation between the lymphocyte subsets and cytokines, while significant differences were noticed between the two groups in CD4 + T, CD8 + T, IL-6 and IL-10. Conclusions: Low levels of CD4+T and CD8+T are common in severe NCP. IL-6 and IL-10 levels were higher in severe patients. T cell subsets and cytokines can be used as one of the basis for predicting the transition from mild to severe. Large number of samples are still needed to confirm the "warning value" of CD4 + T, CD8 + T IL-6 and IL-10.

positive: CoViD-19 Immunopathology and Immunotherapy New evidence on the T-cell immuno-pathology in patient’s with Corona Virus Disease 2019 (CoViD-19) was reported by Diao et al. in MedRxiv (doi: 10.1101/2020.02.18.20024364) [1]. It reports observations on 522 patients with confirmed CoViD-19 symptomatology, compared to 40 control subjects. In brief, notable T cytopoenia was recorded by flow cytometry in the CD4+ and the CD8+ populations, which were significantly yet inversely correlated with remarkably increased serum levels of the pro-inflammatory cytokines IL-6, IL-10 and TNF-a. Flow cytometry established a progressive increase in the expression of programmed cell death marker-1 (PD-1) and T cell immunoglobulin and mucin domain 3 (Tim-3) as patients (n=14) deteriorated from prodromal to symptomatic CoViD-19 requiring intensive care. Here, we interpret these observations of Diao et al from our current understanding of T cell immunophysiology and immunopathology following an immune challenge in the form of sustained viral infection, as is the case in CoViD-19, with emphasis on exhausted T cells (Tex). Recent clinical trials to rescue Tex show promising outcomes. The relevance of these interventions for the prevention and treatment of CoViD-19 is discussed. Taken together, the data of Diao et al could proffer the first glimpse of immunopathology and possible immunotherapy for patients with CoViD-19.

positive: [Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV]. Objective: To explore the clinical characteristics and prognosis of the new coronavirus 2019-nCoV patients combined with cardiovascular disease (CVD). Methods: A retrospective analysis was performed on 112 COVID-19 patients with CVD admitted to the western district of Union Hospital in Wuhan, from January 20, 2020 to February 15, 2020. They were divided into critical group (ICU, n=16) and general group (n=96) according to the severity of the disease and patients were followed up to the clinical endpoint. The observation indicators included total blood count, C-reactive protein (CRP), arterial blood gas analysis, myocardial injury markers, coagulation function, liver and kidney function, electrolyte, procalcitonin (PCT), B-type natriuretic peptide (BNP), blood lipid, pulmonary CT and pathogen detection. Results: Compared with the general group, the lymphocyte count (0.74×10(9) (0.34×10(9), 0.94×10(9))/L vs. 0.99×10(9) (0.71×10(9), 1.29×10(9))/L, P=0.03) was extremely lower in the critical group, CRP (106.98 (81.57, 135.76) mg/L vs. 34.34 (9.55,76.54) mg/L, P<0.001) and PCT (0.20 (0.15,0.48) μg/L vs. 0.11 (0.06,0.20)μg/L, P<0.001) were significantly higher in the critical group. The BMI of the critical group was significantly higher than that of the general group (25.5 (23.0, 27.5) kg/m(2) vs. 22.0 (20.0, 24.0) kg/m(2), P=0.003). Patients were further divided into non-survivor group (17, 15.18%) group and survivor group (95, 84.82%). Among the non-survivors, there were 88.24% (15/17) patients with BMI> 25 kg/m(2), which was significantly higher than that of survivors (18.95% (18/95), P<0.001). Compared with the survived patients, oxygenation index (130 (102, 415) vs. 434 (410, 444), P<0.001) was significantly lower and lactic acid (1.70 (1.30, 3.00) mmol/L vs. 1.20 (1.10, 1.60) mmol/L, P<0.001) was significantly higher in the non-survivors. There was no significant difference in the proportion of ACEI/ARB medication between the critical group and the general group or between non-survivors and survivors (all P>0.05). Conclusion: COVID-19 patients combined with CVD are associated with a higher risk of mortality. Critical patients are characterized with lower lymphocyte counts. Higher BMI are more often seen in critical patients and non-survivor. ACEI/ARB use does not affect the morbidity and mortality of COVID-19 combined with CVD. Aggravating causes of death include fulminant inflammation, lactic acid accumulation and thrombotic events.

positive: Clinical characteristics of 25 death cases with COVID-19: a retrospective review of medical records in a single medical center, Wuhan, China Abstract Objectives This study aims to summarize the clinical characteristics of death cases with COVID-19 and to identify critically ill patients of COVID-19 early and reduce their mortality. Methods The clinical records, laboratory findings and radiological assessments included chest X-ray or computed tomography were extracted from electronic medical records of 25 died patients with COVID-19 in Renmin Hospital of Wuhan University from Jan 14 to Feb 13, 2020. Two experienced clinicians reviewed and abstracted the data. Results The age and underlying diseases (hypertension, diabetes, etc.) were the most important risk factors for death of COVID-19 pneumonia. Bacterial infections may play an important role in promoting the death of patients. Malnutrition was common to severe patients. Multiple organ dysfunction can be observed, the most common organ damage was lung, followed by heart, kidney and liver. The rising of neutrophils, SAA, PCT, CRP, cTnI, D-dimer, LDH and lactate levels can be used as indicators of disease progression, as well as the decline of lymphocytes counts. Conclusions The clinical characteristics of 25 death cases with COVID-19 we summarized, which would be helpful to identify critically ill patients of COVID-19 early and reduce their mortality.

positive: 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: Blood glucose is a representative of the clustered indicators of multi-organ injury for predicting mortality of COVID-19 in Wuhan, China OBJECTIVE Most patients with Coronavirus Disease 2019 (COVID-19) were Mild or Moderate. Severe patients progressed rapidly to Critical condition including multi-organ failure and even death. Identification of early predictive factors is urgently necessary to facilitate appropriate intensive care. METHODS We included all patient admitted to Wuhan Union Hospital and treated by the supportive medical team of Beijing Tongren Hospital as of March 20, 2020. Indicators of injuries for multiple organs, including the heart, kidney and liver, and glucose homeostasis were specifically analyzed for predicting primary outcomes (an intensive care unit (ICU) or death). RESULTS The data of 120 patients with a severity equal to or greater than Moderate, discharged or died were extracted. After excluding patients with history of diabetes, chronic heart, kidney, and liver disease, 69 patients were included in the final analysis. There were 26 cases with primary outcomes including 16 deaths. Univariable analysis indicated that fasting blood glucose (FBG), lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), creatine kinase and creatinine were associated with primary outcomes and death. Among patients with primary outcomes, although FBG levels were much higher on admission, they dramatically decreased subsequently, while in deceased patients they increased continuously. Multivariable Cox regression indicated that FBG≥7mmol/L was the only independent predictor for death (HR = 3.75, 95% CI 1.26-11.15). Cluster analysis found more proximities of FBG (at the time of admission) with LDH, HDDH or Creatinine (after 2-4 days of hospitalization) (r=0.43, 0.43 and 0.50, respectively, P<0.01 for all). Conclusions Blood glucose is a representative of the clustered indicators of multi-organ injury and earlier predictor for poor outcomes and death in the COVID patients. As it is easy to perform for clinical practices and self-monitoring, glucose testing will be much helpful for predicting poor outcomes to facilitate appropriate intensive care.

positive: Diabetes and metabolic syndrome as risk factors for COVID-19 BACKGROUND AND AIMS: Clinical evidence exists that patients with diabetes are at higher risk for Coronavirus disease 2019 (COVID-19). We investigated the physiological origins of this clinical observation linking diabetes with severity and adverse outcome of COVID-19. METHODS: Publication mining was applied to reveal common physiological contexts in which diabetes and COVID-19 have been investigated simultaneously. Overall, we have acquired 1,121,078 publications from PubMed in the time span between 01 and 01-2000 and 17-04-2020, and extracted knowledge graphs interconnecting the topics related to diabetes and COVID-19. RESULTS: The Data Mining revealed three pathophysiological pathways linking diabetes and COVID-19. The first pathway indicates a higher risk for COVID-19 because of an upregulation of Angiotensin-converting enzyme 2. The other two important physiological links between diabetes and COVID-19 are liver dysfunction and chronic systemic inflammation. A deep network analysis has suggested clinical biomarkers predicting the higher risk: Hypertension, elevated serum Alanine aminotransferase, high Interleukin-6, and low Lymphocytes count. CONCLUSIONS: The revealed biomarkers can be applied directly in clinical practice. For newly infected patients, the medical history needs to be checked for evidence of a long-term, chronic dysregulation of these biomarkers. In particular, patients with diabetes, but also those with prediabetic state, deserve special attention.

positive: Development and external validation of a prognostic multivariable model on admission for hospitalized patients with COVID-19 Background: COVID-19 pandemic has developed rapidly and the ability to stratify the most vulnerable patients is vital. However, routinely used severity scoring systems are often low on diagnosis, even in non-survivors. Therefore, clinical prediction models for mortality are urgently required. Methods: We developed and internally validated a multivariable logistic regression model to predict inpatient mortality in COVID-19 positive patients using data collected retrospectively from Tongji Hospital, Wuhan (299 patients). External validation was conducted using a retrospective cohort from Jinyintan Hospital, Wuhan (145 patients). Nine variables commonly measured in these acute settings were considered for model development, including age, biomarkers and comorbidities. Backwards stepwise selection and bootstrap resampling were used for model development and internal validation. We assessed discrimination via the C statistic, and calibration using calibration-in-the-large, calibration slopes and plots. Findings: The final model included age, lymphocyte count, lactate dehydrogenase and SpO2 as independent predictors of mortality. Discrimination of the model was excellent in both internal (c=0.89) and external (c=0.98) validation. Internal calibration was excellent (calibration slope=1). External validation showed some over-prediction of risk in low-risk individuals and under-prediction of risk in high-risk individuals prior to recalibration. Recalibration of the intercept and slope led to excellent performance of the model in independent data. Interpretation: COVID-19 is a new disease and behaves differently from common critical illnesses. This study provides a new prediction model to identify patients with lethal COVID-19. Its practical reliance on commonly available parameters should improve usage of limited healthcare resources and patient survival rate.

positive: Angiopoietin-2 as a marker of endothelial activation is a good predictor factor for intensive care unit admission of COVID-19 patients BACKGROUND: Coronavirus disease-2019 (COVID-19), a respiratory disease has been associated with ischemic complications, coagulation disorders, and an endotheliitis. OBJECTIVES: To explore endothelial damage and activation-related biomarkers in COVID-19 patients with criteria of hospitalization for referral to intensive care unit (ICU) and/or respiratory worsening. METHODS: Analysis of endothelial and angiogenic soluble markers in plasma from patients at admission. RESULTS: Study enrolled 40 consecutive COVID-19 patients admitted to emergency department that fulfilled criteria for hospitalization. Half of them were admitted in conventional wards without any ICU transfer during hospitalization; whereas the 20 others were directly transferred to ICU. Patients transferred in ICU were more likely to have lymphopenia, decreased SpO2 and increased D-dimer, CRP and creatinine levels. In those patients, soluble E-selectin and angiopoietin-2 were significantly increased (p value at 0.009 and 0.003, respectively). Increase in SELE gene expression (gene coding for E-selectin protein) was confirmed in an independent cohort of 32 patients using a whole blood gene expression profile analysis. In plasma, we found a strong association between angiopoetin-2 and CRP, creatinine and D-dimers (with p value at 0.001, 0.001 and 0.003, respectively). ROC curve analysis identified an Angiopoietin-2 cut-off of 5000 pg/mL as the best predictor for ICU outcome (Se = 80.1%, Sp = 70%, PPV = 72.7%, NPV = 77%), further confirmed in multivariate analysis after adjustment for creatinine, CRP or D-dimers. CONCLUSION: Angiopoietin-2 is a relevant predictive factor for ICU direct admission in COVID-19 patients. This result showing an endothelial activation reinforces the hypothesis of a COVID-19-associated microvascular dysfunction.

positive: 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.

positive: Intensive care risk estimation in COVID-19 pneumonia based on clinical and imaging parameters: experiences from the Munich cohort Background: The rapidly evolving dynamics of coronavirus disease 2019 (COVID-19) and the steadily increasing infection numbers require diagnostic tools to identify patients at high risk for a severe disease course. Here we evaluate clinical and imaging parameters for estimating the need of intensive care unit (ICU) treatment. Methods: We collected clinical, laboratory and imaging data from 65 patients with confirmed COVID-19 infection based on PCR positivity. IL-6, CRP, leukocyte and lymphocyte counts were determined in blood samples. Two radiologists evaluated the severity of imaging findings in computed tomography (CT) images on a scale from 1 (no characteristic signs of COVID-19) to 5 (confluent ground glass opacities in over 50% of the lung parenchyma). The volume of affected lung was quantified using commercially available software. Machine learning modelling was performed to estimate the risk for intensive care unit treatment. Findings: Patients with a severe course of COVID-19 had significantly increased IL-6, CRP and leukocyte counts and significantly decreased lymphocyte counts. The radiological severity grading was significantly increased in ICU patients. Multivariate random forest modelling showed a mean +/- standard deviation sensitivity, specificity and accuracy of 0.72 +/- 0.1, 0.86 +/- 0.16 and 0.80 +/- 0.1 and a ROC-AUC of 0.79 +/- 0.1. The most important predictive parameters were affected lung volume, radiological severity score, CRP and IL-6. Summary and Conclusion: Estimation of need for intensive care treatment is possible based on the clinical and radiological parameters.

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: The role of biomarkers in diagnosis of COVID-19 – A systematic review AIMS: As of the 28th April 2020, the COVID-19 pandemic has infiltrated over 200 countries and affected over three million confirmed people. We review different biomarkers to evaluate if they are able to predict clinical outcomes and correlate with the severity of COVID-19 disease. METHODS: A systematic review of the literature was carried out to identify relevant articles using six different databases. Keywords to refine the search included ‘COVID-19’, ‘SARS-CoV2’, ‘Biomarkers’, among others. Only studies which reported data on pre-defined outcomes were included. KEY FINDINGS: Thirty-four relevant articles were identified which reviewed the following biomarkers: C-reactive protein, serum amyloid A, interleukin-6, lactate dehydrogenase, neutrophil-to-lymphocyte ratio, D-dimer, cardiac troponin, renal biomarkers, lymphocytes and platelet count. Of these, all but two, showed significantly higher levels in patients with severe complications of COVID-19 infection compared to their non-severe counterparts. Lymphocytes and platelet count showed significantly lower levels in severe patients compared to non-severe patients. SIGNIFICANCE: Although research is still in its early stages, the discovery of how different biomarkers behave during the course of the disease could help clinicians in identifying severe disease earlier and subsequently improve prognosis. Nevertheless, we urge for more research across the globe to corroborate these findings.

positive: SARS‐CoV‐2‐reactive interferon‐γ‐producing CD8+ T cells in patients hospitalized with coronavirus disease 2019 There is limited information on severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) T‐cell immune responses in patients with coronavirus disease 2019 (COVID‐19). Both CD4+ and CD8+ T cells may be instrumental in resolution of and protection from SARS‐CoV‐2 infection. Here, we tested 25 hospitalized patients either with microbiologically documented COVID‐19 (n = 19) or highly suspected of having the disease (n = 6) for presence of SARS‐CoV‐2‐reactive CD69+ expressing interferon‐γ (IFN‐γ) producing CD8+ T cells using flow‐cytometry for intracellular cytokine staining assay. Two sets of overlapping peptides encompassing the SARS‐CoV‐2 Spike glycoprotein N‐terminal 1 to 643 amino acid sequence and the entire sequence of SARS‐CoV‐2 M protein were used simultaneously as antigenic stimulus. Ten patients (40%) had detectable responses, displaying frequencies ranging from 0.15 to 2.7% (median of 0.57 cells/µL; range, 0.43‐9.98 cells/µL). The detection rate of SARS‐CoV‐2‐reactive IFN‐γ CD8+ T cells in patients admitted to intensive care was comparable (P = .28) to the rate in patients hospitalized in other medical wards. No correlation was found between SARS‐CoV‐2‐reactive IFN‐γ CD8+ T‐cell counts and SARS‐CoV‐2 S‐specific antibody levels. Likewise, no correlation was observed between either SARS‐CoV‐2‐reactive IFN‐γ CD8+ T cells or S‐specific immunoglobulin G‐antibody titers and blood cell count or levels of inflammatory biomarkers. In summary, in this descriptive, preliminary study we showed that SARS‐CoV‐2‐reactive IFN‐γ CD8+ T cells can be detected in a non‐negligible percentage of patients with moderate to severe forms of COVID‐19. Further studies are warranted to determine whether quantitation of these T‐cell subsets may provide prognostic information on the clinical course of COVID‐19.

positive: A novel immune biomarker IFI27 discriminates between influenza and bacteria in patients with suspected respiratory infection. Host response biomarkers can accurately distinguish between influenza and bacterial infection. However, published biomarkers require the measurement of many genes, thereby making it difficult to implement them in clinical practice. This study aims to identify a single-gene biomarker with a high diagnostic accuracy equivalent to multi-gene biomarkers.In this study, we combined an integrated genomic analysis of 1071 individuals with in vitro experiments using well-established infection models.We identified a single-gene biomarker, IFI27, which had a high prediction accuracy (91%) equivalent to that obtained by multi-gene biomarkers. In vitro studies showed that IFI27 was upregulated by TLR7 in plasmacytoid dendritic cells, antigen-presenting cells that responded to influenza virus rather than bacteria. In vivo studies confirmed that IFI27 was expressed in influenza patients but not in bacterial infection, as demonstrated in multiple patient cohorts (n=521). In a large prospective study (n=439) of patients presented with undifferentiated respiratory illness (aetiologies included viral, bacterial and non-infectious conditions), IFI27 displayed 88% diagnostic accuracy (AUC) and 90% specificity in discriminating between influenza and bacterial infections.IFI27 represents a significant step forward in overcoming a translational barrier in applying genomic assay in clinical setting; its implementation may improve the diagnosis and management of respiratory 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: The hemocyte counts as a potential biomarker for predicting disease progression in COVID-19: a retrospective study Objectives In December 2019, there was an outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, and since then, the disease has been increasingly spread throughout the world. Unfortunately, the information about early prediction factors for disease progression is relatively limited. Therefore, there is an urgent need to investigate the risk factors of developing severe disease. The objective of the study was to reveal the risk factors of developing severe disease by comparing the differences in the hemocyte count and dynamic profiles in patients with severe and non-severe COVID-19. Methods In this retrospectively analyzed cohort, 141 confirmed COVID-19 patients were enrolled in Taizhou Public Health Medical Center, Taizhou Hospital, Zhejiang Province, China, from January 17, 2020 to February 26, 2020. Clinical characteristics and hemocyte counts of severe and non-severe COVID patients were collected. The differences in the hemocyte counts and dynamic profiles in patients with severe and non-severe COVID-19 were compared. Multivariate Cox regression analysis was performed to identify potential biomarkers for predicting disease progression. A concordance index (C-index), calibration curve, decision curve and the clinical impact curve were calculated to assess the predictive accuracy. Results The data showed that the white blood cell count, neutrophil count and platelet count were normal on the day of hospital admission in most COVID-19 patients (87.9%, 85.1% and 88.7%, respectively). A total of 82.8% of severe patients had lymphopenia after the onset of symptoms, and as the disease progressed, there was marked lymphopenia. Multivariate Cox analysis showed that the neutrophil count (hazard ratio [HR] = 4.441, 95% CI = 1.954-10.090, p = 0.000), lymphocyte count (HR = 0.255, 95% CI = 0.097-0.669, p = 0.006) and platelet count (HR = 0.244, 95% CI = 0.111-0.537, p = 0.000) were independent risk factors for disease progression. The C-index (0.821 [95% CI, 0.746-0.896]), calibration curve, decision curve and the clinical impact curve showed that the nomogram can be used to predict the disease progression in COVID-19 patients accurately. In addition, the data involving the neutrophil count, lymphocyte count and platelet count (NLP score) have something to do with improving risk stratification and management of COVID-19 patients. Conclusions We designed a clinically predictive tool which is easy to use for assessing the progression risk of COVID-19, and the NLP score could be used to facilitate patient stratification management.

positive: Association Between Clinical Manifestations and Prognosis in Patients with COVID-19 PURPOSE: The purpose of this study was to determine the risk factors associated with pneumonia, acute respiratory distress syndrome (ARDS), and clinical outcome among patients with novel coronavirus disease 2019 (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 polymerase chain reaction detection of target genes of 2019 novel coronavirus (2019-nCoV). Clinical, laboratory, and radiologic results, as well as treatment outcome data, were obtained. ARDS was defined as an oxygenation index (arterial partial pressure of oxygen/fraction of inspired oxygen) ≤300 mm Hg. FINDINGS: Multivariate analysis showed that older age (odds ratio [OR], 1.078; p = 0.008) and high body mass index (OR, 1.327; p = 0.024) were independent risk factors associated with patients with pneumonia. For patients with ARDS, multivariate analysis showed that only high systolic blood pressure (OR, 1.046; p = 0.025) and high lactate dehydrogenase level (OR, 1.010; p = 0.021) were independent risk factors associated with ARDS. A total of 70 patients underwent CT imaging repeatedly after treatment. Patients were divided in a disease exacerbation group (n = 19) and a disease relief group (n = 51). High body mass index (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: These study results help in the risk stratification of patients with 2019-nCoV infection. Patients with risk factors should be given timely intervention to avoid disease progression.

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: Plasma Metabolomic and Lipidomic Alterations Associated with COVID-19 The pandemic of the coronavirus disease 2019 (COVID-19) has become a global public health crisis. COVID-19 is marked by its rapid progression from mild to severe conditions, particularly in the absence of adequate medical care. However, the physiological changes associated with COVID-19 are barely understood. In this study, we performed untargeted metabolomic and lipidomic analyses of plasma from a cohort of COVID-19 patients who had experienced different symptoms. We found the metabolite and lipid alterations exhibit apparent correlation with the course of disease in these COVID-19 patients, indicating that the development of COVID-19 affected patient metabolism. Moreover, many of the metabolite and lipid alterations, particularly ones associated with hepatic functions, have been found to align with the progress and severity of COVID-19. This work provides valuable knowledge about blood biomarkers associated with COVID-19 and potential therapeutic targets, and presents important resource for further studies of COVID-19 pathogenesis.

positive: Serum KL‐6 concentrations as a novel biomarker of severe COVID‐19 Severe acute respiratory syndrome coronavirus 2–induced direct cytopathic effects against type I and II pneumocytes mediate lung damage. Krebs von den Lungen‐6 (KL‐6) is mainly produced by damaged or regenerating alveolar type II pneumocytes. This preliminary study analyzed serum concentrations of KL‐6 in patients with coronavirus disease (COVID‐19) to verify its potential as a prognostic biomarker of severity. Twenty‐two patients (median age [interquartile range] 63 [59‐68] years, 16 males) with COVID‐19 were enrolled prospectively. Patients were divided into mild‐moderate and severe groups, according to respiratory impairment and clinical management. KL‐6 serum concentrations and lymphocyte subset were obtained. Peripheral natural killer (NK) cells/µL were significantly higher in nonsevere patients than in the severe group (P = .0449) and the best cut‐off value was 119 cells/µL. KL‐6 serum concentrations were significantly higher in severe patients than the nonsevere group (P = .0118). Receiver operating characteristic analysis distinguished severe and nonsevere patients according to KL‐6 serum levels and the best cut‐off value was 406.5 U/mL. NK cell analysis and assay of KL‐6 in serum can help identify severe COVID‐19 patients. Increased KL‐6 serum concentrations were observed in patients with severe pulmonary involvement, revealing a prognostic value and supporting the potential usefulness of KL‐6 measurement to evaluate COVID‐19 patients' prognosis.

positive: C-reactive protein, procalcitonin, D-dimer, and ferritin in severe coronavirus disease-2019: a meta-analysis BACKGROUND: Patients critically ill with coronavirus disease-2019 (COVID-19) feature hyperinflammation, and the associated biomarkers may be beneficial for risk stratification. We aimed to investigate the association between several biomarkers, including serum C-reactive protein (CRP), procalcitonin (PCT), D-dimer, and serum ferritin, and COVID-19 severity. METHODS: We performed a comprehensive systematic literature search through electronic databases. The outcome of interest for this study was the composite poor outcome, which comprises mortality, acute respiratory distress syndrome, need for care in an intensive care unit, and severe COVID-19. RESULTS: A total of 5350 patients were pooled from 25 studies. Elevated CRP was associated with an increased composite poor outcome [risk ratio (RR) 1.84 (1.45, 2.33), p < 0.001; I2: 96%] and its severe COVID-19 (RR 1.41; I2: 93%) subgroup. A CRP â©¾10 mg/L has a 51% sensitivity, 88% specificity, likelihood ratio (LR) + of 4.1, LR- of 0.5, and an area under curve (AUC) of 0.84. An elevated PCT was associated with an increased composite poor outcome [RR 3.92 (2.42, 6.35), p < 0.001; I2: 85%] and its mortality (RR 6.26; I2: 96%) and severe COVID-19 (RR 3.93; I2: 63%) subgroups. A PCT â©¾0.5 ng/ml has an 88% sensitivity, 68% specificity, LR+ of 2.7, LR- of 0.2, and an AUC of 0.88. An elevated D-dimer was associated with an increased composite poor outcome [RR 2.93 (2.14, 4.01), p < 0.001; I2: 77%], including its mortality (RR 4.15; I2: 83%) and severe COVID-19 (RR 2.42; I2: 58%) subgroups. A D-dimer >0.5 mg/L has a 58% sensitivity, 69% specificity, LR+ of 1.8, LR- of 0.6, and an AUC of 0.69. Patients with a composite poor outcome had a higher serum ferritin with a standardized mean difference of 0.90 (0.64, 1.15), p < 0.0001; I2: 76%. CONCLUSION: This meta-analysis showed that an elevated serum CRP, PCT, D-dimer, and ferritin were associated with a poor outcome in COVID-19. The reviews of this paper are available via the supplemental material section.

positive: Cytokine biomarkers of COVID-19 We used a new strategy to screen cytokines associated with SARS-CoV-2 infection. Cytokines that can classify populations in different states of SARS-CoV-2 infection were first screened in cross-sectional serum samples from 184 subjects by 2 statistical analyses. The resultant cytokines were then analyzed for their interrelationships and fluctuating features in sequential samples from 38 COVID-19 patients. Three cytokines, M-CSF, IL-8 and SCF, which were clustered into 3 different correlation groups and had relatively small fluctuations during SARS-CoV-2 infection, were selected for the construction of a multiclass classification model. This model discriminated healthy individuals and asymptomatic and nonsevere patients with accuracy of 77.4% but was not successful in classifying severe patients. Further searching led to a single cytokine, hepatocyte growth factor (HGF), which classified severe from nonsevere COVID-19 patients with a sensitivity of 84.6% and a specificity of 97.9% under a cutoff value of 1128 pg/ml. The level of this cytokine did not increase in nonsevere patients but was significantly elevated in severe patients. Considering its potent antiinflammatory function, we suggest that HGF might be a new candidate therapy for critical COVID-19. In addition, our new strategy provides not only a rational and effective way to focus on certain cytokine biomarkers for infectious diseases but also a new opportunity to probe the modulation of cytokines in the immune response.

positive: A machine learning-based model for survival prediction in patients with severe COVID-19 infection The sudden increase of COVID-19 cases is putting a high pressure on healthcare services worldwide. At the current stage, fast, accurate and early clinical assessment of the disease severity is vital. To support decision making and logistical planning in healthcare systems, this study leverages a database of blood samples from 404 infected patients in the region of Wuhan, China to identify crucial predictive biomarkers of disease severity. For this purpose, machine learning tools selected three biomarkers that predict the survival of individual patients with more than 90% accuracy: lactic dehydrogenase (LDH), lymphocyte and high-sensitivity C-reactive protein (hs-CRP). In particular, relatively high levels of LDH alone seem to play a crucial role in distinguishing the vast majority of cases that require immediate medical attention. This finding is consistent with current medical knowledge that high LDH levels are associated with tissue breakdown occurring in various diseases, including pulmonary disorders such as pneumonia. Overall, this paper suggests a simple and operable formula to quickly predict patients at the highest risk, allowing them to be prioritised and potentially reducing the mortality rate.

positive: A New Predictor of Disease Severity in Patients with COVID-19 in Wuhan, China Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in Wuhan, Hubei, China. This study sought to elucidate a novel predictor of disease severity in patients with coronavirus disease-19 (COVID-19) cased by SARS-CoV-2. Methods: Patients enrolled in this study were all hospitalized with COVID-19 in the Central Hospital of Wuhan, China. Clinical features, chronic comorbidities, demographic data, and laboratory and radiological data were reviewed. The outcomes of patients with severe pneumonia and those with non-severe pneumonia were compared using the Statistical Package for the Social Sciences (IBM Corp., Armonk, NY, USA) to explore clinical characteristics and risk factors. The receiver operating characteristic curve was used to screen optimal predictors from the risk factors and the predictive power was verified by internal validation. Results: A total of 377 patients diagnosed with COVID-19 were enrolled in this study, including 117 with severe pneumonia and 260 with non-severe pneumonia. The independent risk factors for severe pneumonia were age [odds ratio (OR): 1.059, 95% confidence interval (CI): 1.036-1.082; p < 0.001], N/L (OR: 1.322, 95% CI: 1.180-1.481; p < 0.001), CRP (OR: 1.231, 95% CI: 1.129-1.341; p = 0.002), and D-dimer (OR: 1.059, 95% CI: 1.013-1.107; p = 0.011). We identified a product of N/L*CRP*D-dimer as having an important predictive value for the severity of COVID-19. The cutoff value was 5.32. The negative predictive value of less than 5.32 for the N/L*CRP*D-dimer was 93.75%, while the positive predictive value was 46.03% in the test sets. The sensitivity and specificity were 89.47% and 67.42%. In the training sets, the negative and positive predictive values were 93.80% and 41.32%, respectively, with a specificity of 70.76% and a sensitivity of 89.87%. Conclusions: A product of N/L*CRP*D-dimer may be an important predictor of disease severity in patients with COVID-19.

positive: Low testosterone levels predict clinical adverse outcomes in SARS-CoV-2 pneumonia patients BACKGROUND: The pandemic of new severe acute respiratory syndrome (SARS) due to coronavirus (CoV) 2 (SARS-CoV-2) has stressed the importance of effective diagnostic and prognostic biomarkers of clinical worsening and mortality. Epidemiological data showing a differential impact of SARS-CoV-2 infection on women and men have suggested a potential role for testosterone (T) in determining gender disparity in the SARS-CoV-2 clinical outcomes. OBJECTIVES: To estimate the association between T level and SARS-CoV-2 clinical outcomes (defined as conditions requiring transfer to higher or lower intensity of care or death) in a cohort of patients admitted in the respiratory intensive care unit (RICU). MATERIALS AND METHODS: A consecutive series of 31 male patients affected by SARS-CoV-2 pneumonia and recovered in the respiratory intensive care unit (RICU) of the "Carlo Poma" Hospital in Mantua were analyzed. Several biochemical risk factors (ie, blood count and leukocyte formula, C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), ferritin, D-dimer, fibrinogen, interleukin 6 (IL-6)) as well as total testosterone (TT), calculated free T (cFT), sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) were determined. RESULTS: Lower TT and cFT were found in the transferred to ICU/deceased in RICU group vs groups of patients transferred to IM or maintained in the RICU in stable condition. Both TT and cFT showed a negative significant correlation with biochemical risk factors (ie, the neutrophil count, LDH, and PCT) but a positive association with the lymphocyte count. Likewise, TT was also negatively associated with CRP and ferritin levels. A steep increase in both ICU transfer and mortality risk was observed in men with TT < 5 nmol/L or cFT < 100 pmol/L. DISCUSSION AND CONCLUSION: Our study demonstrates for the first time that lower baseline levels of TT and cFT levels predict poor prognosis and mortality in SARS-CoV-2-infected men admitted to RICU.

positive: Predictors of fatality including radiographic findings in adults with COVID-19 BACKGROUND: Older age and elevated d-dimer are reported risk factors for coronavirus disease 2019 (COVID-19). However, whether early radiographic change is a predictor of fatality remains unknown. METHODS: We retrospectively reviewed records of all laboratory-confirmed patients admitted to a quarantine unit at Tongji Hospital, a large regional hospital in Wuhan, China, between January 31 and March 5, 2020. Confirmed cases were defined by positive RT-PCR detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in throat-swab specimens. Chest CT images were reviewed independently by two radiologists. The Tongji Hospital ethics committee approved this study. RESULTS: A total of 102 patients were confirmed to have SARS-CoV-2 infection. As of March 25, 85 confirmed patients were discharged, 15 died, and 2 remained hospitalized. When compared with survivors, non-survivors were older (median age, 69 [interquartile range, 58-77] vs. 55 [44-66], p = 0.003), and more likely to have decreased lymphocyte count (0.5 vs. 0.9 × 109/L, p = 0.006), elevated lactate dehydrogenase (LDH) (569.0 vs. 272.0 U/L, p < 0.001), elevated d-dimer (> 1 µg/mL, 86% vs. 37%, p = 0.002) on admission. Older age and elevated LDH were independent risk factors for fatality in a multivariate regression model included the above variables. In a subset of patients with CT images within the first week, higher total severity score, and more involved lung lobes (5 involved lobes) in CT images within the first week were significantly associated with fatality. Moreover, in this subset of patients, higher total severity score was the only independent risk factor in a multivariate analysis incorporating the above mentioned variables. CONCLUSIONS: Older age, elevated LDH on admission, and higher severity score of CT images within the first week are potential predictors of fatality in adults with COVID-19. These predictors may help clinicians identify patients with a poor prognosis at an early stage.

positive: Longitudinal peripheral blood transcriptional analysis of COVID-19 patients captures disease progression and reveals potential biomarkers COVID-19, caused by SARS-CoV-2, is an acute self-resolving disease in most of the patients, but some patients can develop a severe illness or even death. To characterize the host responses and identify potential biomarkers during disease progression, we performed a longitudinal transcriptome analysis for peripheral blood mononuclear cells (PBMCs) collected from 4 COVID-19 patients at 4 different time points from symptom onset to recovery. We found that PBMCs at different COVID-19 disease stages exhibited unique transcriptome characteristics. SARS-CoV-2 infection dysregulated innate immunity especially type I interferon response as well as the disturbed release of inflammatory cytokines and lipid mediators, and an aberrant increase of low-density neutrophils may cause tissue damage. Activation of cell death, exhaustion and migratory pathways may lead to the reduction of lymphocytes and dysfunction of adaptive immunity. COVID-19 induced hypoxia may exacerbate disorders in blood coagulation. Based on our analysis, we proposed a set of potential biomarkers for monitoring disease progression and predicting the risk of severity.

positive: Individualized prediction nomograms for disease progression in mild COVID-19 The coronavirus disease 2019 (COVID-19) has evolved into a pandemic rapidly. The majority of COVID-19 patients are with mild syndromes. This study aimed to develop models for predicting disease progression in mild cases. The risk factors for the requirement of oxygen support in mild COVID-19 were explored using multivariate logistic regression. Nomogram as visualization of the models was developed using R software. A total of 344 patients with mild COVID-19 were included in the final analysis, 45 of whom progressed and needed high-flow oxygen therapy or mechanical ventilation after admission. There were 188 (54.7%) males, and the average age of the cohort was 52.9 ± 16.8 years. When the laboratory data were not included in multivariate analysis, diabetes, coronary heart disease, T ≥ 38.5â and sputum were independent risk factors of progressive COVID-19 (Model 1). When the blood routine test was included the CHD, T ≥ 38.5â and neutrophil-to-lymphocyte ratio were found to be independent predictors (Model 2). The area under the receiver operator characteristic curve of model 2 was larger than model 1 (0.872 vs 0.849, P = .023). The negative predictive value of both models was greater than 96%, indicating they could serve as simple tools for ruling out the possibility of disease progression. In conclusion, two models comprised common symptoms (fever and sputum), underlying diseases (diabetes and coronary heart disease) and blood routine test are developed for predicting the future requirement of oxygen support in mild COVID-19 cases.

positive: A comprehensive appraisal of laboratory biochemistry tests as major predictors of COVID-19 severity Context: A relevant portion of COVID-19 patients develop severe disease with negative outcomes. Several biomarkers have been proposed to predict COVID-19 severity, but no definite interpretative criteria have been established to date for stratifying risk. Objective: To evaluate six serum biomarkers (C-reactive protein, lactate dehydrogenase, D-dimer, albumin, ferritin and cardiac troponin T) for predicting COVID-19 severity and to define related cut-offs able to aid clinicians in risk stratification of hospitalized patients. Design: A retrospective study of 427 COVID-19 patients was performed. Patients were divided into groups based on their clinical outcome: non-survivors vs. survivors and patients admitted to intensive care unit vs. others. ROC curves and likelihood ratios were employed to define predictive cut-offs for evaluated markers. Results: Marker concentrations at peak were significantly different between groups for both selected outcomes. At univariate logistic regression analysis, all parameters were significantly associated with higher odds of death and intensive care. At the multivariate analysis, high concentrations of lactate dehydrogenase and low concentrations of albumin in serum remained significantly associated with higher odds of death, while only low lactate dehydrogenase activities remained associated with lower odds of intensive care admission. The best cut-offs for death prediction were >731 U/L for lactate dehydrogenase and ≤18 g/L for albumin, while a lactate dehydrogenase activity <425 U/L was associated with a negative likelihood ratio of 0.10 for intensive treatment. Conclusions: Our study identifies which biochemistry tests represent major predictors of COVID-19 severity and defines the best cut-offs for their use.

positive: COVID-19 Myocarditis and Severity Factors： An Adult Cohort Study Background Notwithstanding the clinical hallmarks of COVID-19 patients were reported, several critical issues still remain mysterious, i.e., prognostic factors for COVID-19 including extrinsic factors as viral load of SARS-CoV-2 and intrinsic factors as individual's health conditions; myocarditis incidence rate and hallmarks. Methods Demographic, epidemiologic, radiologic and laboratory data were collected by medical record reviews of adult hospitalized patients diagnosed as COVID-19. Cycle threshold (Ct) value data of real-time PCR (RT-PCR) were collected. The time duration was from 21 January to 2 March, 2020. Pulmonary inflammation index (PII) values were used for chest CT findings. Multivariate logistic regression analysis was used to identify independent severity risk factors. RESULTS In total, 84 hospitalized adult patients diagnosed as COVID-19 were included, including 20 severe and 64 nonsevere cases. The viral load of the severe group was significantly higher than that of the non-severe group, regardless of the Ct values for N or ORF1ab gene of virus (all p<0.05).Typical CT abnormalities was more likely existing in the severe group than in the nonsevere group in patchy shadows or ground glass opacities, consolidation, and interlobular septal thickening (all p<0.05). In addition, the PII values in the severe group was significantly higher than that in the nonsevere group (52.5 [42.5-62.5] vs 20 [5.0-31.6]; p<0.001). Amongst 84 patients, 13 patients (15.48%) were noted with abnormal electrocardiograms (ECGs) and serum myocardial enzyme levels; whereas 4 (4.8%) were clinically diagnosed as SARS-CoV-2 myocarditis. Multivariable logistic regress analysis distinguished three key independent risk factors for the severity of COVID-19, including age [OR 2.350; 95% CI (1.206 to 4.580); p=0.012], Ct value [OR 0.158; 95% CI (0.025 to 0.987); p=0.048] and PII [OR 1.912; 95% CI (1.187 to 3.079); p=0.008]. Interpretation Three key-independent risk factors of COVID-19 were identified, including age, PII, and Ct value. The Ct value is closely correlated with the severity of COVID-19, and may act as a predictor of clinical severity of COVID-19 in the early stage. SARS-CoV-2 myocarditis should be highlighted despite a relatively low incidence rate (4.8%). The oxygen pressure and blood oxygen saturation should not be neglected as closely linked with the altitude of epidemic regions.

positive: Biomarkers associated with COVID-19 disease progression The coronavirus disease 2019 (COVID-19) pandemic is a scientific, medical, and social challenge. The complexity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is centered on the unpredictable clinical course of the disease that can rapidly develop, causing severe and deadly complications. The identification of effective laboratory biomarkers able to classify patients based on their risk is imperative in being able to guarantee prompt treatment. The analysis of recently published studies highlights the role of systemic vasculitis and cytokine mediated coagulation disorders as the principal actors of multi organ failure in patients with severe COVID-19 complications. The following biomarkers have been identified: hematological (lymphocyte count, neutrophil count, neutrophil-lymphocyte ratio (NLR)), inflammatory (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT)), immunological (interleukin (IL)-6 and biochemical (D-dimer, troponin, creatine kinase (CK), aspartate aminotransferase (AST)), especially those related to coagulation cascades in disseminated intravascular coagulation (DIC) and acute respiratory distress syndrome (ARDS). New laboratory biomarkers could be identified through the accurate analysis of multicentric case series; in particular, homocysteine and angiotensin II could play a significant role.

positive: Risk Factors Associated with Clinical Outcomes in 323 COVID-19 Hospitalized Patients in Wuhan, China BACKGROUND: With evidence of sustained transmission in more than 190 countries, coronavirus disease 2019 (COVID-19) has been declared a global pandemic. Data are urgently needed about risk factors associated with clinical outcomes. METHODS: A retrospective review of 323 hospitalized patients with COVID-19 in Wuhan was conducted. Patients were classified into three disease severity groups (non-severe, severe, and critical), based on initial clinical presentation. Clinical outcomes were designated as favorable and unfavorable, based on disease progression and response to treatments. Logistic regression models were performed to identify risk factors associated with clinical outcomes, and log-rank test was conducted for the association with clinical progression. RESULTS: Current standard treatments did not show significant improvement in patient outcomes. By univariate logistic regression analysis, 27 risk factors were significantly associated with clinical outcomes. Multivariate regression indicated age over 65 years (p<0.001), smoking (p=0.001), critical disease status (p=0.002), diabetes (p=0.025), high hypersensitive troponin I (>0.04 pg/mL, p=0.02), leukocytosis (>10 x 10(9)/L, p<0.001) and neutrophilia (>75 x 10(9)/L, p<0.001) predicted unfavorable clinical outcomes. By contrast, the administration of hypnotics was significantly associated with favorable outcomes (p<0.001), which was confirmed by survival analysis. CONCLUSIONS: Hypnotics may be an effective ancillary treatment for COVID-19. We also found novel risk factors, such as higher hypersensitive troponin I, predicted poor clinical outcomes. Overall, our study provides useful data to guide early clinical decision making to reduce mortality and improve clinical outcomes of COVID-19.

positive: The value of urine biochemical parameters in the prediction of the severity of coronavirus disease 2019. Background Among patients with coronavirus disease 2019 (COVID-19), the cases of a significant proportion of patients are severe. A viral nucleic acid test is used for the diagnosis of COVID-19, and some hematological indicators have been used in the auxiliary diagnosis and identification of the severity of COVID-19. Regarding body fluid samples, except for being used for nucleic acid testing, the relationship between COVID-19 and routine body fluid parameters is not known. Our aim was to investigate the value of urine biochemical parameters in the prediction of the severity of COVID-19. Methods A total of 119 patients with COVID-19 were enrolled at Renmin Hospital of Wuhan University. According to the severity of COVID-19, the patients were divided into three groups (moderate 67, severe 42 and critical 10), and 45 healthy persons were enrolled in the same period as healthy controls. The relationship between the results of urine biochemical parameters and the severity of COVID-19 was analyzed. Results The positive rates of urine occult blood (BLOOD) and proteinuria (PRO) were higher in COVID-19 patients than in healthy controls (p < 0.05); the urine specific gravity (SG) value was lower in patients than in healthy controls (p < 0.05), and the urine potential of hydrogen (pH) value was higher in patients than in healthy controls (p < 0.01). The positive rates of urine glucose (GLU-U) and PRO in the severe and critical groups were higher than those in the moderate group (p < 0.01 and p < 0.05, respectively); other biochemical parameters of urine were not associated with the severity of COVID-19. Conclusions Some urine biochemical parameters are different between patients with severe acute respiratory syndrome (SARS)-CoV-2 and healthy controls, and GLU-U and PRO may be helpful for the differentiation of COVID-19 severity.

positive: Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan, Hubei province, and rapidly spread to many provinces in China as well as other countries. Here we report the epidemiological, clinical, laboratory, and radiological characteristics, as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen, China. All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS). The most common laboratory abnormalities were hypoalbuminemia, lymphopenia, decreased percentage of lymphocytes (LYM) and neutrophils (NEU), elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased CD8 count. The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity. ALB, LYM, LYM (%), LDH, NEU (%), and CRP were highly correlated to the acute lung injury. Age, viral load, lung injury score, and blood biochemistry indexes, albumin (ALB), CRP, LDH, LYM (%), LYM, and NEU (%), may be predictors of disease severity. Moreover, the Angiotensin II level in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury. Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s11427-020-1643-8 and is accessible for authorized users.

positive: Investigation of Compatibility of SARS-CoV-2 RT-PCR Kits Containing Different Gene Targets During COVID-19 Pandemic Aim:In the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), reverse transcriptase-polymerase chain reaction (RT-PCR) technique is often used. We evaluated the compatibility of SARS-CoV-2 RT-PCR kits containing different gene targets during the pandemic. Materials and methods: Samples were tested by Bio-Speddy (RdRp gene) and Diagnovital (RdRp+E genes). The correlation between two assays were determined by Deming regression and chi-square heatmap analyses. Results: Diagnovital PCR kit showed in a constricted range and conveniently exponential amplification curves than Bio-Speedy PCR kit. While the correlation increased when a secondary biomarker was added to the kit. Conclusion: In an unknown sample, using together different PCR kits that target different genes during the pandemic situation may provide a more accurate diagnosis of SARS-CoV-2.

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

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

positive: Heparin-induced thrombocytopenia is associated with a high risk of mortality in critical COVID-19 patients receiving heparin-involved treatment Background Coronavirus infectious disease 2019 (COVID-19) has developed into a global pandemic. It is essential to investigate the clinical characteristics of COVID-19 and uncover potential risk factors for severe disease to reduce the overall mortality rate of COVID-19. Methods Sixty-one critical COVID-19 patients admitted to the intensive care unit (ICU) and 93 severe non-ICU patients at Huoshenshan Hospital (Wuhan, China) were included in this study. Medical records, including demographic, platelet counts, heparin-involved treatments, heparin-induced thrombocytopenia-(HIT) related laboratory tests, and fatal outcomes of COVID-19 patients were analyzed and compared between survivors and nonsurvivors. Findings Sixty-one critical COVID-19 patients treated in ICU included 15 survivors and 46 nonsurvivors. Forty-one percent of them (25/61) had severe thrombocytopenia, with a platelet count (PLT) less than 50x109/L, of whom 76% (19/25) had a platelet decrease of >50% compared to baseline; 96% of these patients (24/25) had a fatal outcome. Among the 46 nonsurvivors, 52.2% (24/46) had severe thrombocytopenia, compared to 6.7% (1/15) among survivors. Moreover, continuous renal replacement therapy (CRRT) could induce a significant decrease in PLT in 81.3% of critical CRRT patients (13/16), resulting in a fatal outcome. In addition, a high level of anti-heparin-PF4 antibodies, a marker of HIT, was observed in most ICU patients. Surprisingly, HIT occurred not only in patients with heparin exposure, such as CRRT, but also in heparin-naive patients, suggesting that spontaneous HIT may occur in COVID-19. Interpretation Anti-heparin-PF4 antibodies are induced in critical COVID-19 patients, resulting in a progressive platelet decrease. Exposure to a high dose of heparin may trigger further severe thrombocytopenia with a fatal outcome. An alternative anticoagulant other than heparin should be used to treat COVID-19 patients in critical condition.

positive: COVID-19: a meta-analysis of diagnostic test accuracy of commercial assays registered in Brazil Abstract The accuracy of commercially available tests for COVID-19 in Brazil remains unclear. We aimed to perform a meta-analysis to describe the accuracy of available tests to detect COVID-19 in Brazil. We searched at the Brazilian Health Regulatory Agency (ANVISA) online platform to describe the pooled sensitivity (Se), specificity (Sp), diagnostic odds ratio (DOR) and summary receiver operating characteristic curves (SROC) for detection of IgM/IgG antibodies and for tests using naso/oropharyngeal swabs in the random-effects models. We identified 16 tests registered, mostly rapid-tests. Pooled diagnostic accuracy measures [95%CI] were: (i) for IgM antibodies Se=82% [76-87]; Sp=97% [96-98]; DOR=168 [92-305] and SROC=0.98 [0.96-0.99]; (ii) for IgG antibodies Se=97% [90-99]; Sp=98% [97-99]; DOR=1994 [385-10334] and SROC=0.99 [0.98-1.00]; and (iii) for detection of SARS-CoV-2 by antigen or molecular assays in naso/oropharyngeal swabs Se=97% [85-99]; Sp=99% [77-100]; DOR=2649 [30-233056] and SROC=0.99 [0.98-1.00]. These tests can be helpful for emergency testing during the COVID-19 pandemic in Brazil. However, it is important to highlight the high rate of false negative results from tests which detect SARS-CoV-2 IgM antibodies in the initial course of the disease and the scarce evidence-based validation results published in Brazil. Future studies addressing the diagnostic performance of tests for COVID-19 in the Brazilian population are urgently needed.

positive: Clinical and radiographic features of cardiac injury in patients with 2019 novel coronavirus pneumonia Objective: To investigate the correlation between clinical characteristics and cardiac injury of COVID-2019 pneumonia. Methods: In this retrospective, single-center study, 41 consecutive corona virus disease 2019 (COVID-2019) patients (including 2 deaths) of COVID-2019 in Beijing Youan Hospital, China Jan 21 to Feb 03, 2020, were involved in this study. The high risk factors of cardiac injury in different COVID-2019 patients were analyzed. Computed tomographic (CT) imaging of epicardial adipose tissue (EAT) has been used to demonstrate the cardiac inflammation of COVID-2019. ResultsOf the 41 COVID-2019 patients, 2 (4.88%), 32 (78.05%), 4 (9.75%) and 3 (7.32%) patients were clinically diagnosed as light, mild, severe and critical cases, according to the 6th guidance issued by the National Health Commission of China. 10 (24.4%) patients had underlying complications, such as hypertension, CAD, type 2 diabetes mellites and tumor. The peak value of TnI in critical patients is 40-fold more than normal value. 2 patients in the critical group had the onset of atrial fibrillation, and the peak heart rates reached up to 160 bpm. CT scan showed low EAT density in severe and critical patients. Conclusion: Our results indicated that cardiac injury of COVID-2019 was rare in light and mild patients, while common in severe and critical patients. Therefore, the monitoring of the heart functions of COVID-2019 patients and applying potential interventions for those with abnormal cardiac injury related characteristics, is vital to prevent the fatality.

positive: Biochemical biomarkers alterations in Coronavirus Disease 2019 (COVID-19). Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory disease, which can evolve into multi-organ failure (MOF), leading to death. Several biochemical alterations have been described in COVID-19 patients. To date, many biomarkers reflecting the main pathophysiological characteristics of the disease have been identified and associated with the risk of developing severe disease. Lymphopenia represents the hallmark of the disease, and it can be detected since the early stage of infection. Increased levels of several inflammatory biomarkers, including c-reactive protein, have been found in COVID-19 patients and associated with an increased risk of severe disease, which is characterised by the so-called "cytokine storm". Also, the increase of cardiac and liver dysfunction biomarkers has been associated with poor outcome. In this review, we provide an overview of the main biochemical characteristics of COVID-19 and the associated biomarkers alterations.

positive: 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.

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: Prealbumin as a Predictor of Prognosis in Patients With Coronavirus Disease 2019 Background: The predictive value of prealbumin for the prognosis of coronavirus disease 2019 (COVID-19) has not been extensively investigated. Methods: A total of 1,115 patients with laboratory-confirmed COVID-19 were enrolled at Tongji hospital from February to April 2020 and classified into fatal (n = 129) and recovered (n = 986) groups according to the patient's outcome. Prealbumin and other routine laboratory indicators were measured simultaneously. Results: The level of prealbumin on admission was significantly lower in fatal patients than in recovered patients. For predicting the prognosis of COVID-19, the performance of prealbumin was better than most routine laboratory indicators, such as albumin, lymphocyte count, neutrophil count, hypersensitive C-reactive protein, d-dimer, lactate dehydrogenase, creatinine, and hypersensitive cardiac troponin I. When a threshold of 126 mg/L was used to discriminate between fatal and recovered patients, the sensitivity and specificity of prealbumin were, respectively, 78.29 and 90.06%. Furthermore, a model based on the combination of nine indexes showed an improved performance in predicting the death of patients with COVID-19. Using a cut-off value of 0.19, the prediction model was able to distinguish between fatal and recovered individuals with a sensitivity of 86.82% and a specificity of 90.37%. Conclusions: A lower level of prealbumin on admission may indicate a worse outcome of COVID-19. Immune and nutritional status may be vital factors for predicting disease progression in the early stage of COVID-19.

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

positive: Longitudinal hematologic and immunologic variations associated with the progression of COVID-19 patients in China BACKGROUND: Crucial roles of hematologic and immunologic responses in progression of coronavirus disease 2019 (COVID-19) remain largely unclear. OBJECTIVE: We sought to address the dynamic changes in hematologic and immunologic biomarkers and their associations with severity and outcomes of COVID-19. METHODS: A retrospective study including 548 patients with COVID-19 with clarified outcome (discharged or deceased) from a national cohort in China was performed. Cross-sectional and longitudinal variations were compared and the associations with different severity and outcomes were analyzed. RESULTS: On admission, the counts of lymphocytes, T-cell subsets, eosinophils, and platelets decreased markedly, especially in severe/critical and fatal patients. Increased neutrophil count and neutrophils-to-lymphocytes ratio were predominant in severe/critical cases or nonsurvivors. During hospitalization, eosinophils, lymphocytes, and platelets showed an increasing trend in survivors, but maintained lower levels or dropped significantly afterwards in nonsurvivors. Nonsurvivors kept a high level or showed an upward trend for neutrophils, IL-6, procalcitonin, D-dimer, amyloid A protein, and C-reactive protein, which were kept stable or showed a downward trend in survivors. Positive correlation between CD8+ T-cell and lymphocytes count was found in survivors but not in nonsurvivors. A multivariate Cox regression model suggested that restored levels of lymphocytes, eosinophils, and platelets could serve as predictors for recovery, whereas progressive increases in neutrophils, basophils, and IL-6 were associated with fatal outcome. CONCLUSIONS: Hematologic and immunologic impairment showed a significantly different profile between survivors and nonsurvivors in patients with COVID-19 with different severity. The longitudinal variations in these biomarkers could serve to predict recovery or fatal outcome.

positive: Elevation of blood glucose level predicts worse outcomes in hospitalized patients with COVID-19: a retrospective cohort study INTRODUCTION: With intense deficiency of medical resources during COVID-19 pandemic, risk stratification is of strategic importance. Blood glucose level is an important risk factor for the prognosis of infection and critically ill patients. We aimed to investigate the prognostic value of blood glucose level in patients with COVID-19. RESEARCH DESIGN AND METHODS: We collected clinical and survival information of 2041 consecutive hospitalized patients with COVID-19 from two medical centers in Wuhan. Patients without available blood glucose level were excluded. We performed multivariable Cox regression to calculate HRs of blood glucose-associated indexes for the risk of progression to critical cases/mortality among non-critical cases, as well as in-hospital mortality in critical cases. Sensitivity analysis were conducted in patient without diabetes. RESULTS: Elevation of admission blood glucose level was an independent risk factor for progression to critical cases/death among non-critical cases (HR=1.30, 95% CI 1.03 to 1.63, p=0.026). Elevation of initial blood glucose level of critical diagnosis was an independent risk factor for in-hospital mortality in critical cases (HR=1.84, 95% CI 1.14 to 2.98, p=0.013). Higher median glucose level during hospital stay or after critical diagnosis (≥6.1 mmol/L) was independently associated with increased risks of progression to critical cases/death among non-critical cases, as well as in-hospital mortality in critical cases. Above results were consistent in the sensitivity analysis in patients without diabetes. CONCLUSIONS: Elevation of blood glucose level predicted worse outcomes in hospitalized patients with COVID-19. Our findings may provide a simple and practical way to risk stratify COVID-19 inpatients for hierarchical management, particularly where medical resources are in severe shortage during the pandemic.

positive: The 2019 Novel Coronavirus Outbreak - A Global Threat. The 2019 Novel Corona virus infection (COVID 19) is an ongoing public health emergency of international significance. There are significant knowledge gaps in the epidemiology, transmission dynamics, investigation tools and management. In this article, we review the available evidence about this disease. Every decade has witnessed the evolution of a new coronavirus epidemic since the last three decades. The varying transmission patterns, namely, nosocomial transmission and spread through mildly symptomatic cases is an area of concern. There is a spectrum of clinical features from mild to severe life threatening disease with major complications like severe pneumonia, ARDS, acute cardiac injury and septic shock. Presence of bilateral ground glass opacity and consolidation on imaging in appropriate clinical background should raise a suspicion about COVID 19. Poor prognostic factors include Multilobular infiltration on chest imaging, Lymphopenia, Bacterial co-infection, Smoking history, Chronic medical conditions like Hypertension and age >60 years (MuLBSTA score). Diagnosis is confirmed with PCR based testing of appropriate respiratory samples. Management is primarily supportive, with newer antivirals (lopinavir ritonavir and Remdesivir) under investigation. Role of steroids is still inconclusive. Standard infection control and prevention techniques should be followed. Vigilant screening of suspected cases and their contacts is important. Isolation of symptomatic cases and home quarantine of asymptomatic contacts is recommended. To conclude, controlling this highly transmissible disease requires international co-ordination.

positive: Epidemiological and clinical features of asymptomatic patients with SARS-CoV-2 infection Few studies reported the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients with completely asymptomatic throughout the disease course. We investigated the epidemiological and clinical features of patients infected by SARS-CoV-2 without any symptoms. Patients with confirmed SARS-CoV-2 infection were retrospectively recruited. The demographic characteristics, clinical data, treatment, and outcomes of SARS-CoV-2 infected patients without any symptoms were analyzed. Fifteen (4.4%) of 342 SARS-CoV-2 infected patients did not develop any symptom during the course of the disease. The median time from exposure to diagnosis was 7.0 days (interquartile range [IQR]: 1.0-15.0 days). Of the 15 patients, 14 patients were diagnosed by tested positive for SARS-CoV-2 in throat swabs, while one patient was only tested positive for SARS-CoV-2 in anal swabs. During hospitalization, only 1 (6.7%) patient developed lymphopenia. Abnormalities of chest computed tomography examinations were detected in 8 (53.4%) patients on admission. As of 8 March 2020, all patients have been discharged. The median time of SARS-CoV-2 tested negative from admission was 7.0 days (IQR: 4.0-9.0 days). Patients without any symptoms but with SARS-CoV-2 exposure should be closely monitored and tested for SARS-CoV-2 both in anal and throat swabs to excluded the infection. Asymptomatic patients infected by SARS-CoV-2 have favorable outcomes.

positive: C-reactive protein levels in the early stage of COVID-19 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, PË0.05), those in the severe group were higher than those in the moderate group (Mann-Whitney test=0.693, -2.177, PË0.05), and those in the critical group were higher than those in the severe group (Mann-Whitney test=-0.068, -1.549, PË0.05). 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, PË0.001). CONCLUSION: In the early stage of COVID-19 CRP levels were positively correlated with lung lesions and could reflect disease severity.

positive: Prognostic factors for COVID-19 pneumonia progression to severe symptom based on the earlier clinical features: a retrospective analysis Background Approximately 15-20% of COVID-19 patients will develop severe pneumonia, about 10 % of which will die if not properly managed. Methods 125 COVID-19 patients enrolled in this study were classified into mild (93 cases) and severe (32 cases) groups, basing on their 3 to 7-days clinical outcomes. Patients' gender, age, comorbid with underlying diseases, epidemiological history, clinical manifestations, and laboratory tests on admission were collected and subsequently analyzed with single-factor and multivariate logistic regression methods. Finally, we evaluate their prognostic values with the receiver operating characteristic curve (ROC) analysis. Results Seventeen factors on admission differed significantly between mild and severe groups. Next, only four factors, including the comorbid with underlying diseases, increased respiratory rate (>24/min), elevated C-reactive protein (CRP >10mg/liter), and lactate dehydrogenase (LDH >250U/liter), were found to be independently associated with the later disease development. Prognostic value analysis by ROC indicated that individual factors could not confidently predict the occurrence of severe pneumonia, but that the combination of fast respiratory rate and elevated LDH significantly increase the predictive confidence (AUC= 0.944, sensitivity= 0.941, and specificity= 0.902). Three- or four-factors combinations, including elevated LDH and fast respiratory rate, further increased the prognostic value. Additionally, measurable serum viral RNA post-admission could independently predict the severe illness occurrence. Conclusions General clinical characteristics and laboratory tests, such as combinations consisting of elevated LDH and fast respiratory rate, and detectable viral RNA in serum post-admission could provide high confident prognostic value for identifying potential severe COVID-19 pneumonia patients.

positive: Liver injury is associated with severe Coronavirus disease 2019 (COVID‐19) infection: a systematic review and meta‐analysis of retrospective studies AIM: The Coronavirus disease 2019 (COVID‐19) outbreak is a major threat to human beings. Lung injury has been reported as the major outcome of COVID‐19 infection. However, liver damage has also been considered to occur in severe cases. Current meta‐analysis of retrospective studies was done to summarize available findings on the association between liver injury and severity of COVID‐19 infection. METHODS: Online databases including PubMed, Scopus, Web of Science and Cochrane Library were searched to detect relevant publications up to 1 April 2020, using relevant keywords. To pool data, a fixed‐ or random‐effects model was used depending on the heterogeneity between studies. Furthermore, publication bias test and sensitivity analysis were also done. RESULTS: In total, 20 retrospective studies with 3,428 COVID‐19 infected patients (severe cases = 1,455 and mild cases = 1,973), were included in this meta‐analysis. Higher serum levels of Aspartate aminotransferase (weighted mean difference = 8.84 U/L, 95% CI = 5.97 to 11.71, P<0.001), Alanine aminotransferase (weighted mean difference = 7.35 U/L, 95% CI = 4.77 to 9.93, P<0.001), total Bilirubin (weighted mean difference = 2.30 mmol/L, 95% CI = 1.24 to 3.36, P<0.001) and lower serum levels of Albumin (weighted mean difference = ‐4.24 g/L, 95% CI = ‐6.20 to ‐2.28, P<0.001), were associated with a significant increase in the severity of COVID‐19 infection. CONCLUSIONS: The incidence of liver injury, as assessed by serum analysis (AST, ALT, total Bilirubin and Albumin levels), seems to be higher in patients with severe COVID‐19 infection.

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: Bulk and single-cell transcriptomics identify tobacco-use disparity in lung gene expression of ACE2, the receptor of 2019-nCov In current severe global emergency situation of 2019-nCov outbreak, it is imperative to identify vulnerable and susceptible groups for effective protection and care. Recently, studies found that 2019-nCov and SARS-nCov share the same receptor, ACE2. In this study, we analyzed five large-scale bulk transcriptomic datasets of normal lung tissue and two single-cell transcriptomic datasets to investigate the disparities related to race, age, gender and smoking status in ACE2 gene expression and its distribution among cell types. We didn't find significant disparities in ACE2 gene expression between racial groups (Asian vs Caucasian), age groups (>60 vs <60) or gender groups (male vs female). However, we observed significantly higher ACE2 gene expression in former smoker's lung compared to non-smoker's lung. Also, we found higher ACE2 gene expression in Asian current smokers compared to non-smokers but not in Caucasian current smokers, which may indicate an existence of gene-smoking interaction. In addition, we found that ACE2 gene is expressed in specific cell types related to smoking history and location. In bronchial epithelium, ACE2 is actively expressed in goblet cells of current smokers and club cells of non-smokers. In alveoli, ACE2 is actively expressed in remodelled AT2 cells of former smokers. Together, this study indicates that smokers especially former smokers may be more susceptible to 2019-nCov and have infection paths different with non-smokers. Thus, smoking history may provide valuable information in identifying susceptible population and standardizing treatment regimen.

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

positive: Serum Hydrogen Sulfide and Outcome Association in Pneumonia by the SARS-CoV-2 Coronavirusxs. BACKGROUND The pneumonia of COVID-19 illness has often a subtle initial presentation making mandatory the use of biomarkers for evaluation of severity and prediction of final patient disposition. We evaluated the use of hydrogen sulfide (H2S) for the outcome of COVID-19 pneumonia. MATERIALS & METHODS We studied 74 patients with COVID-19. Clinical data were collected, and survival predictors were calculated. Blood was collected within 24 hours after admission (day 1) and on day 7. H2S was measured in sera by monobromobimane derivation (MBB) followed by high performance liquid chromatography and correlated to other markers like procalcitonin (PCT) and C- reactive protein (CRP). Tumor necrosis factor alpha (TNFα) and interleukin (IL)-6 were also measured in serum. RESULTS Survivors had significantly higher H2S levels on day 1 and 7 after admission. A cut-off point of 150.44 μM could discriminate survivors from non-survivors with 80% sensitivity, 73.4% specificity and negative predictive value 95.9%. Mortality after 28 days was 32% with admission levels lower or equal to 150.44 μΜ and 4.1% with levels above 150.44 μΜ (p: 0.0008). Mortality was significantly greater among patients with a decrease of H2S levels from day 1 to day 7 greater or equal to 36% (p: 0.0005). Serum H2S on day 1 was negatively correlated with IL- 6 and CRP and positively correlated with the absolute lymphocyte count in peripheral blood. CONCLUSION It is concluded that H2S is a potential marker for severity and final outcome of pneumonia by the SARS-CoV-2 coronavirus. Its correlation with IL- 6 suggests anti-inflammatory properties.

positive: Changes in blood coagulation in patients with severe coronavirus disease 2019 (COVID‐19): a meta‐analysis Coronavirus disease 2019 (COVID-19) is widely spread and poses a critical threat to global health (Zhang et al). Prominent changes in coagulation function in severe patients of COVID-19 have been reported in a recent study (Han, et al 2020). Therefore, we conducted this quantitative meta-analysis to explore the difference in blood coagulation parameters between severe and mild cases of COVID-19.

positive: Coronavirus disease 2019 (COVID-19) and cardiovascular complications Abstract The coronavirus disease 2019 (COVID-19) has become a global pandemic. It has been spread to more than 100 countries and more than 1 million patients have been confirmed. Although coronavirus causes severe respiratory infections in human, accumulating data have demonstrated cardiac complications and poor outcome in patients with coronavirus disease 2019. A large percent of patients have underlying cardiovascular disease and they are at a high risk of developing cardiac complications. We review the basics of the virus, the clinical manifestation, and the possible mechanisms of cardiac complications in patients with coronavirus disease 2019. Before the effective vaccine or medicine is available, supportive therapy and identifying patients who are at high risk of cardiac complications are important.

positive: A Marker of Systemic Inflammation or Direct Cardiac Injury: Should Cardiac Troponin Levels be Monitored in COVID-19 Patients?

positive: Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China BACKGROUND: In late December 2019, an outbreak of acute respiratory illness, coronavirus disease 2019 (COVID-19), emerged in Wuhan, China. We aimed to study the epidemiology, clinical features and short-term outcomes of patients with COVID-19 in Wuhan, China. METHODS: We performed a single center, retrospective case series study in 221 patients with laboratory confirmed SARS-CoV-2 pneumonia at a university hospital, including 55 severe patients and 166 non-severe patients, from January 2, 2020 to February 10, 2020. RESULTS: Of the 221 patients with COVID-19, the median age was 55.0 years and 48.9% were male and only 8 (3.6%) patients had a history of exposure to the Huanan Seafood Market. Compared to the non-severe pneumonia patients, the median age of the severe patients was significantly older, and they were more likely to have chronic comorbidities. Most common symptoms in severe patients were high fever, anorexia and dyspnea. On admission, 33.0% patients showed leukopenia and 73.8% showed lymphopenia. In addition, the severe patients suffered a higher rate of co-infections with bacteria or fungus and they were more likely to developing complications. As of February 15, 2020, 19.0% patients had been discharged and 5.4% patients died. 80% of severe cases received ICU (intensive care unit) care, and 52.3% of them transferred to the general wards due to relieved symptoms, and the mortality rate of severe patients in ICU was 20.5%. CONCLUSIONS: Patients with elder age, chronic comorbidities, blood leukocyte/lymphocyte count, procalcitonin level, co-infection and severe complications might increase the risk of poor clinical outcomes.

positive: Liver injury is associated with severe Coronavirus disease 2019 (COVID‑19) infection: a systematic review and meta-analysis of retrospective studies Aim: The Coronavirus disease 2019 (COVID-19) outbreak is a major threat to human beings. Lung injury has been reported as the major outcome of COVID-19 infection. However, liver damage has also been considered to occur in severe cases. Current meta-analysis of retrospective studies was done to summarize available findings on the association between liver injury and severity of COVID-19 infection. Methods: Online databases including PubMed, Scopus, Web of Science and Cochrane Library were searched to detect relevant publications up to 1 April 2020, using relevant keywords. To pool data, a fixed- or random-effects model was used depending on the heterogeneity between studies. Furthermore, publication bias test and sensitivity analysis were also done. Results: In total, 20 retrospective studies with 3,428 COVID-19 infected patients (severe cases = 1,455 and mild cases = 1,973), were included in this meta-analysis. Higher serum levels of Aspartate aminotransferase (weighted mean difference = 8.84 U/L, 95% CI = 5.97 to 11.71, P<0.001), Alanine aminotransferase (weighted mean difference = 7.35 U/L, 95% CI = 4.77 to 9.93, P<0.001), total Bilirubin (weighted mean difference = 2.30 mmol/L, 95% CI = 1.24 to 3.36, P<0.001) and lower serum levels of Albumin (weighted mean difference = -4.24 g/L, 95% CI = -6.20 to -2.28, P<0.001), were associated with a significant increase in the severity of COVID-19 infection. Conclusions: The incidence of liver injury seems to be higher in patients with severe COVID-19 infection. This finding could help physicians to identify patients with poor prognosis at an early stage.

positive: Clinical, radiological and laboratory characteristics and risk factors for severity and mortality of 289 hospitalized COVID-19 patients. BACKGROUND The coronavirus disease 2019 (COVID-19) has become a global pandemic, with 10-20% of severe cases and over 508,000 deaths worldwide. OBJECTIVE This study aims to address the risk factors associated with the severity of COVID-19 patients and the mortality of severe patients. METHODS 289 hospitalized laboratory-confirmed COVID-19 patients were included in this study. Electronic medical records, including patient demographics, clinical manifestation, comorbidities, laboratory tests results, and radiological materials were collected and analyzed. According to the severity and outcomes of the patients, they were divided into three groups: non-survived (n=49), survived severe (n=78), and non-severe (n=162) groups. Clinical, laboratory and radiological data were compared among these groups. Principal component analysis (PCA) was applied to reduce the dimensionality and visualize the patients on a low-dimensional space. Correlations between clinical, radiological and laboratory parameters were investigated. Univariate and multivariate logistic regression methods were used to determine the risk factors associated with mortality in severe patients. Longitudinal changes of laboratory findings of survived severe cases and non-survived cases during hospital stay were also collected. RESULTS Of the 289 patients, the median age was 57 years (range, 22 - 88) and 155 (53.4%) patients were male. As of the final follow-up date of this study, 240 (83.0%) patients were discharged from the hospital and 49 (17.0%) patients died. Elder age, underlying comorbidities, and increased laboratory variables, such as leucocyte count, neutrophil count, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), procalcitonin (PCT), D-dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and blood urea nitrogen (BUN) on admission were found in survived severe cases compared to non-severe cases. According to the multivariate logistic regression analysis, elder age, a higher number of affected lobes, elevated CRP levels on admission, increased prevalence of chest tightness/dyspnea and smoking history were independent risk factors for death of severe patients. A trajectory in PCA was observed from "non-severe" towards "non-survived" via "severe and survived" patients. Strong correlations between the age of patients, the affected lobe numbers and laboratory variables were identified. Dynamic changes of laboratory findings of survived severe cases and non-survived cases during hospital stay showed that continuing increase of leucocytes and neutrophil count, sustained lymphopenia and eosinopenia, progressing decrease in platelet count, as well as high levels of NLR, CRP, PCT, AST, BUN, and serum creatinine were associated with in-hospital death. CONCLUSIONS Survived severe and non-survived COVID-19 patients had distinct clinical and laboratory characteristics, which were separated by principle component analysis. Elder age, increased number of affected lobes, higher levels of serum CRP, chest tightness/dyspnea, and smoking history were risk factors for mortality of severe COVID-19 patients. Longitudinal changes of laboratory findings may be helpful in predicting disease progression and clinical outcome of severe patients.

positive: Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study BACKGROUND: In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. METHODS: In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. FINDINGS: Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. INTERPRETATION: The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. FUNDING: National Key R&D Program of China.

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

positive: 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: Comparative analysis of laboratory indexes of severe and non-severe patients infected with COVID-19 BACKGROUND: The pandemic coronavirus disease 2019 (COVID-19) has threaten the global health. The characteristics of laboratory findings of coronavirus are of great significance for clinical diagnosis and treatment. We found indicators that may most effectively predict a non-severe COVID-19 patient develop into a severe patient. METHODS: We conducted a meta-analysis to compare the laboratory findings of severe patients with non-severe patients with COVID-19 from searched articles. RESULTS: Through the analysis of laboratory examination information of patients with COVID-19 from 35 articles (5912 patients), we demonstrated that severe cases possessed higher levels of leukocyte (1.20-fold), neutrophil (1.33-fold), CRP (3.04-fold), PCT (2.00-fold), ESR (1.44-fold), AST (1.40-fold), ALT (1.34-fold), LDH (1.54-fold), CK (1.44-fold), CK-MB (1.39-fold), total bilirubin(1.14-fold), urea (1.28-fold), creatine (1.09-fold), PT (1.03-fold) and D-dimer (2.74-fold), as well as lower levels of lymphocytes (1.44-fold), eosinophil (2.00-fold), monocyte (1.08-fold), Hemoglobin (1.53-fold), PLT (1.15-fold), albumin (1.15-fold), and APTT (1.02-fold). Lymphocyte subsets and series of inflammatory cytokines were also different in severe cases with the non-severe ones, including lower levels of CD4 T cells (2.10-fold) and CD8 T cells (2.00-fold), higher levels of IL-1β (1.02-fold), IL-6 (1.93-fold) and IL-10 (1.55-fold). CONCLUSIONS: Some certain laboratory inspections could predict the progress of the COVID-19 changes, especially lymphocytes, CRP, PCT, ALT, AST, LDH, D-dimer, CD4 T cells and IL6, which provide valuable signals for preventing the deterioration of the disease.

positive: [Relationship between D-dimer concentration and inflammatory factors or organ function in patients with coronavirus disease 2019] OBJECTIVE: To explore the relationship between D-dimer concentration and inflammatory factors or organ function in patients with coronavirus disease 2019 (COVID-19). METHODS: A retrospective study was conducted. The clinical data of 72 patients with COVID-19 admitted to intensive unit of Tongji Guanggu Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology in Wuhan, Hubei Province from February 10th to 29th in 2020 were collected, including their general information, routine blood test, coagulation function, inflammatory parameters, cytokines, and organ function related laboratory parameters at admission. The patients were divided into two groups, namely D-dimer normal group (< 0.5 mg/L) and D-dimer elevated group (≥ 0.5 mg/L). The differences of general data, inflammatory parameters and cytokines between the two groups were compared. Besides, the correlation between D-dimer and organ function was analyzed by linear regression. The change in sequential organ failure assessment (SOFA) between the first visit after the onset of the disease and admission to intensive unit ≥ 2 was defined as being combined with organ damage. Receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of D-dimer on organ damage in patients with COVID-19. RESULTS: 65.3% of the 72 patients had abnormal coagulation. The D-dimer level of COVID-19 patients gradually increased with the aggravation of the disease, and the levels of ordinary type (n = 14), severe type (n = 49), and critical type (n = 9) were 0.43 (0.22, 0.89), 0.66 (0.26, 1.36), and 2.65 (0.68, 15.45) mg/L, respectively, with statistically significant difference (P < 0.05). Thirty-two patients (44.4%) had normal D-dimer, and 40 (55.6%) had elevated D-dimer. Compared with the normal D-dimer group, the patients in the D-dimer elevated group were older (years old: 67.7±11.6 vs. 54.0±13.1), and the levels of white blood cell count (WBC), neutrophil count (NEU), procalcitonin (PCT), high-sensitivity C-reactive protein (hs-CRP), interleukins (IL-6, IL-8, IL-10), IL-2 receptor (IL-2R) and tumor necrosis factor-α (TNF-α) at admission were significantly higher [WBC (×109/L): 7.16 (5.55, 9.75) vs. 5.25 (4.59, 6.98), NEU (×109/L): 7.11±5.46 vs. 3.33±1.58, PCT (µg/L): 0.08 (0.06, 0.21) vs. 0.05 (0.04, 0.06), hs-CRP (mg/L): 27.9 (3.4, 58.8) vs. 1.3 (0.8, 6.6), IL-6 (ng/L): 11.80 (2.97, 30.61) vs. 1.98 (1.50, 4.73), IL-8 (ng/L): 19.90 (13.33, 42.28) vs. 9.40 (12.35, 15.30), IL-10 (ng/L): 5.00 (5.00, 8.38) vs. 5.00 (5.00, 5.00), IL-2R (kU/L): 907.90±458.42 vs. 572.13±274.55, TNF-α (ng/L): 10.94±5.95 vs. 7.77±3.67], while lymphocyte (LYM) and monocyte (MON) counts were lower [LYM (×109/L): 1.14±0.49 vs. 1.46±0.42, MON (×109/L): 0.63±0.25 vs. 0.87±0.21], with significant differences (all P < 0.05). Linear regression analysis showed that D-dimer level was negatively related with pulse oxygen saturation (SpO2), oxygenation index (PaO2/FiO2) and platelet count (PLT) with ß values of -0.493, -11.615, and -0.018, respectively (all P < 0.05). However, D-dimer level was positively related with respiratory rate (RR), aspartate aminotransferase (AST), total bilirubin (TBil) and direct bilirubin (DBil) with ß values of 0.485, 0.107, 0.291, and 0.404 (all P < 0.05). ROC curve analysis showed that the area under ROC curve (AUC) of D-dimer for predicting organ injury in COVID-19 patients was 0.889, and the 95% confidence interval (95%CI) was 0.753-1.000. When the optimal cut-off value was 2.36 mg/L, the sensitivity was 85.7%, and the specificity was 78.1%. CONCLUSIONS: D-dimer levels in COVID-19 patients are correlated with inflammatory factors and organ function, and it can be used to predict organ injury.

positive: Brain natriuretic peptide to predict successful liberation from mechanical ventilation in critically ill patients: a systematic review and meta-analysis BACKGROUND: Predicting successful liberation from mechanical ventilation (MV) in critically ill patients is challenging. Brain natriuretic peptide (BNP) has been proposed to help guide decision-making for readiness to liberate from MV following a spontaneous breathing trial (SBT). METHODS: We performed a systematic review and meta-analysis of randomized and prospective observational studies that measured BNP levels at the time of SBT in patients receiving MV. The primary endpoint was successful liberation from MV (absence of reintubation or non-invasive ventilation at 48 h). Statistical analyses included bi-variate and Moses-Littenberg models and DerSimonian-Laird pooling of areas under ROC curve (AUROC). RESULTS: A total of 731 articles were screened. Eighteen adult and 2 pediatric studies were fulfilled pre-specified eligibility. The measure of the relative variation of BNP during SBT (ΔBNP%) after exclusion of SBT failure by clinical criteria in adults yielded a sensitivity and specificity of 0.889 [0.831–0.929] and 0.828 [0.730–0.896] for successful liberation from MV, respectively, with a pooled AUROC of 0.92 [0.88–0.97]. The pooled AUROC for any method of analysis for absolute variation of BNP (ΔBNP), pre-SBT BNP, and post-SBT BNP were 0.89 [0.83–0.95], 0.77 [0.63–0.91], and 0.85 [0.80–0.90], respectively. CONCLUSION: The relative change in BNP during a SBT has potential value as an incremental tool after successful SBT to predict successful liberation from MV in adults. There is insufficient data to support the use of BNP in children or as an alternate test to clinical indices of SBT, or the use of ΔBNP, BNP-pre, and BNP-post as an alternate or incremental test. TRIAL REGISTRATION: PROSPERO CRD42018087474 (6 February 2018)

positive: A Tool to Early Predict Severe Corona Virus Disease 2019 (COVID-19) : A Multicenter Study using the Risk Nomogram in Wuhan and Guangdong, China BACKGROUND: Due to no reliable risk stratification tool for severe coronavirus disease 2019 (COVID-19) patients at admission, we aimed to construct an effective model for early identification of cases at high risk of progression to severe COVID-19. METHODS: In this retrospective three-centers study, 372 non-severe COVID-19 patients during hospitalization were followed for more than 15 days after admission. Patients who deteriorated to severe or critical COVID-19 and patients who kept non-severe state were assigned to the severe and non-severe group, respectively. Based on baseline data of the two groups, we constructed a risk prediction nomogram for severe COVID-19 and evaluated its performance. RESULTS: The training cohort consisted of 189 patients, while the two independent validation cohorts consisted of 165 and 18 patients. Among all cases, 72 (19.35%) patients developed severe COVID-19. We found that old age, and higher serum lactate dehydrogenase, C-reactive protein, the coefficient of variation of red blood cell distribution width, blood urea nitrogen, direct bilirubin, lower albumin, are associated with severe COVID-19. We generated the nomogram for early identifying severe COVID-19 in the training cohort (AUC 0.912 [95% CI 0.846-0.978], sensitivity 85.71%, specificity 87.58%); in validation cohort (0.853 [0.790-0.916], 77.5%, 78.4%). The calibration curve for probability of severe COVID-19 showed optimal agreement between prediction by nomogram and actual observation. Decision curve and clinical impact curve analysis indicated that nomogram conferred high clinical net benefit. CONCLUSION: Our nomogram could help clinicians to early identify patients who will exacerbate to severe COVID-19, which will enable better centralized management and early treatment of severe patients.

positive: Supplementing the National Early Warning Score (NEWS2) for anticipating early deterioration among patients with COVID-19 infection Importance: An early minimally symptomatic phase is often followed by deterioration in patients with COVID-19 infection. This study shows that the addition of age and a minimal set of common blood tests taken in patients on admission to hospital significantly improves the National Early Warning Score (NEWS2) for risk-stratification of severe COVID disease. Objective: To supplement the NEWS2 score with a small number of easily obtained additional demographic, physiological and blood variables indicative of severity of COVID-19 infection. Design: Retrospective observational cohort with internal and temporal held-out external validation. Setting: Acute secondary care. Participants: 708 patients admitted to an acute multi-site UK NHS hospital with confirmed COVID-19 disease from 1st March to 5th April 2020. Intervention: Not applicable. Main outcome and measures: The primary outcome was patient status at 14 days after symptom onset categorised as severe disease (WHO-COVID-19 Outcomes Scales 6-8: i.e. transferred to intensive care unit or death). 218 of the 708 patients reached the primary end point. A range of physiological and blood biomarkers were assessed for their association with the primary outcome. Adjustments included age, gender, ethnicity and comorbidities (hypertension, diabetes, heart, respiratory and kidney diseases). Results: NEWS2 total score was a weak predictor for severity of COVID-19 infection at 14 days (internally validated AUC = 0.628). The addition of age and common blood tests (CRP, neutrophil count, estimated GFR and albumin) provided substantial improvements to a risk stratification model but performance was still only moderate (AUC = 0.75). Common comorbidities hypertension, diabetes, heart, respiratory and kidney diseases have minor additional predictive value. Conclusions and relevance: Adding age and a minimal set of common blood parameters to NEWS2 improves the risk stratification of patients likely to develop severe COVID-19 outcomes. The addition of a few common parameters is likely to be much easier to implement in a short time-scale than a novel risk-scoring system.

positive: Risk Factors Associated with Clinical Outcomes in 323 COVID-19 Patients in Wuhan, China Background With evidence of sustained transmission in more than 190 countries, coronavirus disease 2019 (COVID-19) has been declared a global pandemic. As such, data are urgently needed about risk factors associated with clinical outcomes. Methods A retrospective chart review of 323 hospitalized patients with COVID-19 in Wuhan was conducted. Patients were classified into three disease severity groups (non-severe, severe, and critical), based on their initial clinical presentation. Clinical outcomes were designated as favorable and unfavorable, based on disease progression and response to treatments. Logistic regression models were performed to identify factors associated with clinical outcomes, and logrank test was conducted for the association with clinical progression. Results Current standard treatments did not show significant improvement on patient outcomes in the study. By univariate logistic regression model, 27 risk factors were significantly associated with clinical outcomes. Further, multivariate regression indicated that age over 65 years, smoking, critical disease status, diabetes, high hypersensitive troponin I (>0.04 pg/mL), leukocytosis (>10 x 109/L) and neutrophilia (>75 x 109/L) predicted unfavorable clinical outcomes. By contrast, the use of hypnotics was significantly associated with favorable outcomes. Survival analysis also confirmed that patients receiving hypnotics had significantly better survival. Conclusions To our knowledge, this is the first indication that hypnotics could be an effective ancillary treatment for COVID-19. We also found that novel risk factors, such as higher hypersensitive troponin I, predicted poor clinical outcomes. Overall, our study provides useful data to guide early clinical decision making to reduce mortality and improve clinical outcomes of COVID-19.

positive: COVID‐19 and the clinical hematology laboratory The ongoing COVID‐19 pandemic originated in Wuhan, Hubei Province, China in December 2019. The etiologic agent is a novel coronavirus of presumed zoonotic origin with structural similarity to the viruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Like SARS and MERS, COVID‐19 infection manifests most frequently with lower respiratory symptoms. A minority of patients progress to acute respiratory distress syndrome/ diffuse alveolar damage. In addition to its central role in the diagnosis of COVID‐19 infection, the clinical laboratory provides critical information to clinicians regarding prognosis, disease course, and response to therapy. The purpose of this review is to 1) provide background context about the origins and course of the pandemic 2) discuss the laboratory’s role in the diagnosis of COVID‐19 infection 3) summarize the current state of biomarker analysis in COVID‐19 infection, with an emphasis on markers derived from the hematology laboratory 4) comment on the impact of COVID‐19 on hematology laboratory safety, and 5) describe the impact the pandemic has had on organized national and international educational activities worldwide.

positive: Diabetes is a risk factor for the progression and prognosis of COVID‐19 BACKGOUND: To figure out whether diabetes is a risk factor influencing the progression and prognosis of 2019 novel coronavirus disease (COVID‐19). METHODS: A total of 174 consecutive patients confirmed with COVID‐19 were studied. Demographic data, medical history, symptoms and signs, laboratory findings, chest computed tomography (CT) as well the treatment measures were collected and analysed. RESULTS: We found that COVID‐19 patients without other comorbidities but with diabetes (n = 24) were at higher risk of severe pneumonia, release of tissue injury‐related enzymes, excessive uncontrolled inflammation responses and hypercoagulable state associated with dysregulation of glucose metabolism. Furthermore, serum levels of inflammation‐related biomarkers such as IL‐6, C‐reactive protein, serum ferritin and coagulation index, D‐dimer, were significantly higher (P < .01) in diabetic patients compared with those without, suggesting that patients with diabetes are more susceptible to an inflammatory storm eventually leading to rapid deterioration of COVID‐19. CONCLUSIONS: Our data support the notion that diabetes should be considered as a risk factor for a rapid progression and bad prognosis of COVID‐19. More intensive attention should be paid to patients with diabetes, in case of rapid deterioration.

positive: Clinical classifiers of COVID-19 infection from novel ultra-high-throughput proteomics The COVID-19 pandemic is an unprecedented global challenge. Highly variable in its presentation, spread and clinical outcome, novel point-of-care diagnostic classifiers are urgently required. Here, we describe a set of COVID-19 clinical classifiers discovered using a newly designed low-cost high-throughput mass spectrometry-based platform. Introducing a new sample preparation pipeline coupled with short-gradient high-flow liquid chromatography and mass spectrometry, our methodology facilitates clinical implementation and increases sample throughput and quantification precision. Providing a rapid assessment of serum or plasma samples at scale, we report 27 biomarkers that distinguish mild and severe forms of COVID-19, of which some may have potential as therapeutic targets. These proteins highlight the role of complement factors, the coagulation system, inflammation modulators as well as pro-inflammatory signalling upstream and downstream of Interleukin 6. Application of novel methodologies hence transforms proteomics from a research tool into a rapid-response, clinically actionable technology adaptable to infectious outbreaks.

positive: Clinical features and multidisciplinary treatment outcome of COVID-19 pneumonia: A report of three cases The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic threatening global public health. In the current paper, we describe our successful treatment of three COVID-19 pneumonia patients cases including severe cases and cases with mortality risk factors. One 32-year-old male COVID-19 patient was diagnosed with severe COVID-19 pneumonia and moderate ARDS. The second COVID-19 pneumonia patient had a history of diabetes and chronic bronchitis. The third case of COVID-19 pneumonia was an 82-year old female patient. All three cases had severe COVID pneumonia and therefore were aggressively managed with a multidisciplinary and personalized therapeutic approach that included nutritional support, antiviral pharmacotherapy, active control of comorbidities, prevention of complication development and psychological intervention. Our experience highlights the importance of the use of a multidisciplinary therapeutic approach that tailors to the specific condition of the patient in achieving a favorable clinical outcome.

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

positive: Clinical decision support tool and rapid point-of-care platform for determining disease severity in patients with COVID-19 SARS-CoV-2 is the virus that causes coronavirus disease (COVID-19) which has reached pandemic levels resulting in significant morbidity and mortality affecting every inhabited continent. The large number of patients requiring intensive care threatens to overwhelm healthcare systems globally. Likewise, there is a compelling need for a COVID-19 disease severity test to prioritize care and resources for patients at elevated risk of mortality. Here, an integrated point-of-care COVID-19 Severity Score and clinical decision support system is presented using biomarker measurements of C-reactive protein (CRP), N-terminus pro B type natriuretic peptide (NT-proBNP), myoglobin (MYO), D-dimer, procalcitonin (PCT), creatine kinase-myocardial band (CK-MB), and cardiac troponin I (cTnI). The COVID-19 Severity Score combines multiplex biomarker measurements and risk factors in a statistical learning algorithm to predict mortality. The COVID-19 Severity Score was trained and evaluated using data from 160 hospitalized COVID-19 patients from Wuhan, China. Our analysis finds that COVID-19 Severity Scores were significantly higher for the group that died versus the group that was discharged with median (interquartile range) scores of 59 (40-83) and 9 (6-17), respectively, and area under the curve of 0.94 (95% CI 0.89-0.99). Although this analysis represents patients with cardiac comorbidities (hypertension), the inclusion of biomarkers from other pathophysiologies implicated in COVID-19 (e.g., D-dimer for thrombotic events, CRP for infection or inflammation, and PCT for bacterial co-infection and sepsis) may improve future predictions for a more general population. These promising initial models pave the way for a point-of-care COVID-19 Severity Score system to impact patient care after further validation with externally collected clinical data. Clinical decision support tools for COVID-19 have strong potential to empower healthcare providers to save lives by prioritizing critical care in patients at high risk for adverse outcomes.

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

positive: 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: Clinical and Genetic Characteristics of Covid-19 Patients from UK Biobank OBJECTIVE: To explore both clinical and genetic risk factors for Covid-19 in a cohort from the United Kingdom. DESIGN: Prospective cohort study. PARTICIPANTS: 669 positive Covid-19 patients within a cohort of 502,536 UK Biobank participants, recruited between 2006 and 2010. MAIN OUTCOME MEASURES: The main outcome measure was Covid-19 positive status, determined by the presence of any positive test for a single individual. We also assessed risk factors for inpatient and outpatient status for Covid-19 positive individuals. RESULTS: We found that black participants were at over three times increased risk of testing positive for Covid-19, relative to white participants, even after adjusting for confounders (adjusted relative risk [ARR] 3.14, 95% confidence interval [CI] 2.28 to 4.31). Asian participants were also at higher risk of Covid-19 (ARR 2.03, 95% CI 1.40 to 2.95). Next, we analyzed the association of comorbidities with Covid-19. We found that participants were at increased risk of Covid-19 if they had chronic obstructive pulmonary disease (ARR 1.54, 95% CI 1.02 to 2.31) or ischemic heart disease (ARR 1.56, 95% CI 1.18 to 2.07). However, there was no evidence that either angiotensin converting enzyme inhibitors (ARR 1.32, 95% CI 0.95 to 1.84) or angiotensin II receptor blockers (ARR 1.37, 95% CI 0.94 to 1.98) increased the risk of Covid-19. We confirmed that blood type A was associated with Covid-19 relative to blood type O individuals, and we also found that the HLA variant DQA1_509 was enriched in Covid-19 positive cases, even after Bonferroni correction (P = 1.0 × 10(−5)). CONCLUSIONS: In this study, we found that black and Asian participants were at increased risk of Covid-19, even after adjusting for confounders. We also identified a novel genetic association with the HLA variant DQA1_509. Further investigations of genetic associations with Covid-19 may lead to important discoveries of genetic drivers of severe disease.

positive: Neutrophil extracellular traps (NETs) as markers of disease severity in COVID-19 In severe cases of coronavirus disease 2019 (COVID-19), viral pneumonia progresses to respiratory failure. Neutrophil extracellular traps (NETs) are extracellular webs of chromatin, microbicidal proteins, and oxidant enzymes that are released by neutrophils to contain infections. However, when not properly regulated, NETs have potential to propagate inflammation and microvascular thrombosis, including in the lungs of patients with acute respiratory distress syndrome. While elevated levels of blood neutrophils predict worse outcomes in COVID-19, the role of NETs has not been investigated. We now report that sera from patients with COVID-19 (n=50 patients, n=84 samples) have elevated levels of cell-free DNA, myeloperoxidase(MPO)-DNA, and citrullinated histone H3 (Cit-H3); the latter two are highly specific markers of NETs. Highlighting the potential clinical relevance of these findings, cell-free DNA strongly correlated with acute phase reactants including C-reactive protein, D-dimer, and lactate dehydrogenase, as well as absolute neutrophil count. MPO-DNA associated with both cell-free DNA and absolute neutrophil count, while Cit-H3 correlated with platelet levels. Importantly, both cell-free DNA and MPO-DNA were higher in hospitalized patients receiving mechanical ventilation as compared with hospitalized patients breathing room air. Finally, sera from individuals with COVID-19 triggered NET release from control neutrophils in vitro. In summary, these data reveal high levels of NETs in many patients with COVID-19, where they may contribute to cytokine release and respiratory failure. Future studies should investigate the predictive power of circulating NETs in longitudinal cohorts, and determine the extent to which NETs may be novel therapeutic targets in severe COVID-19.

positive: A perspective on potential antibody-dependent enhancement of SARS-CoV-2. The possibility of antibody-dependent enhancement (ADE) of disease is a general concern for the development of vaccines and antibody therapies because the mechanisms that underlie antibody protection have the theoretical potential to amplify viral infections or trigger immunopathology. Observations relevant to the risks of ADE of disease require careful review at this critical point in the SARS-CoV-2 pandemic. At present, no clinical findings, immunologic assays or biomarkers are known to differentiate any severe viral infection from immune-enhanced disease, whether by antibodies, T cells or intrinsic host responses. In vitro systems and animal models do not predict the risk of ADE of disease, in part because protective and potentially detrimental antibody-mediated mechanisms are the same, and designing animal models depends on understanding how antiviral host responses may become harmful in people. The implications of our lack of knowledge are twofold. First, comprehensive studies are urgently needed to define clinical correlates of protective immunity against SARS-CoV-2. Second, since we cannot predict ADE of disease reliably after either vaccination or treatment with antibodies, regardless of what virus is the causative agent, it will be essential to depend on careful analysis of safety in humans as immune interventions for COVID-19 disease move forward.

positive: Clinical characteristics and predictors of disease progression in severe patients with COVID-19 infection in Jiangsu Province, China: a descriptive study Background We studied patients with coronavirus disease 2019 (COVID-19) infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a virus that originated in Wuhan, China, and is spreading over the country including Jiangsu Province We studied the clinical characteristics and therapies of severe cases in Jiangsu Province Methods A multicenter retrospective cohort study was conducted to analyze clinical, laboratory data and treatment of 60 severe cases with COVID-19 infection in Jiangsu Province between January 24, 2020 and April 20, 2020 The improvement and deterioration subgroups were compared to identify predictors of disease progression Results A total of 653 infected cases with COVID-19 were reported in Jiangsu Province, of which 60 severe cases were included in this study Up until April 20, 2020, the mortality of severe patients was 0% The median age was 57 years The average body mass index (BMI) of these patients was 25 kg/m² White blood cell counts decreased in 45 0% of patients, lymphopenia in 63 3%, thrombocytopenia in 13 3%, and procalcitonin levels in 88 3% of the patients were less than 0 5 ng/mL There were no statistically significant differences in immunoglobulin therapy and glucocorticoids therapy between the improvement and deterioration subgroups Logistic regression analysis identified higher levels of troponin T (odds ratio [OR]: 1 04;95% confidence interval [CI]: 1 00-1 08;P=0 04), antiviral therapy with aerosol inhalation of interferon (OR: 6 33;95% CI: 1 18-33 98;P=0 03), and the application of non-invasive mechanical ventilation (OR: 1 99;95%CI: 1 17-3 41;P=0 01) as predictors of disease progression, whereas higher lymphocyte count (OR: 0 11;95% CI: 0 02-0 57;P=0 01) and early prone ventilation were associated with improvement (OR: 0 11;95% CI: 0 01-0 98;P=0 04) Conclusions COVID-19 infection had a low mortality rate in Jiangsu Province, China The higher levels of troponin T and lower lymphocyte count were predictors of disease progression Early prone ventilation may be an effective treatment for severe cases

positive: Impact of Congestive Heart Failure and Role of Cardiac Biomarkers in COVID-19 patients: A Systematic Review and Meta-Analysis Background: Coronavirus disease 2019 (COVID-19) has been reported to cause worse outcomes in patients with underlying cardiovascular disease, especially in patients with acute cardiac injury, which is determined by elevated levels of high-sensitivity troponin. There is a paucity of data on the impact of congestive heart failure (CHF) on outcomes in COVID-19 patients. Methods: We conducted a literature search of PubMed/Medline, EMBASE, and Google Scholar databases from 11/1/2019 till 06/07/2020, and identified all relevant studies reporting cardiovascular comorbidities, cardiac biomarkers, disease severity, and survival. Pooled data from the selected studies were used for metanalysis to identify the impact of risk factors and cardiac biomarker elevation on disease severity and/or mortality. Results: We collected pooled data on 5,967 COVID-19 patients from 20 individual studies. We found that both non-survivors and those with severe disease had an increased risk of acute cardiac injury and cardiac arrhythmias, our pooled relative risk (RR) was - 8.52 (95% CI 3.63-19.98) (p<0.001); and 3.61 (95% CI 2.03-6.43) (p=0.001), respectively. Mean difference in the levels of Troponin-I, CK-MB, and NT-proBNP was higher in deceased and severely infected patients. The RR of in-hospital mortality was 2.35 (95% CI 1.18-4.70) (p=0.022) and 1.52 (95% CI 1.12-2.05) (p=0.008) among patients who had pre-existing CHF and hypertension, respectively. Conclusion: Cardiac involvement in COVID-19 infection appears to significantly adversely impact patient prognosis and survival. Pre-existence of CHF and high cardiac biomarkers like NT-pro BNP and CK-MB levels in COVID-19 patients correlates with worse outcomes. Keywords: Acute cardiac injury; cardiac arrhythmia; mortality risk; cardiac biomarkers, COVID-19.

positive: C‐reactive protein correlates with computed tomographic findings and predicts severe COVID‐19 early COVID‐19 has developed into a worldwide pandemic; early identification of severe illness is critical for controlling it and improving the prognosis of patients with limited medical resources. The present study aimed to analyze the characteristics of severe COVID‐19 and identify biomarkers for differential diagnosis and prognosis prediction. In total, 27 consecutive patients with COVID‐19 and 75 patients with flu were retrospectively enrolled. Clinical parameters were collected from electronic medical records. The disease course was divided into four stages: initial, progression, peak, and recovery stages, according to computed tomography (CT) progress. to mild COVID‐19, the lymphocytes in the severe COVID‐19 progressively decreased at the progression and the peak stages, but rebound in the recovery stage. The levels of C‐reactive protein (CRP) in the severe group at the initial and progression stages were higher than those in the mild group. Correlation analysis showed that CRP (R = .62; P < .01), erythrocyte sedimentation rate (R = .55; P < .01) and granulocyte/lymphocyte ratio (R = .49; P < .01) were positively associated with the CT severity scores. In contrast, the number of lymphocytes (R = −.37; P < .01) was negatively correlated with the CT severity scores. The receiver‐operating characteristic analysis demonstrated that area under the curve of CRP on the first visit for predicting severe COVID‐19 was 0.87 (95% CI 0.10–1.00) at 20.42 mg/L cut‐off, with sensitivity and specificity 83% and 91%, respectively. CRP in severe COVID‐19 patients increased significantly at the initial stage, before CT findings. Importantly, CRP, which was associated with disease development, predicted early severe COVID‐19.

positive: Diarrhea and altered inflammatory cytokine pattern in severe COVID-19: impact on disease course and in-hospital mortality. BACKGROUND Dynamic changes of immunocyte subsets and inflammatory profiles in coronavirus disease 2019(COVID-19) patients with gastrointestinal symptoms were undetermined. METHODS A single center retrospective analysis of 409 severe hospitalized COVID-19 patients from Jan 20 to Feb 29, 2020 was performed. The longitudinal characteristics of immune inflammatory cytokines in patients with/without diarrhea were analyzed. The relations of diarrhea and immuno-inflammatory factors with illness course and clinical outcomes were further explored. RESULTS Diarrhea was more common and more serious with longer duration (4.9 ± 1.5 days vs 4.2 ± 1.5 days, P=0.039) and higher frequency (5.5 ± 2.1 times/day vs 4.0 ± 2.0 times/day, P=0.001) in deceased patients than in the survivors. Also, diarrhea patients were more inclined to develop multi-organ damage, who had longer illness course (media 41.0 days vs 36.0 days, P=0.052) and hospital stays (media 27.0 days vs 23.0 days, P=0.041) in survivors, and higher mortality (33.0% vs 22.6%, P=0.045) and earlier death (media 20.0 days vs 25.0 days, P=0.038) in the deceased patients. Progressively neutrophilia and lymphopenia, especially the declined CD8+ T cells, were demonstrated in diarrhea patients relative to the non-diarrhea cases. The inflammatory cytokines including IL-6, IL-10 and TNF-α were intensively increased in patients with diarrhea. The multivariable logistic analysis showed longer duration of diarrhea (P=0.036), higher neutrophil counts (P=0.011) and lower lymphocyte counts (P<0.001) were independent risk factors of in-hospital death. The proportional hazards model indicated longer duration of diarrhea (P=0.002), higher frequency of diarrhea (P=0.058), higher neutrophil counts (P=0.001), lower lymphocyte counts (P=0.035) and decreased proportion of CD8+ T cells (P<0.001) were independently associated with longer illness course of the survivors. CONCLUSIONS Diarrhea patients were more likely to present with neutrophilia, lymphopenia and cytokine storm, and to develop multi-organ damage. The inflammatory patterns were independent factors associated with illness course of the survivors and in-hospital death of severe COVID-19.

positive: Hypokalemia and Clinical Implications in Patients with Coronavirus Disease 2019 (COVID-19) BACKGROUND: SARS-CoV-2 has caused a series of COVID-19 globally. SARS-CoV-2 binds angiotensin I converting enzyme 2 (ACE2) of renin-angiotensin system (RAS) and causes prevalent hypokalemia METHODS: The patients with COVID-19 were classified into severe hypokalemia, hypokalemia, and normokalemia group. The study aimed to determine the relationship between hypokalemia and clinical features, the underlying causes and clinical implications of hypokalemia. RESULTS: By Feb 15, 2020, 175 patients with COVID-19 (92 women and 83 men; median age, 46 [IQR, 34-54] years) were admitted to hospital in Wenzhou, China, consisting 39 severe hypokalemia-, 69 hypokalemia-, and 67 normokalemia patients. Gastrointestinal symptoms were not associated with hypokalemia among 108 hypokalemia patients (P>0.05). Body temperature, CK, CK-MB, LDH, and CRP were significantly associated with the severity of hypokalemia (P<0.01). 93% of severe and critically ill patients had hypokalemia which was most common among elevated CK, CK-MB, LDH, and CRP. Urine K+ loss was the primary cause of hypokalemia. severe hypokalemia patients was given 3 g/day, adding up to an average of 34 (SD=4) g potassium during hospital stay. The exciting finding was that patients responded well to K+ supplements when they were inclined to recovery. CONCLUSIONS: Hypokalemia is prevailing in patients with COVID-19. The correction of hypokalemia is challenging because of continuous renal K+ loss resulting from the degradation of ACE2. The end of urine K+ loss indicates a good prognosis and may be a reliable, in-time, and sensitive biomarker directly reflecting the end of adverse effect on RAS system.

positive: Prognostic value of NT-proBNP in patients with severe COVID-19 The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China has been declared a public health emergency of international concern. The cardiac injury was dominate in the process. However, whether N terminal pro B type natriuretic peptide (NT-proBNP) predicted outcome of COVID-19 patients was unknown. The study initially enrolled 102 patients with severe COVID-19 pneumonia from a continuous sample. After screening out the ineligible cases, 54 patients were analyzed in this study. Results found that patients with higher NT-proBNP (above 88.64 pg/mL) level had more risks of in-hospital death. After adjusting for potential cofounders in separate modes, NT-proBNP presented as an independent risk factor of in-hospital death in patients with severe COVID-19.

positive: Association between ABO blood groups and risk of SARS‐CoV‐2 pneumonia In December, 2019, a cluster of acute respiratory illness caused by a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), occurred in Wuhan, China.1,2 Epidemiological, clinical characteristics, risk factors for mortality of patients infected with SARS-CoV-2, and risk factors in the susceptibility to SARS-CoV-2 included age and chronic disease have been reported.

positive: [Analysis of myocardial injury in patients with COVID-19 and association between concomitant cardiovascular diseases and severity of COVID-19] Objective: To evaluate the cardiovascular damage of patients with COVID-19, and determine the correlation of serum N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin-I (cTnI) with the severity of COVID-19, and the impact of concomitant cardiovascular disease on severity of COVID-19 was also evaluated. Methods: A cross-sectional study was designed on 150 consecutive patients with COVID-19 in the fever clinic of Tongji Hospital in Wuhan from January to February in 2020, including 126 mild cases and 24 cases in critical care. Both univariate and multivariate logistic regression were used to analyze the correlation of past medical history including hypertension, diabetes and coronary heart disease (CHD) , as well as the levels of serum NT-proBNP and cTnI to the disease severity of COVID-19 patients. Results: Age, hypersensitive C-reactive protein(hs-CRP) and serum creatinine levels of the patients were higher in critical care cases than in mild cases(all P<0.05). Prevalence of male, elevated NT-proBNP and cTnI, hypertension and coronary heart disease were significantly higher in critical cases care patients than in the mild cases(all P<0.05). Univariate logistic regression analysis showed that age, male, elevated NT-proBNP, elevated cTnI, elevated hs-CRP, elevated serum creatinine, hypertension, and CHD were significantly correlated with critical disease status(all P<0.05). Multivariate logistic regression analysis showed that elevated cTnI(OR=26.909, 95%CI 4.086-177.226, P=0.001) and CHD (OR=16.609, 95%CI 2.288-120.577, P=0.005) were the independent risk factors of critical disease status. Conclusions: COVID-19 can significantly affect the heart function and lead to myocardial injury. The past medical history of CHD and increased level of cTnI are two independent determinants of clinical disease status in patients with COVID-19.

positive: The impact of 2019 novel coronavirus on heart injury: A systemic review and Meta-analysis Abstract Background Evidence about COVID-19 on cardiac injury is inconsistent. Objectives We aimed to summarize available data on severity differences in acute cardiac injury and acute cardiac injury with mortality during the COVID-19 outbreak. Methods We performed a systematic literature search across Pubmed, Embase and pre-print from December 1, 2019 to March 27, 2020, to identify all observational studies that reported cardiac specific biomarkers (troponin, creatine kinase–MB fraction, myoglobin, or NT-proBNP) during COVID-19 infection. We extracted data on patient demographics, infection severity, comorbidity history, and biomarkers during COVID-19 infection. Where possible, data were pooled for meta-analysis with standard (SMD) or weighted (WMD) mean difference and corresponding 95% confidence intervals (CI). Results We included 4189 confirmed COVID-19 infected patients from 28 studies. More severe COVID-19 infection is associated with higher mean troponin (SMD 0.53, 95% CI 0.30 to 0.75, p < 0.001), with a similar trend for creatine kinase–MB, myoglobin, and NT-proBNP. Acute cardiac injury was more frequent in those with severe, compared to milder, disease (risk ratio 5.99, 3.04 to 11.80; p < 0.001). Meta regression suggested that cardiac injury biomarker differences of severity are related to history of hypertension (p = 0.030). Also COVID19-related cardiac injury is associated with higher mortality (summary risk ratio 3.85, 2.13 to 6.96; p < 0.001). hsTnI and NT-proBNP levels increased during the course of hospitalization only in non-survivors. Conclusion The severity of COVID-19 is associated with acute cardiac injury, and acute cardiac injury is associated with death. Cardiac injury biomarkers mainly increase in non-survivors. This highlights the need to effectively monitor heart health to prevent myocarditis in patients infected with COVID-19.

positive: Elevations of serum cancer biomarkers correlate with severity of COVID-19 In this retrospective study, we evaluated the levels of a series of serum biomarkers in coronavirus disease 2019 (COVID-19) patients (mild: 131; severe: 98; critical: 23). We found that there were significant increases in levels of human epididymis protein 4 (HE4) (73.6 ± 38.3 vs 46.5 ± 14.7 pmol/L; P < .001), cytokeratin-19 fragment (CYFRA21-1) (2.2 ± 0.9 vs 1.9 ± 0.8 µg/L; P < .001), carcinoembryonic antigen (CEA) (3.4 ± 2.2 vs 2.1 ± 1.2 µg/L; P < .001), carbohydrate antigens (CA) 125 (18.1 ± 13.5 vs 10.5 ± 4.6 µg/L; P < .001), and 153 (14.4 ± 8.9 vs 10.1 ± 4.4 µg/L; P < .001) in COVID-19 mild cases as compared to normal control subjects; their levels showed continuous and significant increases in severe and critical cases (HE4, CYFRA21-1, and CA125: P < .001; CEA and CA153: P < .01). Squamous cell carcinoma antigen (SCC) and CA199 increased significantly only in critical cases of COVID-19 as compared with mild and severe cases and normal controls (P < .01). There were positive associations between levels of C-reactive protein and levels of HE4 (R = .631; P < .001), CYFRA21-1 (R = .431; P < .001), CEA (R = .316; P < .001), SCC (R = .351; P < .001), CA153 (R = .359; P < .001) and CA125 (R = .223; P = .031). We concluded that elevations of serum cancer biomarkers positively correlated with the pathological progressions of COVID-19, demonstrating diffuse and acute pathophysiological injuries in COVID-19.

positive: Development of a data-driven COVID-19 prognostication tool to inform triage and step-down care for hospitalised patients in Hong Kong: A population based cohort study Abstract Background: This is the first study on prognostication in an entire cohort of laboratory-confirmed COVID-19 patients in the city of Hong Kong. Prognostic tool is essential in the contingency response for the next wave of outbreak. This study aims to develop prognostic models to predict COVID-19 patients' clinical outcome on day 1 and day 5 of hospital admission. Methods: We did a retrospective analysis of a complete cohort of 1,037 COVID-19 laboratory-confirmed patients in Hong Kong as of 30 April 2020, who were admitted to 16 public hospitals with their data sourced from an integrated electronic health records system. It covered demographic information, chronic disease(s) history, presenting symptoms as well as the worst clinical condition status, biomarkers' readings and Ct value of PCR tests on Day-1 and Day-5 of admission. The study subjects were randomly split into training and testing datasets in a 8:2 ratio. Extreme Gradient Boosting (XGBoost) model was used to classify the training data into three disease severity groups on Day-1 and Day-5. Results: The 1,037 patients had a mean age of 37.8 (SD {+/-} 17.8), 53.8% of them were male. They were grouped under three disease outcome: 4.8% critical/serious, 46.8% stable and 48.4% satisfactory. Under the full models, 30 indicators on Day-1 and Day-5 were used to predict the patients' disease outcome and achieved an accuracy rate of 92.3% and 99.5%. With a trade-off between practical application and predictive accuracy, the full models were reduced into simpler models with seven common specific predictors, including the worst clinical condition status (4-level), age group, and five biomarkers, namely, CRP, LDH, platelet, neutrophil/lymphocyte ratio and albumin/globulin ratio. Day-1 model's accuracy rate, macro- and micro-averaged sensitivity and specificity were 91.3%, 84.9%-91.3% and 96.0%-95.7% respectively, as compared to 94.2%, 95.9%-94.2% and 97.8%-97.1% under Day-5 model. as compared to 94.2%, 95.0%-97.1% and 98.3%-98.6% under Day-5 model. Conclusions: Both Day-1 and Day-5 models can accurately predict the disease severity. Relevant clinical management could be planned according to the predicted patients' outcome. The model is transformed into a simple online calculator to provide convenient clinical reference tools at the point of care, with an aim to inform clinical decision on triage and step-down care. Keywords: COVID-19, prognostic, prediction, clinical outcome, disease severity, triage, step-down care

positive: Kidney Allograft Recipients Diagnosed with Coronavirus Disease-2019: A Single Center Report Background: Organ graft recipients receiving immunosuppressive therapy are likely to be at heighted risk for the Coronavirus Disease 2019 (Covid-19) and adverse outcomes including death. It is therefore important to characterize the clinical course and outcome of Covid-19 in this vulnerable population and identify therapeutic strategies that are safe. Methods: We performed a retrospective chart review of 54 adult kidney transplant patients diagnosed with Covid-19 and managed in New York State, the epicenter of Covid-19 pandemic. The patients were evaluated by video visits, phone interviews, or in the Emergency Room for respiratory illness symptoms consistent with Covid-19 from March 13, 2020 to April 20, 2020. Characteristics of the patients were stratified by hospitalization status and disease severity. Clinical course including alterations in immunosuppressive therapy were retrieved from their electronic medical records. Primary outcomes included recovery from Covid-19 symptoms, acute kidney injury, graft failure, and case fatality rate. Results: Of the 54 SARS-Cov-2 positive kidney transplant recipients, 39 with moderate to severe symptoms were admitted and 15 with mild symptoms were managed at home. Hospitalized patients compared to non-hospitalized patients were more likely to be male, of Hispanic ethnicity, and to have cardiovascular disease. At baseline, all but 2 were receiving tacrolimus, mycophenolate mofetil (MMF) and 32 were on a steroid free immunosuppression regimen. Tacrolimus dosage was reduced in 46% of hospitalized patients and maintained at baseline level in the non-hospitalized cohort. Mycophenolate mofetil (MMF) dosage was maintained at the baseline dosage in 11% of hospitalized patients and 64% of non-hospitalized patients, and was stopped in 61% hospitalized patients and 0% in the non-hospitalized cohort. Azithromycin or doxycycline were prescribed at a similar rate among hospitalized and non-hospitalized patients (38% vs. 40%). Hydroxychloroquine was prescribed in 79% of hospitalized patients and only one of 15 non-hospitalized patients. Acute kidney injury occurred in 51% of hospitalized patients. Patients with severe disease were more likely to have elevations in inflammatory biomarkers at presentation. At a median of 21 days follow up, 67% of patients have had their symptoms resolved or improved and 33% have persistent symptoms. Graft failure requiring hemodialysis occurred in 3 of 39 hospitalized patients (8%). Three of 39 (8%) hospitalized patients expired and none of the 15 non-hospitalized patients expired. Conclusions: Clinical presentation of Covid-19 in kidney transplant recipients was similar to what has been described in the general population. The case fatality rate in our entire cohort of 54 kidney transplant recipients was reassuringly low and patients with mild symptomology could be successfully managed at home. Data from the pilot study suggest that a strategy of systematic screening and triage to inpatient or outpatient care, close monitoring, and judicious use of immunosuppressive drugs rather than cessation is beneficial.

positive: T cell subset counts in peripheral blood can be used as discriminatory biomarkers for diagnosis and severity prediction of COVID-19 This study evaluated the significance of lymphocyte subsets detection in peripheral blood in the diagnosis and prognosis of coronavirus disease 2019 (COVID-19). Our results revealed that CD3+T, CD4+T, CD8+T cells and NK cells were significantly decreased in COVID-19 patients. COVID-19 patients had a relatively slight decrease in CD4+T cells but a severe decrease of CD8+T cells. The significantly elevated CD4/CD8 ratio was observed in COVID-19 patients. T cell subset counts were related to the severity and prognosis of COVID-19. The counts of CD8+T and CD4+T cells can be used as diagnostic markers of COVID-19 and predictors of disease severity.

positive: Clinical and laboratory-derived parameters of 119 hospitalized patients with coronavirus disease 2019 in Xiangyang, Hubei Province, China

positive: COVID-19 infection results in alterations of the kynurenine pathway and fatty acid metabolism that correlate with IL-6 levels and renal status Previous studies suggest a role for systemic reprogramming of host metabolism during viral pathogenesis to fuel rapidly expanding viral proliferation, for example by providing free amino acids and fatty acids as building blocks. In addition, general alterations in metabolism can provide key understanding of pathogenesis. However, little is known about the specific metabolic effects of SARS-COV-2 infection. The present study evaluated the serum metabolism of COVID-19 patients (n=33), identified by a positive nucleic acid test of a nasopharyngeal swab, as compared to COVID-19-negative control patients (n=16). Targeted and untargeted metabolomics analyses specifically identified alterations in the metabolism of tryptophan into the kynurenine pathway, which is well-known to be involved in regulating inflammation and immunity. Indeed, the observed changes in tryptophan metabolism correlated with serum interleukin-6 (IL-6) levels. Metabolomics analysis also confirmed widespread dysregulation of nitrogen metabolism in infected patients, with decreased circulating levels of most amino acids, except for tryptophan metabolites in the kynurenine pathway, and increased markers of oxidant stress (e.g., methionine sulfoxide, cystine), proteolysis, and kidney dysfunction (e.g., creatine, creatinine, polyamines). Increased circulating levels of glucose and free fatty acids were also observed, consistent with altered carbon homeostasis in COVID-19 patients. Metabolite levels in these pathways correlated with clinical laboratory markers of inflammation and disease severity (i.e., IL-6 and C-reactive protein) and renal function (i.e., blood urea nitrogen). In conclusion, this initial observational study of the metabolic consequences of COVID-19 infection in a clinical cohort identified amino acid metabolism (especially kynurenine and cysteine/taurine) and fatty acid metabolism as correlates of COVID-19, providing mechanistic insights, potential markers of clinical severity, and potential therapeutic targets.

positive: Evaluation of organ function in patients with severe COVID-19 infections Abstract Objective: The purpose of our study was to assess organ function in 102 patients with severe COVID-19 infections, using retrospective clinical analysis. Material and Methods: A retrospective analysis was conducted on 102 patients with severe COVID-19 infections. The patients were divided into a survival group (n=73) and a non-survival group (n=29) according to their prognosis. The age, sex, underlying diseases, clinical laboratory data within 48 hours (routine blood tests, ALT, AST, TBIL, ALB, BUN, CR, D-Dimer, PT, APTT, FIB, F VIII:C, CK-MB, CK, and LDH), and ventilation status were collected. The organ functions of these severe COVID-19 patients were assessed by comparing the differences between the two groups. Results: AST, BUN, CR, CK-MB, LDH, and CK in the non-survival group were higher than those in the survival group, and the differences were statistically significant (P＜0.05). D-Dimer, PT, FIB, and F VIII:C in the non-survival group were higher than the values observed in the survival group, and the differences were statistically significant (P＜0.05). PLT, AST, BUN, CR, D-Dimer, PT, FIB, F VIII:C, CK-MB, CK, and LDH predicted the area under the ROC curve (AUC) of the COVID19 endpoint events and were 0.721, 0.854, 0.867, 0.757, 0.699, 0.679, 0.715, 0.811, 0.935, and 0.802, respectively. Conclusion: The results showed that there were different degrees of damage to the liver, kidneys, blood coagulation, and heart function in the non-survival group. In addition, PLT, AST, BUN, CR, D-Dimer, PT, FIB, F VIII:C, CK-MB, CK, and LDH had value in evaluating disease prognosis.

positive: Presepsin in risk stratification of SARS-CoV-2 patients Abstract Background A severe form of pneumonia, is the leading complication of the respiratory Coronavirus disease 2019 (COVID-19), recently renamed SARS-CoV-2. Soluble cluster of differentiation (CD)14 subtype (sCD14-ST also termed presepsin PSP) is a regulatory factor that modulates immune responses by interacting with T and B cells, useful for early diagnosis, prognosis and risk stratification prediction. Methods In 75 consecutive patients suffering from COVID-19 microbiology proven infection, admitted to intensive care unit (ICU, n=21, 28%) and/or in infectious disease ward (IW, n=54, 72%), PSP (Pathfast, Mitsubishi, Japan) has been measured in addition to routine laboratory tests performed during the period of hospitalization (from January to March 2020). Results PSP demonstrates: -statistically significant higher values (Mann-Whitney test) in 6 patients died (median, IQR= 1046, 763-1240; vs 417, 281-678 ng/L, p<0.05); -statistically significant but poor correlations with CRP (r= 0.59 p<0.001), LDH (r=0.52, p<0.001) and PCT (r=0.72, p<0.001) measured at the same day; -a significant relationship between concentrations and ICU stay. In fact patients showing PSP values higher than 250 ng/L (cut-off for risk stratification) did stay in ICU for a significantly longer time (median 17 days, IQR 12-31; p<0.001) than those exhibiting lower values (median 10 days, IQR 7-18). Conclusions The data obtained seems to demonstrate the role of PSP in providing prognostic information in COVID-19 patients, allowing to identify, during the early phase of the monitoring, the patients suffering from a more severe disease which will be hospitalized for a more long time.

positive: Clinical course of 2019 novel coronavirus disease (COVID-19) in individuals present during the outbreak on the Diamond Princess cruise ship Abstract We investigated the clinical course of individuals with 2019 novel coronavirus disease (COVID-19) who were transferred from the Diamond Princess cruise ship to 12 local hospitals. The conditions and clinical courses of patients with pneumonia were compared with those of patients without pneumonia. Among 70 patients (median age: 67 years) analyzed, the major symptoms were fever (64.3%), cough (54.3%), and general fatigue (24.3%). Forty-three patients (61.4%) had pneumonia. Higher body temperature, heart rate, and respiratory rate as well as higher of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and C-reactive protein (CRP) levels and lower serum albumin level and lymphocyte count were associated with the presence of pneumonia. Ground-glass opacity was found in 97.7% of the patients with pneumonia. Patients were administered neuraminidase inhibitors (20%), lopinavir/ritonavir (32.9%), and ciclesonide inhalation (11.4%). Mechanical ventilation and veno-venous extracorporeal membrane oxygenation was performed on 14 (20%) and 2 (2.9%) patients, respectively; two patients died. The median duration of intubation was 12 days. The patients with COVID-19 transferred to local hospitals during the outbreak had severe conditions and needed close monitoring. The severity of COVID-19 depends on the presence of pneumonia. High serum LDH, AST and CRP levels and low serum albumin level and lymphocyte count were found to be predictors of pneumonia. It was challenging for local hospitals to admit and treat these patients during the outbreak of COVID-19. Assessment of severity was crucial to manage a large number of patients.

positive: COVID-19: immunopathology and its implications for therapy Severe coronavirus disease 2019 (COVID-19) is characterized by pneumonia, lymphopenia, exhausted lymphocytes and a cytokine storm. Significant antibody production is observed; however, whether this is protective or pathogenic remains to be determined. Defining the immunopathological changes in patients with COVID-19 provides potential targets for drug discovery and is important for clinical management.

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: Clinical Analysis of 25 Novel Coronavirus Infections in Children. BACKGROUND To describe the characteristics of clinical manifestations of children with 2019 novel coronavirus (2019-nCoV) infection in Chongqing. METHODS All 25 children with laboratory-confirmed 2019-nCoV infection by real-time reverse transcription-PCR (RNA-PCR) were admitted from the 4 designated treatment hospitals of 2019-nCoV in Chongqing from January 19 to March 12, 2020. Clinical data and epidemiological history of these patients were retrospectively collected and analyzed. RESULTS The diagnosis was confirmed through RNA-PCR testing. Among the 25 cases, 14 were males and 11 were females. The median age was 11.0 (6.3-14.5) years (range 0.6-17.0 years). All children were related to a family cluster outbreak, and 7 children (28%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 8 (32%) asymptomatic, 4 (16%) very mild cases and 13 (52%) common cases. No severe or critical cases were identified. The most common symptoms were cough (13 cases, 52%) and fever (6 cases, 24%). The duration time of clinical symptoms was 13.0 (8.0-25.0) days. In the 25 cases, on admission, 21 cases (84%) had normal white blood cell counts, while only 2 cases (8%) more than 10 × 10/L and 2 cases (8%) less than 4 × 10/L, respectively; 22 cases(88%) had normal CD4+ T lymphocyte counts, while in the remaining 3 cases(8%) this increased mildly; 23 cases had normal CD8+ T lymphocyte counts, while in the remaining 2 cases (8%) CD8+ T lymphocyte counts were mildly increased as well. All Lymphocyte counts were normal. There were no statistical differences of lab results between the groups of asymptomatic cases, mild cases and common cases. There were only 13 cases with abnormal CT imaging, most of which were located in the subpleural area of the bottom of the lung. All patients were treated with interferon, 6 cases combined with Ribavirin, and 12 cases combined with lopinavir or ritonavir. The days from onset to RNA turning negative was 15.20 ± 6.54 days. There was no significant difference of RNA turning negative between the groups of interferon, interferon plus ribavirin and interferon plus lopinavir or ritonavir treatment. All the cases recovered and were discharged from hospital. CONCLUSIONS The morbidity of 2019-nCoV infection in children is lower than in adults and the clinical manifestations and inflammatory biomarkers in children are nonspecific and milder than that in adults. RNA-PCR test is still the most reliable diagnostic method, especially for asymptomatic patients.

positive: A systematic review of antibody mediated immunity to coronaviruses: antibody kinetics, correlates of protection, and association of antibody responses with severity of disease The duration and nature of immunity generated in response to SARS-CoV-2 infection is unknown. Many public health responses and modeled scenarios for COVID-19 outbreaks caused by SARSCoV-2 assume that infection results in an immune response that protects individuals from future infections or illness for some amount of time. The timescale of protection is a critical determinant of the future impact of the pathogen. The presence or absence of protective immunity due to infection or vaccination (when available) will affect future transmission and illness severity. The dynamics of immunity and nature of protection are relevant to discussions surrounding therapeutic use of convalescent sera as well as efforts to identify individuals with protective immunity. Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV-1, MERS-CoV and human endemic coronaviruses (HCoVs). We reviewed 1281 abstracts and identified 322 manuscripts relevant to 5 areas of focus: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence. While studies of SARS-CoV-2 are necessary to determine immune responses to it, evidence from other coronaviruses can provide clues and guide future research.

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: Early prediction of mortality risk among severe COVID-19 patients using machine learning Abstract Background Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been spreading globally. The number of deaths has increased with the increase in the number of infected patients. We aimed to develop a clinical model to predict the outcome of severe COVID-19 patients early. Methods Epidemiological, clinical, and first laboratory findings after admission of 183 severe COVID-19 patients (115 survivors and 68 nonsurvivors) from the Sino-French New City Branch of Tongji Hospital were used to develop the predictive models. Five machine learning approaches (logistic regression, partial least squares regression, elastic net, random forest, and bagged flexible discriminant analysis) were used to select the features and predict the patients' outcomes. The area under the receiver operating characteristic curve (AUROC) was applied to compare the models' performance. Sixty-four severe COVID-19 patients from the Optical Valley Branch of Tongji Hospital were used to externally validate the final predictive model. Results The baseline characteristics and laboratory tests were significantly different between the survivors and nonsurvivors. Four variables (age, high-sensitivity C-reactive protein level, lymphocyte count, and d-dimer level) were selected by all five models. Given the similar performance among the models, the logistic regression model was selected as the final predictive model because of its simplicity and interpretability. The AUROCs of the derivation and external validation sets were 0.895 and 0.881, respectively. The sensitivity and specificity were 0.892 and 0.687 for the derivation set and 0.839 and 0.794 for the validation set, respectively, when using a probability of death of 50% as the cutoff. The individual risk score based on the four selected variables and the corresponding probability of death can serve as indexes to assess the mortality risk of COVID-19 patients. The predictive model is freely available at https://phenomics.fudan.edu.cn/risk_scores/. Conclusions Age, high-sensitivity C-reactive protein level, lymphocyte count, and d-dimer level of COVID-19 patients at admission are informative for the patients' outcomes.

positive: Can we predict the severity of COVID-19 with a routine blood test? INTRODUCTION The ongoing worldwide pandemic of Coronavirus Disease 2019 (COVID-19) has posed a huge threat to global public health. However, whether routine blood test could be used to monitor and predict the severity and prognosis of COVID-19 has never been comprehensively investigated. OBJECTIVES To provide an overview of the association of markers in routine blood test with the severity of COVID-19. METHODS PubMed, Embase, Cochrane Library, Wanfang and CNKI database were searched to identify studies reporting the markers in the routine blood test with the severity of COVID-19 until March 20, 2020. STATA software was used for the meta- analysis. RESULTS A total of 15 studies with 3090 COVID-19 patients were included in this analysis. Patients in non-severe group had fewer white blood cells (WBC) (WMD = -0.85 [109/L], 95% CI = [-1.54, -0.16], P = 0.02) and neutrophils (WMD = -1.57 [109/L], 95% CI = [-2.60, -0.54], P = 0.003), more lymphocytes (WMD = 0.29 [109/L], 95% CI = [0.22, 0.36], P < 0.001) and platelets (WMD = 19.05 [109/L], 95% CI = [3.04, 35.06], P = 0.02), and lower neutrophil-to-lymphocyte ratio (NLR) level (WMD = -2.48, 95% CI = [-3.81, -1.15], P < 0.001), compared with those in severe group. There was no statistical difference in monocytes (WMD = 0.01 [109/L], 95% CI = [-0.01, 0.03], P = 0.029) between these two groups. Sensitivity analysis and meta-analysis based on standard mean difference (SMD) did not change the conclusions about neutrophils, lymphocytes and NLR while the results were inconsistent in WBC and platelets. CONCLUSIONS Severe patients had more neutrophils, higher NLR level, and fewer lymphocytes than non-severe patients with COVID-19. Measurement of these markers might assist clinicians to monitor and predict the severity and prognosis of COVID-19.

positive: Risk factors associated with disease progression in a cohort of patients infected with the 2019 novel coronavirus. BACKGROUND The emerging infection of the 2019 novel coronavirus (2019-nCoV) in late December, 2019 in Wuhan, China, has caused an extreme health concern, with many patients having progressed to acute respiratory disease or other complications in a short period. Meanwhile, the risk factors associated with the disease progression still remain elusive. METHODS A cohort of 17 patients with laboratory-confirmed 2019-nCoV infections who were admitted to the Ninth Hospital of Nanchang between January 28 and February 6, 2020, were enrolled in this study. All the patients received standardized treatment. The disease progression was evaluated every 7 days after admission. The clinical, radiologic, and laboratory characteristics were retrospectively analyzed, and the factors associated with the disease progression were screened by binary logistic regression analysis. RESULTS The cohort comprised 11 women (64.7%) and 6 men (35.3%) between the ages of 18 to 70 years old. All patients had a reported history of contact with infection-confirmed patients. Fever (11/64.7%) and cough (8/47.1%) were the most common symptoms, whereas dyspnea (2/11.8%) and fatigue (3/17.6%) were rare, and there was no patient with diarrhea symptoms. There were 5 patients with aggravated disease at the first disease progression evaluation, and no patient received mechanical ventilation, transferred to the intensive care unit (ICU), or progressed to acute respiratory distress syndrome, septic shock, refractory metabolic acidosis, coagulation dysfunction, or death. Based on the disease progression, patients were divided into the non-aggravation group (12 cases) and the aggravation group (5 cases). There were no significant differences between the 2 groups with respect to their clinical characteristics. Chest computed tomography (CT) on admission revealed there were 8 patients (47.1%) with invasive lesions found bilaterally on the lungs on multiple lobes, 4 patients (23.5%) with invasive lesions on 1 lobe, and 5 patients (29.4%) with normal chest CT. The aggravation group had1 patient (20.0%) with invasive lesions on one lobe, 3 (60.0%) with invasive lesions on multiple lobes, bilaterally, and 1 (20.0%) with normal chest CT; meanwhile, the nonaggravation group had 3 patients (25.0%) with invasive lesions on one lobe, 5 (41.7%) with invasive lesions on multiple lobes, bilaterally, and 4 (33.3%) with normal chest CT. No significant difference was found between the 2 groups. In the aggravation group, the total lymphocyte counts significantly decreased in comparison to that in the non-aggravation group. Further analysis showed that the CD4+ T cell count but not the CD8+ T cell count of the aggravation group was significantly lower than that of the non-aggravation group. Correlation analysis indicated total lymphocyte count was positively correlated with CD4+ T cell count, and no significant differences were found between the 2 groups in other laboratory measurements, including those of white blood cell (WBC) count, C-reactive protein (CRP), albumin, lactate dehydrogenase (LDH), and D-dimer. Finally, a binary logistic regression model was used to identify the factors associated with the disease progression. It was found that total lymphocyte count was a risk factor associated with disease progression in patients infected with 2019-nCoV. CONCLUSIONS A higher cell count of total lymphocytes may indicate a better outcome of the disease, and immune response may be a vital factor for directing disease progression in the early stage of 2019-nCoV infection.

positive: Biomarker variation in patients successfully treated with tocilizumab for severe coronavirus disease 2019 (COVID-19): results of a multidisciplinary collaboration OBJECTIVES: Acute respiratory distress syndrome (ARDS) related to SARS-CoV-2 is likely due to a cytokine storm characterised by a major release of pro-inflammatory cytokines, including interleukin-6 (IL-6) Blocking excessive IL-6 production might be the key to the COVID-19-ARDS treatment Beneficial effects of IL-6 blockade using a humanised anti-IL-6 receptor antibody, tocilizumab (TCZ) were previously reported in patients with COVID-19 related ARDS The aim of the study was to study the variation over time of several biomarkers, demonstrated to be predictors of poor prognostic, in subjects successfully treated with TCZ for severe COVID-19 METHODS: Retrospective analysis of a case series of patients with COVID-19-ARDS, evidenced by RT-PCR and lung CT-scan Patients with increasing O2 requirements, within the window of opportunity for TCZ treatment (Day 7 to Day 17 after onset of symptoms) were treated with TCZ (2 infusions of 8 mg/kg) Demographic, biological and clinical data were collected from the patients' files Serum levels of CRP, ferritin, fibrinogen, lymphocytes, platelets, creatinine, D-dimer and liver enzymes were assayed at the time of the first TCZ administration, then every two days for 8 days RESULTS: 40 patients were treated with TCZ Most of them had several comorbidities, and all had multiple biological abnormalities (lymphopenia, increased CRP, ferritin, fibrinogen, D-dimer, liver enzymes) 30 patients (75%) benefited from TCZ and 10 patients died In the survivors, following TCZ administration CRP decreased dramatically as early as day 4 (-86 7%, p<0 0001) and returned to normal at day 6 Fibrinogen and lymphocyte count returned to normal values at day 6 Ferritin also decreased significantly No significant change was observed for D-dimer (p=0 68) and other studied biomarkers (haemoglobin, leucocyte count, AST) CONCLUSIONS: In patients with COVID-19 acute respiratory distress syndrome, treatment with TCZ resulted in favourable evolution in 75% of the cases Biomarkers of inflammation (CRP, ferritin, fibrinogen) decreased dramatically as early as the 4th day after TCZ injection Lymphopenia, a predictor of poor prognostic, was reversed 6 days after TCZ injection

positive: Myocardial injury is associated with in-hospital mortality of confirmed or suspected COVID-19 in Wuhan, China: A single center retrospective cohort study [Background] Since December 2019, a cluster of coronavirus disease 2019 (COVID-19) occurred in Wuhan, Hubei Province, China and spread rapidly from China to other countries. In-hospital mortality are high in severe cases and cardiac injury characterized by elevated cardiac troponin are common among them. The mechanism of cardiac injury and the relationship between cardiac injury and in-hospital mortality remained unclear. Studies focused on cardiac injury in COVID-19 patients are scarce. [Objectives] To investigate the association between cardiac injury and in-hospital mortality of patients with confirmed or suspected COVID-19. [Methods] Demographic, clinical, treatment, and laboratory data of consecutive confirmed or suspected COVID-19 patients admitted in Wuhan No.1 Hospital from 25th December, 2019 to 15th February, 2020 were extracted from electronic medical records and were retrospectively reviewed and analyzed. Univariate and multivariate Cox regression analysis were used to explore the risk factors associated with in-hospital death. [Results] A total of 110 patients with confirmed (n=80) or suspected (n=30) COVID-19 were screened and 48 patients (female 31.3%, mean age 70.58{+/-}13.38 year old) among them with high-sensitivity cardiac troponin I (hs-cTnI) test within 48 hours after admission were included, of whom 17 (17/48, 35.4%) died in hospital while 31 (31/48, 64.6%) were discharged or transferred to other hospital. High-sensitivity cardiac troponin I was levated in 13 (13/48, 27.1%) patents. Multivariate Cox regression analysis showed pulse oximetry of oxygen saturation (SpO2) on admission (HR 0.704, 95% CI 0.546-0.909, per 1% decrease, p=0.007), elevated hs-cTnI (HR 10.902, 95% 1.279-92.927, p=0.029) and elevated d-dimer (HR 1.103, 95%CI 1.034-1.176, per 1mg/L increase, p=0.003) on admission were independently associated with in-hospital mortality. [Conclusions] Cardiac injury defined by hs-cTnI elevation and elevated d-dimer on admission were risk factors for in-hospital death, while higher SpO2 could be seen as a protective factor, which could help clinicians to identify patients with adverse outcome at the early stage of COVID-19.

positive: Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV/ 中华心血管病杂志 Objective@#To explore the clinical characteristics and prognosis of the new coronavirus 2019-nCoV patients combined with cardiovascular disease (CVD).@*Methods@#A retrospective analysis was performed on 112 COVID-19 patients with CVD admitted to the western district of Union Hospital in Wuhan, from January 20, 2020 to February 15, 2020. They were divided into critical group (ICU, n=16) and general group (n=96) according to the severity of the disease and patients were followed up to the clinical endpoint. The observation indicators included total blood count, C-reactive protein (CRP), arterial blood gas analysis, myocardial injury markers, coagulation function, liver and kidney function, electrolyte, procalcitonin (PCT), B-type natriuretic peptide (BNP), blood lipid, pulmonary CT and pathogen detection.@*Results@#Compared with the general group, the lymphocyte count (0.74×109 (0.34×109, 0.94×109)/L vs. 0.99×109 (0.71×109, 1.29×109)/L, P=0.03) was extremely lower in the critical group, CRP (106.98 (81.57, 135.76) mg/L vs. 34.34 (9.55,76.54) mg/L, P<0.001) and PCT (0.20 (0.15,0.48) μg/L vs. 0.11 (0.06,0.20)μg/L, P<0.001) were significantly higher in the critical group. The BMI of the critical group was significantly higher than that of the general group (25.5 (23.0, 27.5) kg/m2 vs. 22.0 (20.0, 24.0) kg/m2, P=0.003). Patients were further divided into non-survivor group (17, 15.18%) group and survivor group (95, 84.82%). Among the non-survivors, there were 88.24% (15/17) patients with BMI> 25 kg/m2, which was significantly higher than that of survivors (18.95% (18/95), P<0.001). Compared with the survived patients, oxygenation index (130 (102, 415) vs. 434 (410, 444), P<0.001) was significantly lower and lactic acid (1.70 (1.30, 3.00) mmol/L vs. 1.20 (1.10, 1.60) mmol/L, P<0.001) was significantly higher in the non-survivors. There was no significant difference in the proportion of ACEI/ARB medication between the critical group and the general group or between non-survivors and survivors (all P>0.05).@*Conclusion@#COVID-19 patients combined with CVD are associated with a higher risk of mortality. Critical patients are characterized with lower lymphocyte counts. Higher BMI are more often seen in critical patients and non-survivor. ACEI/ARB use does not affect the morbidity and mortality of COVID-19 combined with CVD. Aggravating causes of death include fulminant inflammation, lactic acid accumulation and thrombotic events.

positive: Thrombosis risk associated with COVID-19 infection. A scoping review BACKGROUND: Infection by the 2019 novel coronavirus (COVID-19) has been reportedly associated with a high risk of thrombotic complications. So far information is scarce and rapidly emerging. METHODS: We conducted a scoping review using a single engine search for studies assessing thrombosis and coagulopathy in COVID-19 patients. Additional studies were identified by secondary review and alert services. RESULTS: Studies reported the occurrence of venous thromboembolism and stroke in approximately 20% and 3% of patients, respectively. A higher frequency seems to be present in severely ill patients, in particular those admitted to intensive care units. The thrombotic risk is elevated despite the use of anticoagulant prophylaxis but optimal doses of anticoagulation are not yet defined. Although and increase of biomarkers such as D-dimer has been consistently reported in severely ill COVID-19, the optimal cut-off level and prognostic value are not known. DISCUSSION: A number of pressing issues were identified by this review, including defining the true incidence of VTE in COVID patients, developing algorithms to identify those susceptible to develop thrombotic complications and severe disease, determining the role of biomarkers and/or scoring systems to stratify patients' risk, designing adequate and feasible diagnostic protocols for PE, establishing the optimal thromboprophylaxis strategy, and developing uniform diagnostic and reporting criteria.

positive: Elevated RDW is Associated with Increased Mortality Risk in COVID-19 Abstract Background Coronavirus disease 2019 (COVID19) is an acute respiratory illness with a high rate of hospitalization and mortality. Prognostic biomarkers are urgently needed. Red blood cell distribution width (RDW), a component of complete blood counts that reflects cellular volume variation, has been shown to be associated with elevated risk for morbidity and mortality in a wide range of diseases. Methods We retrospectively studied the relationship between RDW and COVID19 mortality risk for 1198 adult patients diagnosed with SARS COV2 at 4 Partners Healthcare Network Hospitals between March 4, 2020, and April 28, 2020. Findings Elevated RDW (> 14.5%) was associated with increased mortality in patients of all ages with a risk ratio of 2.5 (95% CI, 2.3-2.8). Stratified by age, the risk ratio was 6.2 (4.4-7.9, N = 312) < 50 years, 3.2 (2.5-4.1, N = 230) 50-60, 2.3 (1.6-3.1, N = 236) 60-70, 1.2 (0.7-1.8, N = 203) 70-80, and 1.9 (1.5-2.3, N = 216) > 80 years. RDW was significantly associated with mortality in Cox proportional hazards models adjusted for age, D-Dimer, absolute lymphocyte count, and common comorbidities (p < 1e-4 for RDW in all cases). Patients whose RDW increased during admission had a ~3-fold elevation in mortality risk compared to those whose RDW did not change. Interpretation Elevated RDW at diagnosis and an increase in RDW during admission are both associated with increased mortality risk for adult COVID19 patients at a large academic medical center network.

positive: Prompt predicting of early clinical deterioration of moderate-to-severe COVID-19 patients: usefulness of a combined score using IL-6 in a preliminary study Abstract Background The early identification of patients at risk of clinical deterioration is of interest considering the timeline of COVID-19 after the onset of symptoms. Objective The aim of our study was to evaluate the usefulness of testing serum IL-6 and other serological and clinical biomarkers, to predict a short-term negative clinical course of non critical COVID-19 patients. Methods 208 patients with non critical COVID-19 pneumonia at admission were consecutively enrolled. Clinical and laboratory findings obtained upon admission were analyzed by using survival analysis and stepwise logistic regression for variable selection. Three-day worsening as outcome in a logistic model to generate a prognostic score was used. Results Clinical worsening occurred in 63 patients (16=died; 39=transferred to Intensive Care Unit; 8 worsening of respiratory failure). Forty-five of them worsened within 3 days after admission. The risk of clinical worsening was progressively enhanced along with increasing quartiles of IL-6 levels. Multivariate analysis showed that IL-6 (p=0.005), CRP (p=0.003) and SaO2/FiO2 (p=0.014) and were the best predictors for clinical deterioration in the first 3 days after admission. The combined score yielded an AUC=0.88 (95% CI 0.83–0.93). A nomogram predicting the probability of 3-day worsening was generated. The score also showed good performance for 7-day and 14-day or 21-day worsening and in predicting death occurring during all the follow-up. Conclusions Combining IL-6, CRP and SaO2/FiO2 in a score, may help clinicians to identify upon admission those patients with COVID-19 who are at high risk for a further 3-day clinical deterioration.

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: Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, it has rapidly spread across many other countries. While the majority of patients were considered mild, critically ill patients involving respiratory failure and multiple organ dysfunction syndrome are not uncommon, which could result death. We hypothesized that cytokine storm is associated with severe outcome. We enrolled 102 COVID-19 patients who were admitted to Renmin Hospital (Wuhan, China). All patients were classified into moderate, severe and critical groups according to their symptoms. 45 control samples of healthy volunteers were also included. Inflammatory cytokines and C-Reactive Protein (CRP) profiles of serum samples were analyzed by specific immunoassays. Results showed that COVID-19 patients have higher serum level of cytokines (TNF-α, IFN-γ, IL-2, IL-4, IL-6 and IL-10) and CRP than control individuals. Within COVID-19 patients, serum IL-6 and IL-10 levels are significantly higher in critical group (n = 17) than in moderate (n = 42) and severe (n = 43) group. The levels of IL-10 is positively correlated with CRP amount (r = 0.41, P < 0.01). Using univariate logistic regression analysis, IL-6 and IL-10 are found to be predictive of disease severity and receiver operating curve analysis could further confirm this result (AUC = 0.841, 0.822 respectively). Our result indicated higher levels of cytokine storm is associated with more severe disease development. Among them, IL-6 and IL-10 can be used as predictors for fast diagnosis of patients with higher risk of disease deterioration. Given the high levels of cytokines induced by SARS-CoV-2, treatment to reduce inflammation-related lung damage is critical.

negative: Towards improving clinical management of Middle East respiratory syndrome coronavirus infection

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

negative: RNA-based drugs and vaccines RNA-based approaches have provided novel alternatives for modern drug discovery. The application of RNA as therapeutic agents has, until recently, been hampered by issues related to poor delivery and stability, but chemical modifications and new delivery approaches have increased progress. Moreover, the discovery of the importance of RNA in gene regulation and gene silencing has revealed new drug targets, especially related to treatment of cancer and other diseases. Recent engineering of small molecules designed from RNA sequences to target miRNAs opens up new possibilities in drug development. Furthermore, RNA-based vaccines have been engineered applying RNA virus vectors and non-viral delivery for vaccine development.

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: Clinical Characteristics and Outcomes in People Living With Human Immunodeficiency Virus Hospitalized for Coronavirus Disease 2019 We describe the characteristics of 31 people living with human immunodeficiency virus hospitalized for severe acute respiratory syndrome coronavirus 2 infection. All patients were on antiretroviral therapy and virologically suppressed at the time of admission. Clinical course and outcomes were similar to those reported in other hospitalized cohorts.

negative: A novel human coronavirus: Middle East respiratory syndrome human coronavirus In 2012, a novel coronavirus, initially named as human coronavirus EMC (HCoV-EMC) but recently renamed as Middle East respiratory syndrome human coronavirus (MERS-CoV), was identified in patients who suffered severe acute respiratory infection and subsequent renal failure that resulted in death. Ongoing epidemiological investigations together with retrospective studies have found 61 laboratory-confirmed cases of infection with this novel coronavirus, including 34 deaths to date. This novel coronavirus is culturable and two complete genome sequences are now available. Furthermore, molecular detection and indirect immunofluorescence assay have been developed. The present paper summarises the limited recent advances of this novel human coronavirus, including its discovery, genomic characterisation and detection.

negative: Bariatric surgery for type 2 diabetes: weighing the impact for obese patients. Obesity is a potent risk factor for the development and progression of type 2 diabetes, and weight loss is a key component of diabetes management. Bariatric surgery results in significant weight loss and remission of diabetes in most patients. After surgery, glycemic control is restored by a combination of enforced caloric restriction, enhanced insulin sensitivity, and increased insulin secretion.

negative: Personalized Management of Pulmonary Disorders There are a large number of pulmonary disorders some of which present challenges in management. Role of genetic ancestry in lung function is under investigation. There is still limited information on pharmacogenomics and pharmacogenetics of pulmonary therapeutics. Personalized approaches to some pulmonary diseases will be described briefly as examples in this chapter.

negative: [Clinical feature changes of a COVID-19 patient from mild to critical condition and cardiopulmonary pathological results] Objective: To analyse the clinical history, laboratory tests and pathological data of a patient who suffered from novel coronavirus pneumonia(COVID-19) and provide reference for the clinical treatment of similar cases. Methods: Data of clinical manifestation, laboratory examination, bronchoscopy, echocardiography and cardiopulmonary pathological results were retrospectively reviewed in a case of COVID-19 with rapid exacerbation from mild to critical condition. Results: This patient hospitalized at day 9 post 2019 novel coronavirus(2019-nCoV) infection, experienced progressive deterioration from mild to severe at day 11, severe to critical at day 18 and underwent extracorporeal membrane oxygenation(ECMO) and continuous renal replacement therapy(CRRT) as well as heart lung transplantation during day 28-45 day post infection, and died on the second day post heart and lung transplantation. The patient had suffered from hypertension for 8 years. At the early stage of the disease, his symptoms were mild and the inflammatory indices increased and the lymphocyte count decreased continuously. The patient's condition exacerbated rapidly with multi-organ infections, and eventually developed pulmonary hemorrhage and consolidation, pulmonary hypertension, right heart failure, malignant ventricular arrhythmias, liver dysfunction, etc. His clinical manifestations could not be improved despite viral RNAs test results became negative. The patient underwent lung and heart transplantation and finally died of multi organ failure at the second day post lung and heart transplantation. Pathological examination indicated massive mucus, dark red secretions and blood clots in bronchus. The pathological changes were mainly diffused pulmonary hemorrhagic injuries and necrosis, fibrosis, small vessel disease with cardiac edema and lymphocyte infiltration. Conclusions: The clinical course of COVID-19 can exacerbate rapidly from mild to critical with lung, liver and heart injuries. Steadily increased inflammation indices are suggestive of irreversible disease progression and worse outcome. In the early stages of the disease, the progress of the disease should be closely observed and evaluated, and the factors related to the progress of the disease should be identified and managed.

negative: A new factor influencing pathogen detection by molecular assay in children with both mild and severe hand, foot, and mouth disease Abstract This study aimed to find novel information concerning pathogen detection and some probable coinfection factors in hand, foot, and mouth disease (HFMD). In this study, 1104 clinically diagnosed HFMD patients were included. Enterovirus 71 (EV71), coxsackievirus A16 (CA16), and 14 different respiratory pathogens were examined from nasopharyngeal swabs using polymerase chain reaction (PCR) or reverse transcriptase PCR (RT-PCR). To evaluate the immune activation in HFMD patients, 8 cytokines and IgM antibodies to EV71 and CA16 from mild and severe patients were detected. Our results indicated that the severity of HFMD may affect the pathogen detection. The lower positive rates of enterovirus and respiratory viruses in severe HFMD cases by RT-PCR were probably related to stronger immune response. Therefore, immunological tests such as ELISA are essential supplements to PCR or RT-PCR in order to increase pathogen diagnosis in HFMD, especially in severe cases.

negative: Outpatient Antibiotic Stewardship: A Growing Frontier—Combining Myxovirus Resistance Protein A With Other Biomarkers to Improve Antibiotic Use BACKGROUND: The majority of oral antibiotics are prescribed in outpatient primary and urgent care clinics for acute respiratory infections. Effective antibiotic stewardship must include proper prescribing for outpatients as well as for those in a hospital or long-term care facility. METHODS: Major databases, including MEDLINE and the Cochrane Library, were searched for prospective human clinical studies, including children and/or adults published between January 1966 and November 2017 that evaluated Myxovirus resistance protein A (MxA) as a biomarker for diagnosing viral infections as well as both C-reactive protein (CRP) and procalcitonin (PCT) as potential biomarkers for identifying and differentiating true bacterial upper respiratory infection (URI) from colonization. RESULTS: Ten prospective human studies, totaling 1683 patients, were identified that evaluated MxA as a viral biomarker in children and/or adults. Both systematic review articles, meta-analyses, and randomized controlled clinical trials that examined CRP and/or PCT as a biomarker for identifying clinically significant bacterial infections and supporting antibiotic stewardship were identified. CONCLUSIONS: Quick and accurate differentiation between a viral and bacterial respiratory infection is critical to effectively combat antibiotic misuse. MxA expression in peripheral blood is a highly specific marker for viral infection. Combining MxA with other inflammatory biomarkers to test for respiratory infections offers enhanced sensitivity and specificity, forming an excellent tool for antibiotic stewardship in the outpatient setting.

negative: Transcriptome Analysis of Human Peripheral Blood Mononuclear Cells Exposed to Lassa Virus and to the Attenuated Mopeia/Lassa Reassortant 29 (ML29), a Vaccine Candidate Lassa virus (LASV) is the causative agent of Lassa Fever and is responsible for several hundred thousand infections and thousands of deaths annually in West Africa. LASV and the non-pathogenic Mopeia virus (MOPV) are both rodent-borne African arenaviruses. A live attenuated reassortant of MOPV and LASV, designated ML29, protects rodents and primates from LASV challenge and appears to be more attenuated than MOPV. To gain better insight into LASV-induced pathology and mechanism of attenuation we performed gene expression profiling in human peripheral blood mononuclear cells (PBMC) exposed to LASV and the vaccine candidate ML29. PBMC from healthy human subjects were exposed to either LASV or ML29. Although most PBMC are non-permissive for virus replication, they remain susceptible to signal transduction by virus particles. Total RNA was extracted and global gene expression was evaluated during the first 24 hours using high-density microarrays. Results were validated using RT-PCR, flow cytometry and ELISA. LASV and ML29 elicited differential expression of interferon-stimulated genes (ISG), as well as genes involved in apoptosis, NF-kB signaling and the coagulation pathways. These genes could eventually serve as biomarkers to predict disease outcomes. The remarkable differential expression of thrombomodulin, a key regulator of inflammation and coagulation, suggests its involvement with vascular abnormalities and mortality in Lassa fever disease.

negative: Lipid metabolites as potential diagnostic and prognostic biomarkers for acute community acquired pneumonia Abstract Early diagnosis of acute community-acquired pneumonia (CAP) is important in patient triage and treatment decisions. To identify biomarkers that distinguish patients with CAP from non-CAP controls, we conducted an untargeted global metabolome analysis for plasma samples from 142 patients with CAP (CAP cases) and 97 without CAP (non-CAP controls). Thirteen lipid metabolites could discriminate between CAP cases and non-CAP controls with area-under-the-receiver-operating-characteristic curve of >0.8 (P ≤ 10−9). The levels of glycosphingolipids, sphingomyelins, lysophosphatidylcholines and L-palmitoylcarnitine were higher, while the levels of lysophosphatidylethanolamines were lower in the CAP cases than those in non-CAP controls. All 13 metabolites could distinguish CAP cases from the non-infection, extrapulmonary infection and non-CAP respiratory tract infection subgroups. The levels of trihexosylceramide (d18:1/16:0) were higher, while the levels of lysophosphatidylethanolamines were lower, in the fatal than those of non-fatal CAP cases. Our findings suggest that lipid metabolites are potential diagnostic and prognostic biomarkers for CAP.

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: Chapter 11 Systems Virology Why everybody wants to measure everything Abstract Virologists have long known that viral pathogenesis must be studied from the standpoint of both the virus and the host. Nevertheless, given its relative simplicity, studying the virus has always been more tractable. As outlined in the previous chapters, virus-centric approaches have yielded a tremendous amount of information about viral genetics, viral replication cycles, and host and tissue tropisms. Along the way have come insights into host innate and adaptive immune responses and the many ways in which viruses antagonize these responses while exploiting other cellular processes to their advantage. The sequencing of the human genome, however, dramatically changed the field of viral pathogenesis. Virologists are now able to move beyond virus-centric or single-gene approaches and instead investigate the host response to infection on a genome-wide scale. In this chapter, we focus on the insights into viral pathogenesis that are provided by examining the host transcriptional response, including the dynamics of innate and acquired immunity, diagnostic signatures, and the identification of targets for antiviral drugs.

negative: COVID-19 Severity Scoring Tool for low resourced settings

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: Rapid and quantitative detection of COVID-19 markers in micro-liter sized samples COVID-19 pandemic has caused tens of thousands of deaths and is now a severe threat to global health. Clinical practice has demonstrated that the SARS-CoV-2 S1 specific antibodies and viral antigens can be used as diagnostic and prognostic markers of COVID-19. However, the popular point-of-care biomarker detection technologies, such as the lateral-flow test strips, provide only yes/no information and have very limited sensitivities. Thus, it has a high false negative rate and cannot be used for the quantitative evaluation of patient’s immune response. Conventional ELISA (enzyme-linked immunosorbent assay), on the other hand, can provide quantitative, accurate, and sensitive results, but it involves complicated and expensive instruments and long assay time. In addition, samples need to be sent to centralized labs, which significantly increases the turn-around time. Here, we present a microfluidic ELISA technology for rapid (15-20 minutes), quantitative, sensitive detection of SARS-CoV-2 biomarkers using SARS-CoV-2 specific IgG and viral antigen – S protein in serum. We also characterized various humanized monoclonal IgG, and identified a candidate with a high binding affinity towards SARS-CoV-2 S1 protein that can serve as the calibration standard of anti-SARS-CoV-2 S1 IgG in serological analyses. Furthermore, we demonstrated that our microfluidic ELISA platform can be used for rapid affinity evaluation of monoclonal anti-S1 antibodies. The microfluidic ELISA device is highly portable and requires less than 10 μL of samples for each channel. Therefore, our technology will greatly facilitate rapid and quantitative analysis of COVID-19 patients and vaccine recipients at point-of-care.

negative: Diseases of the Liver and Hepatobiliary System

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: Inactivating porcine coronavirus before nuclei acid isolation with the temperature higher than 56 °C damages its genome integrity seriously 2019-Novel Coronavirus (2019-nCoV) is the pathogen of Corona Virus Disease 2019. Nucleic acid detection of 2019-nCoV is one of the key indicators for clinical diagnosis. However, the positive rate is only 30-50%. Currently, fluorescent quantitative RT-PCR technology is mainly used to detect 2019-nCoV. According to “The Laboratory Technical Guidelines for Detection 2019-nCoV (Fourth Edition)” issued by National Health and Commission of China and “The Experts’ Consensus on Nucleic Acid Detection of 2019-nCoV” released by Chinese Society of Laboratory Medicine, the human samples must be placed under 56°C or higher to inactivate the viruses in order to keep the inspectors from virus infection before the nucleic acids were isolated as the template of qRT-PCR. In this study, we demonstrated that the virus inactivation treatment disrupts its genome integrity seriously when using porcine epidemic diarrhea virus (vaccine), a kind of coronavirus, as a model. Our results showed that only 50.11% of the detectable viral templates left after the inactivation of 56 °C for 30 minutes and only 3.36% left after the inactivation of 92 °C for 5 minutes when the samples were preserved by Hank’s solution, one of an isotonic salt solutions currently suggested. However, the detectable templates of viral nucleic acids can be unchanged after the samples were incubated at 56 °C or higher if the samples were preserved with an optimized solution to protect the RNA from being disrupted. We therefore highly recommend to carry out systematic investigation on the impact of high temperature inactivation on the integrity of 2019-nCoV genome and develop a sample preservation solution to protect the detectable templates of 2019-nCoV nucleic acids from high temperature inactivation damage.

negative: Significant expression of FURIN and ACE2 on oral epithelial cells may facilitate the efficiency of SARS-CoV-2 entry Background Leading to a sustained epidemic spread with >2,000,000 confirmed human infections, including >100,000 deaths, COVID-19 was caused by SARS-CoV-2 and resulted in acute respiratory distress syndrome (ARDS) and sepsis, which brought more challenges to the patient’s treatment. The S-glycoprotein, which recognized as the key factor for the entry of SARS-CoV-2 into the cell, contains two functional domains: an ACE2 receptor binding domain and a second domain necessary for fusion of the coronavirus and cell membranes. FURIN activity, exposes the binding and fusion domains, is essential for the zoonotic transmission of SARS-CoV-2. Moreover, it has been reported that ACE2 is likely to be the receptor for SARS-CoV-2. In addition, FURIN enzyme and ACE2 receptor were expressed in airway epithelia, cardiac tissue, and enteric canals, which considered as the potential target organ of the virus. However, report about the expression of FURIN and ACE2 in oral tissues was limited. Methods In order to investigate the potential infective channel of new coronavirus in oral cavity, we analyze the expression of ACE2 and FURIN that mediate the new coronavirus entry into host cells in oral mucosa using the public single-cell sequence datasets. Furthermore, immunohistochemical staining experiment was performed to confirm the expression of ACE2 and FURIN in the protein level. Results The bioinformatics results indicated the differential expression of ACE2 and FURIN on epithelial cells of different oral mucosal tissues and the proportion of FURIN-positive cells was obviously higher than that of ACE2-positive cells. IHC experiments revealed that both the ACE2-positive and FURIN-positive cells in the target tissues were mainly positioned in the epithelial layers, partly expressed in fibroblasts, which further confirm the bioinformatics results. Conclusions Based on these findings, we speculated that SARS-CoV-2 could effectively invade oral mucosal cells though two possible routes: binding to the ACE2 receptor and fusion with cell membrane activated by FURIN protease. Our results indicated that oral mucosa tissues are susceptible to SARS-CoV-2, which provides valuable information for virus-prevention strategy in clinical care as well as daily life.

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

negative: The discriminative capacity of soluble Toll-like receptor (sTLR)2 and sTLR4 in inflammatory diseases BACKGROUND: The extracellular domains of cytokine receptors are released during inflammation, but little is known about the shedding of Toll-like receptors (TLR) and whether they can be used as diagnostic biomarkers. METHODS: The release of sTLR2 and sTLR4 was studied in in-vitro stimulations, as well as in-vivo during experimental human endotoxemia (n = 11, 2 ng/kg LPS), and in plasma of 394 patients with infections (infectious mononucleosis, measles, respiratory tract infections, bacterial sepsis and candidemia) or non-infectious inflammation (Crohn’s disease, gout, rheumatoid arthritis, autoinflammatory syndromes and pancreatitis). Using C-statistics, the value of sTLR2 and sTLR4 levels for discrimination between infections and non-infectious inflammatory diseases, as well as between viral and bacterial infections was analyzed. RESULTS: In-vitro, peripheral blood mononuclear cells released sTLR2 and sTLR4 by exposure to microbial ligands. During experimental human endotoxemia, plasma concentrations peaked after 2 hours (sTLR4) and 4 hours (sTLR2). sTLR4 did not correlate with cytokines, but sTLR2 correlated positively with TNFα (r(s) = 0.80, P < 0.05), IL-6 (r(s) = 0.65, P < 0.05), and IL-1Ra (r(s) = 0.57, P = 0.06), and negatively with IL-10 (r(s) = -0.58, P = 0.06), respectively. sTLR4 had a similar area under the ROC curve [AUC] for differentiating infectious and non-infectious inflammation compared to CRP: 0.72 (95% CI 0.66-0.79) versus 0.74 (95% CI 0.69-0.80) [P = 0.80], while sTLR2 had a lower AUC: 0.60 (95% CI 0.54-0.66) [P = 0.0004]. CRP differentiated bacterial infections better from viral infections than sTLR2 and sTLR4: AUC 0.94 (95% CI 0.90-0.96) versus 0.58 (95% CI 0.51-0.64) and 0.75 (95% CI 0.70-0.80), respectively [P < 0.0001 for both]. CONCLUSIONS: sTLRs are released into the circulation, and suggest the possibility to use sTLRs as diagnostic tool in inflammatory conditions.

negative: Computers and viral diseases. Preliminary bioinformatics studies on the design of a synthetic vaccine and a preventative peptidomimetic antagonist against the SARS-CoV-2 (2019-nCoV, COVID-19) coronavirus Abstract This paper concerns study of the genome of the Wuhan Seafood Market isolate believed to represent the causative agent of the disease COVID-19. This is to find a short section or sections of viral protein sequence suitable for preliminary design proposal for a peptide synthetic vaccine and a peptidomimetic therapeutic, and to explore some design possibilities. The project was originally directed towards a use case for the Q-UEL language and its implementation in a knowledge management and automated inference system for medicine called the BioIngine, but focus here remains mostly on the virus itself. However, using Q-UEL systems to access relevant and emerging literature, and to interact with standard publically available bioinformatics tools on the Internet, did help quickly identify sequences of amino acids that are well conserved across many coronaviruses including 2019-nCoV. KRSFIEDLLFNKV was found to be particularly well conserved in this study and corresponds to the region around one of the known cleavage sites of the SARS virus that are believed to be required for virus activation for cell entry. This sequence motif and surrounding variations formed the basis for proposing a specific synthetic vaccine epitope and peptidomimetic agent. The work can, nonetheless, be described in traditional bioinformatics terms, and readily reproduced by others, albeit with the caveat that new data and research into 2019-nCoV is emerging and evolving at an explosive pace. Preliminary studies using molecular modeling and docking, and in that context the potential value of certain known herbal extracts, are also described.

negative: Specific Serum Markers of IPF: What Is the Significance of KL-6, SP-A, and SP-D? Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive, fibrosing interstitial pneumonia of unknown cause. It is characterized by the progressive worsening of lung function and has a poor prognosis (median survival is approximately 3 years). However, the clinical course of disease shows considerable individual variability. Therefore, it is important to monitor the clinical course and to predict prognosis for optimal therapy. Serum biomarkers are both less invasive and reproducible diagnostic tools. Useful biomarkers for patients with IPF are strongly coveted; however, to date, there are no biomarkers that are globally known. In Japan, surfactant protein (SP)-A, SP-D, and KL-6 are commonly used as serum markers of interstitial pneumonia, including IPF, in the clinical setting, and empirical data has been accumulated over 10 years. SP-A and SP-D are hydrophilic proteins and members of the collectin family. These collectins have been shown to function as host defense lectins in the lung. KL-6 is a high molecular weight glycoprotein and now classified as a human MUC1 mucin protein. These three proteins are mainly synthesized by alveolar type II cells. The mechanisms of increase for these protein levels in sera of patients with IPF are probably a combination of a loss of epithelial integrity due to injury and an increased mass of type II cells due to hyperplasia. It has been revealed that those proteins are useful for monitoring the clinical course and predicting prognosis as well as for the diagnosis of IPF. In this review article, the molecular structures and biological functions of these biomarkers are outlined, and we discuss the clinical application of these biomarkers for patients with IPF.

negative: Current transcriptomics in pig immunity research Swine performance in the face of disease challenge is becoming progressively more important. To improve the pig’s robustness and resilience against pathogens through selection, a better understanding of the genetic and epigenetic factors in the immune response is required. This review highlights results from the most recent transcriptome research, and the meta-analyses performed, in the context of pig immunity. A technological overview is given including wholegenome microarrays, immune-specific arrays, small-scale high-throughput expression methods, high-density tiling arrays, and next generation sequencing (NGS). Although whole genome microarray techniques will remain complementary to NGS for some time in domestic species, research will transition to sequencing-based methods due to cost-effectiveness and the extra information that such methods provide. Furthermore, upcoming high-throughput epigenomic studies, which will add greatly to our knowledge concerning the impact of epigenetic modifications on pig immune response, are listed in this review. With emphasis on the insights obtained from transcriptomic analyses for porcine immunity, we also discuss the experimental design in pig immunity research and the value of the newly published porcine genome assembly in using the pig as a model for human immune response. We conclude by discussing the importance of establishing community standards to maximize the possibility of integrative computational analyses, such as was clearly beneficial for the human ENCODE project. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00335-014-9549-4) contains supplementary material, which is available to authorized users.

negative: Non-lytic antibiotic treatment in community-acquired pneumococcal pneumonia does not attenuate inflammation: the PRISTINE trial BACKGROUND: The inflammatory response in pneumococcal infection is primarily driven by immunoreactive bacterial cell wall components [lipoteichoic acid (LTA)]. An acute release of these components occurs when pneumococcal infection is treated with β-lactam antibiotics. OBJECTIVES: We hypothesized that non-lytic rifampicin compared with lytic β-lactam antibiotic treatment would attenuate the inflammatory response in patients with pneumococcal pneumonia. METHODS: In the PRISTINE (Pneumonia treated with RIfampicin aTtenuates INflammation) trial, a randomized, therapeutic controlled, exploratory study in patients with community-acquired pneumococcal pneumonia, we looked at LTA release and inflammatory and clinical response during treatment with both rifampicin and β-lactam compared with treatment with β-lactam antibiotics only. The trial is registered in the Dutch trial registry, number NTR3751 (European Clinical Trials Database number 2012-003067-22). RESULTS: Forty-one patients with community-acquired pneumonia were included; 17 of them had pneumococcal pneumonia. LTA release, LTA-mediated inflammatory responses, clinical outcomes, inflammatory biomarkers and transcription profiles were not different between treatment groups. CONCLUSIONS: The PRISTINE study demonstrated the feasibility of adding rifampicin to β-lactam antibiotics in the treatment of community-acquired pneumococcal pneumonia, but, despite solid in vitro and experimental animal research evidence, failed to demonstrate a difference in plasma LTA concentrations and subsequent inflammatory and clinical responses. Most likely, an inhibitory effect of human plasma contributes to the low immune response in these patients. In addition, LTA plasma concentration could be too low to mount a response via Toll-like receptor 2 in vitro, but may nonetheless have an effect in vivo.

negative: Origin, Potential Therapeutic Targets and Treatment for Coronavirus Disease (COVID-19) The ongoing episode of coronavirus disease 19 (COVID-19) has imposed a serious threat to global health and the world economy. The disease has rapidly acquired a pandemic status affecting almost all populated areas of the planet. The causative agent of COVID-19 is a novel coronavirus known as SARS-CoV-2. The virus has an approximate 30 kb single-stranded positive-sense RNA genome, which is 74.5% to 99% identical to that of SARS-CoV, CoV-pangolin, and the coronavirus the from horseshoe bat. According to available information, SARS-CoV-2 is inferred to be a recombinant virus that originated from bats and was transmitted to humans, possibly using the pangolin as the intermediate host. The interaction of the SARS-CoV-2 spike protein with the human ACE2 (angiotensin-converting enzyme 2) receptor, and its subsequent cleavage by serine protease and fusion, are the main events in the pathophysiology. The serine protease inhibitors, spike protein-based vaccines, or ACE2 blockers may have therapeutic potential in the near future. At present, no vaccine is available against COVID-19. The disease is being treated with antiviral, antimalarial, anti-inflammatory, herbal medicines, and active plasma antibodies. In this context, the present review article provides a cumulative account of the recent information regarding the viral characteristics, potential therapeutic targets, treatment options, and prospective research questions.

negative: Still puzzling questions in immunology (infection and immunity)

negative: 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.

negative: Bacterial and fungal co-infection in individuals with coronavirus: A rapid review to support COVID-19 antimicrobial prescribing BACKGROUND: To explore and describe the current literature surrounding bacterial/fungal co-infection in patients with coronavirus infection. METHODS: MEDLINE, EMBASE, and Web of Science were searched using broad based search criteria relating to coronavirus and bacterial co-infection. Articles presenting clinical data for patients with coronavirus infection (defined as SARS-1, MERS, SARS-COV-2, and other coronavirus) and bacterial/fungal co-infection reported in English, Mandarin, or Italian were included. Data describing bacterial/fungal co-infections, treatments, and outcomes were extracted. Secondary analysis of studies reporting antimicrobial prescribing in SARS-COV-2 even in the absence of co-infection was performed. RESULTS: 1007 abstracts were identified. Eighteen full texts reported bacterial/fungal co-infection were included. Most studies did not identify or report bacterial/fungal coinfection (85/140;61%). 9/18 (50%) studies reported on COVID-19, 5/18 (28%) SARS-1, 1/18 (6%) MERS, and 3/18 (17%) other coronavirus. For COVID-19, 62/806 (8%) patients were reported as experiencing bacterial/fungal co-infection during hospital admission. Secondary analysis demonstrated wide use of broad-spectrum antibacterials, despite a paucity of evidence for bacterial coinfection. On secondary analysis, 1450/2010 (72%) of patients reported received antimicrobial therapy. No antimicrobial stewardship interventions were described. For non-COVID-19 cases bacterial/fungal co-infection was reported in 89/815 (11%) of patients. Broad-spectrum antibiotic use was reported. CONCLUSIONS: Despite frequent prescription of broad-spectrum empirical antimicrobials in patients with coronavirus associated respiratory infections, there is a paucity of data to support the association with respiratory bacterial/fungal co-infection. Generation of prospective evidence to support development of antimicrobial policy and appropriate stewardship interventions specific for the COVID-19 pandemic are urgently required.

negative: Discovery and validation of serum biomarkers expressed over the first twelve weeks of Fasciola hepatica infection in sheep Abstract Serum biomarkers associated with Fasciola hepatica infection of Corriedale sheep were analysed during the first 12 weeks of infection using surface-enhanced laser desorption ionisation time of flight mass spectrometry (SELDI-TOF MS). In the discovery phase of analysis, pooled sera collected at week 0 and at each week p.i. to week 12 were fractionated by anion-exchange chromatography and the protein mass fingerprints obtained in individual fractions were in the M/z range 1.5–150kDa. A total of 2302 protein clusters (peaks) were identified that varied between time-points following infection with peaks increasing or decreasing in intensity, or showing transient variation in intensity, during the 12 weeks of parasite challenge. In the validation phase, candidate biomarkers in sera of individual sheep at weeks 3 and 9 p.i. were analysed, identifying 100 protein peaks, many of which are small peptides <10kDa in size: 54% of these peaks were up-regulated in intensity at week 3 or 9 p.i. Twenty-six biomarkers were chosen for further study, ranging in size from 1832 to 89,823Da: six biomarkers were up-regulated at weeks 3 and 9 p.i., 16 biomarkers were up-regulated only at week 9 p.i. and four biomarkers were down-regulated at week 9 p.i. Two biomarkers up-regulated at week 9 were identified as transferrin (77.2kDa) and Apolipoprotein A-IV (44.3kDa), respectively. The results show that the interaction between the host and F. hepatica is complex, with changes in biomarker patterns beginning within 3 weeks of infection and either persisting to weeks 9–12 or showing transient changes during infection. Identification of biomarkers expressed during ovine fasciolosis may provide insights into mechanisms of pathogenesis and immunity to Fasciola and may assist in the rational development and delivery of vaccines.

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

negative: Preoperative miRNA-208a as a Predictor of Postoperative Complications in Children with Congenital Heart Disease Undergoing Heart Surgery Major perioperative cardiovascular events are important causes of morbidity in pediatric patients with congenital heart disease who undergo reparative surgery. Current preoperative clinical risk assessment strategies have poor accuracy for identifying patients who will sustain adverse events following heart surgery. There is an ongoing need to integrate clinical variables with novel technology and biomarkers to accurately predict outcome following pediatric heart surgery. We tested whether preoperative levels of miRNAs-208a can serve as such a biomarker. Serum samples were obtained from pediatric patients immediately before heart surgery. MiRNA-208a was quantified by RQ-PCR. Correlations between the patient’s clinical variables and miRNA levels were tested. Lower levels of preoperative miRNA-208a correlated with and could predict the appearance of postoperative cardiac and inflammatory complications. MiRNA-208a may serve as a biomarker for the prediction of patients who are at risk to develop complications following surgery for the repair of congenital heart defects.

negative: Globalized low-income countries may experience higher COVID-19 mortality rates Understanding the factors underpinning COVID-19 infection and mortality rates is essential in order to implement actions that help mitigate the current pandemia. Here we evaluate how a suit of 15 climatic and socio-economic variables influence COVID-19 exponential growth-phase infection and mortality rates across 36 countries. We found that imports of goods and services, international tourism and the number of published scientific papers are good predictors of COVID-19 infection rates, indicating that more globalized countries may have experienced multiple and recurrent introductions of the virus. However, high-income countries showed lower mortality rates, suggesting that the consequences of the current pandemia will be worse for globalized low-income countries. International aid agencies could use this information to help mitigate the consequences of the current pandemia in the most vulnerable countries.

negative: Emerging novel coronavirus (2019-nCoV)—current scenario, evolutionary perspective based on genome analysis and recent developments Coronaviruses are the well-known cause of severe respiratory, enteric and systemic infections in a wide range of hosts including man, mammals, fish, and avian. The scientific interest on coronaviruses increased after the emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) outbreaks in 2002-2003 followed by Middle East Respiratory Syndrome CoV (MERS-CoV). This decade’s first CoV, named 2019-nCoV, emerged from Wuhan, China, and declared as ‘Public Health Emergency of International Concern’ on January 30(th), 2020 by the World Health Organization (WHO). As on February 4, 2020, 425 deaths reported in China only and one death outside China (Philippines). In a short span of time, the virus spread has been noted in 24 countries. The zoonotic transmission (animal-to-human) is suspected as the route of disease origin. The genetic analyses predict bats as the most probable source of 2019-nCoV though further investigations needed to confirm the origin of the novel virus. The ongoing nCoV outbreak highlights the hidden wild animal reservoir of the deadly viruses and possible threat of spillover zoonoses as well. The successful virus isolation attempts have made doors open for developing better diagnostics and effective vaccines helping in combating the spread of the virus to newer areas.

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

negative: Metabolomic-Based Methods in Diagnosis and Monitoring Infection Progression A robust biomarker screening and validation is crucial for overcoming the current limits in the clinical management of infectious diseases. In this chapter, a general workflow for metabolomics is summarized. Subsequently, an overview of the major contributions of this omics science to the field of biomarkers of infectious diseases is discussed. Different approaches using a variety of analytical platforms can be distinguished to unveil the key metabolites for the diagnosis, prognosis, response to treatment and susceptibility for infectious diseases. To allow the implementation of such biomarkers into the clinics, the performance of large-scale studies employing solid validation criteria becomes essential. Focusing on the etiological agents and after an extensive review of the field, we present a comprehensive revision of the main metabolic biomarkers of viral, bacterial, fungal, and parasitic diseases. Finally, we discussed several articles which show the strongest validation criteria. Following these research avenues, precious clinical resources will be revealed, allowing for reduced misdiagnosis, more efficient therapies, and affordable costs, ultimately leading to a better patient management.

negative: Human CD4+ memory T-lymphocyte responses to SARS coronavirus infection Abstract Little is known about CD4+ T-cell immunity to the severe acute respiratory syndrome (SARS) coronavirus. In two SARS patients, we examined the memory CD4+ T-cell responses to peptides derived from SARS coronavirus structural proteins. We generated CD4+ T-cell lines to 3 peptides from the spike (S) protein and defined their HLA restriction. In one patient, the predominant memory CD4+ T-cell response was directed against an epitope outside the S protein receptor-binding domain. In both patients, the frequency of CD4+ memory T-cells to virus structural proteins and anti-SARS coronavirus IgG levels were low by 12 months after infection. This report expands our understanding of the specificity and duration of anti-SARS coronavirus CD4+ T-cell immune responses.

negative: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016 P001 - Sepsis impairs the capillary response within hypoxic capillaries and decreases erythrocyte oxygen-dependent ATP efflux R. M. Bateman, M. D. Sharpe, J. E. Jagger, C. G. Ellis P002 - Lower serum immunoglobulin G2 level does not predispose to severe flu. J. Solé-Violán, M. López-Rodríguez, E. Herrera-Ramos, J. Ruíz-Hernández, L. Borderías, J. Horcajada, N. González-Quevedo, O. Rajas, M. Briones, F. Rodríguez de Castro, C. Rodríguez Gallego P003 - Brain protective effects of intravenous immunoglobulin through inhibition of complement activation and apoptosis in a rat model of sepsis F. Esen, G. Orhun, P. Ergin Ozcan, E. Senturk, C. Ugur Yilmaz, N. Orhan, N. Arican, M. Kaya, M. Kucukerden, M. Giris, U. Akcan, S. Bilgic Gazioglu, E. Tuzun P004 - Adenosine a1 receptor dysfunction is associated with leukopenia: A possible mechanism for sepsis-induced leukopenia R. Riff, O. Naamani, A. Douvdevani P005 - Analysis of neutrophil by hyper spectral imaging - A preliminary report R. Takegawa, H. Yoshida, T. Hirose, N. Yamamoto, H. Hagiya, M. Ojima, Y. Akeda, O. Tasaki, K. Tomono, T. Shimazu P006 - Chemiluminescent intensity assessed by eaa predicts the incidence of postoperative infectious complications following gastrointestinal surgery S. Ono, T. Kubo, S. Suda, T. Ueno, T. Ikeda P007 - Serial change of c1 inhibitor in patients with sepsis – A prospective observational study T. Hirose, H. Ogura, H. Takahashi, M. Ojima, J. Kang, Y. Nakamura, T. Kojima, T. Shimazu P008 - Comparison of bacteremia and sepsis on sepsis related biomarkers T. Ikeda, S. Suda, Y. Izutani, T. Ueno, S. Ono P009 - The changes of procalcitonin levels in critical patients with abdominal septic shock during blood purification T. Taniguchi, M. O P010 - Validation of a new sensitive point of care device for rapid measurement of procalcitonin C. Dinter, J. Lotz, B. Eilers, C. Wissmann, R. Lott P011 - Infection biomarkers in primary care patients with acute respiratory tract infections – Comparison of procalcitonin and C-reactive protein M. M. Meili, P. S. Schuetz P012 - Do we need a lower procalcitonin cut off? H. Hawa, M. Sharshir, M. Aburageila, N. Salahuddin P013 - The predictive role of C-reactive protein and procalcitonin biomarkers in central nervous system infections with extensively drug resistant bacteria V. Chantziara, S. Georgiou, A. Tsimogianni, P. Alexandropoulos, A. Vassi, F. Lagiou, M. Valta, G. Micha, E. Chinou, G. Michaloudis P014 - Changes in endotoxin activity assay and procalcitonin levels after direct hemoperfusion with polymyxin-b immobilized fiber A. Kodaira, T. Ikeda, S. Ono, T. Ueno, S. Suda, Y. Izutani, H. Imaizumi P015 - Diagnostic usefullness of combination biomarkers on ICU admission M. V. De la Torre-Prados, A. Garcia-De la Torre, A. Enguix-Armada, A. Puerto-Morlan, V. Perez-Valero, A. Garcia-Alcantara P016 - Platelet function analysis utilising the PFA-100 does not predict infection, bacteraemia, sepsis or outcome in critically ill patients N. Bolton, J. Dudziak, S. Bonney, A. Tridente, P. Nee P017 - Extracellular histone H3 levels are inversely correlated with antithrombin levels and platelet counts and are associated with mortality in sepsis patients G. Nicolaes, M. Wiewel, M. Schultz, K. Wildhagen, J. Horn, R. Schrijver, T. Van der Poll, C. Reutelingsperger P018 - Il-8: is this a more reliable biomarker for sepsis severity than CRP, Procalcitonin, E-selectin, IL-6 and TNF-[alpha] S. Pillai, G. Davies, G. Mills, R. Aubrey, K. Morris, P. Williams, P. Evans P019 - Relation between adrenomedullin and short-term outcome in ICU patients: Results from the frog ICU study E. G. Gayat, J. Struck, A. Cariou, N. Deye, B. Guidet, S. Jabert, J. Launay, M. Legrand, M. Léone, M. Resche-Rigon, E. Vicaut, A. Vieillard-Baron, A. Mebazaa P020 - Impact of disease severity assessment on performance of heparin-binding protein for the prediction of septic shock R. Arnold, M. Capan, A. Linder, P. Akesson P021 - Kinetics and prognostic value of presepsin (sCD14) in septic patients. A pilot study M. Popescu, D. Tomescu P022 - Comparison of CD64 levels performed by the facs and accellix systems C. L. Sprung, R. Calderon Morales, G. Munteanu, E. Orenbuch-Harroch, P. Levin, H. Kasdan, A. Reiter, T. Volker, Y. Himmel, Y. Cohen, J. Meissonnier P023 - Diagnosing sepsis in 5 minutes: Nanofluidic technology study with pancreatic-stone protein (PSP/ reg) L. Girard, F. Rebeaud P024 - How nanotechnology-based approaches could contribute to sepsis prevention, diagnosis and treatment I. Herrmann P025 - Il7r transcriptional expression analysis during septic shock B. Delwarde, E. Peronnet, E. Cerrato, F. Venet, A. Lepape, T. Rimmelé, G. Monneret, J. Textoris P026 - Disbalance of microbial metabolites of aromatic acids affects the severity in critically ill patients N. Beloborodova, V. Moroz, A. Osipov, A. Bedova, Y. Sarshor, A. Pautova, A. Sergeev, E. Chernevskaya P027 - Copeptin predicts 10-year all-cause mortality in community patients J. Odermatt, R. Bolliger, L. Hersberger, M. Ottiger, M. Christ-Crain, B. Mueller, P. Schuetz P028 - Identification of differential proteomic response in septic patients secondary to community and hospital acquired pneumonia N. K. Sharma, A. K. Tashima, M. K. Brunialti, F. R. Machado, M. Assuncao, O. Rigato, R. Salomao P029 - Monocyte HLA-DR expression in community-acquired bacteremic sepsis - dynamics associated to aetiology and prediction of secondary sepsis S. C. Cajander, G. Rasmussen, E. Tina, B. Söderquist, J. Källman, K. Strålin P030 - Soluble B- and T-lymphocyte attenuator: A possible prognostic marker in sepsis A. L. Lange, J. S. Sundén-Cullberg, A. M. Magnuson, O. H. Hultgren P031 - Fractal dimension: A new biomarker for quantifying clot microstructure in patients across the sepsis spectrum G. Davies, S. Pillai, G. Mills, R. Aubrey, K. Morris, P. Williams, P. Evans P032 - Comparison between the new biomarker for coagulation, clot microstructure (Df) with rotational thromboelastometry (ROTEM) in patients across the sepsis spectrum S. Pillai, G. Davies, G. Mills, R. Aubrey, K. Morris, P. Williams, P. Evans P033 - Changes in fibrinolysis across the sepsis spectrum: The use of rotational thromboelastometry (ROTEM) lysis index (LI60) and D-Dimer concentration S. Pillai, G. Davies, G. Mills, R. Aubrey, K. Morris, P. Williams, P. Evans P034 - The intensive care infection score – a promising marker for the prediction of infection and its severity. P. Van der Geest, M. Mohseni, J. Linssen, R. De Jonge, S. Duran, J. Groeneveld P035 - Challenges in the clinical diagnosis of sepsis R. Miller III, B. K. Lopansri, L. C. McHugh, A. Seldon, J. P. Burke P036 - Does zero heat flux thermometry more accurately identify sepsis on intensive care? J. Johnston, R. Reece-Anthony, A. Bond, A. Molokhia P037 - Advancing quality (AQ) sepsis programme: Improving early identification & treatment of sepsis in North West England. C. Mcgrath, E. Nsutebu P038 - Prehospital transport of acute septic patients P. Bank Pedersen, D. Pilsgaard Henriksen, S. Mikkelsen, A. Touborg Lassen P039 - Vasodilatory plant extracts gel as an alternative treatment for fever in critically ill patients R. Tincu, C. Cobilinschi, D. Tomescu, Z. Ghiorghiu, R. Macovei P040 - Host response and outcome of hypothermic sepsis M. A. Wiewel, M. B. Harmon, L. A. Van Vught, B. P. Scicluna, A. J. Hoogendijk, J. Horn, A. H. Zwinderman, O. L. Cremer, M. J. Bonten, M. J. Schultz, T. Van der Poll, N. P. Juffermans, W. J. Wiersinga P041 - Septic shock alert over SIRS criteria has an impact on outcome but needs to be revised G. Eren, Y Tekdos, M. Dogan, O. Acicbe, E. Kaya, O. Hergunsel P042 - Association between previous prescription of βblockers and mortality rate among septic patients: A retrospective observational study S. Alsolamy, G. Ghamdi, L. Alswaidan, S. Alharbi, F. Alenezi, Y. Arabi P043 - Recognition and treatment of sepsis on labour ward– teaching & information resources can improve knowledge J. Heaton, A. Boyce, L. Nolan, J. Johnston, A. Dukoff-Gordon, A. Dean, A. Molokhia P044 - Culture negative sepsis in the ICU – what is unique to this patient population? T. Mann Ben Yehudah P045 - Organ dysfunction in severe sepsis patients identified in administrative data in Germany, 2007-2013 C. Fleischmann, D. Thomas-Rueddel, C. Haas, U. Dennler, K. Reinhart P046 - A comparison of residents’ knowledge regarding; the Surviving Sepsis Campaign 2012 guideline O. Suntornlohanakul, B. Khwannimit P047 - Effectiveness of a septic shock bundle to improve outcomes in the ICU F. Breckenridge, A. Puxty P048 - Dose of norepinephrine in the first 24 hours as a parameter evaluating the effectiveness of treatment in patients with severe sepsis and septic shock P. Szturz, P. Folwarzcny, J. Svancara, R. Kula, P. Sevcik P049 - Norepinephrine or vasopressin + norepinephrine in septic shock. A retrospective series of 39 patients L. Caneva, A. Casazza, E. Bellazzi, S. Marra, L. Pagani, M. Vetere, R. Vanzino, D. Ciprandi, R. Preda, R. Boschi, L. Carnevale P050 - Methylene blue effectiveness as contributory treatment in patients with septic shock V. Lopez, M. Aguilar Arzapalo, L. Barradas, A. Escalante, J. Gongora, M. Cetina P051 - Coagulation disorders in patients with severe sepsis and DIC evaluated with thromboelastometry. B Adamik, D Jakubczyk, A Kübler P052 - Frequency and outcome of early sepsis-associated coagulopathy A. Radford, T. Lee, J. Singer, J. Boyd, D. Fineberg, M. Williams, J. Russell P053 - Assessment of coagulopathy in cancer patients with severe sepsis or septic shock. A case-control pilot study E. Scarlatescu, D. Tomescu, G. Droc, S. Arama P054 - Thromboelastometry in critically ill patients with disseminated intravascular coagulation M. Müller, M. Straat, S. S. Zeerleder, N. P. Juffermans P055 - Cessation of a preexisting chronic antiplatelet therapy is associated with increased mortality rates in severe sepsis and septic shock C. F. Fuchs, C. S. Scheer, S. W. Wauschkuhn, M. V. Vollmer, K. M. Meissner, S. K. Kuhn, K. H. Hahnenkamp, S. R. Rehberg, M. G. Gründling P056 - Neutrophil Extracellular Traps (NETs) production under hypoxic condition N. Yamamoto, M. Ojima, S. Hamaguchi, T. Hirose, Y. Akeda, R. Takegawa, O. Tasaki, T. Shimazu, K. Tomono P057 - Impact of ultraviolet air sterilizer in intensive care unit room, and clinical outcomes of patients E. Gómez-Sánchez, M. Heredia-Rodríguez, E. Álvarez-Fuente, M. Lorenzo-López, E. Gómez-Pesquera, M. Aragón-Camino, P. Liu-Zhu, A. Sánchez-López, A. Hernández-Lozano, M. T. Peláez-Jareño, E. Tamayo P058 - Focus of infection in severe sepsis - comparison of administrative data and prospective cohorts from Germany D. O. Thomas-Rüddel, C. Fleischmann, C. Haas, U. Dennler, K. Reinhart P059 - “Zero CLABSI” – can we get there? Obstacles on the 4 year journey and our strategies to overcome them – experience from an Indian ICU V. Adora, A. Kar, A. Chakraborty, S. Roy, A. Bandyopadhyay, M. Das P060 - Novel molecular techniques to identify central venous catheter (CVC) associated blood stream infections (BSIs) T. Mann Ben Yehudah, G. Ben Yehudah, M. Salim, N. Kumar, L. Arabi, T. Burger, P. Lephart, E. Toth-martin P061 - Zero clabsi” – can we get there? Obstacles on the 4 year journey and our strategies to overcome them – experience from an Indian ICU R. Rao, A. Kar, A. Chakraborty P062 - Prevention of central line-associated bloodstream infections in intensive care units: An international online survey C. Valencia, N. Hammami, S. Blot, J. L. Vincent, M. L. Lambert P063 - 30 days antimicrobial efficacy of non-leaching central venous catheters J. Brunke, T. Riemann, I. Roschke P064 - Efficacy of noble metal alloy-coated catheter in prevention of bacteriuria R. Tincu, C. Cobilinschi, D. Tomescu, Z. Ghiorghiu, R. Macovei P065 - Predicting bacteremic urinary tract infection in community setting: A prospective observational study S. Nimitvilai, K. Jintanapramote, S. Jarupongprapa P066 - Eight-year analysis of acinetobacter spp. monobacteremia in surgical and medical intensive care units at university hospital in Lithuania D. Adukauskiene, D. Valanciene P067 - Group A and group B streptococcal infections in intensive care unit – our experience in a tertiary centre G. Bose, V. Lostarakos, B. Carr P068 - Improved detection of spontaneous bacterial peritonitis by uritop + tm strip test and inoculation of blood culture bottles with ascitic fluid S. Khedher, A. Maaoui, A. Ezzamouri, M. Salem P069 - Increased risk of cellulitis in patients with congestive heart failure: a population based cohort study J. Chen P070 - Outcomes of severe cellulitis and necrotizing fasciitis in the critically ill D. R. Cranendonk, L. A. Van Vught, M. A. Wiewel, O. L. Cremer, J. Horn, M. J. Bonten, M. J. Schultz, T. Van der Poll, W. J. Wiersinga P071 - Botulism outbreak associated with people who inject drugs (PWIDs) in Scotland. M. Day, G. Penrice, K. Roy, P. Robertson, G. Godbole, B. Jones, M. Booth, L. Donaldson P072 - Surveillance of ESBL-producing enterobacteriaceae fecal carriers in the ICU Y. Kawano, H. Ishikura P073 - Prevalence of ESBL and carbapenemase producing uropathogens in a newly opened hospital in south India S. Sreevidya, N. Brahmananda Reddy, P. Muraray Govind, R. Pratheema, J. Devachandran Apollo Speciality Hospital - OMR, Chennai, India P074 - Prevalence, risk factors and outcomes of methicillin-resistant staphylococcus aureus nasal colonization in critically ill patients H. Al-Dorzi, M. Almutairi, B. Alhamadi, A. Crizaldo Toledo, R. Khan, B. Al Raiy, Y. Arabi P075 - Multidrug-resistant Acinetobacter baumannii infection in intensive care unit patients in a hospital with building construction: Is there an association? H. Talaie P076 - Multidrug-resistant organisms in a Dutch ICU J. A. Van Oers, A. Harts, E. Nieuwkoop, P. Vos P077 - Epidemiology and risk factors of ICU acquired infections caused by multidrug-resistant gram negative bacilli Y. Boussarsar, F. Boutouta, S. Kamoun, I. Mezghani, S. Koubaji, A. Ben Souissi, A. Riahi, M. S. Mebazaa P078 - Improving outcomes of severe infections by multidrug-resistant pathogens with polyclonal IgM-enriched immunoglobulins E. Giamarellos-Bourboulis, N. Tziolos, C. Routsi, C. Katsenos, I. Tsangaris, I. Pneumatikos, G. Vlachogiannis, V. Theodorou, A. Prekates, E. Antypa, V. Koulouras, N. Kapravelos, C. Gogos, E. Antoniadou, K. Mandragos, A. Armaganidis P079 - Must change the medical practice in ICU? A. R. Robles Caballero, B. Civantos, J. C. Figueira, J. López P080 - Mediterranean spotted fever in an infectious diseases intensive care unit A. Silva-Pinto, F. Ceia, A. Sarmento, L. Santos P081 - Clinical features and outcomes of patients with Middle East respiratory syndrome requiring admission to a saudi intensive care unit: A retrospective analysis of 31 cases G. Almekhlafi, Y. Sakr P082 - The ICU response to a hospital outbreak of Middle East respiratory syndrome coronavirus infection H. Al-Dorzi, R. Khan, S. Baharoon, A. Aldawood, A. Matroud, J. Alchin, S. Al Johani, H. Balkhy, Y. Arabi P083 - Middle East respiratory syndrome: Surveillance data analysis S. Alsolamy, S. Y. Yousif, B. O. Alotabi, A. S. Alsaawi P085 - Use of Taqman array card molecular diagnostics in severe pneumonia: A case series J. Ang, MD Curran, D. Enoch, V. Navapurkar, A. Conway Morris P086 - ‘BUNS’: An investigation protocol improves the ICU management of pneumonia R. Sharvill, J. Astin P087 - Pneumonia in patients following secondary peritonitis: epidemiological features and impact on mortality M. Heredia-Rodríguez, E. Gómez-Sánchez, M. T. Peláez-Jareño, E. Gómez-Pesquera, M. Lorenzo-López, P. Liu-Zhu, M. Aragón-Camino, A. Hernández-Lozano, A. Sánchez-López, E. Álvarez-Fuente, E. Tamayo P088 - The use of the “CURB-65 score” by emergency room clinicians in a large teaching hospital J. Patel, C. Kruger P089 - Incidence of community acquired pneumonia with viral infection in mechanically ventilated patients in the medical intensive care unit J. O’Neal, H. Rhodes, J. Jancik P090 - The SAATELLITE Study: Prevention of S aureus Nosocomial Pneumonia (NP) with MEDI4893, a Human Monoclonal Antibody (mAb) Against S aureus B. François, P. F. Laterre, P. Eggimann, A. Torres, M. Sánchez, P. F. Dequin, G. L. Bassi, J. Chastre, H. S. Jafri P091 - Risk factors and microbiological profile for nosocomial infections in trauma patients M. Ben Romdhane, Z. Douira, S. Kamoun, M. Bousselmi, A. Ben Souissi, Y. Boussarsar, A. Riahi, M.S. Mebazaa P092 - Correlation between percentages of ventilated patients developed vap and use of antimicrobial agents in ICU patients. A. Vakalos, V. Avramidis P093 - A comparison of two ventilator associated pneumonia surveillance techniques T. H. Craven, G. Wojcik, K. Kefala, J. McCoubrey, J. Reilly, R. Paterson, D. Inverarity, I. Laurenson, T. S. Walsh P094 - Lung ultrasound before and after fiberbronchoscopy - modifications may improve ventilator-associated pneumonia diagnosis S. Mongodi, B. Bouhemad, A. Orlando, A. Stella, G. Via, G. Iotti, A. Braschi, F. Mojoli P095 - Comparing the accuracy of predictors of mortality in ventilator-associated pneumonia M. Haliloglu, B. Bilgili, U. Kasapoglu, I. Sayan, M. Süzer Aslan, A. Yalcın, I. Cinel P096 - Impact of pRBCs transfusion on percentage of ventilated patients developed VAP in ICU patients A. Vakalos, V. Avramidis P097 - The impact of a series of interventions on the rate of ventilator associated pneumonia in a large teaching hospital H. E. Ellis, K. Bauchmuller, D. Miller, A Temple P098 - The EVADE study: Prevention of Nosocomial Pneumonia (NP) caused by P aeruginosa with MEDI3902, a Novel Bispecific Monoclonal Antibody, against P aeruginosa virulence factors J. Chastre, B. François, A. Torres, C. E. Luyt, M. Sánchez, M. Singer, H. S. Jafri P099 - Short-term inhaled colistin adjunctive therapy for ventilator-associated pneumonia Y. Nassar, M. S. Ayad P100 - Effect of aerosolised colistin on weaning from mechanical ventilation A. Trifi, S. Abdellatif, F. Daly, R. Nasri, S. Ben Lakhal P101 - Septic shock is an independent risk factor for colistin-induced severe acute kidney injury: a retrospective cohort study B. Bilgili, M. Haliloglu, F. Gul, I. Cinel P102 - Nosocomial pneumonia - emphasis on inhaled tobramycin A. Kuzovlev, A. Shabanov, S. Polovnikov, V. Moroz P103 - In vitro evaluation of amikacin inhale and commercial nebulizers in a mechanical ventilator N. Kadrichu, T. Dang, K. Corkery, P. Challoner P104 - The effects of nebulized amikacin/fosfomycin and systemic meropenem on severe amikacin-resistant meropenem-susceptible P.aeruginosa pneumonia G. Li Bassi, E. Aguilera, C. Chiurazzi, C. Travierso, A. Motos, L. Fernandez, R. Amaro, T. Senussi, F. Idone, J. Bobi, M. Rigol, A. Torres P105 - Optimization of gentamicin peak concentrations in critically ill patients C. J. Hodiamont, N. P. Juffermans, J. M. Janssen, C. S. Bouman, R. A. Mathôt, M. D. De Jong, R. M. Van Hest P106 - Systematic review of cefepime induced neurotoxicity L. Payne, G. L. Fraser P107 - Unasyn® causes QT prolongation during treatment of intensive care patients B. Tudor, M. Lahner, G. Roth, C. Krenn P108 - Comparative study between teicoplanin and vancomycin in methicillin-resistant staphylococcus aureus (mrsa) infectious of toxicological intensive care unit (ticu) patients – Tehran, Iran H. Talaie P109 - Phage therapy against antimicrobial resistance, design of the first clinical study phagoburn P. Jault, J. Gabard, T. Leclerc, S. Jennes, Y. Que, A. Rousseau, F. Ravat P110 - Antibiotic dosing errors in critically ill patients with severe sepsis or septic shock H. Al-Dorzi, A. Eissa, S. Al-Harbi, T. Aldabbagh, R. Khan, Y. Arabi P111 - Does empiric antifungal therapy improve survival in septic critically ill patients? (immunocompromised excluded) A. Trifi, S. Abdellatif, F. Daly, R. Nasri, S. Ben Lakhal P112 - Neurocysticercosis-Qatar experience F. Paramba, N. Purayil, V. Naushad, O. Mohammad, V. Negi, P. Chandra P113 - Early indicators in acute haemorrhagic shock A. Kleinsasser P114 - Filtering of red blood cells reduces the inflammatory response of pulmonary cells in an in vitro model of mechanical ventilation M. R. Witrz, J. F. Buchner-Doeven, A. M. Tuip-de Boer, J. C. Goslings, N. P. Juffermans P115 - Microparticles from red blood cell transfusion induce a pro-coagulant and pro-inflammatory endothelial cell response M. Van Hezel, M. Straat, A Boing, R Van Bruggen, N Juffermans P116 - The contribution of cytokines on thrombosis development during hospitalization in ICU D. Markopoulou, K. Venetsanou, V. Kaldis, D. Koutete, D. Chroni, I. Alamanos P117 - Prophylactic enoxaparin dosing and adjustment through anti-xa monitoring in an inpatient burn unit L. Koch, J. Jancik, H. Rhodes, E. Walter P118 - Determination of optimal cut-off values of haemoglobin, platelet count and fibrinogen at 24 hours after injury associated with mortality in trauma patients K. Maekawa, M. Hayakawa, S. Kushimoto, A. Shiraishi, H. Kato, J. Sasaki, H. Ogura, T. Matauoka, T. Uejima, N. Morimura, H. Ishikura, A. Hagiwara, M. Takeda P119 - Trauma-induced coagulopathy - prothrombin complex concentrate vs fresh frozen plasma O. Tarabrin, S. Shcherbakow, D. Gavrychenko, G. Mazurenko, V. Ivanova, O. Chystikov P120 - First study to prove the superiority of prothrombin complex concentrates on mortality rate over fresh frozen plasma in patients with acute bleeding C. Plourde, J. Lessard, J. Chauny, R. Daoust P121 - Prothrombin complex concentrate vs fresh frozen plasma in obstetric massive bleeding S. Shcherbakow, O. Tarabrin, D. Gavrychenko, G. Mazurenko, O. Chystikov P122 - Impact of FFP transfusion on VAP in ICU patients A. Vakalos, V. Avramidis P123 - Preoperative platelet function test and the thrombin generation assay are predictive for blood loss after cardiac surgery L. Kropman, L. In het Panhuis, J. Konings, D. Huskens, E. Schurgers, M. Roest, B. De Laat, M. Lance P124 - Rotational thromboelastometry versus standard coagulation tests before surgical interventions M. Durila, P. Lukas, M. Astraverkhava, J. Jonas P125 - Correction of impaired clot quality and stability by fibrinogen and activated prothrombin complex concentrate in a model of severe thrombocytopenia I. Budnik, B. Shenkman P126 - Assessment of point-of-care prothrombin time analyzer as a monitor after cardiopulmonary bypass H. Hayami, Y. Koide, T. Goto P127 - Disseminated intravascular coagulation (dic) is underdiagnosed in critically ill patients: do we need d-dimer measurements? R. Iqbal, Y. Alhamdi, N. Venugopal, S. Abrams, C. Downey, C. H. Toh, I. D. Welters P128 - Validity of the age-adjusted d-dimer cutoff in patients with COPD B. Bombay, J. M. Chauny, R. D. Daoust, J. L. Lessard, M. M. Marquis, J. P. Paquet P129 - A scoping review of strategies for prevention and management of bleeding following paediatric cardiopulmonary bypass surgery K. Siemens, D. Sangaran, B. J. Hunt, A. Durward, A. Nyman, I. A. Murdoch, S. M. Tibby P130 - Nadir hemoglobulin during cardiopulmonary bypass: impact on postoperative morbidity and mortality F. Ampatzidou, D. Moisidou, E. Dalampini, M. Nastou, E. Vasilarou, V. Kalaizi, H. Chatzikostenoglou, G. Drossos P131 - Red blood cell transfusion do not influence the prognostic value of RDW in critically ill patients S. Spadaro, A. Fogagnolo, T. Fiore, A. Schiavi, V. Fontana, F. Taccone, C. Volta P132 - Reasons for admission in the paediatric intensive care unit and the need for blood and blood products transfusions E. Chochliourou, E. Volakli, A. Violaki, E. Samkinidou, G. Evlavis, V. Panagiotidou, M. Sdougka P133 - The implementation of a massive haemorrhage protocol (mhp) for the management of major trauma: a ten year, single-centre study R. Mothukuri, C. Battle, K. Guy, G. Mills, P. Evans P134 - An integrated major haemorrhage protocol for pre-hospital and retrieval medical teams J. Wijesuriya, S. Keogh P135 - The impact of transfusion thresholds on mortality and cardiovascular events in patients with cardiovascular disease (non-cardiac surgery): a systematic review and meta-analysis A. Docherty, R. O’Donnell, S. Brunskill, M. Trivella, C. Doree, L. Holst, M. Parker, M. Gregersen, J. Almeida, T. Walsh, S. Stanworth P136 - The relationship between poor pre-operative immune status and outcome from cardiac surgery is specific to the peri-operative antigenic threat S. Moravcova, J. Mansell, A. Rogers, R. A. Smith, C. Hamilton-Davies P137 - Impact of simple clinical practice guidelines for reducing post-operative atrial fibrillation after cardiac surgery. A. Omar, M. Allam, O. Bilala, A. Kindawi, H. Ewila P138 - Dexamethasone administration during cardiopulmonary bypass has no beneficial effects on elective postoperative cardiac surgery patients F. Ampatzidou, D. Moisidou, M. Nastou, E. Dalampini, A. Malamas, E. Vasilarou, G. Drossos P139 - Intra-aortic balloon counterpulsation in patients undergoing cardiac surgery (IABCS): preliminary results G. Ferreira, J. Caldas, J. Fukushima, E. A. Osawa, E. Arita, L. Camara, S. Zeferino, J. Jardim, F. Gaioto, L. Dallan, F. B. Jatene, R. Kalil Filho, .F Galas, L. A. Hajjar P140 - Effects of low-dose atrial natriuretic peptide infusion on cardiac surgery-associated acute kidney injury C. Mitaka, T. Ohnuma, T. Murayama, F. Kunimoto, M. Nagashima, T. Takei, M. Tomita P141 - Acute kidney injury influence on high sensitive troponin measurements after cardiac surgery A. Omar, K. Mahmoud, S. Hanoura, S. Sudarsanan, P. Sivadasan, H. Othamn, Y. Shouman, R. Singh, A. Al Khulaifi P142 - Complex evaluation of endothelial dysfunction markers for prognosis of outcomes in patients undergoing cardiac surgery I. Mandel, S. Mikheev, I. Suhodolo, V. Kiselev, Y. Svirko, Y. Podoksenov P143 - New-onset atrial fibrillation in intensive care: incidence, management and outcome S. A. Jenkins, R. Griffin P144 - One single spot measurement of the sublingual microcirculation during acute pulmonary hypertension in a pig model of shock M. S. Tovar Doncel, A. Lima, C. Aldecoa, C. Ince P145 - Assessment of levosimendan as a therapeutic option to recruit the microcirculation in cardiogenic shock – initial experience in cardiac ICU A. Taha, A. Shafie, M. Mostafa, N. Syed, H. Hon P146 - Terlipressin vs. norepinephrine in the Potential Multiorgan Donor(PMD) F. Righetti, E. Colombaroli, G. Castellano P147 - Echocardiography in the potential heart donor exposed to substitution hormonotherapy F. Righetti, E. Colombaroli P148 - Machine learning can reduce rate of monitor alarms M. Hravnak, L. C. Chen, A. D. Dubrawski, G. C. Clermont, M. R. Pinsky P149 - Peripherally inserted central catheters placed in the ICU S. Gonzalez, D. Macias, J. Acosta, P. Jimenez, A. Loza, A. Lesmes, F. Lucena, C. Leon P150 - Recordings of abnormal central venous pressure waveform morphology during an episode of pulmonary hypertension in a porcine shock model M. S. Tovar Doncel, C. Ince, C. Aldecoa, A. Lima P151 - Ultrasound guided central venous access technique among French intensivists M. Bastide, J. Richecoeur, E. Frenoy, C. Lemaire, B. Sauneuf, F. Tamion, S. Nseir, D. Du Cheyron, H. Dupont, J. Maizel P152 - Predictive ability of the Pv-aCO2 gap in patients with shock M. Shaban, R. Kolko, N. Salahuddin, M. Sharshir, M. AbuRageila, A. AlHussain P153 - Comparison of echocardiography and pulmonary artery catheter measurements of hemodynamic parameters in critical ill patients P. Mercado, J. Maizel, L. Kontar, D. Titeca, F. Brazier, A. Riviere, M. Joris, T. Soupison, B. De Cagny, M. Slama P154 - The volume clamp method for noninvasive cardiac output measurement in postoperative cardiothoracic surgery patients: a comparison with intermittent pulmonary artery thermodilution J. Wagner, A. Körner, M. Kubik, S. Kluge, D. Reuter, B. Saugel P155 - Hemodynamic monitoring in patients with septic shock (SS) – CPCCO (continuous pulse contour cardiac output) vs. TEE (transesophageal echocardiography) E. Colombaroli, F. Righetti, G. Castellano P156 - Cardiac output measurement with transthoracic echocardiography in critically ill patients: a pragmatic clinical study T. Tran, D. De Bels, A. Cudia, M. Strachinaru, P. Ghottignies, J. Devriendt, C. Pierrakos P157 - Left ventricular outflow tract velocity time integral correlates with stroke volume index in mechanically ventilated patients Ó. Martínez González, R. Blancas, J. Luján, D. Ballesteros, C. Martínez Díaz, A. Núñez, C. Martín Parra, B. López Matamala, M. Alonso Fernández, M. Chana P158 - Transpulmonary thermodilution (TPTD) derived from femoral vs. jugular central venous catheter: validation of a previously published correction formula and a proprietary correction formula for global end-diastolic volume index (GEDVI) W. Huber, M. Eckmann, F. Elkmann, A. Gruber, I. Klein, R. M. Schmid, T. Lahmer P160 - Dynamic arterial elastance calculated with lidcoplus monitor does not predict changes in arterial pressure after a fluid challenge in postsurgical patients D. Bastoni, H. Aya, L. Toscani, L. Pigozzi, A. Rhodes, M. Cecconi P159 - Venous return driving pressure and resistance in acute blood volume changes P. W. Moller, S. Sondergaard, S. M. Jakob, J. Takala, D. Berger P160 - Dynamic arterial elastance calculated with lidcoplus monitor does not predict changes in arterial pressure after a fluid challenge in postsurgical patients D. Bastoni, H. Aya, L. Toscani, L. Pigozzi, A. Rhodes, M. Cecconi P161 - Analysis of duration of post-operative goal-directed therapy protocol C. Ostrowska, H. Aya, A. Abbas, J. Mellinghoff, C. Ryan, D. Dawson, A. Rhodes, M. Cecconi P162 - Hemodynamic optimization – back to square one? M. Cronhjort, O. Wall, E. Nyberg, R. Zeng, C. Svensen, J. Mårtensson, E. Joelsson-Alm P163 - Effectiveness of fluid thoracic content measurement by bioimpedance guiding intravascular volume optimization in patients with septic shock M. Aguilar Arzapalo, L. Barradas, V. Lopez, M. Cetina P164 - A systematic review on the role of internal jugular vein ultrasound measurements in assessment of volume status in critical shock patients N. Parenti, C. Palazzi, L. A. Amidei, F. B. Borrelli, S. C. Campanale, F. T. Tagliazucchi, G. S. Sedoni, D. L. Lucchesi, E. C. Carella, A. L Luciani P165 - Importance of recognizing dehydration in medical Intensive Care Unit M. Mackovic, N. Maric, M. Bakula P166 - Effect of volume for a fluid challenge in septic patients H. Aya, A. Rhodes, R. M. Grounds, N. Fletcher, M. Cecconi P167 - Fluid bolus practices in a large Australian intensive care unit B. Avard, P. Zhang P168 - Liberal late fluid management is associated with longer ventilation duration and worst outcome in severe trauma patients: a retrospective cohort of 294 patients M. Mezidi, J. Charbit, M. Ould-Chikh, P. Deras, C. Maury, O. Martinez, X. Capdevila P169 - Association of fluids and outcomes in emergency department patients hospitalized with community-acquired pneumonia P. Hou, W. Z. Linde-Zwirble, I. D. Douglas, N. S. Shapiro P170 - Association of positive fluid balance with poor outcome in medicosurgical ICU patients A. Ben Souissi, I. Mezghani, Y. Ben Aicha, S. Kamoun, B. Laribi, B. Jeribi, A. Riahi, M. S. Mebazaa P171 - Impact of fluid balance to organ dysfunction in critically ill patients C. Pereira, R. Marinho, R. Antunes, A. Marinho P172 - Volume bolus in ICU patients: do we need to balance our crystalloids? M. Crivits, M. Raes, J. Decruyenaere, E. Hoste P173 - The use of 6 % HES solution do not reduce total fluid requirement in the therapy of patients with burn shock V. Bagin, V. Rudnov, A. Savitsky, M. Astafyeva, I. Korobko, V. Vein P174 - Electron microscopic assessment of acute kidney injury in septic sheep resuscitated with crystalloids or different colloids T. Kampmeier , P. Arnemann, M. Hessler, A. Wald, K. Bockbreder, A. Morelli, H. Van Aken, S. Rehberg, C. Ertmer P175 - Alterations of conjunctival microcirculation in a sheep model of haemorrhagic shock and resuscitation with 0.9 % saline or balanced tetrastarch P. Arnemann, M. Hessler, T. Kampmeier, S. Rehberg, H. Van Aken, C. Ince, C. Ertmer P176 - A single centre nested pilot study investigating the effect of using 0.9 % saline or Plasma-Lyte 148 ® as crystalloid fluid therapy on gastrointestinal feeding intolerance in mechanically ventilated patients receiving nasogastric enteral nutrition S. Reddy, M. Bailey, R. Beasley, R. Bellomo, D. Mackle, A. Psirides, P. 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Abisheganaden P182 - Plasma NGAL and urinary output: potential parameters for early initiation of renal replacement therapy K. Maas, H. De Geus P183 - Renal replacement therapy for critically ill patients: an intermittent continuity E. Lafuente, R. Marinho, J. Moura, R. Antunes, A. Marinho P184 - A survey of practices related to renal replacement therapy in critically ill patients in the north of England. T. E. Doris, D. Monkhouse, T. Shipley, S. Kardasz, I Gonzalez P185 - High initiation creatinine associated with lower 28-day mortality in critically ill patients necessitating continuous renal replacement therapy S. Stads, A. J. Groeneveld P186 - The impact of Karnofsky performance scale on outcomes in acute kidney injury patients receiving renal replacement therapy on the intensive care unit I. Elsayed, N. Ward, A. Tridente, A. Raithatha P187 - Severe hypophosphatemia during citrate-anticoagulated CRRT A. Steuber, C. Pelletier, S. Schroeder, E. Michael, T. Slowinski, D. Kindgen-Milles P188 - Citrate regional anticoagulation for post dilution continuous renal replacement therapy S. Ghabina P189 - Citrate 18 mmol/l improves anticoagulation during RRT with adsorbing filters F. Turani, A. Belli, S. Busatti, G. Barettin, F. Candidi, F. Gargano, R. Barchetta, M. Falco P190 - Calcium gluconate instead of calcium chloride in citrate-anticoagulated CVVHD O. Demirkiran, M. Kosuk, S. Bozbay P191 - Enhanced clearance of interleukin-6 with continuous veno-venous haemodialysis (CVVHD) using Ultraflux EMiC2 vs. Ultraflux AV1000S V. Weber, J. Hartmann, S. Harm, I. Linsberger, T. Eichhorn, G. Valicek, G. Miestinger, C. Hoermann P192 - Removal of bilirubin with a new adsorbent system: in vitro kinetics S. Faenza, D. Ricci, E. Mancini, C. Gemelli, A. Cuoghi, S. Magnani, M. Atti P193 - Case series of patients with severe sepsis and septic shock treated with a new extracorporeal sorbent T. Laddomada, A. Doronzio, B. Balicco P194 - In vitro adsorption of a broad spectrum of inflammatory mediators with CytoSorb® hemoadsorbent polymer beads M. C. Gruda, P. O’Sullivan, V. P. Dan, T. Guliashvili, A. Scheirer, T. D. Golobish, V. J. Capponi, P. P. Chan P195 - Observations in early vs. late use of cytosorb therapy in critically ill patients K. Kogelmann, M. Drüner, D. Jarczak P196 - Oxiris membrane decreases endotoxin during rrt in septic patients with basal EAA > 0,6 F. Turani, A. B. Belli, S. M. Martni, V. C. Cotticelli, F. Mounajergi, R. Barchetta P197 - An observational prospective study on the onset of augmented renal clearance: the first report S. Morimoto, H. Ishikura P198 - An ultrasound- guided algorithm for the management of oliguria in severe sepsis I. Hussain, N. Salahuddin, A. Nadeem, K. Ghorab, K. Maghrabi P199 - Ultrasound in acute kidney injury (aki). First findings of farius, an education-programme in structural ultrasonography S. K. Kloesel, C. Goldfuss, A. Stieglitz, A. S. Stieglitz, L. Krstevska, G. Albuszies P200 - Effectiveness of renal angina index score predicting acute kidney injury on critically ill patients M. Aguilar Arzapalo, L. Barradas, V. Lopez, A. Escalante, G. Jimmy, M. Cetina P201 - Time length below blood pressure thresholds and progression of acute kidney injury in critically ill patients with or without sepsis: a retrospective, exploratory cohort study J. Izawa, T. Iwami, S. Uchino, M. Takinami, T. Kitamura, T. Kawamura P202 - Anaemia does not affect renal recovery in acute kidney injury J. G. Powell-Tuck, S. Crichton, M. Raimundo, L. Camporota, D. Wyncoll, M. Ostermann P203 - Estimated glomerular filtration rate based on serum creatinine: actual practice in Dutch ICU’s A. Hana, H. R. De Geus P204 - Comparison of estimated glomerular filtration rate calculated by mdrd, ckd-epi-serum-creatinine and ckd-epi-cystatin-c in adult critically ill patients H. R. De Geus, A. Hana P205 - Early diagnosis of septic acute kidney injury in medical critical care patients with a urine cell cycle arrest marker: insulin like growth factor binding protein-7 (IGFBP-7) M. Aydogdu, N. Boyaci, S. Yuksel, G. Gursel, A. B. Cayci Sivri P206 - Urinary neutrophil gelatinase-associated lipocalin as early biomarker of severe acute kidney injury in intensive care J. Meza-Márquez, J. Nava-López, R. Carrillo-Esper P207 - Shrunken pore syndrome is associated with a sharp rise in mortality in patients undergoing elective coronary artery bypass grafting A. Dardashti, A. Grubb P208 - The biomarker nephrocheck™ can discriminate the septic shock patients with an akin 1 or 2 acute renal failure who will not progress toward the akin 3 level J. Maizel, M. Wetzstein, D. Titeca, L. Kontar, F. Brazier, B. De Cagny, A. Riviere, T. Soupison, M. Joris, M. 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O’Sullivan, L. Sweeney, R. MacLoughlin P232 - Evaluation of vibrating mesh and jet nebuliser performance at two different attachment setups in line with a humidifier nebuliser system A. O’Sullivan, P. Kelly, L. Sweeney, E. Mukeria, M. Wolny , R. MacLoughlin P233 - Psv-niv versus cpap in the treatment of acute cardiogenic pulmonary edema A. Pagano, F. Numis, G. Vison, L. Saldamarco, T. Russo, G. Porta, F. Paladino P234 - Noninvasive ventilation in patients with haematologic malignancy: a retrospective review C. Bell, J. Liu, J. Debacker, C. Lee, E. Tamberg, V. Campbell, S. Mehta P235 - Use of non-invasive ventilation in infectious diseases besides classical indications A. Silva-Pinto, A. Sarmento, L. Santos P236 - The impact of fragility on noninvasive mechanical ventilation application and results in the ICU Ý. Kara, F. Yýldýrým, A. Zerman, Z. Güllü, N. Boyacý, B. Basarýk Aydogan, Ü. Gaygýsýz, K. Gönderen, G. Arýk, M. Turkoglu, M. Aydogdu, G. Aygencel, Z. Ülger, G. 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Zakynthinos P269 - Cell counts in endobronchial aspirate to assess airway inflammation in ARDS patients: a pilot study S. Spadaro, I. Kozhevnikova, F. Dalla Corte, S. Grasso, P. Casolari, G. Caramori, C. Volta P270 - Epidemiological and clinical profile of patients with acute respiratory distress syndrome in the surgical intensive care unit surgical, hospital JRA, Antananarivo T. Andrianjafiarinoa, T. Randriamandrato, T. Rajaonera P271 - Effect of high PEEP after recruitment maneuver on right ventricular function in ARDS. Is it good for the lung and for the heart? S. El-Dash, ELV Costa, MR Tucci, F Leleu, L Kontar, B. De Cagny, F. Brazier, D. Titeca, G. Bacari-Risal, J. Maizel, M. Amato, M. Slama P272 - Effect of recruitment maneuver on left ventricular systolic strain P. Mercado, J. Maizel, L. Kontar, D. Titeca, F. Brazier, A. Riviere, M. Joris, T. Soupison, B. De Cagny, S. El Dash, M. Slama P273 - Inhaled nitric oxide – is switching supplier cost effective? Remmington, A. 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Varo Pérez P279 - Diarrhea is a risk factor for liver injury and may lead to intestinal failure associated liver disease in critical illness N. Lefel, F. Schaap, D. Bergmans, S. Olde Damink, M. Van de Poll P280 - Bowel care on the intensive care unit: constipation guideline compliance and complications K. Tizard, C. Lister, L. Poole P281 - Malnutrition assessed by phase angle determines outcomes in low risk cardiac surgery patients D. Ringaitiene, D. Gineityte, V. Vicka, I. Norkiene, J. Sipylaite P282 - Preoperative fasting times in an irish hospital A. O’Loughlin, V. Maraj, J. Dowling P283 - Costs and final outcome of early x delayed feeding in a private Brazil ICU M. B. Velasco, D. M. Dalcomune, E. B. Dias, S. L. Fernandes P284 - Can ventilator derived energy expenditure measurements replace indirect calorimetry? T. Oshima, S. Graf, C. Heidegger, L. Genton, V. Karsegard, Y. Dupertuis, C. Pichard P285 - Revisiting the refeeding syndrome: results of a systematic review N. Friedli, Z. Stanga, B. Mueller, P. Schuetz P286 - Compliance with the new protocol for parenteral nutrition in our ICU L. Vandersteen, B. Stessel, S. Evers, A. Van Assche, L. Jamaer, J. Dubois P287 - Nutrition may be another treatment in the intensive care unit where less is more? R. Marinho, H. Castro, J. Moura, J. Valente, P. Martins, P. Casteloes, C. Magalhaes, S. Cabral, M. Santos, B. Oliveira, A. Salgueiro, A. Marinho P288 - Should we provide more protein to critically ill patients? R. Marinho, M. Santos, E. Lafuente, H. Castro, S. Cabral, J. Moura, P. Martins, B. Oliveira, A. Salgueiro, S. Duarte, S. Castro, M. Melo, P. Casteloes, A. Marinho P289 Protein provision in an adult intensive care unit S. Gray P290 - Prevalence and clinical outcomes of vitamin d deficiency in the medical critically ill patients in Songklanagarind hospital K. Maipang, R. Bhurayanontachai P291 - Vitamin d deficiency strongly predicts adverse medical outcome across different medical inpatient populations: results from a prospective study L. G. Grädel, P. Schütz P292 - Omega-3 fatty acids in patients undergoing cardiac surgery: a systematic review and meta-analysis P. Langlois, W. Manzanares P293 - Can 5-hydroxytriptophan prevent post-traumatic stress disorder in critically ill patients? R. Tincu, C. Cobilinschi, D. Tomescu, Z. Ghiorghiu, R. Macovei P294 - Parenteral selenium in the critically ill: an updated systematic review and meta-analysis W. Manzanares, P. Langlois, M. Lemieux, G. Elke, F. Bloos, K. Reinhart, D. Heyland P295 - Probiotics in the critically ill: an updated systematic review and meta-analysis P. Langlois, M. Lemieux, I. Aramendi, D. Heyland, W. Manzanares P296 - Diabetes with hyperglycemic crisis episodes may be associated with higher risk of pancreatic cancer: a population-based cohort study Y. Su P297 - Incidence of hypoglycemia in an intensive care unit depending on insulin protocol R. Marinho, N. Babo, A. Marinho P298 - Severity of the diseases is two-dimensionally correlated to blood glucose, including blood glucose variability, especially in moderately to severely ill patients with glucose intolerance. M. Hoshino, Y. Haraguchi, S. Kajiwara, T. Mitsuhashi, T. Tsubata, M. Aida P299 - A study of glycemic control by subcutaneous glargine injection transition from continuous regular insulin infusion in critically ill patients T. Rattanapraphat, R. Bhurayanontachai, C. Kongkamol, B. Khwannimit P300 - Glycemic control in Portuguese intensive care unit R. Marinho, M. Santos, H. Castro, E. Lafuente, A. Salgueiro, S. Cabral, P. Martins, J. Moura, B. Oliveira, M. Melo, B. Xavier, J. Valente, C. Magalhaes, P. Casteloes, A. Marinho P301 - Impact of hyperglycemia duration on the day of operation on short-term outcome of cardiac surgery patients D. Moisidou, F. Ampatzidou, C. Koutsogiannidis, M. Moschopoulou, G. Drossos P302 - Lactate levels in diabetic ketoacidosis patients at ICU admissions G. Taskin, M. Çakir, AK Güler, A. Taskin, N. Öcal, S. Özer, L. Yamanel P303 - Intensive care implications of merging heart attack centre units in London J. M. Wong, C. Fitton, S. Anwar, S. Stacey P304 - Special characteristics of in-hospital cardiac arrests M. Aggou, B. Fyntanidou, S. Patsatzakis, E. Oloktsidou, K. Lolakos, E. Papapostolou, V. Grosomanidis P305 - Clinical evaluation of ICU-admitted patients who were resuscitated in the general medicine ward S. Suda , T. Ikeda, S. Ono, T. Ueno, Y. Izutani P306 - Serious game evaluation of a one-hour training basic life support session for secondary school students: new tools for future bystanders S. Gaudry, V. Desailly, P. Pasquier, PB Brun, AT Tesnieres, JD Ricard, D. Dreyfuss, A. Mignon P307 - Public and clinical staff perceptions and knowledge of CPR compared to local and national data J. C White, A. Molokhia, A. Dean, A. Stilwell, G. Friedlaender P308 Dispatcher-assisted telephone cardiopulmonary resuscitation using a French-language compression-ventilation pediatric protocol M. Peters, S. Stipulante, A. Delfosse, AF Donneau, A. Ghuysen P309 Dantrolene versus amiodarone for resuscitation – an experimental study C. Feldmann, D. Freitag, W. Dersch, M. Irqsusi, D. Eschbach, T. Steinfeldt, H. Wulf, T. Wiesmann P310 Long term survival and functional neurological outcome in comatose survivors undergoing therapeutic hypothermia N. Kongpolprom, J. Cholkraisuwat P311 Impact of kidney disease on mortality and neurological outcome in out-of-hospital cardiac arrest: a prospective observational study S. Beitland , E. Nakstad, H. Stær-Jensen , T. Drægni , G. Andersen , D. Jacobsen , C. Brunborg, B. Waldum-Grevbo , K. Sunde P312 ICU dependency of patients admitted after primary percutaneous coronary intervention (PPCI) following out of the hospital cardiac arrest K. Hoyland, D. Pandit P313 Prognostic indicators and outcome prediction model for patients with return of spontaneous circulation from cardiopulmonary arrest: comprehensive registry of in-hospital intensive care on OHCA survival (critical) study in Osaka, Japan K. Hayakawa P314 Cerebral oxygen saturation during resuscitation in a porcine model of cardiac arrest E. Oloktsidou, K. Kotzampassi, B. Fyntanidou, S. Patsatzakis, L. Loukipoudi, E. Doumaki, V. Grosomanidis P315 Presumption of cardiopulmonary resuscitation for sustaining cerebral oxidation using regional cerebral saturation of oxygen: observational cohort study (press study) H. Yasuda P316 EEG reactivity in patients after cardiac arrest: a close look at stimuli MM Admiraal, M. Van Assen, MJ Van Putten, M. Tjepkema-Cloostermans, AF Van Rootselaar, J. Horn P317 Prognostic value of neuron-specific enolase after cardiac arrest F. Ragusa, A. Marudi , S. Baroni, A. Gaspari, E. Bertellini P318 Correlation between electroencephalographic findings and serum neuron specific enolase with outcome of post cardiac arrest patients A. Taha, T. Abdullah, S. Abdel Monem P319 Introduction of a targeted temperature management strategy following cardiac arrest in a district general hospital intensive care unit. S. Alcorn, S. McNeill, S. Russell P320 The evolution of cerebral oxygen saturation in post-cardiac arrest patients treated with therapeutic hypothermia W. Eertmans, C. Genbrugge, I. Meex, J. Dens, F. Jans, C. De Deyne P321 Prognostic factors and neurological outcomes of therapeutic hypothermia in comatose survivors from cardiac arrest: 8-year single center experience J. Cholkraisuwat, N. Kongpolprom P322 Adherence to targeted temperature management after out of hospital cardiac arrest B. Avard, R. Burns P323 Implementation of a therapeutic hypothermia protocol for comatose survivors of out-of-hospital cardiac arrest. A. Patarchi, T. Spina P324 Factors associated with ventilator weaning after targeted temperature management for cardiac arrest patients in japan H. Tanaka, N. Otani, S. Ode, S. Ishimatsu P325 Differential activation of c-fos in paraventricular nuclei of the hypothalamus and thalamus of the rat following myocardial infarction J. Cho, J. B. Moon, C. W. Park, T. G. Ohk, M. C. Shin, M. H. Won P326 Monitoring of cTroponin I in patients with acute ischemic stroke - predictor of inhospital mortality S. Dakova, Z. Ramsheva, K. Ramshev P327 Hyperthermic preconditioning severely accelerates neuronal damage in the gerbil ischemic hippocampal dentate gyrus via decreasing sods expressions J. Cho, J. B. Moon, C. W. Park, T. G. Ohk, M. C. Shin P328 Failure in neuroprotection of remote limb ischemic post conditioning in the hippocampus of a gerbil model of transient cerebral ischemia J. Cho, J. B. Moon, C. W. Park, T. G. Ohk, M. C. 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Perkins P335 Timing of endovascular and surgical treatment for aneurysmal subarachnoid haemorrhage: early but not so fast. J. Rubio, J. A. Rubio, R. Sierra P336 Red blood cell transfusion in aneurysmal subarachnoid hemorrhage – the Sahara cohort study S. English, M. Chasse, A. Turgeon, F. Lauzier, D. Griesdale, A. Garland, D. Fergusson, R. Zarychanski, A. Tinmouth, C. Van Walraven, K. Montroy, J. Ziegler, R. Dupont Chouinard, R. Carignan, A. Dhaliwal, C. Lum, J. Sinclair, G. Pagliarello, L. McIntyre P337 - Aneurysmal subarachnoid hemorrhage and anemia: a canadian multi-centre retrospective cohort study S. English, M. Chasse, A. Turgeon, F. Lauzier, D. Griesdale, A. Garland, D. Fergusson, R. Zarychanski, A. Tinmouth, C. Van Walraven, K. Montroy, J. Ziegler, R. Dupont Chouinard, R. Carignan, A. Dhaliwal, C. Lum, J. Sinclair, G. Pagliarello, L. McIntyre P338 - Does the neutrophil-to-lymphocyte (NLR) ratio predict symptomatic vasospasm or delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (SAH)? T. Groza, N. Moreau, D. Castanares-Zapatero, P. Hantson P339 - ICU-acquired infections in aneurysmal subarachnoid hemorrhage patients: impact on ICU and hospital length of stay M. Carbonara , F. Ortolano, T. Zoerle, S. Magnoni, S. Pifferi, V. Conte, N. Stocchetti P340 - Cerebral metabolic effects of normobaric hyperoxia during the acute phase of aneurysmal subarachnoid hemorrhage L. Carteron, T. Suys, C. Patet, H. Quintard, M. Oddo P341 - Postoperative care for elective craniotomy: where is best done? J. A. Rubio, J. Rubio, R. Sierra P342 - 5-year follow-up of patients after transplantation of organs from donors from neurocritical care V. Spatenkova, E. Pokorna, P. Suchomel P343 - Evaluation of levetiracetam pharmacokinetics after severe traumatic brain injury in neurocritical care patients at a level one trauma center N. Ebert, J. Jancik, H. Rhodes P344 - Model based time series cluster analysis to determine unique patient states in traumatic brain injury T. Bylinski, C. Hawthorne, M. Shaw, I. Piper, J. Kinsella P345 - Brain compartment monitoring capabilities from ICP to BI (bioimpedance) during HS (hypertonic saline) administration. State of art simulation outcome depending on brain swelling type A. K. Kink , I. R. Rätsep P346 - Transfusion of red blood cells in patients with traumatic brain injury admitted to Canadian trauma health centers: a multicenter cohort study A. Boutin, L. Moore, M. Chasse, R. Zarychanski, F. Lauzier, S. English, L. McIntyre, J. Lacroix, D. Griesdale, P. Lessard-Bonaventure, A. F. Turgeon P347 - Hemoglobin thresholds and red blood cell transfusions in adult patients with moderate or severe traumatic brain injury: a retrospective cohort study A. Boutin, L. Moore, R. Green, P. Lessard-Bonaventure, M. Erdogan, M. Butler, F. Lauzier, M. Chasse, S. English, L. McIntyre, R. Zarychanski, J. Lacroix, D. Griesdale, P. Desjardins, D. A. Fergusson, A. F. Turgeon P348 - Characteristics of patients with gunshot wounds to the head - an observational Brazilian study B. Goncalves, B. Vidal, C. Valdez, A. C. Rodrigues, L. Miguez, G. Moralez P349 - Base excess as predictor for ICU admission and the injury severity in blunt trauma patients T. Hong P350 - Enhancement of usual emergency department care with proadrenomedullin to improve outcome prediction - Results from the multi-national, prospective, observational TRIAGE study A. Kutz, P. Hausfater, D. Amin, T. Struja, S. Haubitz, A. Huber, B. Mueller, P. Schuetz P351 - Developing an innovative emergency medicine point-of-care simulation programme T. Brown, J. Collinson, C. Pritchett, T. Slade P352 - The InSim program: an in situ simulation program for junior trainees in intensive care M. Le Guen, S. Hellings, R. Ramsaran P353 - Impact of excessive and inappropriate troponin testing in the emergency setting how good are we A. Alsheikhly P354 - The development of time tracking monitor at emergency department T. Abe P355 - Role of focussed echocardiography in emergency assessment of syncope L. Kanapeckaite, M. Abu-Habsa, R. Bahl P356 - Insertion of an open-ended 14-gauge catheter through the chest wall causes a significant pneumothorax in a self-ventilating swine model M. Q Russell, K. J. Real, M. Abu-Habsa , R. M. Lyon, N. P. Oveland P357 - Ez-io® intraosseous access teaching in the workplace using a mobile ‘tea trolley’ training method J. Penketh, M. Mcdonald, F. 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Leclerc P364 - A comparison of mortality scores in burns patients on the intensive care unit. O. Howarth, K. Davenport, P. Jeanrenaud, S. Raftery P365 - Clasification of pain and its treatment and an intensive care rehabiliation clinic P. MacTavish, H. Devine, J. McPeake, M. Daniel, J. Kinsella, T. Quasim P366 - Pain management adequacy in critical care areas ,the process and the barriers perceived by critical care nurses S. Alrabiee, A. Alrashid , S. Alsolamy P367 - Pain assessment in critically ill adult patients: validation of the Turkish version of the critical-care pain observation tool O. Gundogan, C. Bor, E. Akýn Korhan, K. Demirag , M. Uyar P368 - An audit of pain and sedation assessments in the intensive care unit: recommendations for clinical practice F. Frame, C. Ashton, L. Bergstrom Niska P369 - Impact of pharmaceutical care on treatment of pain and agitation in medical intensive care unit P. Dilokpattanamongkol, T. Suansanae, C. Suthisisang, S. Morakul, C. Karnjanarachata, V. Tangsujaritvijit P370 - Agitation in trauma ICU, prevention and outcome S. Mahmood, H. Al Thani, A. Almenyar P371 Correlation between percentages of ventilated patients developed vap and use of sedative agents in icu patients. A. Vakalos , V. Avramidis P372 - Improving recording of sedation events in the Emergency Department: The implementation of the SIVA International Taskforce adverse event reporting tool for procedural sedation R. Sharvill, J. Penketh P373 - Impact of sedative drug use on the length of mechanical ventilation S. E. Morton, Y. S. Chiew, C. Pretty, J. G. Chase, G. M. Shaw P374 - Co-administration of nitric oxide and sevoflurane using anaconda R. Knafelj, P. Kordis P375 - A retrospective study of the use of Dexmedetomidine in an oncological critical care setting S. Patel, V. Grover P376 - Dexmedetomidine and posttraumatic stress disorder incidence in alcohol withdrawal icu patients I. Kuchyn, K. Bielka P377 - Hemodynamic effects of dexmedetomidine in a porcine model of septic shock Z. Aidoni, V. Grosomanidis, K. Kotzampassi, G. Stavrou, B. Fyntanidou, S. Patsatzakis, C. Skourtis P378 - Ketamine for analgosedation in severe hypoxic respiratory failure S. D. Lee, K. Williams, I. D. Weltes P379 - Madness from the moon? lunar cycle and the incidence of delirium on the intensive care unit S. Berhane, C. Arrowsmith, C. Peters, S. Robert P380 - Impaired dynamic cerebral autoregulation after coronary artery bypass grafting and association with postoperative delirium J. Caldas, R. B. Panerai, T. G. Robinson, L. Camara, G. Ferreira, E. Borg-Seng-Shu, M. De Lima Oliveira, N. C. Mian, L. Santos, R. Nogueira, S. P. Zeferino, M. Jacobsen Teixeira, F. Galas, L. A. Hajjar P381 - Risk factors predicting prolonged intensive care unit length of stay after major elective surgery. P. Killeen, M. McPhail, W. Bernal, J. Maggs, J. Wendon, T. Hughes P382 - Systemic inflammatory response syndrome criteria and hospital mortality prediction in a brazilian cohort of critically ill patients L. U. Taniguchi, E. M. Siqueira, J. M. Vieira Jr, L. C. Azevedo P383 - Evaluating the efficacy of a risk predictor panel in identifying patients at elevated risk of morbidity following emergency admission A. N. Ahmad, M. Abu-Habsa, R. Bahl, E. Helme, S. Hadfield, R. Loveridge P384 - A retrospective comparison of outcomes for elective surgical patients admitted post-operatively to the critical care unit or general ward J. Shak, C. Senver, R. Howard-Griffin P385 - Effect of obesity on mortality in surgical critically ill patients. P. Wacharasint, P. Fuengfoo, N. Sukcharoen, R. Rangsin P386 - The national early warning score (news) reliably improves adverse clinical outcome prediction in community-acquired pneumonia - results from a 6 year follow-up D. Sbiti-Rohr, P. Schuetz P387 - Clinical usefulness of the charlson¡¯s weighted index of comorbidities _as prognostic factor in patients with prolonged acute mechanical ventilation H. Na, S. Song, S. Lee, E. Jeong, K. Lee P388 - Comparison of mortality prediction scoring systems in patients with cirrhosis admitted to general intensive care unit M. Cooper, K. Milinis, G. Williams, E. McCarron, S. Simants, I. Patanwala, I. D. Welters P389 - Impact of admission source and time of admission on outcome of pediatric intensive care patients: retrospective 15 years study E. Zoumpelouli, EA Volakli, V. Chrysohoidou, S. Georgiou, K. Charisopoulou, E. Kotzapanagiotou, V. Panagiotidou, K. Manavidou, Z. Stathi, M. Sdougka P390 - Heart rate variability and outcomes prediction in critical illness N. Salahuddin, B. AlGhamdi, Q. Marashly, K. Zaza, M. Sharshir, M. Khurshid, Z. Ali, M. Malgapo, M. Jamil, A. Shafquat, M. Shoukri, M. 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Vander Perre, T. Dufour, S. E. Thiessen, F. Güiza, T. Janssens, G. Hermans, I. Vanhorebeek, K. De Bock, G. Van den Berghe, L. Langouche P416 - Physical outcome measures for critical care patients following intensive care unit (icu) discharge H. Devine, P. MacTavish, T. Quasim, J. Kinsella, M. Daniel, J. McPeake P417 - Improving active mobilisation in a general intensive care unit B. Miles , S. Madden, H. Devine P418 - Mobilization in patients on vasoactive drugs use – a pilot study. M. Weiler, P. Marques, C. Rodrigues, M. Boeira, K. Brenner, C. Leães, A. Machado, R. Townsend, J. Andrade P419 - Pharmacy intervention at an intensive care rehabilitation clinic P. MacTavish, J. McPeake, H. Devine, J. Kinsella, M. Daniel, R. Kishore, C. Fenlon, T. Quasim P420 - Interactive gaming is feasible and potentially increases icu patients’ motivation to be engaged in rehabilitation programs T. Fiks, A. Ruijter, M. Te Raa, P. Spronk P421 - Simulation-based design of a robust stopping rule to ensure patient safety Y. S. Chiew, P. Docherty, J. Dickson, E. Moltchanova, C. Scarrot, C. Pretty, G. M. Shaw, J. G. Chase P422 - Are daily blood tests on the intensive care unit necessary? T. Hall, W. C. Ngu, J. M. Jack, P. Morgan P423 - Measuring urine output in ward patients: is it helpful? B. Avard, A. Pavli, X. Gee P424 - The incidence of pressure ulcers in an adult mixed intensive care unit in turkey C . Bor, E. Akin Korhan, K. Demirag, M. Uyar P425 - Intensivist/patient ratios in closed ICUs in Alexandria, Egypt; an overview M. Shirazy, A. Fayed P426 - Eicu (electronic intensive care unit): impact on ALOS (average length of stay) in a developing country like India S. Gupta, A. Kaushal, S. Dewan, A. Varma P427 - Predicting deterioration in general ward using early deterioration indicator E. Ghosh, L. Yang, L. Eshelman, B. Lord, E. Carlson P428 - High impact enhanced critical care outreach - the imobile service: making a difference E. Helme, R. Broderick, S. Hadfield, R. Loveridge P429 - Impact of bed availability and cognitive load on intensive care unit (ICU) bed allocation: a vignette-based trial J. Ramos, D. Forte P430 - Characteristics of critically ill patients admitted through the emergency department F. Yang, P. Hou P431 - Admission to critical care: the quantification of functional reserve J. Dudziak, J. Feeney, K. Wilkinson, K. Bauchmuller, K. Shuker, M. Faulds, A. Raithatha, D. Bryden, L. England, N. Bolton, A. Tridente P432 - Admission to critical care: the importance of frailty K. Bauchmuller, K Shuker, A Tridente, M Faulds, A Matheson, J. Gaynor, D Bryden, S South Yorkshire Hospitals Research Collaboration P433 - Development of an instrument to aid triage decisions for intensive care unit admission J. Ramos, B. Peroni, R. Daglius-Dias, L. Miranda, C. Cohen, C. Carvalho, I . Velasco, D. Forte P434 - Using selective serotonin re-uptake inhibitors and serotonin-norepinephrine re-uptake inhibitors in critical care: a systematic review of the evidence for benefit or harm J. M. Kelly, A. Neill, G. Rubenfeld, N. Masson, A. Min P435 - Measuring adaptive coping of hospitalized patients with a severe medical condition:the sickness insight in coping questionnaire (sicq) E. Boezeman, J. Hofhuis , A. Hovingh, R. De Vries, P. Spronk P436 - Results of a national survey regarding intensive care medicine training G. Cabral-Campello, I. Aragão, T. Cardoso P437 - Work engagement among healthcare professionals in the intensive care unit M. Van Mol, M. Nijkamp, E . Kompanje P438 - Empowering the intensive care practitioners. is it a burnout ameliorating intervention? P. Ostrowski, A. Omar P439 - Icu patients suffer from circadian rhythm desynchronisation K. Kiss , B. Köves, V. Csernus, Z. Molnár P440 - Noise reduction in the ICU: feasible ? Y. Hoydonckx, S. Vanwing, B. Stessel, A. Van Assche, L. Jamaer, J. Dubois P441 - Accidental removal of invasive devices in the critical patient into the bed-washing. does the presence of professional nurse modify his incidence? V. Medo, R. Galvez, J. P. Miranda P442 - Deprivation of liberty safeguards (dols): audit of compliance in a of a 16-bed specialist cancer critical care unit. C. Stone, T. Wigmore P443 - Use of a modified cristal score to predict futility of critical care in the elderly Y. Arunan, A. Wheeler, K. Bauchmuller, D. Bryden P444 - Improvement of Referral Rate to Palliative Care for Patients with Poor Prognosis in Neurosurgical Intensive Care Unit Y. Wong, C. Poi, C. Gu P445 - Factors associated with limitation of life supporting care (lsc) in a medico-surgical intermediate care unit, and outcome of patients with lsc limitation: a monocentric, six-month study. P. Molmy, N. Van Grunderbeeck, O. Nigeon, M. Lemyze, D. Thevenin, J. Mallat P446 - Palliative care consultation and intensive care unit admission request: a cohort study J. Ramos, M. Correa, R. T. Carvalho, D. Forte P447 - Nursing and medicine together in postsurgical intensive care unit: situations of prognostic conflict at the end of life. our critical care nurses suffer with our medical activism? A. Fernandez, C. McBride P448 - End of life who may decide E. Koonthalloor, C. Walsh P449 - Correctly diagnosing death A. Webber, M. Ashe, K. Smith, P. Jeanrenaud P450 - Skin procurement performed by intensive care physicians: yes, we can. A. Marudi , S. Baroni, F. Ragusa, E. Bertellini P451 - Death analysis in pediatric intensive care patients E. A. Volakli , E. Chochliourou, M. Dimitriadou, A. Violaki, P. Mantzafleri, E. Samkinidou, O. Vrani, A. Arbouti, T. Varsami, M. Sdougka P452 - The potential impact of euthanasia on organ donation: analysis of data from belgium J. A. Bollen, T. C. Van Smaalen, W. C. De Jongh, M. M. Ten Hoopen, D. Ysebaert, L. W. Van Heurn, W. N. Van Mook P453 - Communication within an intensive care setting K. Sim, A. Fuller P454 - Development and implementation of a longitudinal communication curriculum for critical care medicine fellows A. Roze des Ordons, P. Couillard, C. Doig P455 - Staff-family conflict in a multi-ethnic intensive care unit R. V. Van Keer, R. D. Deschepper, A. F. Francke, L. H. Huyghens, J. B. Bilsen P456 - Does the source of admission to critical care affect family satisfaction? B. Nyamaizi, C. Dalrymple, A. Molokhia, A. Dobru P457 - A simple alternative to the family satisfaction survey (fs-icu) E. Marrinan, A. Ankuli, A. Molokhia P458 - A study to explore the experiences of patient and family volunteers in a critical care environment: a phenomenological analysis J. McPeake, R. Struthers, R. Crawford , H. Devine , P. Mactavish , T. Quasim P459 - Prevalence and risk factors of anxiety and depression in relatives of burn patients. P. Morelli, M. Degiovanangelo, F. Lemos, V. MArtinez, F. Verga, J. Cabrera, G. Burghi P460 - Guidance of visiting children at an adult intensive care unit (icu) A. Rutten , S. Van Ieperen, S. De Geer, M. Van Vugt, E. Der Kinderen P461 - Visiting policies in Italian pediatric ICUs: an update A. Giannini, G Miccinesi, T Marchesi, E Prandi

negative: Improved Diagnostics Help to Identify Clinical Features and Biomarkers That Predict Mycoplasma pneumoniae Community-acquired Pneumonia in Children BACKGROUND: There are no reliable signs or symptoms that differentiate Mycoplasma pneumoniae (Mp) infection in community-acquired pneumonia (CAP) from other etiologies. Additionally, current diagnostic tests do not reliably distinguish between Mp infection and carriage. We previously determined that the measurement of Mp-specific immunoglobulin M antibody-secreting cells (ASCs) by enzyme-linked immunospot assay allowed for differentiation between infection and carriage. Using this new diagnostic test, we aimed to identify clinical and laboratory features associated with Mp infection. METHODS: This is a prospective cohort study of children, 3–18 years of age, with CAP from 2016 to 2017. Clinical features and biomarkers were compared between Mp-positive and -negative groups by Mann-Whitney U test or Fisher exact test, as appropriate. Area under the receiver operating characteristic curve (AUC) differences and optimal thresholds were determined by using the DeLong test and Youden J statistic, respectively. RESULTS: Of 63 CAP patients, 29 were Mp-positive (46%). Mp positivity was statistically associated with older age (median, 8.6 vs 4.7 years), no underlying disease, family with respiratory symptoms, prior antibiotic treatment, prolonged prodromal respiratory symptoms and fever, and extrapulmonary (skin) manifestations. Lower levels of C-reactive protein, white blood cell count, absolute neutrophil count, and procalcitonin (PCT), specifically PCT <0.25 μg/L, were statistically associated with Mp infection. A combination of age >5 years (AUC = 0.77), prodromal fever and respiratory symptoms >6 days (AUC = 0.79), and PCT <0.25 μg/L (AUC = 0.81) improved diagnostic performance (AUC = 0.90) (P = .05). CONCLUSIONS: A combination of clinical features and biomarkers may aid physicians in identifying patients at high risk for Mp CAP.

negative: Clinical characteristics of hospitalized patients with SARS‐CoV‐2 infection: A single arm meta‐analysis OBJECTIVE: We aim to summarize reliable evidence of evidence‐based medicine for the treatment and prevention of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) by analyzing all the published studies on the clinical characteristics of patients with SARS‐CoV‐2. METHODS: PubMed, Cochrane Library, Embase, and other databases were searched. Several studies on the clinical characteristics of SARS‐CoV‐2 infection were collected for meta‐analysis. RESULTS: Ten studies were included in Meta‐analysis, including a total number of 50466 patients with SARS‐CoV‐2 infection. Meta‐analysis shows that, among these patients, the incidence of fever was 0.891 (95% CI: 0.818, 0.945), the incidence of cough was 0.722 (95% CI: 0.657, 0.782), and the incidence of muscle soreness or fatigue was 0.425 (95% CI: 0.213, 0.652). The incidence of acute respiratory distress syndrome (ARDS) was 0.148 (95% CI: 0.046, 0.296), the incidence of abnormal chest computer tomography (CT) was 0.966 (95% CI: 0.921, 0.993), the percentage of severe cases in all infected cases was 0.181 (95% CI: 0.127, 0.243), and the case fatality rate of patients with SARS‐CoV‐2 infection was 0.043 (95% CI: 0.027, 0.061). CONCLUSION: Fever and cough are the most common symptoms in patients with SARS‐CoV‐2 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 are rare. The case fatality rate of patients with SARS‐CoV‐2 infection is lower than that of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). This meta‐analysis also has limitations, so the conclusions of this Meta‐analysis still need to be verified by more relevant studies with more careful design, more rigorous execution, and larger sample size.

negative: Mechano-genomic regulation of coronaviruses and its interplay with ageing Coronaviruses employ various nuclear signalling mechanisms for their propagation. Here we link replication of coronaviruses, including SARS-CoV-2, the coronavirus disease 2019 (COVID-19)-causing virus, with cytoskeleton-dependent signalling and 3D genome organization. This link could provide novel insights into the high coronavirus pathogenicity in certain cellular states, particularly those associated with ageing.

negative: COVID‐19 and hypertension—evidence and practical management: Guidance from the HOPE Asia Network There are several risk factors for worse outcomes in patients with coronavirus 2019 disease (COVID‐19). Patients with hypertension appear to have a poor prognosis, but there is no direct evidence that hypertension increases the risk of new infection or adverse outcomes independent of age and other risk factors. There is also concern about use of renin‐angiotensin system (RAS) inhibitors due to a key role of angiotensin‐converting enzyme 2 receptors in the entry of the SARS‐CoV‐2 virus into cells. However, there is little evidence that use of RAS inhibitors increases the risk of SARS‐CoV‐2 virus infection or worsens the course of COVID‐19. Therefore, antihypertensive therapy with these agents should be continued. In addition to acute respiratory distress syndrome, patients with severe COVID‐19 can develop myocardial injury and cytokine storm, resulting in heart failure, arteriovenous thrombosis, and kidney injury. Troponin, N‐terminal pro‐B‐type natriuretic peptide, D‐dimer, and serum creatinine are biomarkers for these complications and can be used to monitor patients with COVID‐19 and for risk stratification. Other factors that need to be incorporated into patient management strategies during the pandemic include regular exercise to maintain good health status and monitoring of psychological well‐being. For the ongoing management of patients with hypertension, telemedicine‐based home blood pressure monitoring strategies can facilitate maintenance of good blood pressure control while social distancing is maintained. Overall, multidisciplinary management of COVID‐19 based on a rapidly growing body of evidence will help ensure the best possible outcomes for patients, including those with risk factors such as hypertension.

negative: A Combined approach of MALDI-TOF Mass Spectrometry and multivariate analysis as a potential tool for the detection of SARS-CoV-2 virus in nasopharyngeal swabs Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The rapid, sensitive and specific diagnosis of SARS-CoV-2 by fast and unambiguous testing is widely recognized to be critical in responding to the ongoing outbreak. Since the current testing capacity of RT-PCR-based methods is being challenged due to the extraordinary demand of supplies, such as RNA extraction kits and PCR reagents worldwide, alternative and/or complementary testing assays should be developed. Here, we exploit the potential of mass spectrometry technology combined with machine learning algorithms as an alternative fast tool for SARS-CoV-2 detection from nasopharyngeal swabs samples. According to our preliminary results, mass spectrometry-based methods combined with multivariate analysis showed an interesting potential as a complementary diagnostic tool and further steps should be focused on sample preparation protocols and the improvement of the technology applied.

negative: Up-regulation of IL-6 and TNF-α induced by SARS-coronavirus spike protein in murine macrophages via NF-κB pathway Abstract The clinical picture of severe acute respiratory syndrome (SARS) is characterized by an over-exuberant immune response with lung lymphomononuclear cells infilteration and proliferation that may account for tissue damage more than the direct effect of viral replication. To understand how cells response in the early stage of virus–host cell interaction, in this study, a purified recombinant S protein was studied for stimulating murine macrophages (RAW264.7) to produce proinflammatory cytokines (IL-6 and TNF-α) and chemokine IL-8. We found that direct induction of IL-6 and TNF-α release in the supernatant in a dose-, time-dependent manner and highly spike protein-specific, but no induction of IL-8 was detected. Further experiments showed that IL-6 and TNF-α production were dependent on NF-κB, which was activated through I-κBα degradation. These results suggest that SARS-CoV spike protein may play an important role in the pathogenesis of SARS, especially in inflammation and high fever.

negative: Biomarkers of Infection: Are They Useful in the ICU? Biomarkers are increasingly used in patients with serious infections in the critical care setting to complement clinical judgment and interpretation of other diagnostic and prognostic tests. The main purposes of such blood markers are (1) to improve infection diagnosis (i.e., differentiation between bacterial vs. viral vs. fungal vs. noninfectious), (2) to help in the early risk stratification and thus provide prognostic information regarding the risk for mortality and other adverse outcomes, and (3) to optimize antibiotic tailoring to individual needs of patients (“antibiotic stewardship”). Especially in critically ill patients, in whom sepsis is a major cause of morbidity and mortality, rapid diagnosis is desirable to start timely and specific treatment. Besides some biomarkers, such as procalcitonin, which is well established and has shown positive effects in regard to utilization of antimicrobials and clinical outcomes, there is a growing number of novel markers from different pathophysiological pathways, where the final proof of an added value to clinical judgment and ultimately clinical benefit to patients is still lacking. Without a doubt, the addition of blood biomarkers to clinical medicine has had a strong impact on the way we care for patients today. Recent trials show that as an adjunct to other clinical and laboratory parameters these markers provide important information about risks for bacterial infection and resolution of infection. Moreover, biomarkers can help to optimize management of patients with serious illness in the intensive care unit, thereby offering more individualized treatment courses with overall improvements in clinical outcomes.

negative: Dynamical asymmetry exposes 2019-nCoV prefusion spike The novel coronavirus (2019-nCoV) spike protein is a smart molecular machine that instigates the entry of coronavirus to the host cell causing the COVID-19 pandemic. In this study, a structural-topology based model Hamiltonian of C3 symmetric trimeric spike is developed to explore its complete conformational energy landscape using molecular dynamic simulations. The study finds 2019-nCoV to adopt a unique strategy by undertaking a dynamic conformational asymmetry induced by a few unique inter-chain interactions. This results in two prevalent asymmetric structures of spike where one or two spike heads lifted up undergoing a dynamic transition likely to enhance rapid recognition of the host-cell receptor turning on its high-infectivity. The crucial interactions identified in this study are anticipated to potentially affect the efficacy of therapeutic targets. One Sentence Summary Inter-chain-interaction driven rapid symmetry breaking strategy adopted by the prefusion trimeric spike protein likely to make 2019-nCoV highly infective.

negative: Timely mental health care for the 2019 novel coronavirus outbreak is urgently needed

negative: Chest CT features of the novel coronavirus disease (COVID-19). A new type of coronavirus (2019-nCoV) is rapidly spreading worldwide and causes pneumonia, respiratory distress, thromboembolic events, and death. Chest computed tomography (CT) plays an essential role in the diagnosis of viral pneumonia, monitoring disease progression, determination of disease severity, and evaluating therapeutic efficacy. Chest CT can show important clues of 2019-nCoV disease (also known as COVID-19) in patients with an appropriate clinic. Prompt diagnosis of COVID-19 is essential to prevent disease transmission and provide close clinical observation of patients with clinically severe disease. Therefore, radiologists and clinicians should be familiar with the CT imaging findings of COVID-19 pneumonia. Herein we aimed to review the imaging findings of COVID-19 pneumonia and to examine the critical points to be considered for imaging in cases with COVID-19 suspicion.

negative: 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.

negative: The differential expression of micro-RNAs 21, 200c, 204, 205, and 211 in benign, dysplastic and malignant melanocytic lesions and critical evaluation of their role as diagnostic biomarkers Overlapping histological features between benign and malignant lesions and a lack of firm diagnostic criteria for malignancy result in high rates of inter-observer variation in the diagnosis of melanocytic lesions. We aimed to investigate the differential expression of five miRNAs (21, 200c, 204, 205, and 211) in benign naevi (n = 42), dysplastic naevi (n = 41), melanoma in situ (n = 42), and melanoma (n = 42) and evaluate their potential as diagnostic biomarkers of melanocytic lesions. Real-time PCR showed differential miRNA expression profiles between benign naevi; dysplastic naevi and melanoma in situ; and invasive melanoma. We applied a random forest machine learning algorithm to classify cases based on their miRNA expression profiles, which resulted in a ROC curve analysis of 0.99 for malignant melanoma and greater than 0.9 for all other groups. This indicates an overall very high accuracy of our panel of miRNAs as a diagnostic biomarker of benign, dysplastic, and malignant melanocytic lesions. However, the impact of variable lesion percentage and spatial expression patterns of miRNAs on these real-time PCR results was also considered. In situ hybridisation confirmed the expression of miRNA 21 and 211 in melanocytes, while demonstrating expression of miRNA 205 only in keratinocytes, thus calling into question its value as a biomarker of melanocytic lesions. In conclusion, we have validated some miRNAs, including miRNA 21 and 211, as potential diagnostic biomarkers of benign, dysplastic, and malignant melanocytic lesions. However, we also highlight the crucial importance of considering tissue morphology and spatial expression patterns when using molecular techniques for the discovery and validation of new biomarkers.

negative: Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China A novel coronavirus (2019-nCoV) originating in Wuhan, China presents a potential respiratory viral pandemic to the world population. Current efforts are focused on containment and quarantine of infected individuals. Ultimately, the outbreak could be controlled with a protective vaccine to prevent 2019-nCoV infection. While vaccine research should be pursued intensely, there exists today no therapy to treat 2019-nCoV upon infection, despite an urgent need to find options to help these patients and preclude potential death. Herein, I review the potential options to treat 2019-nCoV in patients, with an emphasis on the necessity for speed and timeliness in developing new and effective therapies in this outbreak. I consider the options of drug repurposing, developing neutralizing monoclonal antibody therapy, and an oligonucleotide strategy targeting the viral RNA genome, emphasizing the promise and pitfalls of these approaches. Finally, I advocate for the fastest strategy to develop a treatment now, which could be resistant to any mutations the virus may have in the future. The proposal is a biologic that blocks 2019-nCoV entry using a soluble version of the viral receptor, angiotensin-converting enzyme 2 (ACE2), fused to an immunoglobulin Fc domain (ACE2-Fc), providing a neutralizing antibody with maximal breath to avoid any viral escape, while also helping to recruit the immune system to build lasting immunity. The ACE2-Fc therapy would also supplement decreased ACE2 levels in the lungs during infection, thereby directly treating acute respiratory distress pathophysiology as a third mechanism of action. The sequence of the ACE2-Fc protein is provided to investigators, allowing its possible use in recombinant protein expression systems to start producing drug today to treat patients under compassionate use, while formal clinical trials are later undertaken. Such a treatment could help infected patients before a protective vaccine is developed and widely available in the coming months to year(s).

negative: Pathogen screening and prognostic factors in children with severe ARDS of pulmonary origin BACKGROUND: Acute respiratory distress syndrome (ARDS) is one of the most lethal diseases encountered in the pediatric intensive care unit (PICU). The etiological pathogens and prognostic factors of severe ARDS of pulmonary origin in children with respiratory virus infections were prospectively investigated. METHODS: Enrolled children fulfilled the following criteria: (1) PICU admission; (2) age of 1 month to 16 years; (3) diagnosis of infectious pneumonia and respiratory virus infection; and (4) development of severe ARDS within 72 h after PICU admission. Pathogens were detected in the blood and tracheal lavage fluid using molecular techniques and a conventional culture system. The serum levels of inflammatory mediators on the day of PICU admission were examined. RESULTS: Fifty‐seven patients (32 boys; median age, 9 months) were enrolled. Multiple virus infections, co‐infection with bacteria/fungus, and bacteremia/fungemia were observed in 60%, 49%, and 32% of children, respectively. Adenovirus‐B, measles virus, and cytomegalovirus were detected predominantly in tracheal lavage fluid. There were no statistically significant differences between non‐survivors and survivors regarding the types of pathogen, incidence of multiple virus infection, gender, age, clinical features, and treatment. The serum levels of interferon (IFN)‐γ and the IFN‐γ/interleukin (IL)‐10 ratio were higher in non‐survivors. CONCLUSIONS: IFN‐γ upregulation as detected on the day of PICU admission was found to be one of the possible prognostic factors affecting a fatal outcome. These results suggest that modulation of inflammatory responses is critical for the clinical management of children with ARDS.

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

negative: SERUM BIOMARKERS FOR PSYCHIATRIC DISORDERS

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

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

negative: Letter to the Editor: Acute hypertriglyceridemia in patients with COVID‐19 receiving tocilizumab Tocilizumab is an interleukin‐6 (IL‐6) receptor antibody and is progressing as a viable and promising treatment option in patients with severe coronavirus disease 2019 (COVID‐19). IL‐6 is known to have both immunomodulatory and metabolic actions. In this letter we outline two cases of acute hypertriglyceridemia in patients with COVID‐19 treated with tocilizumab: one with elevated biomarkers consistent with acute pancreatitis the other without. Given the paucity of robust clinical trial data for most COVID‐19 pharmacotherapies at this time, clinicians should continue to remain steadfast in recognition of interventions that improve clinical outcomes and vigilant in monitoring for acute adverse effects that are difficult to detect in clinical trials with small sample sizes. The observations from our two cases highlight the complex, not fully elucidated interrelationship between elevated IL‐6 and pharmacologic interventions impacting this pathway. Clinicians should consider monitoring for hypertriglyceridemia and acute pancreatitis as described with chronic tocilizumab use for rheumatoid arthritis in those receiving it for COVID‐19. This article is protected by copyright. All rights reserved.

negative: Inflammatory Cytokine Expression Is Associated with Chikungunya Virus Resolution and Symptom Severity The Chikungunya virus infection zones have now quickly spread from Africa to parts of Asia, North America and Europe. Originally thought to trigger a disease of only mild symptoms, recently Chikungunya virus caused large-scale fatalities and widespread economic loss that was linked to recent virus genetic mutation and evolution. Due to the paucity of information on Chikungunya immunological progression, we investigated the serum levels of 13 cytokines/chemokines during the acute phase of Chikungunya disease and 6- and 12-month post-infection follow-up from patients of the Italian outbreak. We found that CXCL9/MIG, CCL2/MCP-1, IL-6 and CXCL10/IP-10 were significantly raised in the acute phase compared to follow-up samples. Furthermore, IL-1β, TNF-α, Il-12, IL-10, IFN-γ and IL-5 had low initial acute phase levels that significantly increased at later time points. Analysis of symptom severity showed association with CXCL9/MIG, CXCL10/IP-10 and IgG levels. These data give insight into Chikungunya disease establishment and subsequent convalescence, which is imperative to the treatment and containment of this quickly evolving and frequently re-emerging disease.

negative: Angiotensin II plasma levels are linked to disease severity and predict fatal outcomes in H7N9-infected patients A novel influenza A (H7N9) virus of avian origin emerged in eastern China in the spring of 2013. This virus causes severe disease in humans, including acute and often lethal respiratory failure. As of January 2014, 275 cases of H7N9-infected patients had been reported, highlighting the urgency of identifying biomarkers for predicting disease severity and fatal outcomes. Here, we show that plasma levels of angiotensin II, a major regulatory peptide of the renin–angiotensin system, are markedly elevated in H7N9 patients and are associated with disease progression. Moreover, the sustained high levels of angiotensin II in these patients are strongly correlated with mortality. The predictive value of angiotensin II is higher than that of C-reactive protein and some clinical parameters such as the PaO(2)/FiO(2) ratio (partial pressure of arterial oxygen to the fraction of inspired oxygen). Our findings indicate that angiotensin II is a biomarker for lethality in flu infections. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/ncomms4595) contains supplementary material, which is available to authorized users.

negative: Hundreds of people volunteer to be infected with coronavirus

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

negative: Aetiology of community-acquired pneumonia among adults in an H1N1 pandemic year: the role of respiratory viruses This study aimed to determine the aetiology of community-acquired pneumonia (CAP) by adding polymerase chain reaction (PCR) to conventional methods and to describe the clinical and laboratory features between patients with bacterial pneumonia (BP) and viral pneumonia (VP). Adults with CAP admitted from November 2009 to October 2010 were included. Demographics, comorbidities, severity and clinical features were recorded. Conventional microbiological methods included blood and sputum cultures, acute and convalescent serologic samples, and antigen urinary detection. New methods included multiplex PCR for Mycoplasma pneumoniae, Legionella pneumophila, Chlamydophila pneumoniae, Bordetella pertussis and 15 respiratory viruses. A total of 169 patients were included. Using conventional methods, we identified a pathogen in 51 % of cases. With PCR, up to 70 % of cases had an aetiological diagnosis. Forty-five patients had BP (34 %), 22 had VP (17 %) and 25 (19 %) had co-infection (BP and VP). Pneumococci and respiratory syncytial virus (RSV) were the most frequently identified pathogens. Procalcitonin (PCT) and C-reactive protein (CRP) median values were significantly higher in BP than in VP patients. Shaking chills, higher CURB score and shock were significantly more frequent in BP. A viral infection was identified in more than one-third of patients with CAP. Clinical and laboratory features could help to differentiate between VP and BP and to guide empirical therapy.

negative: Strategies for the development of drugs targeting novel coronavirus 2019-nCoV/ 药学学报 @# There is no specific drug that has been approved for 2019-nCoV. There are a number of factors that pose major challenges in their development. Approaches to the development of anti-2019-nCoV include screening existing broad-spectrum antiviral drugs, repositioning of readily available clinical compounds, and <italic>de novo</italic> development of novel and specific agents for 2019-nCoV. Candidate compounds can be developed either to inhibit virus-based targets, such as RNA proteases, polymerase, spike glycoproteins, and viral envelop and membrane proteins, or to inhibit host-based targets, such as receptors and proteases that are utilized by virus for viral entry and endocytosis. Recently, the RNA polymerase remdesivir had demonstrated clinical efficacy in one patient with severe novel coronavirus pneumonia (NCP). The broad-spectrum viral protease inhibitor Kaletra<sup>®</sup> is also recommended in the current NCP clinical practice. Both drugs had lately been proceeded into multiple controlled phase III clinical trials to test their safety and efficacy in NCP. Combinational therapies consisting of multiple drugs provide other viable options against 2019-nCoV, based on scientific and clinical rationales. Using bioinformatics and database analysis, we have identified 75 clinically compounds, including 20 marketed compounds, that are efficacious in inhibiting key targets in virus- and host-based approaches, which may facilitate the development of new therapeutic options for 2019-nCoV.

negative: A Novel Scoring System for Prediction of Disease Severity in COVID-19 Background: A novel enveloped RNA beta coronavirus, Corona Virus Disease 2019 (COVID-19) caused severe and even fetal pneumonia in China and other countries from December 2019. Early detection of severe patients with COVID-19 is of great significance to shorten the disease course and reduce mortality. Methods: We assembled a retrospective cohort of 80 patients (including 56 mild and 24 severe) with COVID-19 infection treated at Beijing You'an Hospital. We used univariable and multivariable logistic regression analyses to select the risk factors of severe and even fetal pneumonia and build scoring system for prediction, which was validated later on in a group of 22 COVID-19 patients. Results: Age, white blood cell count, neutrophil, glomerular filtration rate, and myoglobin were selected by multivariate analysis as candidates of scoring system for prediction of disease severity in COVID-19. The scoring system was applied to calculate the predictive value and found that the percentage of ICU admission (20%, 6/30) and ventilation (16.7%, 5/30) in patients with high risk was much higher than those (2%, 1/50; 2%, 1/50) in patients with low risk (p = 0.009; p = 0.026). The AUC of scoring system was 0.906, sensitivity of prediction is 70.8%, and the specificity is 89.3%. According to scoring system, the probability of patients in high risk group developing severe disease was 20.24 times than that in low risk group. Conclusions: The possibility of severity in COVID-19 infection predicted by scoring system could help patients to receiving different therapy strategies at a very early stage. Topic: COVID-19, severe and fetal pneumonia, logistic regression, scoring system, prediction.

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: Optical techniques for fast screening – towards prevention of the coronavirus COVID-19 outbreak • Coronavirus disease 2019 (COVID-19) is emerging and requires early diagnostics. • Biomarkers are present for coronaviruses. • Raman and FT-IR spectroscopy are green technologies capable of high-throughput virus sensing.

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: Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody The newly identified 2019 novel coronavirus (2019-nCoV) has caused more than 11,900 laboratory-confirmed human infections, including 259 deaths, posing a serious threat to human health. Currently, however, there is no specific antiviral treatment or vaccine. Considering the relatively high identity of receptor-binding domain (RBD) in 2019-nCoV and SARS-CoV, it is urgent to assess the cross-reactivity of anti-SARS CoV antibodies with 2019-nCoV spike protein, which could have important implications for rapid development of vaccines and therapeutic antibodies against 2019-nCoV. Here, we report for the first time that a SARS-CoV-specific human monoclonal antibody, CR3022, could bind potently with 2019-nCoV RBD (KD of 6.3 nM). The epitope of CR3022 does not overlap with the ACE2 binding site within 2019-nCoV RBD. These results suggest that CR3022 may have the potential to be developed as candidate therapeutics, alone or in combination with other neutralizing antibodies, for the prevention and treatment of 2019-nCoV infections. Interestingly, some of the most potent SARS-CoV-specific neutralizing antibodies (e.g. m396, CR3014) that target the ACE2 binding site of SARS-CoV failed to bind 2019-nCoV spike protein, implying that the difference in the RBD of SARS-CoV and 2019-nCoV has a critical impact for the cross-reactivity of neutralizing antibodies, and that it is still necessary to develop novel monoclonal antibodies that could bind specifically to 2019-nCoV RBD.

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

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

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

negative: 2015 ACVIM Forum Research Abstract Program

negative: Characteristics and Outcomes of Coronavirus Infection in Children: The Role of Viral Factors and an Immunocompromised State BACKGROUND: Immunocompromised children might be predisposed to serious infections from human coronaviruses (HCoVs), including strains OC43, NL63, HKU1, and 229E; however, the virologic and clinical features of HCoV infection in immunocompromised children have not been compared to those in nonimmunocompromised children. METHODS: We retrospectively analyzed a cohort of children who presented to Seattle Children’s Hospital and in whom HCoV was detected by a multiplex respiratory polymerase chain reaction assay of a nasal sample between October 2012 and March 2016. Lower respiratory tract disease (LRTD) was defined as possible or definite infiltrate seen in chest imaging, need for oxygen, or abnormal lung examination in conjunction with a physician diagnosis of LRTD. We used logistic regression modeling to evaluate risk factors for LRTD and LRTD that necessitated oxygen use (severe LRTD), including an immunocompromised state, in children with HCoV infection. RESULTS: The median ages of 85 immunocompromised and 1152 nonimmunocompromised children with HCoV infection were 6.3 and 1.6 years, respectively. The prevalence of LRTD and of severe LRTD did not differ greatly between the immunocompromised and nonimmunocompromised patients (22% vs 26% [LRTD] and 15% vs 11% [severe LRTD], respectively); however, in a multivariable model, an immunocompromised state was associated with an increased likelihood of severe LRTD (adjusted odds ratio, 2.5 [95% confidence interval, 1.2–4.9]; P = .01). Younger age, having an underlying pulmonary disorder, and the presence of respiratory syncytial virus were also associated with LRTD or severe LRTD in multivariable models. The risks of LRTD or severe LRTD did not differ among the children with different HCoV strains. CONCLUSIONS: The presence of a copathogen and host factors, including an immunocompromised state, were associated with increased risk for severe LRTD. Recognizing risk factors for severe respiratory illness might assist in risk stratification.

negative: Protein Structure and Sequence Reanalysis of 2019-nCoV Genome Refutes Snakes as Its Intermediate Host and the Unique Similarity between Its Spike Protein Insertions and HIV-1 [Image: see text] As the infection of 2019-nCoV coronavirus is quickly developing into a global pneumonia epidemic, the careful analysis of its transmission and cellular mechanisms is sorely needed. In this Communication, we first analyzed two recent studies that concluded that snakes are the intermediate hosts of 2019-nCoV and that the 2019-nCoV spike protein insertions share a unique similarity to HIV-1. However, the reimplementation of the analyses, built on larger scale data sets using state-of-the-art bioinformatics methods and databases, presents clear evidence that rebuts these conclusions. Next, using metagenomic samples from Manis javanica, we assembled a draft genome of the 2019-nCoV-like coronavirus, which shows 73% coverage and 91% sequence identity to the 2019-nCoV genome. In particular, the alignments of the spike surface glycoprotein receptor binding domain revealed four times more variations in the bat coronavirus RaTG13 than in the Manis coronavirus compared with 2019-nCoV, suggesting the pangolin as a missing link in the transmission of 2019-nCoV from bats to human.

negative: Drug allergy labeling and delabeling in the coronavirus disease 2019 era: What is important and what do we need to know

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: Risk interactions of coronavirus infection across age groups after the peak of COVID-19 epidemic Background: the COVID-19 epidemic has incurred significant disease burden worldwide, particularly on elderly population. This study aims to explore how risks of infection interact across age groups and compared risk patterns between South Korea and US Florida state. Methods: Daily new COVID-19 cases were scraped from online sources. A multivariate vector autoregressive model for time series count data was used to examine the risk interactions across age groups. Case counts from previous days were included as predictors to dynamically examine the change of risk patterns. Results: In both South Korea and Florida, the risk of coronavirus infection among elderly people was significantly affected by other age groups. An increase of virus infection among people aged 20 -39 could double the risk of infection among elderly people. Meanwhile, an increase in virus infection among elderly people also significantly increased risks of infection among other age groups. The risks of infection among younger people were relatively unaffected by that of other age groups. Conclusions: Protecting elderly people from coronavirus infection could not only reduce the risk of infection among themselves but also ameliorate the risks of virus infection among other age groups. Such interventions should be effective and for long term.

negative: 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.

negative: A survey of 434 clinical trials about coronavirus disease 2019 in China

negative: Saliva is a reliable tool to detect SARS-CoV-2 Summary Objectives This study analyzed salivary samples of COVID-19 patients and compared the results with their clinical and laboratory data. Methods Salivary samples of 25 COVID-19 patients were analyzed by rRT-PCR. The following data were collected: age, sex, comorbidities, drugs. Lactate dehydrogenase (LDH) and ultrasensitive reactive C protein (usRCP) values were registered on the same day when a salivary swab was collected. Prevalence of positivity in saliva and association between clinical data and the cycle threshold as a semiquantitative indicator of viral load were considered. Results Twenty-five subjects were recruited into this study, 17 males and 8 females. The mean age was 61.5 +/− 11.2 years. Cardiovascular and/or dysmetabolic disorders were observed in 65.22% of cases. All the samples tested positive for the presence of SARS-CoV-2, while there was an inverse association between LDH and Ct values. Two patients showed positive salivary results on the same days when their pharyngeal or respiratory swabs showed conversion. Conclusions Saliva is a reliable tool to detect SARS-CoV-2. The role of saliva in COVID-19 diagnosis could not be limited to a qualitative detection of the virus, but it may also provide information about the clinical evolution of the disease.

negative: Pathophysiology and biomarkers of acute respiratory distress syndrome Acute respiratory distress syndrome (ARDS) is defined as an acute-onset, progressive, hypoxic condition with radiographic bilateral lung infiltration, which develops after several diseases or injuries, and is not derived from hydrostatic pulmonary edema. One specific pathological finding of ARDS is diffuse alveolar damage. In 2012, in an effort to increase diagnostic specificity, a revised definition of ARDS was published in JAMA. However, no new parameters or biomarkers were adopted by the revised definition. Discriminating between ARDS and other similar diseases is critically important; however, only a few biomarkers are currently available for diagnostic purposes. Furthermore, predicting the severity, response to therapy, or outcome of the illness is also important for developing treatment strategies for each patient. However, the PaO(2)/FIO(2) ratio is currently the sole clinical parameter used for this purpose. In parallel with progress in understanding the pathophysiology of ARDS, various humoral factors induced by inflammation and molecules derived from activated cells or injured tissues have been shown as potential biomarkers that may be applied in clinical practice. In this review, the current understanding of the basic pathophysiology of ARDS and associated candidate biomarkers will be discussed.

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: Emergence of deadly severe acute respiratory syndrome coronavirus-2 during 2019–2020 Wuhan, the city in Hubei province in China is in the focus of global community due to the outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), formerly known as 2019-nCoV. The virus emerged in humans from Wuhan seafood market probably via zoonotic transmission. Within a few days the virus spread its tentacles rapidly to neighboring cities in China and to different geographical regions through travelers and to some extent by human to human transmission leading to significant disease burden globally. More than 2,00,000 people (including more than 8000 deaths) have been infected with this respiratory illness across 167 countries and territories worldwide leading to a pandemic. The present review provides an outline about emergence and spread of SARS-CoV-2 from Wuhan, China in 2019–2020. We have also provided information about the classification, genome, proteins, clinical presentation of COVID-19, type of clinical specimens to be collected and diagnostic methods adopted to identify the respiratory illness. In addition we have also provided information about transmission dynamics, prevention measures and treatment options that are available at the present. Subsequently, we have given a comprehensive overview of the spread of this infection from China to the other parts of the globe. Management of the ongoing outbreak of SARS-CoV-2 encompassing surveillance, clinical, immunological, genetic and evolutionary investigations are likely to provide the desired results. Joint efforts of global scientific community are needed at this hour in terms of enhancement of research on development of accurate diagnostics, antiviral therapeutics and finally into formation of an effective vaccine against the emerging novel coronavirus.

negative: Screening and identification of T helper 1 and linear immunodominant antibody-binding epitopes in the spike 2 domain and the nucleocapsid protein of feline infectious peritonitis virus The antibody-dependent enhancement (ADE) of feline infectious peritonitis virus (FIPV) infection has been recognized in experimentally infected cats, and cellular immunity is considered to play an important role in preventing the onset of feline infectious peritonitis (FIP). In the present study, we synthesized eighty-one kinds of peptides derived from the spike (S)2 domain of type I FIPV KU-2 strain, the S2 domain of type II FIPV 79-1146 strain, and the nucleocapcid (N) protein of FIPV KU-2 strain. To detect the T helper (Th)1 epitope, peripheral blood mononuclear cells (PBMCs) obtained from FIPV-infected cats were cultured with each peptide, and Th1-type immune responses were measured using feline interferon (fIFN)-γ production as an index. To detect the linear immunodominant antibody-binding epitope, we investigated the reactivity of plasma collected from FIPV-infected cats against each peptide by ELISA. Four and 2 peptides containing Th1 epitopes were identified in the heptad repeat (HR)1 and inter-helical (IH) regions of the S2 domain of type I FIPV, respectively, and these were located on the N-terminal side of the regions. In the S2 domain of type II FIPV, 2, 3, and 2 peptides containing Th1 epitopes were identified in the HR1, IH, and HR2 regions, respectively, and these were mainly located on the C-terminal side of the regions. In the S2 domain of type I FIPV, 3 and 7 peptides containing linear immunodominant antibody-binding epitopes were identified in the IH and HR2 regions, respectively. In the S2 domain of type II FIPV, 4 peptides containing linear immunodominant antibody-binding epitopes were identified in the HR2 region. The Th1 epitopes in the S2 domain of type I and II FIPV were located in different regions, but the linear immunodominant antibody-binding epitopes were mostly located in the HR2 region. Eight peptides containing Th1 epitopes were identified in N protein, and 3 peptides derived from residues 81 to 100 and 137 to 164 showed strong inductivity of fIFN-γ production in PBMCs isolated from type I FIPV- and type II FIPV-infected non-FIP cats. In N protein, 4 peptides containing linear immunodominant antibody-binding epitopes were identified, and 2 peptides derived from residues 345 to 372 showed strong reactivity with plasma of type I FIPV- and type II FIPV-infected cats. The Th1 and linear immunodominant antibody-binding epitopes were located at different positions in both the S2 domain and N protein. Our results may provide important information for the development of peptide-based vaccine against FIPV infection.

negative: METATRYP v 2.0: Metaproteomic Least Common Ancestor Analysis for Taxonomic Inference Using Specialized Sequence Assemblies - Standalone Software and Web Servers for Marine Microorganisms and Coronaviruses We present METATRYP version-2 software that identifies shared peptides across organisms within environmental metaproteomics studies to enable accurate taxonomic attribution of peptides during protein inference. Improvements include: ingestion of complex sequence assembly data categories (metagenomic and metatranscriptomic assemblies, single cell amplified genomes, and metagenome assembled genomes), prediction of the Least Common Ancestor (LCA) for a peptide shared across multiple organisms, increased performance through updates to the backend architecture, and development of a web portal (https://metatryp.whoi.edu). Major expansion of the marine database confirms low occurrence of shared tryptic peptides among disparate marine microorganisms, implying tractability for targeted metaproteomics. METATRYP was designed for ocean metaproteomics and has been integrated into the Ocean Protein Portal (https://oceanproteinportal.org); however, it can be readily applied to other domains. We describe the rapid deployment of a coronavirus-specific web portal (https://metatryp-coronavirus.whoi.edu/) to aid in use of proteomics on coronavirus research during the ongoing pandemic. A Coronavirus-focused METATRYP database identified potential SARS-CoV-2 peptide biomarkers and indicated very few shared tryptic peptides between SARS-CoV-2 and other disparate taxa, sharing 0.1% peptides or less (1 peptide) with the Influenza A & B pan-proteomes, establishing that taxonomic specificity is achievable using tryptic peptide-based proteomic diagnostic approaches. Statement of significance When assigning taxonomic attribution in bottom-up metaproteomics, the potential for shared tryptic peptides among organisms in mixed communities should be considered. The software program METATRYP v 2 and associated interactive web portals enables users to identify the frequency of shared tryptic peptides among taxonomic groups and evaluate the occurrence of specific tryptic peptides within complex communities. METATRYP facilitates phyloproteomic studies of taxonomic groups and supports the identification and evaluation of potential metaproteomic biomarkers.

negative: Potential of large “first generation” human‐to‐human transmission of 2019‐nCoV To investigate the genetic diversity, time origin, and evolutionary history of the 2019‐nCoV outbreak in China and Thailand, a total of 12 genome sequences of the virus with known sampling date (24 December 2019 and 13 January 2020) and geographic location (primarily Wuhan city, Hubei Province, China, but also Bangkok, Thailand) were analyzed. Phylogenetic and likelihood‐mapping analyses of these genome sequences were performed. On the basis of our results, the star‐like signal and topology of 2019‐nCoV may be indicative of potentially large “first generation” human‐to‐human virus transmission. We estimated that 2019‐nCoV likely originated in Wuhan on 9 November 2019 (95% credible interval: 25 September 2019 and 19 December 2019), and that Wuhan is the major hub for the spread of the 2019‐nCoV outbreak in China and elsewhere. Our results could be useful for designing effective prevention strategies for 2019‐nCoV in China and beyond.

negative: A Case Series of children with 2019 novel coronavirus infection: clinical and epidemiological features We first described the 2019 novel coronavirus infection in 10 children occurring in areas other than Wuhan. The coronavirus diseases in children are usually mild and epidemiological exposure is a key clue to recognize pediatric case. Prolonged virus shedding is observed in respiratory tract and feces at the convalescent stage.

negative: Persistent viral RNA positivity during recovery period of a patient with SARS‐CoV‐2 infection As an emerging infectious disease, the clinical course and virological course of SARS‐CoV‐2 infection remain to be further investigated. In this case report, we described a case of SARS‐CoV‐2 infection with clinical course more than two months. This patient had recovered from the pneumonia after treatment. The viral RNA of throat swabs became negative and the viral specific antibodies were produced during recovery period. However, the viral RNA reappeared and additionally persisted in throat swabs for more than 40 days. In addition, the viral RNA was detected in multiple types of specimens with extremely high titers in the saliva. In conclusion, these findings indicate that SARS‐CoV‐2 can cause a long clinical course. The coexistence of viral RNA and viral specific antibodies may imply an immune evasion of SARAS‐CoV‐2 from host's immune system. This article is protected by copyright. All rights reserved.

negative: Fulminant myocarditis and COVID-19. Response

negative: COVID-19: disease pathways and gene expression changes predict methylprednisolone can improve outcome in severe cases

negative: Commentary: COVID-19 in patients with diabetes

negative: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral–fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral–fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.

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: Rapid SARS-CoV-2 whole genome sequencing for informed public health decision making in the Netherlands SARS-CoV-2 is a novel coronavirus that has rapidly spread across the globe. In the Netherlands, the first case of SARS-CoV-2 has been notified on the 27th of February. Here, we describe the first three weeks of the SARS-CoV-2 outbreak in the Netherlands, which started with several different introductory events from Italy, Austria, Germany and France followed by local amplification in, and later also, outside the South of the Netherlands. The timely generation of whole genome sequences combined with epidemiological investigations facilitated early decision making in an attempt to control local transmission of SARS-CoV-2 in the Netherlands.

negative: Rapid detection of taxonomically important fatty acid methyl ester and steroid biomarkers using in situ thermal hydrolysis/methylation mass spectrometry (THM-MS): implications for bioaerosol detection Abstract Implications for the rapid interrogation of biological materials collected from the atmosphere using a simple, one step, sample preparation technique was explored. For this purpose, various samples of whole bacteria, fungi, pollen, media contaminated with viruses, and proteins were treated with an aliquot of methanolic tetramethylammonium hydroxide prior to thermal introduction into the ion source of a triple quadrupole mass spectrometer. Molecular and fragment ions, consistent with fatty acid methyl esters (FAMEs) and steroids (non-methylated and methylated), generated during electron ionization (70 eV) of the volatile hydrolysates were subsequently detected. The varying distributions and relative intensities of these ions were used to discriminate between the different biological samples. More specifically, it was found that polyunsaturated FAMEs and steroids could be used to differentiate eukaryotic cells from prokaryotic cells since the latter do not generally synthesize either of these lipid membrane constituents. Further discrimination of the different eukaryotic samples was made based on the detection of ergosterol for fungi, cholesterol for the viral media, and C18:3Me for pollen. Multivariate statistical analysis was employed to evaluate and compare the large set of mass spectra generated during the study and to build a trained model for predicting the class membership of test samples entered as unknowns. Of 132 different samples subjected to the model as unknowns, 131 were correctly classified into their proper biological categories. Moreover, 29 out of 30 bacteria test samples representing five species of pathogenic bacteria were correctly classified at the species level.

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: Prediction of Antimicrobial Potential of a Chemically Modified Peptide From Its Tertiary Structure Designing novel antimicrobial peptides is a hot area of research in the field of therapeutics especially after the emergence of resistant strains against the conventional antibiotics. In the past number of in silico methods have been developed for predicting the antimicrobial property of the peptide containing natural residues. This study describes models developed for predicting the antimicrobial property of a chemically modified peptide. Our models have been trained, tested and evaluated on a dataset that contains 948 antimicrobial and 931 non-antimicrobial peptides, containing chemically modified and natural residues. Firstly, the tertiary structure of all peptides has been predicted using software PEPstrMOD. Structure analysis indicates that certain type of modifications enhance the antimicrobial property of peptides. Secondly, a wide range of features was computed from the structure of these peptides using software PaDEL. Finally, models were developed for predicting the antimicrobial potential of chemically modified peptides using a wide range of structural features of these peptides. Our best model based on support vector machine achieve maximum MCC of 0.84 with an accuracy of 91.62% on training dataset and MCC of 0.80 with an accuracy of 89.89% on validation dataset. To assist the scientific community, we have developed a web server called “AntiMPmod” which predicts the antimicrobial property of the chemically modified peptide. The web server is present at the following link (http://webs.iiitd.edu.in/raghava/antimpmod/).

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

negative: Host Biomarkers and Paediatric Infectious Diseases: From Molecular Profiles to Clinical Application Infectious diseases are an important cause of death among children under the age of 5 (Stein et al., 2004). Most of these deaths are caused by preventable or curable infections. Limited access to medical care, antibiotics, and vaccinations remains a major problem in developing countries. But infectious diseases also continue to be an important public health issue in developed countries. With the help of modern technologies, some infections have been effectively controlled; however, new diseases such as SARS and West Nile virus infections are constantly emerging. In addition, other diseases such as malaria, tuberculosis, and bacterial pneumonia are increasingly resistant to antimicrobial treatment.

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

negative: Coronaviruses — drug discovery and therapeutic options In humans, infections with the human coronavirus (HCoV) strains HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1 usually result in mild, self-limiting upper respiratory tract infections, such as the common cold. By contrast, the CoVs responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), which were discovered in Hong Kong, China, in 2003, and in Saudi Arabia in 2012, respectively, have received global attention over the past 12 years owing to their ability to cause community and health-care-associated outbreaks of severe infections in human populations. These two viruses pose major challenges to clinical management because there are no specific antiviral drugs available. In this Review, we summarize the epidemiology, virology, clinical features and current treatment strategies of SARS and MERS, and discuss the discovery and development of new virus-based and host-based therapeutic options for CoV infections. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrd.2015.37) contains supplementary material, which is available to authorized users.

negative: COVID-19 diagnosis and study of serum SARS-CoV-2 specific IgA, IgM and IgG by a quantitative and sensitive immunoassay Background The current pandemic of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a great loss in lives and economy. Detecting viral RNAs on nasopharyngeal and throat swabs is the standard approach for SARS-CoV-2 diagnosis with variable success. Currently, there are only a few studies describing the serological diagnostic methods that involve the detection of SARS-CoV-2-specific IgM and IgG. Here, we aimed to develop a more quantitative and sensitive serological test for COVID-19 diagnosis, monitoring and clinical investigation, based on the detection of antigen-specific IgA as well as IgM and IgG in blood in response to SARS-CoV-2 infection. Methods In this investigation, we report the development of a set of validated diagnostic kits for detecting serum IgA, IgM, and IgG specific to SARS-CoV-2 nucleocapsid protein (NP) and receptor-binding domain (RBD) of the spike protein by chemi-luminescence immuno-analysis. The kits were tested with a cohort of 216 sera from 87 laboratory-confirmed COVID-19 patients, and 483 sera from SARS-CoV-2 negative or healthy individuals as negative controls. A standard receiver operating characteristic (ROC) analysis was conducted to evaluate the diagnostic accuracy. Using the kits, serum levels of IgA, IgM, and IgG were analyzed, in response to SARS-CoV-2 infection and COVID-19 pathogenesis. Findings The diagnostic kits based on the RBD antigen outperformed those based on the NP. RBD-specific IgA, IgM, and IgG detection kits showed sensitivities of 98.6%, 96.8%, and 96.8%, and specificities of 98.1%, 92.3%, and 99.8%, respectively. In addition, using purified RBD-specific immunoglobulins from a serum pool of COVID-19 patients as standards, the serum concentrations of RBD-specific IgA, IgM, and IgG proteins were determined. The concentrations varied widely among different patients. Median concentration of IgA and IgM reached peaks at 16-20 days after illness onset at 8.84 μg/mL and 7.25 μg/mL, respectively, while median concentration of IgG peaked during 21-25 days after illness onset at 16.47 μg/mL. Furthermore, the serum IgA level positively correlates with COVID-19 severity. Interpretation Our immunoassay of measuring SARS-CoV-2 specific antibodies IgA, IgM, and IgG in serum provides a better serological testing with improved sensitivity and specificity. Data of IgA, IgM, and IgG responses in blood of COVID-19 patients may provide novel insight for the monitoring and treatments of COVID-19. The kits are also suitable for epidemiological studies and vaccine validations.

negative: Detection of Severe Acute Respiratory Syndrome Coronavirus in the Brain: Potential Role of the Chemokine Mig in Pathogenesis Background. Previous studies have shown that common human coronavirus might be neurotropic, although it was first isolated as a pathogen of the respiratory tract. We noticed that a few patients with severe acute respiratory syndrome (SARS) experienced central nervous symptoms during the course of illness. In the present study, we isolated a SARS coronavirus strain from a brain tissue specimen obtained from a patient with SARS with significant central nervous symptoms. Methods. Using transmission electronic microscopy and nested reverse transcription–polymerase chain reaction, the causative pathogen was identified in cultures of a brain tissue specimen obtained from the patient with SARS. Histopathologic examination of the brain tissue was performed using the methods of immunohistochemistry analysis and double immunofluorescence staining. Fifteen cytokines and chemokines were detected in the blood of the patient with SARS by means of a bead-based multiassay system. Results. A fragment specific for SARS human coronavirus was amplified from cultures of the brain suspension, and transmission electronic microscopy revealed the presence of an enveloped virus morphologically compatible with a coronavirus isolated in the cultures. Pathologic examination of the brain tissue revealed necrosis of neuron cells and broad hyperplasia of gliocytes. Immunostaining demonstrated that monokine induced by interferon-Γ (Mig) was expressed in gliocytes with the infiltration of CD68(+) monocytes/macrophages and CD3(+) T lymphocytes in the brain mesenchyme. Cytokine/chemokine assay revealed that levels of interferon-Γ–inducible protein 10 and Mig in the blood were highly elevated, although the levels of other cytokines and chemokines were close to normal. Conclusions. This study provides direct evidence that SARS human coronavirus is capable of infecting the central nervous system, and that Mig might be involved in the brain immunopathology of SARS.

negative: A comparative-descriptive analysis of clinical characteristics in 2019-Coronavirus-infected children and adults. Acute respiratory disease (ARD) caused by 2019 novel coronavirus (2019-nCoV) has rapidly spread throughout China. Children and adults show a different clinical course. The purpose of the current study is to comparatively analyze the clinical characteristics of 2019-nCoV infection in children and adults and to explore the possible causes for the discrepancies present. The medical records of 25 adults and 7 children confirmed cases of 2019-nCoV ARD were reviewed retrospectively. All children were family clusters. The total adult patients were differentiated into: the local residents of Wuhan, a history of travel to Wuhan and direct contact with people from Wuhan. The numbers were 14 (56%), 10 (40%) & 1 (4%), respectively. The median incubation period of children and adults was 5 days (range 3-12 days) and 4 days (range 2-12 days), respectively. Diarrhoea and/or vomiting (57.1%) were more common in children, whereas for adults it was myalgia or fatigue (52%). On admission, the percentage of children having pneumonia (5, 71.4%) was roughly the same as adults (20, 80%). 20% of adults had leucopoenia, but leukocytosis was more frequently in children (28.6%, P=0.014). A higher number of children had elevated creatine kinase isoenzyme (57.1% vs. 4%, P=0.004). Antiviral therapy was given to all adult patients but to none of the children. In summary, knowledge of these differences between children and adults will not only be helpful for the clinical diagnosis of 2019 novel coronavirus disease (COVID-19), but also for a future discussion on age-specific coronavirus infection. This article is protected by copyright. All rights reserved.

negative: Immune response biomarkers in human and veterinary research Abstract Biomarkers are increasingly utilised in biological research and clinical practice for diagnosis of disease, monitoring of therapeutic prognosis, or as end points in clinical studies. Cytokines are small molecules that orchestrate immune responses and as such have great potential as biomarkers for both human and veterinary fields. Given the ease of sampling in the blood, and their high prevalence in clinical applications we will focus on protein detection as an area for biomarker discovery. This is facilitated by new technological developments such as digital ELISA that have led to significant increases in sensitivity. Two highly relevant examples include type I interferons, namely IFNα, that is now directly quantifiable by digital ELISA from biological samples. The application of this approach to the study of the unique bat interferon response may reveal novel findings with applications in both human and veterinary research. As a second example we will describe the use of CXCL10 as a disease biomarker in Tuberculosis, highlighting findings from human and mouse studies that should be considered in veterinary research. In summary, we describe how cytokines may be applied as novel biomarkers and illustrate two key examples where human and veterinary research may complement each other in line with the One Health objectives.

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

negative: Sensitivity evaluation of 2019 novel coronavirus (SARS-CoV-2) RT-PCR detection kits and strategy to reduce false negative An ongoing outbreak of pneumonia associated with SARS-CoV-2 has now been confirmed globally. In absence of effective vaccines, infection prevention and control through diagnostic testing and quarantine is critical. Early detection and differential diagnosis of respiratory infections increases the chances for successful control of COVID-19 disease. The nucleic acid RT-PCR test is regarded as the current standard for molecular diagnosis with high sensitivity. However, the highest specificity confirmation target ORF1ab gene is considered to be less sensitive than other targets in clinical application. In addition, a large amount of recent evidence indicates that the initial missed diagnosis of asymptomatic patients with SARS-CoV-2 and discharged patients with "re-examination positive" may be due to low viral load, and the ability of rapid mutation of coronavirus also increases the rate of false negative results. We aimed to evaluate the sensitivity of different nucleic acid detection kits so as to make recommendations for the selection of validation kit, and amplify the suspicious result to be reportable positive by means of simple continuous amplification, which is of great significance for the prevention and control of the current epidemic and the discharge criteria of low viral load patients.

negative: Exosomes and the kidney: prospects for diagnosis and therapy of renal diseases Exosomes are 40–100 nm membrane vesicles secreted into the extracellular space by numerous cell types. These structures can be isolated from body fluids including urine and plasma. Exosomes contain proteins, mRNAs, miRNAs, and signaling molecules that reflect the physiological state of their cells of origin and consequently provide a rich source of potential biomarker molecules. Aside from diagnostic uses, exosome-mediated transfer of proteins, mRNAs, miRNAs, and signaling molecules offer the promise that they may be used for therapeutic purposes. In this review, we integrate new knowledge about exosomes from outside the field of nephrology with recent progress by renal researchers in order to provide a basis for speculation about how the study of exosomes may impact the fields of nephrology and renal physiology in the next few years.

negative: Veno‐venous extracorporeal membrane oxygenation for severe pneumonia: COVID‐19 case in Japan BACKGROUND: Veno‐venous extracorporeal membrane oxygenation (VV‐ECMO) is one of the ultimate treatments for acute respiratory failure. However, the effectiveness of ECMO in patients with novel coronavirus disease (COVID‐19) is unknown. CASE PRESENTATION: A 72‐year‐old woman who was a passenger of a cruise ship tested positive for the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) while in quarantine on board using throat swab. Three days after admission, her condition deteriorated, and she was subsequently intubated. On day 6, VV‐ECMO was introduced. Lopinavir/ritonavir was given; continuous renal replacement therapy was also introduced. On day 10, her chest radiography and lung compliance improved. She was weaned off ECMO on day 12. CONCLUSION: Treatment of severe pneumonia in COVID‐19 by ECMO should recognize lung plasticity considering time to ECMO introduction and interstitial biomarkers. In Japan, centralization of ECMO patients has not been sufficient. Thus, we suggest nationwide centralization and further research to respond to the crisis caused by COVID‐19.

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: Aspects of nano-enabling biosensing systems for intelligent healthcare; towards COVID-19 management Biosensors are emerging as efficient (sensitive and selective) and affordable analytical diagnostic tools for early-stage disease detection, as required for personalized health wellness management. Low-level detection of a targeted disease biomarker (pM level) has emerged extremely useful to evaluate the progression of disease under therapy. Such collected bioinformatics and its multi-aspects-oriented analytics is in demand to explore the effectiveness of prescribed treatment, optimize therapy, and correlate biomarker level with disease pathogenesis. Owing to nanotechnology-enabled advancements in sensing unit fabrication, device integration, interfacing, packaging, and sensing performance at point-of-care (POC) made diagnostics according to the requirements of disease management and patient disease profile i.e., in a personalized manner. Efforts are continuously being made to promote state of art biosensing technology as a next-generation non-invasive disease diagnostics methodology. Keeping this in view, this progressive opinion article describes personalized health care management related analytical tools which provide access to better health for everyone, overall to manage healthy tomorrow timely. Considering accomplishments and predictions, such affordable intelligent diagnostics tools are urgently required to manage COVID-19 pandemic, a life-threatening respiratory infectious disease, where a rapid, selective and sensitive detection of human beta severe acute respiratory system coronavirus (SARS-COoV-2) protein is the key factor.

negative: Recombinant nucleocapsid protein-based enzyme-linked immunosorbent assay for detection of antibody to turkey coronavirus Abstract Nucleocapsid (N) protein gene of turkey coronavirus (TCoV) was expressed in a prokaryotic system and used to develop an enzyme-linked immunosorbent assay (ELISA) for detection of antibody to TCoV. Anti-TCoV hyperimmune turkey serum and normal turkey serum were used as positive or negative controls for optimization of the ELISA. Goat anti-turkey IgG (H+L) conjugated with horseradish peroxidase was used as detector antibody. Three hundred and twenty two turkey sera from the field were used to evaluate the performance of ELISA and determine the cut-off point of ELISA. The established ELISA was also examined with serum samples obtained from turkeys experimentally infected with TCoV. Those serum samples were collected at various time intervals from 1 to 63 days post-infection. The optimum conditions for differentiation between anti-TCoV hyperimmune serum and normal turkey serum were recombinant TCoV N protein concentration at 20μg/ml, serum dilution at 1:800, and conjugate dilution at 1:10,000. Of the 322 sera from the field, 101 were positive for TCoV by immunofluorescent antibody assay (IFA). The sensitivity and specificity of the ELISA relative to IFA test were 86.0% and 96.8%, respectively, using the optimum cut-off point of 0.2 as determined by logistic regression method. Reactivity of anti-rotavirus, anti-reovirus, anti-adenovirus, or anti-enterovirus antibodies with the recombinant N protein coated on the ELISA plates was not detected. These results indicated that the established antibody-capture ELISA in conjunction with recombinant TCoV N protein as the coating protein can be utilized for detection of antibodies to TCoV in turkey flocks.

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

negative: Influence of viral infection on the relationships between airway cytokines and lung function in asthmatic children BACKGROUND: Few longitudinal studies examine inflammation and lung function in asthma. We sought to determine the cytokines that reduce airflow, and the influence of respiratory viral infections on these relationships. METHODS: Children underwent home collections of nasal lavage during scheduled surveillance periods and self-reported respiratory illnesses. We studied 53 children for one year, analyzing 392 surveillance samples and 203 samples from 85 respiratory illnesses. Generalized estimated equations were used to evaluate associations between nasal lavage biomarkers (7 mRNAs, 10 proteins), lung function and viral infection. RESULTS: As anticipated, viral infection was associated with increased cytokines and reduced FVC and FEV(1). However, we found frequent and strong interactions between biomarkers and virus on lung function. For example, in the absence of viral infection, CXCL10 mRNA, MDA5 mRNA, CXCL10, IL-4, IL-13, CCL4, CCL5, CCL20 and CCL24 were negatively associated with FVC. In contrast, during infection, the opposite relationship was frequently found, with IL-4, IL-13, CCL5, CCL20 and CCL24 levels associated with less severe reductions in both FVC and FEV(1). CONCLUSIONS: In asthmatic children, airflow obstruction is driven by specific pro-inflammatory cytokines. In the absence of viral infection, higher cytokine levels are associated with decreasing lung function. However, with infection, there is a reversal in this relationship, with cytokine abundance associated with reduced lung function decline. While nasal samples may not reflect lower airway responses, these data suggest that some aspects of the inflammatory response may be protective against viral infection. This study may have ramifications for the treatment of viral-induced asthma exacerbations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-018-0922-9) contains supplementary material, which is available to authorized users.

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

negative: Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2 Human coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV) and 2019 novel coronavirus (2019-nCoV, also known as SARS-CoV-2), lead global epidemics with high morbidity and mortality. However, there are currently no effective drugs targeting 2019-nCoV/SARS-CoV-2. Drug repurposing, representing as an effective drug discovery strategy from existing drugs, could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we present an integrative, antiviral drug repurposing methodology implementing a systems pharmacology-based network medicine platform, quantifying the interplay between the HCoV–host interactome and drug targets in the human protein–protein interaction network. Phylogenetic analyses of 15 HCoV whole genomes reveal that 2019-nCoV/SARS-CoV-2 shares the highest nucleotide sequence identity with SARS-CoV (79.7%). Specifically, the envelope and nucleocapsid proteins of 2019-nCoV/SARS-CoV-2 are two evolutionarily conserved regions, having the sequence identities of 96% and 89.6%, respectively, compared to SARS-CoV. Using network proximity analyses of drug targets and HCoV–host interactions in the human interactome, we prioritize 16 potential anti-HCoV repurposable drugs (e.g., melatonin, mercaptopurine, and sirolimus) that are further validated by enrichment analyses of drug-gene signatures and HCoV-induced transcriptomics data in human cell lines. We further identify three potential drug combinations (e.g., sirolimus plus dactinomycin, mercaptopurine plus melatonin, and toremifene plus emodin) captured by the “Complementary Exposure” pattern: the targets of the drugs both hit the HCoV–host subnetwork, but target separate neighborhoods in the human interactome network. In summary, this study offers powerful network-based methodologies for rapid identification of candidate repurposable drugs and potential drug combinations targeting 2019-nCoV/SARS-CoV-2.

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: Potential preanalytical and analytical vulnerabilities in the laboratory diagnosis of coronavirus disease 2019 (COVID-19). A novel zoonotic coronavirus outbreak is spreading all over the world. This pandemic disease has now been defined as novel coronavirus disease 2019 (COVID-19), and is sustained by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As the current gold standard for the etiological diagnosis of SARS-CoV-2 infection is (real time) reverse transcription polymerase chain reaction (rRT-PCR) on respiratory tract specimens, the diagnostic accuracy of this technique shall be considered a foremost prerequisite. Overall, potential RT-PCR vulnerabilities include general preanalytical issues such as identification problems, inadequate procedures for collection, handling, transport and storage of the swabs, collection of inappropriate or inadequate material (for quality or volume), presence of interfering substances, manual errors, as well as specific aspects such as sample contamination and testing patients receiving antiretroviral therapy. Some analytical problems may also contribute to jeopardize the diagnostic accuracy, including testing outside the diagnostic window, active viral recombination, use of inadequately validated assays, insufficient harmonization, instrument malfunctioning, along with other specific technical issues. Some practical indications can hence be identified for minimizing the risk of diagnostic errors, encompassing the improvement of diagnostic accuracy by combining clinical evidence with results of chest computed tomography (CT) and RT-PCR, interpretation of RT-PCR results according to epidemiologic, clinical and radiological factors, recollection and testing of upper (or lower) respiratory specimens in patients with negative RT-PCR test results and high suspicion or probability of infection, dissemination of clear instructions for specimen (especially swab) collection, management and storage, together with refinement of molecular target(s) and thorough compliance with analytical procedures, including quality assurance.

negative: Blood parameters measured on admission as predictors of outcome for COVID-19; a prospective UK cohort study Abstract: Introduction: COVID-19 has an unpredictable clinical course so prognostic biomarkers would be invaluable when triaging patients on admission to hospital. Many biomarkers have been suggested using large observational datasets but sample timing is crucial to ensure prognostic relevance. The DISCOVER study prospectively recruited patients with COVID-19 admitted to a UK hospital and analysed a panel of putative prognostic biomarkers on the admission blood sample to identify markers of poor outcome. Methods: Consecutive patients admitted to hospital with proven or clinicoradiological suspected COVID-19 were recruited. Admission bloods were extracted from the clinical laboratory. A panel of biomarkers (IL-6, suPAR, KL-6, Troponin, Ferritin, LDH, BNP, Procalcitonin) were performed in addition to routinely performed markers (CRP, neutrophils, lymphocytes, neutrophil:lymphocyte ratio). Age, NEWS score and CURB-65 were included as comparators. All biomarkers were tested in logistic regression against a composite outcome of non-invasive ventilation, intensive care admission, or death, with Area Under the Curve (AUC) figures calculated. Results: 155 patients had 28-day outcomes at the time of analysis. CRP (AUC 0.51 ,CI:0.40-0.62), lymphocyte count (AUC 0.62 ,CI:0.51-0.72), and other routine markers did not predict the primary outcome. IL-6 (AUC: 0.78,0.65-0.89) and suPAR (AUC 0.77 ,CI: 0.66-0.85) showed some promise, but simple clinical features alone such as NEWS score (AUC: 0.74 ,0.64-0.83) or age (AUC: 0.70 ,0.61-0.78) performed nearly as well. Discussion: Admission blood biomarkers have only moderate predictive value for predicting COVID-19 outcomes, while simple clinical features such as age and NEWS score outperform many biomarkers. IL-6 and suPAR had the best performance, and further studies should validate these biomarkers in a prospective fashion.

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: Differential expression of serum/plasma proteins in various infectious diseases: Specific or nonspecific signatures Apart from direct detection of the infecting organisms or biomarker of the pathogen itself, surrogate host markers are also useful for sensitive and early diagnosis of pathogenic infections. Early detection of pathogenic infections, discrimination among closely related diseases with overlapping clinical manifestations, and monitoring of disease progression can be achieved by analyzing blood biomarkers. Therefore, over the last decade large numbers of proteomics studies have been conducted to identify differentially expressed human serum/plasma proteins in different infectious diseases with the intent of discovering novel potential diagnostic/prognostic biomarkers. However, in‐depth review of the literature indicates that many reported biomarkers are altered in the same way in multiple infectious diseases, regardless of the type of infection. This might be a consequence of generic acute phase reactions, while the uniquely modulated candidates in different pathogenic infections could be indicators of some specific responses. In this review article, we will provide a comprehensive analysis of differentially expressed serum/plasma proteins in various infectious diseases and categorize the protein markers associated with generic or specific responses. The challenges associated with the discovery, validation, and translational phases of serum/plasma biomarker establishment are also discussed.

negative: The clinical value of biomarkers in respiratory complications in hematopoietic SCT To determine the role of biomarkers in the clinical management of respiratory complications (RC) in hematopoietic stem cell transplantation (HSCT) recipients, we have prospectively evaluated a cohort of 175 patients followed-up for 1 year after HSCT. To avoid misinterpretation, we have excluded both unidentified respiratory infections (RI) and mixed RI. A total of 64 RC were included. Plasma levels of C-reactive protein (CRP), procalcitonin (PCT) and proadrenomedullin (proADM) were measured at diagnosis and on day 3 and 7. Different cytokines were evaluated in serum on the first day. No HSCT recipients without RC were included as a control group. Compared with RI, non-infectious RC showed a significant increase in CRP, proADM and interleukin 6 on day 0 (P=0.005; P=0.03 and P=0.04, respectively). When only RI were considered, we observed that bacterial–fungal PI showed higher levels of CRP (P=0.02), PCT (P=0.04) and proADM (P<0.01). Persistent low levels of proADM biomarkers suggest viral infection (specificity and positive predictive value 100%). Patients dying of RC had PCT and proADM levels higher than survivors (P=0.002 and P=0.03, respectively). In HSCT recipients biomarkers increase in both infectious and non-infectious RC. They may have utility in the assessment of the severity of RC and in suspecting a viral etiology. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/bmt.2016.280) contains supplementary material, which is available to authorized users.

negative: The Antidepressant Treatment Response Index as a Predictor of Reboxetine Treatment Outcome in Major Depressive Disorder. Biomarkers to predict clinical outcomes early during the treatment of major depressive disorder (MDD) could reduce suffering and improve outcomes. A quantitative electroencephalogram (qEEG) biomarker, the Antidepressant Treatment Response (ATR) index, has been associated with outcomes of treatment with selective serotonin reuptake inhibitor antidepressants in patients with MDD. Here, we report the results of a post hoc analysis initiated to evaluate whether the ATR index may also be associated with reboxetine treatment outcome, given that its putative mechanism of action is via norepinephrine reuptake inhibition (NRI). Twenty-five adults with MDD underwent qEEG studies during open-label treatment with reboxetine at doses of 8 to 10 mg daily for 8 weeks. The ATR index calculated after 1 week of reboxetine treatment was significantly associated with overall Hamilton Depression Rating Scale (HAM-D) improvement at week 8 (r=0.605, P=.001), even after controlling for baseline depression severity (P=.002). The ATR index predicted response (≥50% reduction in HAM-D) with 70.6% sensitivity and 87.5% specificity, and remission (final HAM-D≤7) with 87.5% sensitivity and 64.7% specificity. These results suggest that the ATR index may be a useful biomarker of clinical response during NRI treatment of adults with MDD. Future studies are warranted to investigate further the potential utility of the ATR index as a predictor of noradrenergic antidepressant treatment response.

negative: Interleukin-5, interleukin-6, interferon induced protein-10, procalcitonin and C-reactive protein among mechanically ventilated severe community-acquired viral and bacterial pneumonia patients Abstract Background The serum cytokine levels among 45 mechanically ventilated, intensive care unit (ICU)-treated severe community-acquired pneumonia (SCAP) patients with known microbial etiology in three different etiology groups were assessed. Methods Blood samples for C-reactive protein (CRP), procalcitonin (PCT), interleukin (IL)-5, IL-6, IL-10, human interferon gamma induced protein (IP)-10, and TNF-α (tumor necrosis factor alpha) were collected at time points 0, 12, 24, 48, 72 and 96 h after study inclusion. Results There were 21 (43%) pure bacterial infections (bacterial group, BG), 5 (10%) pure viral infections (viral group, VG), and 19 (39%) mixed bacterial-viral infections (mixed group, MG) among 45 mechanically ventilated SCAP patients. CRP and PCT levels were significantly higher in the MG and values decreased with time in all groups. PCT differed also in time and group analysis (P = 0.001), the highest being in the MG. IL-5 levels were significantly higher in the VG compared to others (Ptime = 0.001, Pgroup = 0.051 and Ptimexgroup = 0.016). IL-6 and IP-10 levels decreased over time (Ptime = 0.003 and Ptime = 0.021), but there were no differences between groups. Conclusion SCAP patients with viral etiology have higher IL-5 levels. Patients with mixed viral and bacterial group have higher PCT compared to other etiologies.

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: Delivery Systems for the Direct Application of siRNAs to Induce RNA Interference (RNAi) In Vivo RNA interference (RNAi) is a powerful method for specific gene silencing which may also lead to promising novel therapeutic strategies. It is mediated through small interfering RNAs (siRNAs) which sequence-specifically trigger the cleavage and subsequent degradation of their target mRNA. One critical factor is the ability to deliver intact siRNAs into target cells/organs in vivo. This review highlights the mechanism of RNAi and the guidelines for the design of optimal siRNAs. It gives an overview of studies based on the systemic or local application of naked siRNAs or the use of various nonviral siRNA delivery systems. One promising avenue is the the complexation of siRNAs with the polyethylenimine (PEI), which efficiently stabilizes siRNAs and, upon systemic administration, leads to the delivery of the intact siRNAs into different organs. The antitumorigenic effects of PEI/siRNA-mediated in vivo gene-targeting of tumor-relevant proteins like in mouse tumor xenograft models are described.

negative: Translation from the 5' untranslated region (UTR) of mRNA 1 is repressed, but that from the 5' UTR of mRNA 7 is stimulated in coronavirus-infected cells. Viral gene products are generally required in widely differing amounts for successful virus growth and assembly. For coronaviruses, regulation of transcription is a major contributor to these differences, but regulation of translation may also be important. Here, we examine the possibility that the 5' untranslated regions (UTRs), unique for each of the nine species of mRNA in the bovine coronavirus and ranging in length from 70 nucleotides (nt) to 210 nt (inclusive of the common 5'-terminal 65-nt leader), can differentially affect the rate of protein accumulation. When the natural 77-nt 5' UTR on synthetic transcripts of mRNA 7 (mRNA for N and I proteins) was replaced with the 210-nt 5' UTR from mRNA 1 (genomic RNA, mRNA for viral polymerase), approximately twofold-less N, or (N) CAT fusion reporter protein, was made in vitro. Twofold less was also made in vivo in uninfected cells when a T7 RNA polymerase-driven transient-transfection system was used. In coronavirus-infected cells, this difference surprisingly became 12-fold as the result of both a stimulated translation from the 77-nt 5' UTR and a repression of translation from the 210-nt 5' UTR. These results reveal that a differential 5' UTR-directed regulation of translation can occur in coronavirus-infected cells and lead us to postulate that the direction and degree of regulation is carried out by viral or virally induced cellular factors acting in trans on cis-acting elements within the 5' UTR.

negative: Study of the lymphocyte change between COVID-19 and non-COVID-19 pneumonia cases suggesting other factors besides uncontrolled inflammation contributed to multi-organ injury Background: The corona virus disease 2019 (COVID-19) shows unusually high transmission rate and unique clinical characteristics, with key pathological mechanism remaining unclear. Here, we analysed the laboratory data based on clinical samples from COVID-19 patients, in parallel comparison with non-COVID-19 pneumonia cases, in an attempt to elucidate the key pathological features of COVID-19 during its infection of the human body. Methods: We analysed biochemical indices and lymphocyte subpopulation in COVID-19 patients, and compare these data from non-COVID-19 pneumonia cases. Correlation analysis was performed between leukocyte subgroups count and biochemical indexes in COVID-19 patients. Results: The study enrolled 110 patients, comprising 88 COVID-19 patients and 22 non-COVID-19 pneumonia cases. We observed significant differences, including abnormal biochemical indices (CRP, LDH, AST, eGFR, and sodium ion concentration) and reduced lymphocyte subsets count, between the COVID-19 patients and non-COVID-19-caused pneumonia cases. Correlation analysis indicates that the count for lymphocyte subsets-but not that for neutrophils and monocytes-exhibits a significant negative correlation with biochemical indices relating to organ injury, in the COVID-19 infected patients. Conclusions: The study indicates significantly different clinical features between 2019 novel coronavirus (2019-nCoV)-caused and non-2019-nCoV-caused pneumonia, especially in terms of lymphocytopenia and organ injury. Notably, correlation analysis demonstrates that tissue damage in COVID-19 patients is attributed to virus infection itself rather than uncontrolled inflammatory responses ("cytokine storm"). These findings provide new insights for developing efficient therapeutic strategies against COVID-19 infection.

negative: Outcome of a public consultation on the Draft Opinion of the EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA) on a guidance on the scientific requirements for health claims related to gut and immune function

negative: The differential expression of micro-RNAs 21, 200c, 204, 205, and 211 in benign, dysplastic and malignant melanocytic lesions and critical evaluation of their role as diagnostic biomarkers. Overlapping histological features between benign and malignant lesions and a lack of firm diagnostic criteria for malignancy result in high rates of inter-observer variation in the diagnosis of melanocytic lesions. We aimed to investigate the differential expression of five miRNAs (21, 200c, 204, 205, and 211) in benign naevi (n = 42), dysplastic naevi (n = 41), melanoma in situ (n = 42), and melanoma (n = 42) and evaluate their potential as diagnostic biomarkers of melanocytic lesions. Real-time PCR showed differential miRNA expression profiles between benign naevi; dysplastic naevi and melanoma in situ; and invasive melanoma. We applied a random forest machine learning algorithm to classify cases based on their miRNA expression profiles, which resulted in a ROC curve analysis of 0.99 for malignant melanoma and greater than 0.9 for all other groups. This indicates an overall very high accuracy of our panel of miRNAs as a diagnostic biomarker of benign, dysplastic, and malignant melanocytic lesions. However, the impact of variable lesion percentage and spatial expression patterns of miRNAs on these real-time PCR results was also considered. In situ hybridisation confirmed the expression of miRNA 21 and 211 in melanocytes, while demonstrating expression of miRNA 205 only in keratinocytes, thus calling into question its value as a biomarker of melanocytic lesions. In conclusion, we have validated some miRNAs, including miRNA 21 and 211, as potential diagnostic biomarkers of benign, dysplastic, and malignant melanocytic lesions. However, we also highlight the crucial importance of considering tissue morphology and spatial expression patterns when using molecular techniques for the discovery and validation of new biomarkers.

negative: Detection of SARS Coronavirus RNA in the Cerebrospinal Fluid of a Patient with Severe Acute Respiratory Syndrome

negative: Influenza A (H10N7) Virus Causes Respiratory Tract Disease in Harbor Seals and Ferrets Avian influenza viruses sporadically cross the species barrier to mammals, including humans, in which they may cause epidemic disease. Recently such an epidemic occurred due to the emergence of avian influenza virus of the subtype H10N7 (Seal/H10N7) in harbor seals (Phoca vitulina). This epidemic caused high mortality in seals along the north-west coast of Europe and represented a potential risk for human health. To characterize the spectrum of lesions and to identify the target cells and viral distribution, findings in 16 harbor seals spontaneously infected with Seal/H10N7 are described. The seals had respiratory tract inflammation extending from the nasal cavity to bronchi associated with intralesional virus antigen in respiratory epithelial cells. Virus infection was restricted to the respiratory tract. The fatal outcome of the viral infection in seals was most likely caused by secondary bacterial infections. To investigate the pathogenic potential of H10N7 infection for humans, we inoculated the seal virus intratracheally into six ferrets and performed pathological and virological analyses at 3 and 7 days post inoculation. These experimentally inoculated ferrets displayed mild clinical signs, virus excretion from the pharynx and respiratory tract inflammation extending from bronchi to alveoli that was associated with virus antigen expression exclusively in the respiratory epithelium. Virus was isolated only from the respiratory tract. In conclusion, Seal/H10N7 infection in naturally infected harbor seals and experimentally infected ferrets shows that respiratory epithelial cells are the permissive cells for viral replication. Fatal outcome in seals was caused by secondary bacterial pneumonia similar to that in fatal human cases during influenza pandemics. Productive infection of ferrets indicates that seal/H10N7 may possess a zoonotic potential. This outbreak of LPAI from wild birds to seals demonstrates the risk of such occasions for mammals and thus humans.

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: Chest CT score in COVID-19 patients: correlation with disease severity and short-term prognosis OBJECTIVES: To correlate a CT-based semi-quantitative score of pulmonary involvement in COVID-19 pneumonia with clinical staging of disease and laboratory findings. We also aimed to investigate whether CT findings may be predictive of patients’ outcome. METHODS: From March 6 to March 22, 2020, 130 symptomatic SARS-CoV-2 patients were enrolled for this single-center analysis and chest CT examinations were retrospectively evaluated. A semi-quantitative CT score was calculated based on the extent of lobar involvement (0:0%; 1, < 5%; 2:5–25%; 3:26–50%; 4:51–75%; 5, > 75%; range 0–5; global score 0–25). Data were matched with clinical stages and laboratory findings. Survival curves and univariate and multivariate analyses were performed to evaluate the role of CT score as a predictor of patients’ outcome. RESULTS: Ground glass opacities were predominant in early-phase (≤ 7 days since symptoms’ onset), while crazy-paving pattern, consolidation, and fibrosis characterized late-phase disease (> 7 days). CT score was significantly higher in critical and severe than in mild stage (p < 0.0001), and among late-phase than early-phase patients (p < 0.0001). CT score was significantly correlated with CRP (p < 0.0001, r = 0.6204) and D-dimer (p < 0.0001, r = 0.6625) levels. A CT score of ≥ 18 was associated with an increased mortality risk and was found to be predictive of death both in univariate (HR, 8.33; 95% CI, 3.19–21.73; p < 0.0001) and multivariate analysis (HR, 3.74; 95% CI, 1.10–12.77; p = 0.0348). CONCLUSIONS: Our preliminary data suggest the potential role of CT score for predicting the outcome of SARS-CoV-2 patients. CT score is highly correlated with laboratory findings and disease severity and might be beneficial to speed-up diagnostic workflow in symptomatic cases. KEY POINTS: • CT score is positively correlated with age, inflammatory biomarkers, severity of clinical categories, and disease phases. • A CT score ≥ 18 has shown to be highly predictive of patient’s mortality in short-term follow-up. • Our multivariate analysis demonstrated that CT parenchymal assessment may more accurately reflect short-term outcome, providing a direct visualization of anatomic injury compared with non-specific inflammatory biomarkers.

negative: A globally available COVID-19 - Template for clinical imaging studies Background The pandemic spread of COVID-19 has caused worldwide implications on societies and economies. Chest computed tomography (CT) has been found to support both, current diagnostic and disease monitoring. A joint approach to collect, analyze and share clinical and imaging information about COVID-19 in the highest quality possible is urgently needed. Methods An evidence-based reporting template was developed for assessing COVID-19 pneumonia using an FDA-approved medical software. The annotation of qualitative and quantitative findings including radiomics features is performed directly on primary imaging data. For data collection, secondary information from the patient history and clinical data such as symptoms and comorbidities are queried. Results License-royalty free, cloud-based web platform and on-premise deployments are offered. Hospitals can upload, assess, report and if pseudonymized share their COVID-19 cases. The aggregation of radiomics in correlation with rt-PCR, patient history, clinical and radiological findings, systematically documented in a single database, will lead to optimized diagnosis, risk stratification and response evaluation. A customizable analytics dashboard allows the explorative real-time data analysis of imaging features and clinical information. Conclusions The COVID-19-Template is based on a systematic, computer-assisted and context-guided approach to collect, analyze and share data. Epidemiological and clinical studies for therapies and vaccine candidates can be implemented in compliance with high data quality, integrity and traceability.

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

negative: 46 How can biomarkers be used to differentiate between infection and non-infectious causes of inflammation? Abstract: Diagnosis of sepsis is based on recognition of systemic inflammation and organ failure in the context of an inciting infection. Since none of the diagnostic criteria are specific to sepsis, it is easy to confound sepsis with noninfectious causes of systemic inflammation, including pancreatitis, cardiac ischemia, bowel perforation, vasculitis, and pulmonary embolism amongst others. Two widely used biomarkers, C-reactive protein and procalcitonin, have proven promising in sepsis diagnosis. Each has found varying success in the clinical context, with some centers relying heavily on these markers and others eschewing their use almost entirely. In this chapter, we present the evidence for their use in the diagnosis of sepsis and management of antibiotic therapy in the intensive care unit context.

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: Network-Based Prediction of the 2019-nCoV Epidemic Outbreak in the Chinese Province Hubei At the moment of writing (12 February, 2020), the future evolution of the 2019-nCoV virus is unclear. Predictions of the further course of the epidemic are decisive to deploy targeted disease control measures. We consider a network-based model to describe the 2019-nCoV epidemic in the Hubei province. The network is composed of the cities in Hubei and their interactions (e.g., traffic flow). However, the precise interactions between cities is unknown and must be inferred from observing the epidemic. We propose a network-based method to predict the future prevalence of the 2019-nCoV virus in every city. Our results indicate that network-based modelling is beneficial for an accurate forecast of the epidemic outbreak.

negative: Molecular approaches to the diagnosis and monitoring of production diseases in pigs Abstract Production disease in pigs is caused by a variety of different pathogens, mainly enteric and respiratory and can result in significant economic loss. Other factors such as stress, poor husbandry and nutrition can also contribute to an animal's susceptibility to disease. Molecular biomarkers of production disease could be of immense value by improving diagnosis and risk analysis to determine best practice with an impact on increased economic output and animal welfare. In addition to the use of multiplex PCR or microarrays to detect individual or mixed pathogens during infection, these technologies can also be used to monitor the host response to infection via gene expression. The patterns of gene expression associated with cellular damage or initiation of the early immune response may indicate the type of pathology and, by extension the types of pathogen involved. Molecular methods can therefore be used to monitor both the presence of a pathogen and the host response to it during production disease. The field of biomarker discovery and implementation is expanding as technologies such as microarrays and next generation sequencing become more common. Whilst a large number of studies have been carried out in human medicine, further work is needed to identify molecular biomarkers in veterinary medicine and in particular those associated with production disease in the pig industry. The pig transcriptome is highly complex and still not fully understood. Further gene expression studies are needed to identify molecular biomarkers which may have predictive value in identifying the environmental, nutritional and other risk factors which are associated with production diseases in pigs.

negative: Serum Mycoplasma Pneumoniae IgG in COVID-19: A Protective Factor Abstract Background: A correlation between prior exposure to Mycoplasma pneumoniae (IgG positive) and better clinical response to COVID-19 was elusive. Methods: A retrospective review of all COVID-19 infected patients treated at Wuhan Union Hospital from Feb 1 to Mar 20 was carried out. Continuous variables were described as mean, median, and interquartile range (IQR), while categorical variables were compared by X2 test or Fisher's exact test between COVID-19 infected patients with mycoplasma lgG (-) and mycoplasma lgG (+). Results: Statistically significant differences were shown in terms of laboratory test results. COVID-19 infected patients with mycoplasma lgG positivity had a higher lymphocyte count and percentage (p=0.026, p=0.017), monocyte count and percentage (p=0.028, p=0.006) and eosinophil count and percentage (p=0.039, p=0.007), and a lower neutrophil count and percentage (p=0.044, p=0.006) than COVID-19 infected patients without mycoplasma lgG. Other routine blood tests, including coagulation tests, blood biochemistry and infection-related biomarkers did not significantly differ except for thrombin time (p=0.001) and lactate dehydrogenase (p=0.008). Furthermore, requirement and use of a nasal catheter or oxygen mask was significantly lower in COVID-19 infected patients with mycoplasma lgG positivity (p=0.029). Conclusions: Our findings indicate that mycoplasma IgG positivity is a potential protective factor for SARS-CoV-2 infection.

negative: Evaluating the accuracy of different respiratory specimens in the laboratory diagnosis and monitoring the viral shedding of 2019-nCoV infections Background: The outbreak of novel coronavirus pneumonia (NCP) caused by 2019-nCoV spread rapidly, and elucidation the diagnostic accuracy of different respiratory specimens is crucial for the control and treatment of this diseases. Methods: Respiratory samples including nasal swabs, throat swabs, sputum and bronchoalveolar lavage fluid (BALF) were collected from Guangdong CDC confirmed NCP patients, and viral RNAs were detected using a CFDA approved detection kit. Results were analyzed in combination with sample collection date and clinical information. Finding: Except for BALF, the sputum possessed the highest positive rate (74.4%~88.9%), followed by nasal swabs (53.6%~73.3%) for both severe and mild cases during the first 14 days after illness onset (d.a.o). For samples collected ≥ 15 d.a.o, sputum and nasal swabs still possessed a high positive rate ranging from 42.9%~61.1%. The positive rate of throat swabs collected ≥ 8 d.a.o was low, especially in samples from mild cases. Viral RNAs could be detected in all the lower respiratory tract of severe cases, but not the mild cases. CT scan of cases 02, 07 and 13 showed typical viral pneumonia with ground glass opacity, while no viral RNAs were detected in first three or all the upper respiratory samples. Interpretation: Sputum is most accurate for laboratory diagnosis of NCP, followed by nasal swabs. Detection of viral RNAs in BLAF is necessary for diagnosis and monitoring of viruses in severe cases. CT scan could serve as an important make up for the diagnosis of NCP. Funding National Science and Technology Major Project, Sanming Project of Medicine and China Postdoctoral Science Foundation.

negative: Will novel virus go pandemic or be contained?

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: 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.

negative: Analysis of meteorological conditions and prediction of epidemic trend of 2019-nCoV infection in 2020 Objective: To investigate the meteorological condition for incidence and spread of 2019-nCoV infection, to predict the epidemiology of the infectious disease, and to provide a scientific basis for prevention and control measures against the new disease. Methods: The meteorological factors during the outbreak period of the novel coronavirus pneumonia in Wuhan in 2019 were collected and analyzed, and were confirmed with those of Severe Acute Respiratory Syndrome (SARS) in China in 2003. Data of patients infected with 2019-nCoV and SARS coronavirus were collected from WHO website and other public sources. Results: This study found that the suitable temperature range for 2019-nCoV coronavirus survival is (13-24 degree Celsius), among which 19 degree Celsius lasting about 60 days is conducive to the spread between the vector and humans; the humidity range is 50%-80%, of which about 75% humidity is conducive to the survival of the coronavirus; the suitable precipitation range is below 30 mm/ month. Cold air and continuous low temperature over one week are helpful for the elimination of the virus. The prediction results show that with the approach of spring, the temperature in north China gradually rises, and the coronavirus spreads to middle and high latitudes along the temperature line of 13-18 degree Celsius. The population of new coronavirus infections is concentrated in Beijing, Tianjin, Hebei, Jiangsu, Zhejiang, Shanghai and other urban agglomerations. Starting from May 2020, the Beijing-Tianjin-Hebei urban agglomeration, the Central China Zhengzhou-Wuhan urban agglomeration, the eastern Jiangsu-Zhejiang-Shanghai urban agglomeration, and the southern Pearl River Delta urban agglomeration are all under a high temperature above 24 degree Celsius, which is not conducive to the survival and reproduction of coronaviruses, so the epidemic is expected to end. Conclusions: A wide range of continuous warm and dry weather is conducive to the survival of 2019-nCoV. The coming of spring, in addition to the original Wuhan-Zhengzhou urban agglomeration in central China, means that the prevention and control measures in big cities located in mid-latitude should be strengthened, especially the monitoring of transportation hubs. The Pearl River Delta urban agglomeration is a concentrated area of population in south China, with a faster temperature rise than those in mid-high latitudes, and thus the prevention in this area should be prioritized. From a global perspective, cities with a mean temperature below 24 degree Celsius are all high-risk cities for 2019-nCoV transmission before June.

negative: Human Coronavirus NL63 Infection and Other Coronavirus Infections in Children Hospitalized with Acute Respiratory Disease in Hong Kong, China Background. Human coronavirus NL63 (HCoV-NL63) is a recently discovered human coronavirus found to cause respiratory illness in children and adults that is distinct from the severe acute respiratory syndrome (SARS) coronavirus and human coronaviruses 229E (HCoV-229E) and OC43 (HCoV-OC43). Methods. We investigated the role that HCoV-NL63, HCoV-OC43, and HCoV-229E played in children hospitalized with fever and acute respiratory symptoms in Hong Kong during the period from August 2001 through August 2002. Results. Coronavirus infections were detected in 26 (4.4%) of 587 children studied; 15 (2.6%) were positive for HCoV-NL63, 9 (1.5%) were positive for HCoV-OC43, and 2 (0.3%) were positive for HCoV-229E. In addition to causing upper respiratory disease, we found that HCoV-NL63 can present as croup, asthma exacerbation, febrile seizures, and high fever. The mean age (± standard deviation [SD]) of the infected children was 30.7 ± 19.8 months (range, 6–57 months). The mean maximum temperature (±SD) for the 12 children who were febrile was 39.3°C ± 0.9°C, and the mean total duration of fever (±SD) for all children was 2.6 ± 1.2 days (range, 1–5 days). HCoV-NL63 infections were noted in the spring and summer months of 2002, whereas HCoV-OC43 infection mainly occurred in the fall and winter months of 2001. HCoV-NL63 viruses appeared to cluster into 2 evolutionary lineages, and viruses from both lineages cocirculated in the same season. Conclusions. HCoV-NL63 is a significant pathogen that contributes to the hospitalization of children, and it was estimated to have caused 224 hospital admissions per 100,000 population aged ⩽6 years each year in Hong Kong.

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: A comprehensive collection of systems biology data characterizing the host response to viral infection The Systems Biology for Infectious Diseases Research program was established by the U.S. National Institute of Allergy and Infectious Diseases to investigate host-pathogen interactions at a systems level. This program generated 47 transcriptomic and proteomic datasets from 30 studies that investigate in vivo and in vitro host responses to viral infections. Human pathogens in the Orthomyxoviridae and Coronaviridae families, especially pandemic H1N1 and avian H5N1 influenza A viruses and severe acute respiratory syndrome coronavirus (SARS-CoV), were investigated. Study validation was demonstrated via experimental quality control measures and meta-analysis of independent experiments performed under similar conditions. Primary assay results are archived at the GEO and PeptideAtlas public repositories, while processed statistical results together with standardized metadata are publically available at the Influenza Research Database (www.fludb.org) and the Virus Pathogen Resource (www.viprbrc.org). By comparing data from mutant versus wild-type virus and host strains, RNA versus protein differential expression, and infection with genetically similar strains, these data can be used to further investigate genetic and physiological determinants of host responses to viral infection.

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: Clinical features of atypical 2019 novel coronavirus pneumonia with an initially negative RT-PCR assay

negative: Thrombocytopenia Is Associated with Acute Respiratory Distress Syndrome Mortality: An International Study BACKGROUND: Early detection of the Acute Respiratory Distress Syndrome (ARDS) has the potential to improvethe prognosis of critically ill patients admitted to the intensive care unit (ICU). However, no reliable biomarkers are currently available for accurate early detection of ARDS in patients with predisposing conditions. OBJECTIVES: This study examined risk factors and biomarkers for ARDS development and mortality in two prospective cohort studies. METHODS: We examined clinical risk factors for ARDS in a cohort of 178 patients in Beijing, China who were admitted to the ICU and were at high risk for ARDS. Identified biomarkers were then replicated in a second cohort of1,878 patients in Boston, USA. RESULTS: Of 178 patients recruited from participating hospitals in Beijing, 75 developed ARDS. After multivariate adjustment, sepsis (odds ratio [OR]:5.58, 95% CI: 1.70–18.3), pulmonary injury (OR: 3.22; 95% CI: 1.60–6.47), and thrombocytopenia, defined as platelet count <80×10(3)/µL, (OR: 2.67; 95% CI: 1.27–5.62)were significantly associated with increased risk of developing ARDS. Thrombocytopenia was also associated with increased mortality in patients who developed ARDS (adjusted hazard ratio [AHR]: 1.38, 95% CI: 1.07–1.57) but not in those who did not develop ARDS(AHR: 1.25, 95% CI: 0.96–1.62). The presence of both thrombocytopenia and ARDS substantially increased 60-daymortality. Sensitivity analyses showed that a platelet count of <100×10(3)/µLin combination with ARDS provide the highest prognostic value for mortality. These associations were replicated in the cohort of US patients. CONCLUSIONS: This study of ICU patients in both China and US showed that thrombocytopenia is associated with an increased risk of ARDS and platelet count in combination with ARDS had a high predictive value for patient mortality.

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

negative: Viral etiology and seasonality of influenza-like illness in Gabon, March 2010 to June 2011 BACKGROUND: Surveillance of influenza-like illness (ILI) in Central Africa began only recently, and few data are therefore available on the circulation of influenza virus and other respiratory viruses. In Gabon, a Central African country, we established a surveillance network in four major towns in order to analyze cases of ILI among patients who visited health centers between March 2010 and June 2011, and to determine the viral etiology. METHODS: Nasal swabs were sent for analysis to the Centre International de Recherches Médicales de Franceville, where they were screened for 17 respiratory viruses in a multiplex real-time reverse transcription polymerase chain reaction for all pathogens according the following pairs: adenovirus/parainfluenza virus 4, respiratory syncytial virus/human metapneumovirus, parainfluenza virus 1/parainfluenza virus 2, pandemic influenza virus A/seasonal influenza virus A (H1N1, H3N2)/seasonal influenza virus B, human coronaviruses 229E/OC43, human coronaviruses NL63/HKU1, rhinovirus/human parechovirus, and enterovirus/parainfluenza virus 3. RESULTS: We analyzed a total of 1041 specimens, of which 639 (61%) were positive for at least one virus. Three-quarters of the patients were children under five years old. We therefore focused on this age group, in which 68.1% of patients were positive for at least one virus. The most common viruses were adenoviruses (17.5%), followed by parainfluenza viruses (PIVs) 1–4 (16.8%), enteroviruses (EV) (14.7%), respiratory syncytial virus (RSV) (13.5%), and influenza virus (11.9%). The prevalence of some viruses was subject to geographic and seasonal variations. One-third of positive samples contained more than one virus. CONCLUSIONS: Like most studies in the world, the virus PIVs, EV, RSV, Influenza virus, HRV were predominant among children under five years old in Gabon. An exception is made for adenoviruses which have a high prevalence in our study. However adenoviruses can be detected in asymptomatic persons. These finding gave a better knowledge of the circulation and the seasonality of the viruses involved in ILI in Gabon.

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

negative: The use of Nanotrap particles for biodefense and emerging infectious disease diagnostics Detection of early infectious disease may be challenging due to the low copy number of organisms present. To overcome this limitation and rapidly measure low concentrations of the pathogen, we developed a novel technology: Nanotrap particles, which are designed to capture, concentrate, and protect biomarkers from complex biofluids. Nanotrap particles are thermoresponsive hydrogels that are capable of antigen capture through the coupling of affinity baits to the particles. Here, we describe recent findings demonstrating that Nanotrap particles are able to capture live infectious virus, viral RNA, and viral proteins. Capture is possible even in complex mixtures such as serum and allows the concentration and protection of these analytes, providing increased performance of downstream assays. The Nanotrap particles are a versatile sample preparation technology that has far reaching implications for biomarker discovery and diagnostic assays.

negative: Identification of Pathogens by Mass Spectrometry Background: Mass spectrometry (MS) is a suitable technology for microorganism identification and characterization. Content: This review summarizes the MS-based methods currently used for the analyses of pathogens. Direct analysis of whole pathogenic microbial cells using MS without sample fractionation reveals specific biomarkers for taxonomy and provides rapid and high-throughput capabilities. MS coupled with various chromatography- and affinity-based techniques simplifies the complexity of the signals of the microbial biomarkers and provides more accurate results. Affinity-based methods, including those employing nanotechnology, can be used to concentrate traces of target microorganisms from sample solutions and, thereby, improve detection limits. Approaches combining amplification of nucleic acid targets from pathogens with MS-based detection are alternatives to biomarker analyses. Many data analysis methods, including multivariate analysis and bioinformatics approaches, have been developed for microbial identification. The review concludes with some current clinical applications of MS in the identification and typing of infectious microorganisms, as well as some perspectives. Summary: Advances in instrumentation (separation and mass analysis), ionization techniques, and biological methodologies will all enhance the capabilities of MS for the analysis of pathogens.

negative: Alignment using genetic programming with causal trees for identification of protein functions Abstract A hybrid evolutionary model is used to propose a hierarchical homology of protein sequences to identify protein functions systematically. The proposed model offers considerable potentials, considering the inconsistency of existing methods for predicting novel proteins. Because some novel proteins might align without meaningful conserved domains, maximizing the score of sequence alignment is not the best criterion for predicting protein functions. This work presents a decision model that can minimize the cost of making a decision for predicting protein functions using the hierarchical homologies. Particularly, the model has three characteristics: (i) it is a hybrid evolutionary model with multiple fitness functions that uses genetic programming to predict protein functions on a distantly related protein family, (ii) it incorporates modified robust point matching to accurately compare all feature points using the moment invariant and thin-plate spline theorems, and (iii) the hierarchical homologies holding up a novel protein sequence in the form of a causal tree can effectively demonstrate the relationship between proteins. This work describes the comparisons of nucleocapsid proteins from the putative polyprotein SARS virus and other coronaviruses in other hosts using the model.

negative: Pregnant women with new coronavirus infection: a clinical characteristics and placental pathological analysis of three cases Objective To investigate the clinical characteristics and placental pathology of 2019-nCoV infection in pregnancy, and to evaluate intrauterine vertical transmission potential of 2019-nCoV infection Methods The placentas delivered from pregnant women with confirmed 2019-nCoV infection which were received in the Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology collected by February 4th, 2020 and retrospectively studied Their clinical material including placental tissue and lung CT, and laboratory results were collected, meanwhile, nucleic acid detection of 2019-nCoV of the placentas were performed by RT-PCR Results Three placentas delivered from pregnant women with confirmed 2019-nCoV infection, who were all in their third trimester with emergency caesarean section All of the three patients presented with fever (one before caesarean and two in postpartum), and had no significant leukopenia and lymphopenia Neonatal throat swabs from three newborns were tested for 2019-nCoV, and all samples were negative for the nucleic acid of 2019-nCoV One premature infant was transferred to Department of Neonatology due to low birth weight By the end of February 25, 2020, none of the three patients developed severe 2019-nCoV pneumonia or died(two patients had been cured and discharged, while another one had been transferred to a square cabin hospital for isolation treatment) There were various degrees of fibrin deposition inside and around the villi with local syncytial nodule increases in all three placentas One case of placenta showed the concomitant morphology of chorionic hemangioma and another one with massive placental infarction No pathological change of villitis and chorioamnionitis was observed in our observation of three cases All samples from three placentas were negative for the nucleic acid of 2019-nCoV Conclusions The clinical characteristics of pregnant women with 2019-nCoV infection in late pregnancy are similar to those of non-pregnant patients, and no severe adverse pregnancy outcome is found in the 3 cases of our observation Pathological study suggests that there are no morphological changes related to infection in the three placentas Currently no evidence for intrauterine vertical transmission of 2019-nCoV is found in the three women infected by 2019-nCoV in their late pregnancy

negative: 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, γ-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.

negative: Geroprotective and senoremediative strategies to reduce the comorbidity, infection rates, severity, and lethality in gerophilic and gerolavic infections The recently identified SARS-CoV-2 betacoronavirus responsible for the COVID-19 pandemic has uncovered the age-associated vulnerability in the burden of disease and put aging research in the spotlight. The limited data available indicates that COVID-19 should be referred to as a gerolavic (from Greek, géros “old man” and epilavís, “harmful”) infection because the infection rates, severity, and lethality are substantially higher in the population aged 60 and older. This is primarily due to comorbidity but may be partially due to immunosenescence, decreased immune function in the elderly, and general loss of function, fitness, and increased frailty associated with aging. Immunosenescence is a major factor affecting vaccination response, as well as the severity and lethality of infectious diseases. While vaccination reduces infection rates, and therapeutic interventions reduce the severity and lethality of infections, these interventions have limitations. Previous studies showed that postulated geroprotectors, such as sirolimus (rapamycin) and its close derivative rapalog everolimus (RAD001), decreased infection rates in a small sample of elderly patients. This article presents a review of the limited literature available on geroprotective and senoremediative interventions that may be investigated to decrease the disease burden of gerolavic infections. This article also highlights a need for rigorous clinical validation of deep aging clocks as surrogate markers of biological age. These could be used to assess the need for, and efficacy of, geroprotective and senoremediative interventions and provide better protection for elderly populations from gerolavic infections. This article does not represent medical advice and the medications described are not yet licensed or recommended as immune system boosters, as they have not undergone clinical evaluation for this purpose.

negative: Clinical Implications of SARS-Cov2 Interaction with Renin Angiotensin System Abstract SARS-CoV2 host cell infection is mediated by the binding to angiotensin-converting enzyme 2 (ACE2). Systemic dysregulation observed in SARS-CoV was previously postulated to be due to ACE2/Ang1-7/Mas axis downregulation, increased ACE2 activity was shown to mediate disease protection. Since angiotensin II receptor blockers (ARBs), ACE inhibitors, and mineralocorticoid receptor antagonists (MRAs) increase ACE2 receptor expression, it has been tacitly believed that the use of these agents may facilitate viral disease, thus they should not be used in high-risk patients with cardiovascular disease. Based on the anti-inflammatory benefits of the upregulation of the ACE2/Ang1-7/Mas axis and previously demonstrated benefits of lung function improvement in SARS-CoV infections, we hypothesize that the benefits of treatment with renin-angiotensin system inhibitors in SARS-COV2 may outweigh the risks and at the very least should not be withheld.

negative: Pharmacovigilance and protective medication for drug-induced liver injury in treatment of COVID-19/ 注重新型冠状病毒肺炎（COVID-19）治疗中药物性肝损伤的预警与保护 The outbreak of COVID-19 coronavirus pneumonia in December 2019 has aroused great concern worldwide. At present, the COVID-19 coronavirus pneumonia is highly contagious, rapid and widespread. It has been reported that COVID-19 virus is spread by respiratory droplets and direct contact transmission, and it has various clinical manifestations and recurrent is common. Some patients do not even appear obvious fever and have negative results for throat swab virus culture at the onset of the disease, but the rapid deterioration in their clinical condition usually occurred, which bring difficulties to scientific diagnosis and treatment. At present, western medicine treats most patients with anti-viral drugs, hormones and other drugs, or treats critically ill patients with ECMO oxygenation, important organ function support and other emergency treatments. Traditional Chinese medicine (TCM) based on syndrome differentiation and treatment has obtained curative effects in this outbreak. In order to improve the effects and safety of Chinese and western drug therapy, we applied literature-mining method and network pharmacology, summarized the potential liver injury during the application of western medicine and discussed hepatotoxicity networks and potential pathway targets of ingredients in Chinese patent medicine and Chinese herbal compound. This study not only summarizes essential information regarding potential drug-induced liver injury and biomarkers for pharmacovigilance, but also provides insights for liver protection by TCM or TCM in combination with western medicine in the treatment of novel coronavirus.

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

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

negative: Chronic obstructive pulmonary disease is associated with severe coronavirus disease 2019 (COVID-19)

negative: Role of the Eye in Transmitting Human Coronavirus: What We Know and What We Do Not Know The outbreak of the current 2019 novel coronavirus (2019-nCoV, now named SARS-CoV-2) infection has become a worldwide health threat. Currently, more information is needed so as to further understand the transmission and clinical characteristics of 2019-nCoV infection and the infection control procedures required. Recently, the role of the eye in transmitting 2019-nCoV has been intensively discussed. Previous investigations of other highly infectious human CoVs, that is, severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), may provide useful information. In this review, we describe the genomics and morphology of human CoVs, the epidemiology, systemic and ophthalmic manifestations, and mechanisms of human CoV infection, and recommendations for infection control procedures. The role of the eye in the transmission of 2019-nCoV is discussed in detail. Although the conjunctiva is directly exposed to extraocular pathogens, and the mucosa of the ocular surface and upper respiratory tract are connected by the nasolacrimal duct and share the same entry receptors for some respiratory viruses, the eye is rarely involved in human CoV infection, conjunctivitis is quite rare in patients with 2019-nCoV infection, and the CoV RNA positive rate by RT-PCR test in tears and conjunctival secretions from patients with 2019-nCoV and SARS-CoV infection is also extremely low. This suggests that the eye is neither a preferred organ of human CoV infection nor a preferred gateway of entry for human CoVs for infecting the respiratory tract. However, pathogens that the ocular surface is exposed to might be transported to nasal and nasopharyngeal mucosa by constant tear rinsing through the lacrimal duct system and then cause respiratory tract infection. Considering that close doctor-patient contact is quite common in ophthalmic practice and is apt to transmit human CoVs by droplets and fomites, strict hand hygiene and proper personal protection are highly recommended for health care workers to avoid hospital-related viral transmission during ophthalmic practice.

negative: Lack of a 5.9 kDa Peptide C-Terminal Fragment of Fibrinogen α Chain Precedes Fibrosis Progression in Patients with Liver Disease Early detection of fibrosis progression is of major relevance for the diagnosis and management of patients with liver disease. This study was designed to find non-invasive biomarkers for fibrosis in a clinical context where this process occurs rapidly, HCV-positive patients who underwent liver transplantation (LT). We analyzed 93 LT patients with HCV recurrence, 41 non-LT patients with liver disease showing a fibrosis stage F≥1 and 9 patients without HCV recurrence who received antiviral treatment before LT, as control group. Blood obtained from 16 healthy subjects was also analyzed. Serum samples were fractionated by ion exchange chromatography and their proteomic profile was analyzed by SELDI-TOF-MS. Characterization of the peptide of interest was performed by ion chromatography and electrophoresis, followed by tandem mass spectrometry identification. Marked differences were observed between the serum proteome profile of LT patients with early fibrosis recurrence and non-recurrent LT patients. A robust peak intensity located at 5905 m/z was the distinguishing feature of non-recurrent LT patients. However, the same peak was barely detected in recurrent LT patients. Similar results were found when comparing samples of healthy subjects with those of non-LT fibrotic patients, indicating that our findings were not related to either LT or HCV infection. Using tandem mass-spectrometry, we identified the protein peak as a C-terminal fragment of the fibrinogen α chain. Cell culture experiments demonstrated that TGF-β reduces α-fibrinogen mRNA expression and 5905 m/z peak intensity in HepG2 cells, suggesting that TGF-β activity regulates the circulating levels of this protein fragment. In conclusion, we identified a 5.9 kDa C-terminal fragment of the fibrinogen α chain as an early serum biomarker of fibrogenic processes in patients with liver disease.

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

negative: Quantitative mass spectrometry-based techniques for clinical use: Biomarker identification and quantification() The potential for development of personalised medicine through the characterisation of novel biomarkers is an exciting prospect for improved patient care. Recent advances in mass spectrometric (MS) techniques, liquid phase analyte separation and bioinformatic tools for high throughput now mean that this goal may soon become a reality. However, there are challenges to be overcome for the identification and validation of robust biomarkers. Bio-fluids such as plasma and serum are a rich source of protein, many of which may reflect disease status, and due to the ease of sampling and handling, novel blood borne biomarkers are very much sought after. MS-based methods for high throughput protein identification and quantification are now available such that the issues arising from the huge dynamic range of proteins present in plasma may be overcome, allowing deep mining of the blood proteome to reveal novel biomarker signatures for clinical use. In addition, the development of sensitive MS-based methods for biomarker validation may bypass the bottleneck created by the need for generation and usage of reliable antibodies prior to large scale screening. In this review, we discuss the MS-based methods that are available for clinical proteomic analysis and highlight the progress made and future challenges faced in this cutting edge area of research.

negative: Better Tests, Better Care: Improved Diagnostics for Infectious Diseases In this IDSA policy paper, we review the current diagnostic landscape, including unmet needs and emerging technologies, and assess the challenges to the development and clinical integration of improved tests. To fulfill the promise of emerging diagnostics, IDSA presents recommendations that address a host of identified barriers. Achieving these goals will require the engagement and coordination of a number of stakeholders, including Congress, funding and regulatory bodies, public health agencies, the diagnostics industry, healthcare systems, professional societies, and individual clinicians.

negative: Molecular Diagnostics in Pulmonary Infections Infection of the lung parenchyma, or pneumonia, accounts for over four million deaths per year worldwide (Ferkol and Schraufnagel, Ann Am Thorac Soc 11:404–406, 2014). The condition is common, but also over-diagnosed, in part due to relatively poor laboratory and radiographic diagnostics. Indeed, we continue to rely on antiquated tools such as sputum culture and chest X-ray – the former of which lacks speed and sensitivity, and the latter specificity (Albaum et al. Chest 110:343–50, 1996). The resulting presumptive diagnoses of pneumonia lead to excessive use of empiric broad spectrum antibiotics; indeed, by some estimates, 30–70% of antibiotic prescriptions for lower respiratory tract infection are inappropriate (Kraus, PLoS One 12(3): e0174584, 2017). This approach begets microbial resistance, exposes patients to medication side effects, and puts patients at risk of potentially life-threatening complications including Clostridium difficile colitis. To improve diagnostic certainty in patients with suspected pneumonia, we must begin to consider and implement emerging technologies for efficient and accurate characterization of host responses to infection and identification of pathogens. In this chapter, we will discuss precision diagnostics already in common practice and those poised to be, and how these tools may ultimately enable personalization in the diagnosis of pneumonia.

negative: The Easter and Passover Blip in New York City Abstract and Executive Summary - When it comes to pandemics such as the currently present COVID-19 [1], various issues and problems arise for infrastructures and institutions. Due to possible extreme effects, such as hospitals potentially running out of beds or medical equipment, it is essential to lower the infection rate to create enough space to attend to the affected people and allow enough time for a vaccine to be developed. Unfortunately, this requires that measures put into place are upheld long enough to reduce the infection rate sufficiently. In this paper, we describe research simulating the influences of the contact rate on the spread of the pandemic using New York City as an example (Section IV) and especially already observed effects of contact rate increases during holidays [2-4] (Section V). In multiple simulations scenarios for Passover and Easter holidays, we evaluated 25%, 50%, 75%, and 100% temporary increases in contact rates using a scenario close to the currently reported numbers as reference and contact rates based on bioterrorism research as a 'normal' baseline for NYC. The first general finding from the simulations is that singular events of increased visits/contacts amplify each other disproportionately if they are happening in close proximity (time intervals) together. The second general observation was that contact rate spikes leave a permanently increased and devastating infection rate behind, even after the contact rate returns to the reduced one. In case of a temporary sustained increase of contact rate for just three days in a row, the aftermath results in an increase of infection rate up to 40%, which causes double the fatalities in the long run. In numbers, given that increases of 25% and 50% seem to be most likely given the data seen in Germany for the Easter weekend for example [2, 3], our simulations show the following increases (compared to the realistic reference run): for a temporary 25% surge in contact rate, the total cases grew by 215,880, the maximum of required hospitalizations over time increased to 63,063, and the total fatalities climbed by 8,844 accumulated over 90 days. As for the 50% surge, we saw the total number of cases rise by 461,090, the maximum number of required hospitalizations increase to 79,733, and the total number of fatalities climb by 19,125 over 90 days in NYC. All in all, we conclude that even very short, temporary increases in contact rates can have disproportionate effects and result in unrecoverable phenomena that can hardly be reversed or managed later. The numbers show possible phenomena before they might develop effects in reality. This is important because phenomena such as the described blip can impact the hospitals in reality. Therefore, we warn that a wave of infections due to increased contact rates during Passover/Easter might come as a result!

negative: Ecosystem approaches to the risk for schizophrenia

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

negative: Bacterial Complications of Respiratory Tract Viral Illness: A Comprehensive Evaluation Background. Respiratory tract infection is one of the most common reasons for hospitalization among adults, and recent evidence suggests that many of these illnesses are associated with viruses. Although bacterial infection is known to complicate viral infections, the frequency and impact of mixed viral-bacterial infections has not been well studied. Methods. Adults hospitalized with respiratory illness during 3 winters underwent comprehensive viral and bacterial testing. This assessment was augmented by measuring the serum level of procalcitonin (PCT) as a marker of bacterial infection. Mixed viral-bacterial infection was defined as a positive viral test result plus a positive bacterial assay result or a serum PCT level of ≥ 0.25 ng/mL on admission or day 2 of hospitalization. Results. Of 842 hospitalizations (771 patients) evaluated, 348 (41%) had evidence of viral infection. A total of 212 hospitalizations (61%) involved patients with viral infection alone. Of the remaining 136 hospitalizations (39%) involving viral infection, results of bacterial tests were positive in 64 (18%), and PCT analysis identified bacterial infection in an additional 72 (21%). Subjects hospitalized with mixed viral-bacterial infections were older and more commonly received a diagnosis of pneumonia. Over 90% of hospitalizations in both groups involved subjects who received antibiotics. Notably, 4 of 10 deaths among subjects hospitalized with viral infection alone were secondary to complications of Clostridium difficile colitis. Conclusions. Bacterial coinfection is associated with approximately 40% of viral respiratory tract infections requiring hospitalization. Patients with positive results of viral tests should be carefully evaluated for concomitant bacterial infection. Early empirical antibiotic therapy for patients with an unstable condition is appropriate but is not without risk.

negative: A systematic review of the overlap of fluid biomarkers in delirium and advanced cancer-related syndromes BACKGROUND: Delirium is a serious and distressing neurocognitive disorder of physiological aetiology that is common in advanced cancer. Understanding of delirium pathophysiology is largely hypothetical, with some evidence for involvement of inflammatory systems, neurotransmitter alterations and glucose metabolism. To date, there has been limited empirical consideration of the distinction between delirium pathophysiology and that of the underlying disease, for example, cancer where these mechanisms are also common in advanced cancer syndromes such as pain and fatigue. This systematic review explores biomarker overlap in delirium, specific advanced cancer-related syndromes and prediction of cancer prognosis. METHODS: A systematic review (PROSPERO CRD42017068662) was conducted, using MEDLINE, PubMed, Embase, CINAHL, CENTRAL and Web of Science, to identify body fluid biomarkers in delirium, cancer prognosis and advanced cancer-related syndromes of interest. Studies were excluded if they reported delirium tremens only; did not measure delirium using a validated tool; the sample had less than 75% of participants with advanced cancer; measured tissue, genetic or animal biomarkers, or were conducted post-mortem. Articles were screened for inclusion independently by two authors, and data extraction and an in-depth quality assessment conducted by one author, and checked by two others. RESULTS: The 151 included studies were conducted in diverse settings in 32 countries between 1985 and 2017, involving 28130 participants with a mean age of 69.3 years. Seventy-one studies investigated delirium biomarkers, and 80 studies investigated biomarkers of an advanced cancer-related syndrome or cancer prognosis. Overall, 41 biomarkers were studied in relation to both delirium and either an advanced cancer-related syndrome or prognosis; and of these, 24 biomarkers were positively associated with either delirium or advanced cancer syndromes/prognosis in at least one study. The quality assessment showed large inconsistency in reporting. CONCLUSION: There is considerable overlap in the biomarkers in delirium and advanced cancer-related syndromes. Improving the design of delirium biomarker studies and considering appropriate comparator/controls will help to better understanding the discrete pathophysiology of delirium in the context of co-existing illness.

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: Rigidity of the Outer Shell Predicted by a Protein Intrinsic Disorder Model Sheds Light on the COVID-19 (Wuhan-2019-nCoV) Infectivity The world is currently witnessing an outbreak of a new coronavirus spreading quickly across China and affecting at least 24 other countries. With almost 65,000 infected, a worldwide death toll of at least 1370 (as of 14 February 2020), and with the potential to affect up to two-thirds of the world population, COVID-19 is considered by the World Health Organization (WHO) to be a global health emergency. The speed of spread and infectivity of COVID-19 (also known as Wuhan-2019-nCoV) are dramatically exceeding those of the Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). In fact, since September 2012, the WHO has been notified of 2494 laboratory-confirmed cases of infection with MERS-CoV, whereas the 2002–2003 epidemic of SARS affected 26 countries and resulted in more than 8000 cases. Therefore, although SARS, MERS, and COVID-19 are all the result of coronaviral infections, the causes of the coronaviruses differ dramatically in their transmissibility. It is likely that these differences in infectivity of coronaviruses can be attributed to the differences in the rigidity of their shells which can be evaluated using computational tools for predicting intrinsic disorder predisposition of the corresponding viral proteins.

negative: Clinical diagnosis of 8274 samples with 2019-novel coronavirus in Wuhan Background: 2019-Novel coronavirus (2019-nCoV) outbreaks create challenges for hospital laboratories because thousands of samples must be evaluated each day. Sample types, interpretation methods, and corresponding laboratory standards must be established. The possibility of other infections should be assessed to provide a basis for clinical classification, isolation, and treatment. Accordingly, in the present study, we evaluated the testing methods for 2019-nCoV and co-infections. Methods: We used a fluorescence-based quantitative PCR kit urgently distributed by the Chinese CDC to detect 8274 close contacts in the Wuhan region against two loci on the 2019-nCoV genome. We also analyzed 613 patients with fever who underwent multiple tests for 13 respiratory pathogens; 316 subjects were also tested for 2019-nCoV. Findings: Among the 8274 subjects, 2745 (33.2%) had 2019-nCoV infection; 5277 (63.8%) subjects showed negative results in the 2019-nCoV nucleic acid test (non-019-nCoV); and 252 cases (3.0%) because only one target was positive, the diagnosis was not definitive. Sixteen patients who originally had only one positive target were re-examined a few days later; 14 patients (87.5%) were finally defined as 2019-nCoV-positive, and 2 (12.5%) were finally defined as negative. The positive rates of nCoV-NP and nCovORF1ab were 34.7% and 34.7%, respectively. nCoV-NP-positive only and nCovORF1ab-positive cases accounted for 1.5% and 1.5%, respectively. In the 316 patients with multiple respiratory pathogens, 104 were positive for 2019-nCov and 6/104 had co-infection with coronavirus (3/104), influenza A virus (2/104), rhinovirus (2/104), and influenza A H3N2 (1/104); the remaining 212 patients had influenza A virus (11/202), influenza A H3N2 (11/202), rhinovirus (10/202), respiratory syncytial virus (7/202), influenza B virus (6/202), metapneumovirus (4/202), and coronavirus (2/202). Interpretation: Clinical testing methods for 2019-nCoV require improvement. Importantly, 5.8% of 2019-nCoV infected and 18.4% of non-2019-nCoV-infected patients had other pathogen infections. It is important to treat combined infections and perform rapid screening to avoid cross-contamination of patients. A test that quickly and simultaneously screens as many pathogens as possible is needed.

negative: Artificial intelligence for rapid identification of the coronavirus disease 2019 (COVID-19) The coronavirus disease 2019 (COVID-19) outbreak that originated in Wuhan, China has rapidly propagated due to widespread person-to-person transmission and has resulted in over 1,133,758 cases in 197 countries with a total of 62,784 deaths as of April 5, 2020. Laboratory confirmation of SARS-CoV-2 is performed with a virus-specific reverse transcriptase polymerase chain reaction (RT-PCR) test. This test can take up to two days to complete, and, due to the possibility of false negatives, serial testing may be required to reliably exclude infection. A current supply shortage of RT-PCR test kits compounds the shortcomings of entrusting diagnosis to the PCR test alone and underscores the urgent need to provide alternative methods for the rapid and accurate diagnosis of SARS-CoV-2 patients. Chest computed tomography (CT) is a valuable component in the evaluation of patients with suspected SARS-CoV-2 infection. Nevertheless, CT alone may have limited negative predictive value to fully exclude infection, because of the normal radiologic findings in some early disease patients. In this study, we use artificial intelligence (AI) algorithms to integrate chest CT findings with clinical symptoms, exposure history, and/or laboratory testing to more accurately and rapidly diagnose SARS-CoV-2 (+) patients. We included 905 RT-PCR confirmed patients. 419 (46.2%) tested positive for SARS-CoV-2 by laboratory-confirmed real-time RT-PCR assay and next-generation sequencing, while 486 patients (53.8%) tested negative (confirmed by at least two additional negative RT-PCR tests and clinical observation). The proposed AI system achieved an AUC of 0.92 and performed equally well in sensitivity compared to a senior thoracic radiologist on a testing set of 279 cases. The AI system also improved the detection of RT-PCR positive SARS-CoV-2 patients who presented with normal CTs, correctly identifying 17/25 (68%) patients, whereas all 25 RT-PCR SARS-CoV-2-positive CT-normal patients were classified as SARS-CoV-2 negative by radiologists.

negative: From SARS to MERS, Thrusting Coronaviruses into the Spotlight Coronaviruses (CoVs) have formerly been regarded as relatively harmless respiratory pathogens to humans. However, two outbreaks of severe respiratory tract infection, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), as a result of zoonotic CoVs crossing the species barrier, caused high pathogenicity and mortality rates in human populations. This brought CoVs global attention and highlighted the importance of controlling infectious pathogens at international borders. In this review, we focus on our current understanding of the epidemiology, pathogenesis, prevention, and treatment of SARS-CoV and MERS-CoV, as well as provides details on the pivotal structure and function of the spike proteins (S proteins) on the surface of each of these viruses. For building up more suitable animal models, we compare the current animal models recapitulating pathogenesis and summarize the potential role of host receptors contributing to diverse host affinity in various species. We outline the research still needed to fully elucidate the pathogenic mechanism of these viruses, to construct reproducible animal models, and ultimately develop countermeasures to conquer not only SARS-CoV and MERS-CoV, but also these emerging coronaviral diseases.

negative: [Pregnancy with new coronavirus infection: clinical characteristics and placental pathological analysis of three cases] Objective: To investigate the clinical characteristics and placental pathology of 2019-nCoV infection in pregnancy,and to evaluate intrauterine vertical transmission potential of 2019-nCoV infection. Methods: The placentas delivered from pregnant women with confirmed 2019-nCoV infection which were received in the Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology by February 4, 2020 were retrospectively studied. Their clinical material including placental tissue and lung CT, and laboratory results were collected, meanwhile, nucleic acid detection of 2019-nCoV of the placentas were performed by RT-PCR. Results: Three placentas delivered from pregnant women with confirmed 2019-nCoV infection, who were all in their third trimester with emergency caesarean section. All of the three patients presented with fever (one before caesarean and two in postpartum), and had no significant leukopenia and lymphopenia. Neonatal throat swabs from three newborns were tested for 2019-nCoV, and all samples were negative for the nucleic acid of 2019-nCoV. One premature infant was transferred to Department of Neonatology due to low birth weight. By the end of February 25, 2020, none of the three patients developed severe 2019-nCoV pneumonia or died(two patients had been cured and discharged, while another one had been transferred to a square cabin hospital for isolation treatment). There were various degrees of fibrin deposition inside and around the villi with local syncytial nodule increases in all three placentas. One case of placenta showed the concomitant morphology of chorionic hemangioma and another one with massive placental infarction. No pathological change of villitis and chorioamnionitis was observed in our observation of three cases. All samples from three placentas were negative for the nucleic acid of 2019-nCoV. Conclusions: The clinical characteristics of pregnant women with 2019-nCoV infection in late pregnancy are similar to those of non-pregnant patients, and no severe adverse pregnancy outcome is found in the 3 cases of our observation. Pathological study suggests that there are no morphological changes related to infection in the three placentas. Currently no evidence for intrauterine vertical transmission of 2019-nCoV is found in the three women infected by 2019-nCoV in their late pregnancy.

negative: Why Are Lopinavir and Ritonavir Effective against the Newly Emerged Coronavirus 2019? Atomistic Insights into the Inhibitory Mechanisms [Image: see text] Since the emergence of a novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported from Wuhan, China, neither a specific vaccine nor an antiviral drug against SARS-CoV-2 has become available. However, a combination of two HIV-1 protease inhibitors, lopinavir and ritonavir, has been found to be effective against SARS-CoV, and both drugs could bind well to the SARS-CoV 3C-like protease (SARS-CoV 3CL(pro)). In this work, molecular complexation between each inhibitor and SARS-CoV-2 3CL(pro) was studied using all-atom molecular dynamics simulations, free energy calculations, and pair interaction energy analyses based on MM/PB(GB)SA and FMO-MP2/PCM/6-31G* methods. Both anti-HIV drugs interacted well with the residues at the active site of SARS-CoV-2 3CL(pro). Ritonavir showed a somewhat higher number atomic contacts, a somewhat higher binding efficiency, and a somewhat higher number of key binding residues compared to lopinavir, which correspond with the slightly lower water accessibility at the 3CL(pro) active site. In addition, only ritonavir could interact with the oxyanion hole residues N142 and G143 via the formation of two hydrogen bonds. The interactions in terms of electrostatics, dispersion, and charge transfer played an important role in the drug binding. The obtained results demonstrated how repurposed anti-HIV drugs could be used to combat COVID-19.

negative: Predicting the Immunogenicity of T cell epitopes: From HIV to SARS-CoV-2 We describe a physics-based learning model for predicting the immunogenicity of Cytotoxic T Lymphocyte (CTL) epitopes derived from diverse pathogens, given a Human Leukocyte Antigen (HLA) genotype. The model was trained and tested on experimental data on the relative immunodominance of CTL epitopes in Human Immunodeficiency Virus infection. The method is more accurate than publicly available models. Our model predicts that only a fraction of SARS-CoV-2 epitopes that have been predicted to bind to HLA molecules is immunogenic. The immunogenic CTL epitopes across all SARS-CoV-2 proteins are predicted to provide broad population coverage, but the immunogenic epitopes in the SARS-CoV-2 spike protein alone are unlikely to do so. Our model predicts that several immunogenic SARS-CoV-2 CTL epitopes are identical to those contained in low-pathogenicity coronaviruses circulating in the population. Thus, we suggest that some level of CTL immunity against COVID-19 may be present in some individuals prior to SARS-CoV-2 infection.

negative: COVID-19 outbreak in Algeria: A mathematical Model to predict cumulative cases Introduction: Since December 29, 2019 a pandemic of new novel coronavirus-infected pneumonia named COVID-19 has started from Wuhan, China, has led to 254 996 confirmed cases until midday March 20, 2020. Sporadic cases have been imported worldwide, in Algeria, the first case reported on February 25, 2020 was imported from Italy, and then the epidemic has spread to other parts of the country very quickly with 139 confirmed cases until March 21, 2020. Methods: It is crucial to estimate the cases number growth in the early stages of the outbreak, to this end, we have implemented the Alg-COVID-19 Model which allows to predict the incidence and the reproduction number R0 in the coming months in order to help decision makers. The Alg-COVIS-19 Model initial equation 1, estimates the cumulative cases at t prediction time using two parameters: the reproduction number R0 and the serial interval SI. Results: We found R0=2.55 based on actual incidence at the first 25 days, using the serial interval SI= 4,4 and the prediction time t=26. The herd immunity HI estimated is HI=61%. Also, The Covid-19 incidence predicted with the Alg-COVID-19 Model fits closely the actual incidence during the first 26 days of the epidemic in Algeria Fig. 1.A. which allows us to use it.

negative: Upper-Respiratory Viral Infection, Biomarkers, and COPD Exacerbations Background Respiratory viruses frequently are recovered in the upper-respiratory tract during acute exacerbations of COPD (AECOPD), but their role as contributing pathogens remains unclear. The usefulness of procalcitonin and C-reactive protein as indicators of the presence or absence of viral infection in this setting also needs to be evaluated. Methods The study was of a prospective cohort of patients with COPD admitted to the ED for AECOPD. Reverse transcriptase-polymerase chain reaction (RT-PCR) for 14 respiratory viruses was performed on nasopharyngeal swabs collected at admission and after recovery in stable condition. Results Eighty-six patients (mean age, 72 years; male, 64%) were included. During AECOPD, upper-respiratory viral infections were detected in 44 (51%) patients: picornavirus in 22, metapneumovirus in seven, coronavirus in eight, influenza A/B in two, parainfluenza in two, and respiratory syncytial virus in three. A dual infection was present in three patients. After recovery, viruses were detected in only eight (11%) of 71 patients (P < .001 compared with AECOPD phase). In five of these patients, no virus had been identified during the initial exacerbation, thus suggesting a new viral infection acquired during follow-up. During AECOPD, procalcitonin and C-reactive protein levels did not differ significantly between patients with or without a proven viral infection. Conclusions Prevalence of upper-respiratory viral infection, as detected from nasopharyngeal swab by RT-PCR, is high in AECOPD and low after clinical recovery, suggesting that AECOPD frequently are triggered by viral infections initiated in the upper-respiratory tract. In our study, serum procalcitonin and C-reactive protein did not discriminate virus-associated exacerbations from others. Trial registration clinicaltrials.gov; Identifier: NCT00448604.

negative: Understanding nurses’ dual practice: a scoping review of what we know and what we still need to ask on nurses holding multiple jobs BACKGROUND: Mounting evidence suggests that holding multiple concurrent jobs in public and private (dual practice) is common among health workers in low- as well as high-income countries. Nurses are world’s largest health professional workforce and a critical resource for achieving Universal Health Coverage. Nonetheless, little is known about nurses’ engagement with dual practice. METHODS: We conducted a scoping review of the literature on nurses’ dual practice with the objective of generating hypotheses on its nature and consequences, and define a research agenda on the phenomenon. The Arksey and O’Malley’s methodological steps were followed to develop the research questions, identify relevant studies, include/exclude studies, extract the data, and report the findings. PRISMA guidelines were additionally used to conduct the review and report on results. RESULTS: Of the initial 194 records identified, a total of 35 met the inclusion criteria for nurses’ dual practice; the vast majority (65%) were peer-reviewed publications, followed by nursing magazine publications (19%), reports, and doctoral dissertations. Twenty publications focused on high-income countries, 16 on low- or middle-income ones, and two had a multi country perspective. Although holding multiple jobs not always amounted to dual practice, several ways were found for public-sector nurses to engage concomitantly in public and private employments, in regulated as well as in informal, casual fashions. Some of these forms were reported as particularly prevalent, from over 50% in Australia, Canada, and the UK, to 28% in South Africa. The opportunity to increase a meagre salary, but also a dissatisfaction with the main job and the flexibility offered by multiple job-holding arrangements, were among the reported reasons for engaging in these practices. DISCUSSION AND CONCLUSIONS: Limited and mostly circumstantial evidence exists on nurses’ dual practice, with the few existing studies suggesting that the phenomenon is likely to be very common and carry implications for health systems and nurses’ welfare worldwide. We offer an agenda for future research to consolidate the existing evidence and to further explore nurses’ motivation; without a better understanding of nurse dual practice, this will continue to be a largely ‘hidden’ element in nursing workforce policy and practice, with an unclear impact on the delivery of care. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12960-018-0276-x) contains supplementary material, which is available to authorized users.

negative: Proposal for detection of 2019-nCoV nucleic acid in clinical laboratories/ 中华检验医学杂志 In December, the outbreak of a novel coronavirus (2019-nCoV) in Wuhan, China, has attracted extensive global attention. On January 20, 2020,the Chinese health authorities upgraded the coronavirus to a Class B infectious disease in the Law of the People's Republic of China on the Prevention and Treatment of Infectious Diseases, and considered it as Class A infectious diseases in disease control and prevention. On January 22, 2020, the 2019-nCoV nucleic acid detection test was listed as the diagnostic criteria in the "guidelines for diagnosis and treatment of pneumonia due to 2019-nCoV (Trial Version 2)" . Therefore, standardizing the operation process of the 2019-nCoV nucleic acid detection in clinical laboratories has become a top priority. It is of paramount importance to establish standard protocols for detection of the 2019-nCoV nucleic acids in clinical laboratories to improve the reliability of the results and ensure the biosafety of laboratory personnel.

negative: The Functional Protein Microarray as Molecular Decathlete: A Versatile Player in Clinical Proteomics Functional protein microarrays were developed as a high-throughput tool to overcome the limitations of DNA microarrays and to provide a versatile platform for protein functional analyses. Recent years have witnessed tremendous growth in the use of protein microarrays, particularly functional protein microarrays, to address important questions in the field of clinical proteomics. In this review, we will summarize some of the most innovative and exciting recent applications of protein microarrays in clinical proteomics, including biomarker identification, pathogen-host interactions, and cancer biology.

negative: SYSTEMATIC REVIEW OF THE ONGOING CLINICAL TRIALS EVALUATING THE DIAGNOSTIC AND THERAPEUTIC INTERVENTIONS TO MANAGE THE RESPIRATORY INFECTION CAUSED BY 2019 NOVEL CORONAVIRUS (2019-NCOV) TYPE: Abstract Publication TOPIC: Respiratory Care PURPOSE: 2019 novel coronavirus (2019-nCoV) is attributed for outbreak with first human infection detected in December 2019 in Wuhan, China, which has caused clusters of severe respiratory illness like severe acute respiratory syndrome coronavirus. The latest mortality was 2.07%. Currently, the standard care is supportive care, and no treatment is proven to be effective METHODS: We systematically analysed the contemporary protocols of the seven ongoing trials through the Chinese Clinical Trial Registry (4 trials) and the trials registry (3 trials) database. The latest evaluation was on January 29, 2020 with key word ‘2019-nCoV’, for the trials evaluating the diagnostic and the therapeutic interventions to manage the respiratory infection caused by 2019-nCoV RESULTS: Therapeutic interventions include, lopinavir-ritonavir with aerosolized interferon-alpha compared with the adjunctive IV methylprednisolone, umifenovir (broad-spectrum antiviral), SARI-nCoV trial for role of glucocorticoid, three comparative antiviral therapies utilising ribavirin, interferon alpha-1b, lopinavir -ritonavir, Xue-Bi-Jing injection (only Chinese medicine injection approved for sepsis) and novel isothermal nucleic acid amplification technique is under trial for simple, fast and portable diagnosis. The mean number of patients being enrolled is 193 (SD ± 183, maximum 500, minimum 40, range 460, 95% CI 24 to 362). Cumulatively, 1350 patients are targeted across 7 trials. CONCLUSIONS: Varied novel approaches based on the current scientific understanding of the disease are being evaluated for quick and effective management CLINICAL IMPLICATIONS: As the 2019-nCoV becomes a global threat, the rapidity of the Chinese trials for an evidence-based approach are in direction to provide rational, efficacious and potential solutions to effectively manage the disease DISCLOSURE: No significant relationships. KEYWORDS: Ongoing Trials, Systematic Review, 2019-nCoV

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: Etiological agents of lower respiratory tract infections in Japanese children. To investigate the etiology of pediatric community-acquired pneumonia and bronchitis, we conducted a prospective, population-based study covering the total population < 15 years of age in 16 municipalities in Hokkaido, Japan, during the period of April 2000 to March 2001. Chest radiographs were available for all cases (n = 921; 398 as pneumonia and 523 as bronchitis) and paired sera for serologic assays were available for more than half of the cases. The following specimens were also collected: nasopharyngeal swabs for viral, bacteriological, mycoplasmal and chlamydial studies, blood for serology and blood culture. The children were then followed-up on days 3, 7 and 14. Specific infecting organisms were identified in a total of 853 (92.6%) out of 921 patients (398 cases of pneumonia and 523 cases of bronchitis) including 205 with mixed infection as follows: Mycoplasma pneumoniae, 252 (274%) patients; respiratory syncytial (RS) virus, 188 (20.4%); influenza A virus, 110 (11.9%); Streptococcus pneumoniae, 95 (10.3%); Haemophilus influenzae, 90 (9.8%); Haemophilus parainfluenzae, 35 (3.8%); Staphylococcus aureus, 29 (3.1%); adenovirus, 27 (2.9%); Moraxella catarrhalis, 12 (1.3%); Pseudomonas aeruginosa , 7 (0.8%); Chlamydia pneumoniae, 6 (0.7%); and other agents, 2 (0.2%). Mycoplasma infections were seen even in patients less than 5 years and RS and influenza A virus infections in patients more than 5 years of age. The importance of M. pneumoniae and RS virus in the etiology of lower respiratory infections in Japanese children was confirmed.

negative: Novel coronavirus (COVID-19) infection: What a doctor on the frontline needs to know Coronavirus disease 2019 (COVID-19) is a zoonotic respiratory infection originating from Wuhan, China. Rapidly spreading from Wuhan to all inhabited continents of the world, the World Health Organisation declared COVID-19 a pandemic on March 11, 2019. Infected patients present with fever and cough; radiological features include bilateral infiltrates on chest x-ray and computed tomography scanning. Management is supportive with oxygen supplementation, broad-spectrum antibiotics as well as careful fluid balancing. A number of drugs, both new and old, are currently in clinical trials and being used on an experimental basis in clinical practice. The COVID-19 pandemic is the greatest worldwide public health crisis of a generation, and has led to seismic political, economic and social changes. This review provides an overview of COVID-19 for junior doctors who find themselves on a new frontline of healthcare.

negative: Lipocalin-2 is a Sensitive and Specific Marker of Bacterial Infection in Children Bacterial infection is the leading cause of death in children globally. Clinical algorithms to identify children who are likely to benefit from antimicrobial treatment remain suboptimal. Biomarkers that accurately identify serious bacterial infection (SBI) could improve diagnosis and clinical management. Lipocalin 2 (LCN2) and neutrophil collagenase (MMP-8) are neutrophil-derived biomarkers associated with bacterial infection. We evaluated LCN2 and MMP-8 as candidate biomarkers in 40 healthy controls and 151 febrile children categorised confirmed SBI, probable SBI, or viral infection. The diagnostic performance of LCN2 and MMP-8 to predict SBI was estimated by the area under the receiver operating characteristic curve (AUROC) and compared to the performance of C-reactive protein (CRP). Plasma LCN2 and MMP-8 concentration were predictive of SBI. The AUROC (95% CI) for LCN2, MMP8 and CRP to predict SBI was 0.88 (0.82-0.94); 0.80 (0.72-0.87) and 0.89 (0.84-0.94), respectively. The diagnostic performance of LCN2 in combination with CRP was significantly superior to either marker alone: AUROC 0.92 (95% CI: 0.88-0.96). LCN2 is a sensitive and specific predictor of SBI in children which could be used to improve clinical management and antimicrobial stewardship. LCN2 should be further evaluated in prospective clinical studies.

negative: First Case of 2019 Novel Coronavirus in the United States An outbreak of novel coronavirus (2019-nCoV) that began in Wuhan, China, has spread rapidly, with cases now confirmed in multiple countries. We report the first case of 2019-nCoV infection confirmed in the United States and describe the identification, diagnosis, clinical course, and management of the case, including the patient’s initial mild symptoms at presentation with progression to pneumonia on day 9 of illness. This case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels, as well as the need for rapid dissemination of clinical information related to the care of patients with this emerging infection.

negative: Plasma Erythropoietin, IL-17A, and IFNγ as Potential Biomarkers of Motor Function Recovery in a Canine Model of Spinal Cord Injury. Traumatic spinal cord injury (SCI) is a devastating neurological disease for which an accurate, cost-effective prediction of motor function recovery is in pressing need. A plethora of neurochemical changes involved in the pathophysiological process of SCI may serve as a new source of biomarkers for patient outcomes. Five dogs were included in this study. We characterized the plasma cytokine profiles in acute phase (0, 1, and 3 days after SCI) and subacute phase (7, 14, and 21 days after SCI) with microarray analysis. The motor function recovery following SCI was monitored by Olby scores. The expression level of differentially expressed proteins (DEPs) was measured with enzyme-linked immunosorbent assay (ELISA). Then, correlations with the Olby scores and receiver operating characteristic curve (ROC) analysis were performed. We identified 12 DEPs including 10 pro-inflammatory and 2 anti-inflammatory cytokines during the 21-day study period. Among those, the expression levels of erythropoietin (EPO), IL-17A, and IFNγ significantly correlated with the Olby scores with R2 values of 0.870, 0.740, and 0.616, respectively. The results of the ROC analysis suggested that plasma EPO, IL-17A, and IFNγ exhibited a significant predictive power with an area under the curve (AUC) of 0.656, 0.848, and 0.800 for EPO, IL-17A, and IFNγ, respectively. Our results provide a longitudinal description of the changes in plasma cytokine expression in the acute and subacute stages of canine SCI. These data reveal novel panels of inflammation-related cytokines which have the potential to be evaluated as biomarkers for predicting motor function prognosis after SCI.

negative: Proteomic fingerprinting in HIV/HCV co-infection reveals serum biomarkers for the diagnosis of fibrosis staging BACKGROUND: Hepatic complications of hepatitis C virus (HCV), including fibrosis and cirrhosis are accelerated in human immunodeficiency virus (HIV)-infected individuals. Although, liver biopsy remains the gold standard for staging HCV-associated liver disease, this test can result in serious complications and is subject to sampling errors. These challenges have prompted a search for non-invasive methods for liver fibrosis staging. To this end, we compared serum proteome profiles at different stages of fibrosis in HIV/HCV co- and HCV mono-infected patients using surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF MS). METHODS: Sera from 83 HIV/HCV co- and 68 HCV mono-infected subjects in 4 stages of fibrosis were tested. Sera were fractionated, randomly applied to protein chip arrays (IMAC, CM10 and H50) and spectra were generated at low and high laser intensities. RESULTS: Sixteen biomarkers achieved a p value < 0.01 (ROC values > 0.75 or < 0.25) predictive of fibrosis status in co-infected individuals and 14 in mono infected subjects. Five of these candidate biomarkers contributed to both mono- and co-infected subjects. Candidate diagnostic algorithms were created to distinguish between non-fibrotic and fibrotic individuals using a panel of 4 biomarker peaks. CONCLUSION: These data suggest that SELDI MS profiling can identify diagnostic serum biomarkers for fibrosis that are both common and distinct in HIV/HCV co-infected and HCV mono-infected individuals.

negative: High EREG Expression Is Predictive of Better Outcomes in Rectal Cancer Patients Receiving Neoadjuvant Concurrent Chemoradiotherapy. BACKGROUND/AIM A great proportion of patients with rectal cancer initially present with locally advanced disease and can potentially benefit from neoadjuvant concurrent chemoradiotherapy (CCRT) for downstaging before surgery. However, risk and clinical outcome stratification remain a great challenge. We aimed to find the potential biomarker to predict the effect of neoadjuvant CCRT on rectal cancer. METHODS We identified epiregulin (EREG) as the most significant predictive marker for neoadjuvant CCRT response from the published rectal cancer transcriptome data set GSE35452. We collected 172 biopsy specimens from rectal cancer patients who received neoadjuvant CCRT followed by radical proctectomy, performed EREG immunohistochemistry, and analyzed the H-scores. We further examined the correlations between the expression level of EREG and clinicopathological features, tumor regression grade, and survival, including disease-specific survival (DSS), locoregional recurrence-free survival (LRFS), and metastasis-free survival (MeFS). RESULTS High EREG expression was significantly related to early pretreatment (pre-Tx) and posttreatment (post-Tx) tumor status (T1, T2, p = 0.047 and p < 0.001), pre-Tx and post-Tx negative nodal status (N0, p < 0.001 and p = 0.004), less vascular and perineurial invasion (p = 0.015 and p = 0.023), and higher tumor regression grade (p < 0.001). In the survival analysis, high EREG expression was significantly associated with better DSS (p < 0.0001), LRFS (p = 0.0004), and MeFS (p < 0.0001). In the multivariate analysis, high EREG expression remained prognostically significant for better DSS (p = 0.003; hazard ratio: 5.599). CONCLUSION These data suggest that EREG is a potential predictive marker and therapeutic target in rectal cancer patients receiving neoadjuvant CCRT.

negative: Genomic determinants of pathogenicity in SARS-CoV-2 and other human coronaviruses Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses an immediate, major threat to public health across the globe. Here we report an in-depth molecular analysis to reconstruct the evolutionary origins of the enhanced pathogenicity of SARS-CoV-2 and other coronaviruses that are severe human pathogens. Using integrated comparative genomics and machine learning techniques, we identify key genomic features that differentiate SARS-CoV-2 and the viruses behind the two previous deadly coronavirus outbreaks, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), from less pathogenic coronaviruses. These features include enhancement of the nuclear localization signals in the nucleocapsid protein and distinct inserts in the spike glycoprotein that appear to be associated with high case fatality rate of these coronaviruses as well as the host switch from animals to humans. The identified features could be crucial contributors to coronavirus pathogenicity and possible targets for diagnostics, prognostication, and interventions.

negative: Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus Recently, a novel coronavirus (2019-nCoV) has emerged from Wuhan, China, causing symptoms in humans similar to those caused by severe acute respiratory syndrome coronavirus (SARS-CoV). Since the SARS-CoV outbreak in 2002, extensive structural analyses have revealed key atomic-level interactions between the SARS-CoV spike protein receptor-binding domain (RBD) and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. Here, we analyzed the potential receptor usage by 2019-nCoV, based on the rich knowledge about SARS-CoV and the newly released sequence of 2019-nCoV. First, the sequence of 2019-nCoV RBD, including its receptor-binding motif (RBM) that directly contacts ACE2, is similar to that of SARS-CoV, strongly suggesting that 2019-nCoV uses ACE2 as its receptor. Second, several critical residues in 2019-nCoV RBM (particularly Gln493) provide favorable interactions with human ACE2, consistent with 2019-nCoV’s capacity for human cell infection. Third, several other critical residues in 2019-nCoV RBM (particularly Asn501) are compatible with, but not ideal for, binding human ACE2, suggesting that 2019-nCoV has acquired some capacity for human-to-human transmission. Last, while phylogenetic analysis indicates a bat origin of 2019-nCoV, 2019-nCoV also potentially recognizes ACE2 from a diversity of animal species (except mice and rats), implicating these animal species as possible intermediate hosts or animal models for 2019-nCoV infections. These analyses provide insights into the receptor usage, cell entry, host cell infectivity and animal origin of 2019-nCoV and may help epidemic surveillance and preventive measures against 2019-nCoV. IMPORTANCE The recent emergence of Wuhan coronavirus (2019-nCoV) puts the world on alert. 2019-nCoV is reminiscent of the SARS-CoV outbreak in 2002 to 2003. Our decade-long structural studies on the receptor recognition by SARS-CoV have identified key interactions between SARS-CoV spike protein and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. One of the goals of SARS-CoV research was to build an atomic-level iterative framework of virus-receptor interactions to facilitate epidemic surveillance, predict species-specific receptor usage, and identify potential animal hosts and animal models of viruses. Based on the sequence of 2019-nCoV spike protein, we apply this predictive framework to provide novel insights into the receptor usage and likely host range of 2019-nCoV. This study provides a robust test of this reiterative framework, providing the basic, translational, and public health research communities with predictive insights that may help study and battle this novel 2019-nCoV.

negative: 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

negative: Biomarker Development in Chronic Inflammatory Diseases Chronic inflammatory diseases, such as inflammatory bowel disease—namely, Crohn’s disease and ulcerative colitis—psoriasis, multiple sclerosis, rheumatoid arthritis, and many others affect millions of people worldwide, causing a high burden of disease, socioeconomic impact, and healthcare cost. These diseases have common features including autoimmune pathogenesis and frequent co morbidity. The treatment of these chronic inflammatory diseases usually requires long-term immunosuppressive therapies with undesirable side effects. The future of chronic inflammatory disease prevention, detection, and treatment will be greatly influenced by the use of more effective biomarkers with enhanced performance. Given the practical issues of collecting tissue samples in inflammatory diseases, biomarkers derived from body fluids have great potential for optimized patient management through the circumvention of the abovementioned limitations. In this chapter, peripheral blood, urine, and cerebrospinal fluid biomarkers used in chronic inflammatory conditions are reviewed. In detail, this chapter reviews biomarkers to fore used or emerging to be used in patients with chronic inflammatory conditions. Those include inflammatory bowel diseases, chronic inflammatory conditions of the liver, biliary tract, pancreas, psoriasis, atopic disease, inflammatory skin diseases, rheumatic diseases, demyelination, and also the chronic inflammatory component of various other diseases in general medicine—including diabetes, cardiovascular disease, renal disease, and chronic obstructive pulmonary disease. Development of personalized medicine is closely linked to biomarkers, which may serve as the basis for diagnosis, drug discovery, and monitoring of diseases.

negative: Antiproliferative and apoptotic activity of glycyrrhizinic acid in MCF-7 human breast cancer cells and evaluation of its effect on cell cycle, cell migration and m-TOR/PI3K/Akt signalling pathway INTRODUCTION: Glycyrrhizinic acid is a natural product of pharmacological relevance and its anticancer activity against breast cancer cell lines has not been evaluated. Therefore the main purpose of the present study was to investigate the anticancer effects of glycyrrhizinic acid in MCF-7 human breast cancer cells. MATERIAL AND METHODS: The MTT assay was used to evaluate the anticancer effects while a clonogenic assay was used to study its effects on colony formation tendency. Flow cytometry was used to study the effects on cell cycle phase distribution and apoptosis. Western blot assay was used to study changes in protein expression of the m-TOR/PI3K/Akt pathway. RESULTS: The results indicated that glycyrrhizinic acid caused significant (p < 0.01). The growth inhibitory effects MCF-7 human breast cancer cells. The growth inhibitory effects of glycyrrhizinic acid exhibited concentration-dependent as well as time-dependent growth inhibitory trend. Different doses of glycyrrhizinic acid had a tendency to significantly (p < 0.01) inhibit the colony formation tendency of MCF-7 cells. As compared to the control group, glycyrrhizinic acid-treated cells showed a high percentage of apoptotic cells. Cells treated with a 10, 50 and 100 µM dose of glycyrrhizinic acid led to a 24.3%, 41.5% and 82.1% increase in the sub-G1 phase (apoptotic) cells. Glycyrrhizinic acid also led to significant (p < 0.01) inhibition of cell invasion along with downregulation of m-TOR/PI3K/Akt protein expression. CONCLUSIONS: Glycyrrhizinic acid inhibited MCF-7 human breast cancer cell growth and therefore may prove essential lead molecule in the treatment of breast cancer.

negative: Sensitivity and Specificity of Soluble Triggering Receptor Expressed on Myeloid Cells-1, Midregional Proatrial Natriuretic Peptide and Midregional Proadrenomedullin for Distinguishing Etiology and to Assess Severity in Community-Acquired Pneumonia STUDY DESIGN: This study aimed to evaluate the diagnostic accuracy of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), midregional proatrial natriuretic peptide (MR-proANP) and midregional proadrenomedullin (MR-proADM) to distinguish bacterial from viral community-acquired pneumonia (CAP) and to identify severe cases in children hospitalized for radiologically confirmed CAP. Index test results were compared with those derived from routine diagnostic tests, i.e., white blood cell (WBC) counts, neutrophil percentages, and serum C-reactive protein (CRP) and procalcitonin (PCT) levels. METHODS: This prospective, multicenter study was carried out in the most important children’s hospitals (n = 11) in Italy and 433 otherwise healthy children hospitalized for radiologically confirmed CAP were enrolled. Among cases for whom etiology could be determined, CAP was ascribed to bacteria in 235 (54.3%) children and to one or more viruses in 111 (25.6%) children. A total of 312 (72.2%) children had severe disease. RESULTS: CRP and PCT had the best performances for both bacterial and viral CAP identification. The cut-off values with the highest combined sensitivity and specificity for the identification of bacterial and viral infections using CRP were ≥7.98 mg/L and ≤7.5 mg/L, respectively. When PCT was considered, the cut-off values with the highest combined sensitivity and specificity were ≥0.188 ng/mL for bacterial CAP and ≤0.07 ng/mL for viral CAP. For the identification of severe cases, the best results were obtained with evaluations of PCT and MR-proANP. However, in both cases, the biomarker cut-off with the highest combined sensitivity and specificity (≥0.093 ng/mL for PCT and ≥33.8 pmol/L for proANP) had a relatively good sensitivity (higher than 70%) but a limited specificity (of approximately 55%). CONCLUSIONS: This study indicates that in children with CAP, sTREM-1, MR-proANP, and MR-proADM blood levels have poor abilities to differentiate bacterial from viral diseases or to identify severe cases, highlighting that PCT maintains the main role at this regard.

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

negative: Reliability of self-sampling for accurate assessment of respiratory virus viral and immunologic kinetics The SARS-CoV-2 pandemic demonstrates the need for accurate and convenient approaches to diagnose and therapeutically monitor respiratory viral infections. We demonstrated that self-sampling with foam swabs is well-tolerated and provides quantitative viral output concordant with flocked swabs. Using longitudinal home-based self-sampling, we demonstrate nasal cytokine levels correlate and cluster according to immune cell of origin. Periods of stable viral loads are followed by rapid elimination, which could be coupled with cytokine expansion and contraction using mathematical models. Nasal foam swab self-sampling at home provides a precise, mechanistic readout of respiratory virus shedding and local immune responses.

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

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

negative: Screening and Identification of APOC1 as a Novel Potential Biomarker for Differentiate of Mycoplasma pneumoniae in Children Background: Although Mycoplasma pneumoniae (MP) is a common cause of community-acquired pneumonia (CAP) in children, the currently used diagnostic methods are not optimal. Proteomics is increasingly being used to study the biomarkers of infectious diseases. Methods: Label-free quantitative proteomics and liquid chromatography-mass/mass spectrometry were used to analyze the fold change of protein expression in plasma of children with MP pneumonia (MPP), infectious disease control (IDC), and healthy control (HC) groups. Selected proteins that can distinguish MPP from HC and IDC were further validated by enzyme-linked immunosorbent assay (ELISA). Results: After multivariate analyses, 27 potential plasma biomarkers were identified to be expressed differently among child MPP, HC, and IDC groups. Among these proteins, SERPINA3, APOC1, ANXA6, KNTC1, and CFLAR were selected for ELISA verification. SERPINA3, APOC1, and CFLAR levels were significantly different among the three groups and the ratios were consistent with the trends of proteomics results. A comparison of MPP patients and HC showed APOC1 had the largest area under the curve (AUC) of 0.853, with 77.6% sensitivity and 81.1% specificity. When APOC1 levels were compared between MPP and IDC patients, it also showed a relatively high AUC of 0.882, with 77.6% sensitivity and 85.3% specificity. Conclusion: APOC1 is a potential biomarker for the rapid and noninvasive diagnosis of MPP in children. The present finding may offer new insights into the pathogenesis and biomarker selection of MPP in children.

negative: IDBD: Infectious Disease Biomarker Database Biomarkers enable early diagnosis, guide molecularly targeted therapy and monitor the activity and therapeutic responses across a variety of diseases. Despite intensified interest and research, however, the overall rate of development of novel biomarkers has been falling. Moreover, no solution is yet available that efficiently retrieves and processes biomarker information pertaining to infectious diseases. Infectious Disease Biomarker Database (IDBD) is one of the first efforts to build an easily accessible and comprehensive literature-derived database covering known infectious disease biomarkers. IDBD is a community annotation database, utilizing collaborative Web 2.0 features, providing a convenient user interface to input and revise data online. It allows users to link infectious diseases or pathogens to protein, gene or carbohydrate biomarkers through the use of search tools. It supports various types of data searches and application tools to analyze sequence and structure features of potential and validated biomarkers. Currently, IDBD integrates 611 biomarkers for 66 infectious diseases and 70 pathogens. It is publicly accessible at http://biomarker.cdc.go.kr and http://biomarker.korea.ac.kr.

negative: 9G DNAChip Technology: Self-Assembled Monolayer (SAM) of ssDNA for Ultra-Sensitive Detection of Biomarkers A 9G DNAChip obtained by allowing the formation of a self-assembled monolayer (SAM) of oligonucleotides appended with nine consecutive guanines on the chip surface has been applied in the detection of biomarkers. Using a 9G DNAChip, biomarker in the concentration range of 4 pg/mL to 40 fg/mL can be easily differentiated in the buffer matrix. Moreover, it is the first time that a biomarker with a concentration of 40 fg/mL has been detected in a mixture of proteins without use of any signal amplification technique.

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

negative: Epitope mapping and the detection of transmissible gastroenteritis viral proteins in cell culture using biotinylated monoclonal antibodies in a fixed-cell ELISA A fixed-cell ELISA was developed using swine testicle (ST) cells infected with the virulent Miller strain of transmissible gastroenteritis virus (TGEV) and purified biotinylated monoclonal antibodies (b-MAbs). Five of the b-MAbs were specific for the peplomer (E2), five reacted to the nucleocapsid (N), and one reacted to the E1 protein of the Miller strain of TGEV. Protein A-Sepharose purification of MAbs yielded protein concentrations ranging from 0.40 to 3 mg per ml of ascites. Separate pools of N-MAbs and E2-MAbs, and the E1-MAb were used to monitor synthesis of TGE viral antigen in ST cells from 0 to 16 h post-infection at various multiplicities of infection (MOI). Epitopes of N proteins appeared sooner and at a lower MOI than those for the E1 and E2 proteins. The fixed-cell ELISA was also used to examine relative binding affinities of TGEV MAbs. Concentrations of b-MAbs producing a half-maximal signal ranged from 0.11 to 3.8 µg/ml for E2-MAbs, from 0.05 to 0.82 µg/ml for N-MAbs, and 6 µg/ml for the E1-MAb. The assay was used to determine the 50% neutralization concentrations for four neutralizing E2-MAbs (0.1 µg/ml to 6.9 µg/ml) and one E1-MAb (1.2 µg/ml). Competition assays between b-MAbs and unlabeled competitors indicated that at least two major antigenic sites exist on the E2-protein and 2 to 3 antigenic sites are present on the N-protein of Miller TGEV.

negative: Precaution of 2019 novel coronavirus infection in department of oral and maxillofacial surgery Abstract The epidemic of the 2019 novel coronavirus (2019-nCoV) infection has presented as a critical period. Until February 23th 2020, more than 77 000 cases of 2019-nCoV infection have been confirmed in China, which has a great impact on economy and society. It has also interferred with ordinary medical practice of oral and maxillofacial surgery seriously. In order to protect oral and maxillofacial surgery medical staff from 2019-nCoV infection during the outbreak period, this paper suggests the necessary medical protective measures for oral and maxillofacial surgery outpatient and ward.

negative: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review Rapid diagnostics, vaccines and therapeutics are important interventions for the management of the 2019 novel coronavirus (2019-nCoV) outbreak. It is timely to systematically review the potential of these interventions, including those for Middle East respiratory syndrome-Coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS)-CoV, to guide policymakers globally on their prioritization of resources for research and development. A systematic search was carried out in three major electronic databases (PubMed, Embase and Cochrane Library) to identify published studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Supplementary strategies through Google Search and personal communications were used. A total of 27 studies fulfilled the criteria for review. Several laboratory protocols for confirmation of suspected 2019-nCoV cases using real-time reverse transcription polymerase chain reaction (RT-PCR) have been published. A commercial RT-PCR kit developed by the Beijing Genomic Institute is currently widely used in China and likely in Asia. However, serological assays as well as point-of-care testing kits have not been developed but are likely in the near future. Several vaccine candidates are in the pipeline. The likely earliest Phase 1 vaccine trial is a synthetic DNA-based candidate. A number of novel compounds as well as therapeutics licensed for other conditions appear to have in vitro efficacy against the 2019-nCoV. Some are being tested in clinical trials against MERS-CoV and SARS-CoV, while others have been listed for clinical trials against 2019-nCoV. However, there are currently no effective specific antivirals or drug combinations supported by high-level evidence.

negative: Clinical features of 2019 novel coronavirus infection patients and a feasible screening procedure/ 中华急诊医学杂志 Objective@#To study the clinical characteristics of 2019 coronavirus (2019-nCoV) pneumonia patients and make a feasible screening process in fever clinic.@*Methods@#Epidemiologic features, clinical presentation, laboratory findings and image features of the screened patients were retrospectively collected and analyzed.@*Results@#Totally, 46 patients were screened, 9 of them were laboratory-confirmed 2019-nCoV infection, and others were defined as laboratory-excluded patients. Laboratory-confirmed patients had higher frequency of travelling or residence in Wuhan within two weeks of onset (P<0.05), but there were no differences on age, sex, other epidemiologic features and comorbidities between the two groups (P>0.05). The most common feature of the laboratory-confirmed patients was fever (100%), but the symptoms showed no differences between the two groups (P>0.05). Laboratory-confirmed patients had lower white blood cell count than the laboratory-excluded patients (P<0.05), and all of them had pneumonia in chest CT scan. None of the patients with normal chest CT had positive 2019-nCoV nucleic acid test.@*Conclusions@#No specific symptom was helpful in the diagnosis of 2019-nCoV infection. However, patients without chest CT scan changes had a very low risk of 2019-nCoV infection despite of the epidemiologic history and fever. We recommended a screening procedure that might be helpful to reduce the rate of miss diagnosis and improve screening efficiency.

negative: Molecular targets for the rational design of drugs to inhibit SARS coronavirus Despite years of research, the precise determinants of coronavirus replication and pathogenesis remain unidentified. What is known of the pathogenesis of the severe acute respiratory syndrome coronavirus (SARS-CoV) is limited, but clinical observations suggest that both viral-induced cytotoxicity and host immune-mediated destruction contribute to the severity of disease. This summary discusses recent advances in coronavirus research that will facilitate the identification of crucial molecular targets for the rational design of SARS therapeutics. Section Editor: Anne Moscona – Department of Pediatrics, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1198, New York, NY 10029, USA When the SARS coronavirus came dramatically to attention as a fatal and potentially pandemic respiratory disease, the scientific response was swift and effective. The etiological agent was identified, the genome was cloned and sequenced, and large strides have been made in understanding key points in the viral life cycle, including recent identification of a functional host cell receptor and solution of the three-dimensional structure of the viral attachment protein. Much of this progress was possible only because a foundation of basic coronavirus biology existed. The Denison laboratory has been at the forefront of the small group of investigators who have dissected the basic features of coronaviruses. Denison has discovered critical mechanisms in the life cycle of the coronaviruses and is a key figure in the effective and urgent application of this knowledge to SARS.

negative: Epidemiologic and Clinical Characteristics of Coronavirus and Bocavirus Respiratory Infections after Allogeneic Stem Cell Transplantation: A Prospective Single-Center Study Abstract Epidemiologic data about coronaviruses (CoVs) and human bocavirus (HBoV) in the setting of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are scarce. We conducted a prospective longitudinal study on respiratory viral infections (RVIs) in allo-HSCT recipients with respiratory symptoms from December 2013 until June 2016. Respiratory virus in upper and/or lower respiratory tract (URT and LRT) specimens were tested using Luminex xTAG RVP Fast v1 assay. Seventy-nine consecutive allo-HSCT recipients developed a total of 192 virologically documented RVI episodes over 30 months. The median follow-up after RVI was 388 days (range, 5 to 923). CoV or HBoV was detected in 27 of 192 episodes (14%); 18 of 79 recipients (23%) developed a total of 21 CoV RVI episodes, whereas 6 recipients (8%) had 1 HBoV RVI episode each. Fourteen CoV RVI episodes were limited to the URT, whereas 7 affected the LRT. Co-pathogens were detected in 8 (38%) CoV cases. Type OC43 CoV was the dominant type (48%) followed by NL63 (24%), KHU1 (19%), and 229E (9%); the CoV hospitalization rate was 19%, whereas mortality was 5% (1 patient without any other microbiologic documentation). Among the 6 recipients with HBoV (3%), only 1 had LRT involvement and no one died from respiratory failure. In 5 cases (83%) HBoV was detected along with other viral co-pathogens. CoV RVIs are common after allo-HSCT, and in a significant proportion of cases CoV progressed to LRT and showed moderate to severe clinical features. In contrast, HBoV RVIs were rare and mostly presented in the context of co-infections.

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

negative: Candidate targets for immune responses to 2019-Novel Coronavirus (nCoV): sequence homology- and bioinformatic-based predictions Effective countermeasures against the recent emergence and rapid expansion of the 2019-Novel Coronavirus (2019-nCoV) require the development of data and tools to understand and monitor viral spread and immune responses. However, little information about the targets of immune responses to 2019-nCoV is available. We used the Immune Epitope Database and Analysis Resource (IEDB) resource to catalog available data related to other coronaviruses, including SARS-CoV, which has high sequence similarity to 2019-nCoV, and is the best-characterized coronavirus in terms of epitope responses. We identified multiple specific regions in 2019-nCoV that have high homology to SARS virus. Parallel bionformatic predictions identified a priori potential B and T cell epitopes for 2019-nCoV. The independent identification of the same regions using two approaches reflects the high probability that these regions are targets for immune recognition of 2019-nCoV. ONE SENTENCE SUMMARY We identified potential targets for immune responses to 2019-nCoV and provide essential information for understanding human immune responses to this virus and evaluation of diagnostic and vaccine candidates.

negative: DNA Aptamers in the Diagnosis and Treatment of Human Diseases Aptamers have a promising role in the field of life science and have been extensively researched for application as analytical tools, therapeutic agents and as vehicles for targeted drug delivery. Compared with RNA aptamers, DNA aptamers have inherent advantages in stability and facility of generation and synthesis. To better understand the specific potential of DNA aptamers, an overview of the progress in the generation and application of DNA aptamers in human disease diagnosis and therapy are presented in this review. Special attention is given to researches that are relatively close to practical application. DNA aptamers are expected to have great potential in the diagnosis and treatment of human diseases.

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: Achievements and highlights for Infection, Disease and Health

negative: Nephrectomy induced chronic renal insufficiency is associated with increased risk of cardiovascular death and death from any cause in patients with localized cT1b renal masses. PURPOSE Radical nephrectomy has traditionally been preferred to partial nephrectomy in patients with localized renal cell cancer because of its simplicity and established cancer control. Recent data suggest that these patients have significant competing risks of death, some of which may be increased by chronic renal insufficiency. Therefore, we compared overall survival, cancer specific survival and cardiac specific survival in patients undergoing partial or radical nephrectomy for cT1b tumors. MATERIALS AND METHODS From 1999 to 2006, 1,004 patients with renal masses between 4 and 7 cm underwent extirpative surgery, partial nephrectomy (524) or radical nephrectomy (480). We generated a propensity model based on preoperative patient characteristics, and then modeled survival with the additional variables of pathological stage and new baseline renal function. RESULTS On multivariate analysis cancer specific survival was equivalent for patients treated with partial nephrectomy or radical nephrectomy. Those patients undergoing radical nephrectomy lost significantly more renal function than those undergoing partial nephrectomy. The average excess loss of renal function observed with radical nephrectomy was associated with a 25% (95% CI 3-73) increased risk of cardiac death and 17% (95% CI 12-27) increased risk of death from any cause on multivariate analysis. CONCLUSIONS Partial nephrectomy offers cancer specific survival equivalent to that of radical nephrectomy and is technically feasible in at least 50% of patients with cT1b tumors. Preservation of renal function was significantly better in patients treated with partial nephrectomy. Postoperative renal insufficiency was a significant independent predictor of overall and cardiovascular specific survival, and efforts should be made to limit the renal function loss associated with surgery for localized renal masses.

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

negative: Old Weapon for New Enemy: Drug Repurposing for Treatment of Newly Emerging Viral Diseases

negative: 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.

negative: Acute respiratory failure in immunocompromised adults Summary Acute respiratory failure occurs in up to half of patients with haematological malignancies and 15% of those with solid tumours or solid organ transplantation. Mortality remains high. Factors associated with mortality include a need for invasive mechanical ventilation, organ dysfunction, older age, frailty or poor performance status, delayed intensive care unit admission, and acute respiratory failure due to an invasive fungal infection or unknown cause. In addition to appropriate antibacterial therapy, initial clinical management aims to restore oxygenation and predict the most probable cause based on variables related to the underlying disease, acute respiratory failure characteristics, and radiographic findings. The cause of acute respiratory failure must then be confirmed using the most efficient, least invasive, and safest diagnostic tests. In patients with acute respiratory failure of undetermined cause, a standardised diagnostic investigation should be done immediately at admission before deciding whether to perform more invasive diagnostic procedures or to start empirical treatments. Collaborative and multidisciplinary clinical and research networks are crucial to improve our understanding of disease pathogenesis and causation and to develop less invasive diagnostic strategies and more targeted treatment options.

negative: Analysis of viral infection and biomarkers in patients with acute exacerbation of chronic obstructive pulmonary disease OBJECTIVE: To investigate viral infection in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Shanghai, and to analyze the clinical characteristics and biomarkers in viral infection. METHODS: This study included all consecutive patients who were admitted for a diagnosis of AECOPD during June 2013 to May 2015. Thirty‐one stable COPD patients and 31 healthy controls were also recruited. Oropharyngeal samples were assessed, PCR for respiratory viruses were performed. Patients were divided into AECOPD virus‐positive (+) group and AECOPD virus‐negative (−) group according to viral detection. Luminex was used to detect the concentrations of inflammatory cytokines in the serum. RESULTS: A total of 264 patients were included with a mean age of 75 ± 0.5 years. There were 72 patients (27.3%) identified with viral positive, of whom two patients were detected with double viral infections (FluA + FluB and RSVA + HRV, respectively). The rate of viral detection was associated with season, highest in winter. Comparisons of clinical characteristics showed no significant differences between AECOPD virus+ group and AECOPD virus− group. However, serum concentrations of interferon‐inducible protein‐10 (IP‐10) and interferon‐gamma (IFN‐γ) in virus+ AECOPD patients were significantly higher than those in the virus− AECOPD, stable COPD and healthy control groups (P < .05). CONCLUSION: Viral infection was an important pathogen in AECOPD patients; the most common viruses included FluA, HRV and FluB. It was very difficult to diagnose the viral infection according to clinical characteristics. The increased of serum IP‐10 and IFN‐γ levels might be value to indicate viral infection in AECOPD.

negative: Diagnostic methods and potential portable biosensors for coronavirus disease 2019 Timely detection and diagnosis are urgently needed to guide epidemiological measures, infection control, antiviral treatment, and vaccine research. In this review, biomarkers/indicators for diagnosis of coronavirus disease 2019 (COVID-19) or detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the environment are summarized and discussed. It is concluded that the detection methods targeting antibodies are not suitable for screening of early and asymptomatic cases since most patients had an antibody response at about 10 days after onset of symptoms. However, antibody detection methods can be combined with quantitative real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) to significantly improve the sensitivity and specificity of diagnosis, and boost vaccine research. Fast, sensitive and accurate detection methods targeting antigens need to be developed urgently. Various specimens for diagnosis or detection are compared and analyzed. Among them, deep throat saliva and induced sputum are desired for RT-qPCR test or other early detection technologies. Chest computerized tomography (CT) scan, RT-qPCR, lateral flow immunochromatographic strip (LFICS) for diagnosis of COVID-19 are summarized and compared. Specially, potential electrochemical biosensor, surface enhanced Raman scattering (SERS)-based biosensor, and artificial intelligence (AI) assisted diagnosis of COVID-19 are emphasized. Finally, some commercialized portable detection device, current challenges and future directions are discussed.

negative: Obesity is associated with worse outcomes in COVID‐19: Analysis of Early Data From New York City OBJECTIVE: The 2019 novel coronavirus disease (COVID‐19) has triggered a rapidly‐expanding global pandemic in which patients exhibit a wide spectrum of disease severity. Given the high prevalence of obesity in the United States, we hypothesized that the presence of obesity may play a role in the clinical course of COVID‐19 patients. METHODS: This is a retrospective review of adult patients admitted with confirmed SARS‐CoV‐2. Demographics, clinical characteristics, laboratory data, and clinical outcomes were abstracted. BMI (kg/m(2)) was analyzed with regard to a composite outcome of ICU admission or death, and intubation rate. RESULTS: 770 patients were included (61% male, mean age 63.5 yrs). Obese patients were more likely to present with fever, cough and shortness of breath. Obesity was also associated with a significantly higher rate of ICU admission or death (RR = 1.58, p = 0.002) even after adjusting for age, race and troponin level. CONCLUSIONS: Obese patients had an increased risk of critical illness leading to ICU admission or death compared to normal weight individuals. This study confirms that obesity is a major risk factor for COVID‐19 disease severity, significantly impacting disease presentation and critical care requirements.

negative: Any possible role of phosphodiesterase type 5 inhibitors in the treatment of severe COVID19 infections? A lesson from urology

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

negative: Elevated interleukin 6 activity in aqueous humor of cats with uveitis Abstract The purpose of this study was to assess the role of interleukin 6 (IL-6) in feline uveitis by measuring IL-6 activity in the serum and aqueous humor of cats. Serum and aqueous humor was collected from clinically normal, random source cats (n = 10); clinically normal, specific-pathogen free cats experimentally inoculated with Toxoplasma gondii strain ME49 and sampled sequentially for 20 months (n = 4); and client-owned cats with uveitis (n = 27). Interleukin 6 activity was measured in each sample. Client-owned cats with uveitis were also evaluated for evidence of present or prior exposure to T. gondii, feline leukemia virus, feline immunodeficiency virus, and feline coronaviruses. Interleukin 6 activity was non-detectable or low in serum from cats of each group. Interleukin 6 activity was not detected in aqueous humor of clinically normal cats. Interleukin 6 activity was detected in 22 27 (81.5%) aqueous humor samples from cats with uveitis, with a range of 28.9 U ml−1-15702.9 U ml−1 (mean = 1911.9 U ml−1, SD = 3946.7 U ml−1). Serologic evidence of exposure to T gondii, feline immunodeficiency virus, feline leukemia virus, or a coronavirus was present in 21 27 (77.8%) cats with uveitis. Interleukin 6 was detected in the aqueous humor of 18 21 (85.7%) and 3 6 (50%) of the cats with and without serologic evidence of exposure to one to the infectious diseases, respectively. Statistically significant increases in mean IL-6 activity in aqueous humor were found for cats with any evidence of infection with T. gondii, for cats with T. gondii antigen in aqueous humor and for cats with coronavirus antibody titers ≥ 1:100. Aqueous humor IL-6 activity was greater than corresponding serum IL-6 activity in 21 27 cats. These results show that IL-6 is produced intraocularly in some cats with uveitis and that IL-6 may be a mediator of uveitis in cats.

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: Development of a risk assessment tool for contact tracing people after contact with infectious patients while travelling by bus or other public ground transport: a Delphi consensus approach BACKGROUND: Tracing persons who have been in contact with an infectious patient may be very effective in preventing the spread of communicable diseases. However, criteria to decide when to conduct contact tracing are not well established. We have investigated the available evidence for contact tracing with a focus on public ground transport aiming to give guidance in what situations contact tracing should be considered. METHODS: Relevant infectious diseases suitable for contact tracing in ground transport and a set of disease-specific epidemiological criteria were defined through literature search and structured multistep expert consultations. We developed continuous scales for each criterion to be rated for its relevance to contact tracing in ground transport. We used the Delphi method with an international expert panel to position the values of criteria on the respective scales. RESULTS: The study led to the development of the ‘Contact Tracing-Risk Assessment Profile’ (CT-RAP), a decision-making instrument, taking into account pathogen-specific as well as situation-specific criteria. This report describes the methodology of this instrument and presents two examples of ready-to-use CT-RAP for tuberculosis and for meningococcal disease in public ground transport. DISCUSSION: The systematic and transparent use of the CT-RAP for tuberculosis and meningococcal disease is likely to facilitate reasonable, efficient and user-friendly decisions with respect to contact tracing. New CT-RAPs for additional pathogens and different settings such as schools and kindergartens are being planned.

negative: Allergy and asthma in children and adolescents during the COVID outbreak: What we know and how we could prevent allergy and asthma flares Coronavirus disease 2019 (COVID-19) pandemic is affecting people at any age with a more severe course in patients with chronic diseases or comorbidities, males and elderly patients. The Center for Disease Control and Prevention (CDC) initially proposed that patients with chronic lung diseases, including moderate-severe asthma, and allergy may have a higher risk of developing severe COVID-19 than otherwise healthy people (https://www.cdc.gov/coronavirus/2019-ncov/specific-groups/asthma.html).

negative: Deiminated proteins in extracellular vesicles and serum of llama (Lama glama)—Novel insights into camelid immunity Abstract Peptidylarginine deiminases (PADs) are phylogenetically conserved calcium-dependent enzymes which post-translationally convert arginine into citrulline in target proteins in an irreversible manner, causing functional and structural changes in target proteins. Protein deimination causes generation of neo-epitopes, affects gene regulation and also allows for protein moonlighting. Furthermore, PADs have been found to be a phylogenetically conserved regulator for extracellular vesicle (EVs) release. EVs are found in most body fluids and participate in cellular communication via transfer of cargo proteins and genetic material. In this study, post-translationally deiminated proteins in serum and serum-EVs are described for the first time in camelids, using the llama (Lama glama L. 1758) as a model animal. We report a poly-dispersed population of llama serum EVs, positive for phylogenetically conserved EV-specific markers and characterised by TEM. In serum, 103 deiminated proteins were overall identified, including key immune and metabolic mediators including complement components, immunoglobulin-based nanobodies, adiponectin and heat shock proteins. In serum, 60 deiminated proteins were identified that were not in EVs, and 25 deiminated proteins were found to be unique to EVs, with 43 shared deiminated protein hits between both serum and EVs. Deiminated histone H3, a marker of neutrophil extracellular trap formation, was also detected in llama serum. PAD homologues were identified in llama serum by Western blotting, via cross reaction with human PAD antibodies, and detected at an expected 70 kDa size. This is the first report of deiminated proteins in serum and EVs of a camelid species, highlighting a hitherto unrecognized post-translational modification in key immune and metabolic proteins in camelids, which may be translatable to and inform a range of human metabolic and inflammatory pathologies.

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

negative: Chapter 15 Proteomics of viruses Publisher Summary Proteomics is a promising approach for the study of viruses allowing a better understanding of disease processes and the development of new biomarkers for diagnosis and early detection of disease, thus accelerating drug development. Viral proteomics has included the analysis of viral particles to determine all proteins that compose the infectious virus, the examination of cellular proteins associated with a single viral protein in the hopes of determining all the functions of that viral protein, or the determination of cellular proteins induced or altered during a particular disease state. Viral particles of human cytomegalovirus (HCMV) and Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) have been recently examined. During the herpesviral replicative cycle, different viral particles are formed. For HCMV, this includes mature, infectious virions, noninfectious enveloped particles, and dense bodies. A proteome database of B-lymphoblastoid cell lines (LCLs), before and after transformation, has been developed to identify the cellular mechanisms of virus-induced immortalization. 2DE is used to first separate proteins based on their relative charge (pI) and then based on their molecular weight. Proteomic analysis has provided a unique tool for the identification of diagnostic biomarkers, evaluation of disease progression, and drug development. It is also an important approach for clinical diagnostics.

negative: Establishment a real-time reverse transcription PCR based on host biomarkers for the detection of the subclinical cases of Mycobacterium avium subsp. paratuberculosis Bovine paratuberculosis (PTB) is a chronic enteric inflammatory disease of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP) that causes large economic losses in the dairy industry. Spread of PTB is mainly provoked by a long subclinical stage during which MAP is shed into the environment with feces; accordingly, detection of subclinical animals is very important to its control. However, current diagnostic methods are not suitable for detection of subclinical animals. Therefore, the current study was conducted to develop a diagnostic method for analysis of the expression of genes of prognostic potential biomarker candidates in the whole blood of cattle naturally infected with MAP. Real-time PCR with nine potential biomarker candidates was developed for the diagnosis of MAP subclinical infection. Animals were divided into four groups based on fecal MAP PCR and serum ELISA. Eight genes (Timp1, Hp, Serpine1, Tfrc, Mmp9, Defb1, Defb10, and S100a8) were up-regulated in MAP-infected cattle (p <0.05). Moreover, ROC analysis revealed that eight genes (Timp1, Hp, Serpine1, Tfrc, Mmp9, Defb1, Defb10, and S100a8) showed fair diagnostic performance (AUC≥0.8). Four biomarkers (Timp1, S100a8, Defb1, and Defb10) showed the highest diagnostic accuracy in the PCR positive and ELISA negative group (PN group) and three biomarkers (Tfrc, Hp, and Serpine1) showed the highest diagnostic accuracy in the PCR negative and ELISA positive group (NP group). Moreover, three biomarkers (S100a8, Hp, and Defb10) were considered the most reliable for the PCR positive and ELISA positive group (PP group). Taken together, our data suggest that real-time PCR based on eight biomarkers (Timp1, Hp, Serpine1, Tfrc, Mmp9, Defb1, Defb10, and S100a8) might be useful for diagnosis of JD, including subclinical stage cases.

negative: Individual risk management strategy and potential therapeutic options for the COVID-19 pandemic Abstract It is an ugly fact that a significant amount of the world's population will contract SARS-CoV infection with the current spreading. While specific treatment is not yet coming soon, individual risk assessment and management strategies are crucial. The individual preventive and protective measures drive the personal risk of getting the disease. Among the virus-contracted hosts, their different metabolic status, as determined by their diet, nutrition, age, sex, medical conditions, lifestyle, and environmental factors, govern the personal fate toward different clinical severity of COVID-19, from asymptomatic, mild, moderate, to death. The careful individual assessment for the possible dietary, nutritional, medical, lifestyle, and environmental risks, together with the proper relevant risk management strategies, is the sensible way to deal with the pandemic of SARS-CoV-II.

negative: Protein Chip Array Profiling Analysis in Patients with Severe Acute Respiratory Syndrome Identified Serum Amyloid A Protein as a Biomarker Potentially Useful in Monitoring the Extent of Pneumonia Background: A new strain of coronavirus (CoV) has caused an outbreak of severe acute respiratory syndrome (SARS), with 8098 individuals being infected and 774 deaths worldwide. We carried out protein chip array profiling analysis in an attempt to identify biomarkers that might be useful in monitoring the clinical course of SARS patients. Methods: We performed surface-enhanced laser desorption ionization time-of-flight mass spectrometry on 89 sera collected from 28 SARS patients, 72 sera from 51 control patients with various viral or bacterial infections, and 10 sera from apparently healthy individuals. Results: Nine significantly increased and three significantly decreased serum biomarkers were discovered in the SARS patients compared with the controls. Among these biomarkers, one (11 695 Da) was identified to be serum amyloid A (SAA) protein by peptide mapping and tandem mass spectrometric analysis. When we monitored the SAA concentrations longitudinally in 45 sera from four SARS patients, we found a good correlation of SAA concentration with the extent of pneumonia as assessed by a serial chest x-ray opacity score. Increased SAA occurred in three of four patients at the time of extensive pneumonia as indicated by high x-ray scores. Over the course of gradual recovery in two patients, as assessed clinically and radiologically, SAA concentrations gradually decreased. In the third patient, the concentrations were initially increased, but were further increased with superimposed multiple bacterial infections. SAA was not markedly increased in the fourth patient, who had low x-ray scores and whose clinical course was relatively mild. Conclusions: Protein chip array profiling analysis could be potentially useful in monitoring the severity of disease in SARS patients.

negative: Evaluating the potential of different inhibitors on RNA-dependent RNA polymerase of severe acute respiratory syndrome coronavirus 2: A molecular modeling approach BACKGROUND: Coronavirus disease 2019 (COVID-19) has already affected 2883603 and killed 198842 people, as of April 27, 2020. Because there is no specific therapeutic drug, drug repurposing has been proposed. RNA-dependent RNA polymerase (RdRp) is a promising drug against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to control its replication, and several compounds have been suggested. The present study predicts relative efficacies of thirty known or repurposed compounds in inhibiting the RdRp. METHODS: The three-dimensional structure of the target enzyme was loaded into Molegro virtual docker software, followed by chemical structures of the test compounds. The docking was performed between the compounds and the active site of the enzyme to determine docking scores, and the energy liberated when the two dock. Thus, docking scores signify the affinity of ligand(s) with the active site of enzyme(s) and thus its inhibitory potential. RESULTS: Among known inhibitors, remdesivir was found to have the highest affinity for the active site of the RdRp. Among all compounds, chlorhexidine was predicted as the most potent inhibitor. Furthermore, the results predict the relative efficacy of different drugs as inhibitors of the drug target. CONCLUSION: While the study identifies several compounds as inhibitors of RdRp of SARS-CoV-2, the prediction of their relative efficacies may be useful in future studies. While nucleoside analogs compete with the natural substrate of RdRp, thereby terminating RNA replication, other compounds would physically block entry of the natural substrates into the active site. Thus, based on the findings, we recommend in vitro and in vivo studies and clinical trials to determine their effectiveness against COVID-19.

negative: Hypothesis for potential pathogenesis of SARS-CoV-2 infection–a review of immune changes in patients with viral pneumonia Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with droplets and contact as the main means of transmission. Since the first case appeared in Wuhan, China, in December 2019, the outbreak has gradually spread nationwide. Up to now, according to official data released by the Chinese health commission, the number of newly diagnosed patients has been declining, and the epidemic is gradually being controlled. Although most patients have mild symptoms and good prognosis after infection, some patients developed severe and die from multiple organ complications. The pathogenesis of SARS-CoV-2 infection in humans remains unclear. Immune function is a strong defense against invasive pathogens and there is currently no specific antiviral drug against the virus. This article reviews the immunological changes of coronaviruses like SARS, MERS and other viral pneumonia similar to SARS-CoV-2. Combined with the published literature, the potential pathogenesis of COVID-19 is inferred, and the treatment recommendations for giving high-doses intravenous immunoglobulin and low-molecular-weight heparin anticoagulant therapy to severe type patients are proposed.

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: Glioblastoma extracellular vesicles: reservoirs of potential biomarkers Glioblastoma multiforme (GBM) is the most frequent and most devastating of the primary central nervous system tumors, with few patients living beyond 2 years postdiagnosis. The damage caused by the disease and our treatments for the patients often leave them physically and cognitively debilitated. Generally, GBMs appear after very short clinical histories and are discovered by imaging (using magnetic resonance imaging [MRI]), and the diagnosis is validated by pathology, following surgical resection. The treatment response and diagnosis of tumor recurrence are also tracked by MRI, but there are numerous problems encountered with these monitoring modalities, such as ambiguous interpretation and forms of pseudoprogression. Diagnostic, prognostic, and predictive biomarkers would be an immense boon in following treatment schemes and in determining recurrence, which often requires an invasive intracranial biopsy to verify imaging data. Extracellular vesicles (EVs) are stable, membrane-enclosed, virus-sized particles released from either the cell surface or from endosomal pathways that lead to the systemic release of EVs into accessible biofluids, such as serum/plasma, urine, cerebrospinal fluid, and saliva. EVs carry a wide variety of proteins, nucleic acids, lipids, and other metabolites, with many common features but with enough individuality to be able to identify the cell of origin of the vesicles. These components, if properly interrogated, could allow for the identification of tumor-derived EVs in biofluids, indicating tumor progression, relapse, or treatment failure. That knowledge would allow clinicians to continue with treatment regimens that were actually effective or to change course if the therapies were failing. Here, we review the features of GBM EVs, in terms of EV content and activities that may lead to the use of EVs as serially accessible biomarkers for diagnosis and treatment response in neuro-oncology.

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

negative: Applications of protein microarrays for biomarker discovery. The search for new biomarkers for diagnosis, prognosis, and therapeutic monitoring of diseases continues in earnest despite dwindling success at finding novel reliable markers. Some of the current markers in clinical use do not provide optimal sensitivity and specificity, with the prostate cancer antigen (PSA) being one of many such examples. The emergence of proteomic techniques and systems approaches to study disease pathophysiology has rekindled the quest for new biomarkers. In particular the use of protein microarrays has surged as a powerful tool for large-scale testing of biological samples. Approximately half the reports on protein microarrays have been published in the last two years especially in the area of biomarker discovery. In this review, we will discuss the application of protein microarray technologies that offer unique opportunities to find novel biomarkers.

negative: Prediction of receptorome for human-infecting virome The virus receptor is key for viral infection of host cells. Identification of the virus receptor is still challenging at present. Our previous study has shown that human virus receptor proteins have some unique features including high level of N-glycosylation, high number of interaction partners and high expressions. Here, we built a random-forest model to identify human virus receptorome from human cell membrane proteins with accepted accuracy based on combination of unique features of human virus receptors and protein sequences. A total of 729 human cell membrane proteins were predicted to constitute the receptorome for the human-infecting virome. Combination of the random-forest model with protein-protein interactions between human and viruses predicted in previous studies further predicted receptors for 693 human-infecting viruses, such as the Enterovirus, Norovirus and West Nile virus. Finally, we predicted the candidate alternative receptors for the 2019-nCoV. The study would greatly facilitate identification of receptors for human-infecting virome.

negative: Host-response biomarkers for diagnosis of late-onset septicemia and necrotizing enterocolitis in preterm infants. Preterm infants are highly susceptible to life-threatening infections that are clinically difficult to detect, such as late-onset septicemia and necrotizing enterocolitis (NEC). Here, we used a proteomic approach to identify biomarkers for diagnosis of these devastating conditions. In a case-control study comprising 77 sepsis/NEC and 77 nonsepsis cases (10 in each group being monitored longitudinally), plasma samples collected at clinical presentation were assessed in the biomarker discovery and independent validation phases. We validated the discovered biomarkers in a prospective cohort study with 104 consecutively suspected sepsis/NEC episodes. Proapolipoprotein CII (Pro-apoC2) and a des-arginine variant of serum amyloid A (SAA) were identified as the most promising biomarkers. The ApoSAA score computed from plasma apoC2 and SAA concentrations was effective in identifying sepsis/NEC cases in the case-control and cohort studies. Stratification of infants into different risk categories by the ApoSAA score enabled neonatologists to withhold treatment in 45% and enact early stoppage of antibiotics in 16% of nonsepsis infants. The negative predictive value of this antibiotic policy was 100%. The ApoSAA score could potentially allow early and accurate diagnosis of sepsis/NEC. Upon confirmation by further multicenter trials, the score would facilitate rational prescription of antibiotics and target infants who require urgent treatment.

negative: Latest outbreak news from ProMED-mail Novel coronavirus – Middle East

negative: Emergence of deadly severe acute respiratory syndrome coronavirus-2 during 2019-2020 Wuhan, the city in Hubei province in China is in the focus of global community due to the outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), formerly known as 2019-nCoV. The virus emerged in humans from Wuhan seafood market probably via zoonotic transmission. Within a few days the virus spread its tentacles rapidly to neighboring cities in China and to different geographical regions through travelers and to some extent by human to human transmission leading to significant disease burden globally. More than 2,00,000 people (including more than 8000 deaths) have been infected with this respiratory illness across 167 countries and territories worldwide leading to a pandemic. The present review provides an outline about emergence and spread of SARS-CoV-2 from Wuhan, China in 2019-2020. We have also provided information about the classification, genome, proteins, clinical presentation of COVID-19, type of clinical specimens to be collected and diagnostic methods adopted to identify the respiratory illness. In addition we have also provided information about transmission dynamics, prevention measures and treatment options that are available at the present. Subsequently, we have given a comprehensive overview of the spread of this infection from China to the other parts of the globe. Management of the ongoing outbreak of SARS-CoV-2 encompassing surveillance, clinical, immunological, genetic and evolutionary investigations are likely to provide the desired results. Joint efforts of global scientific community are needed at this hour in terms of enhancement of research on development of accurate diagnostics, antiviral therapeutics and finally into formation of an effective vaccine against the emerging novel coronavirus.

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

negative: PCR sequencing of the spike genes of geographically and chronologically distinct human coronaviruses 229E Abstract A reverse transcription nested PCR (RT-PCR) sequencing methodology was developed and used to generate sequence data from the spike genes of three geographically and chronologically distinct human coronaviruses 229E. These three coronaviruses were isolated originally from the USA in the 1960s (human coronavirus 229E strain ATCC VR-74), the UK in the 1990s (human coronavirus 229E LRI 281) and Ghana (human coronavirus 229E A162). Upon translation and alignment with the published spike protein sequence of human coronavirus 229E ‘LP’ (isolated in the UK in the 1970s), it was found that variation within the translated protein sequences was rather limited. In particular, minimal variation was observed between the translated spike protein sequence of human coronaviruses 229E LP and ATCC VR-74 (1/1012 amino acid differences), whilst most variation was observed between the translated spike protein sequence of human coronaviruses 229E LP and A162 (47/1012 amino acid changes). Further, the translated spike protein sequence of human coronavirus 229E A162 showed three clusters of amino acid changes, situated within the 5′ half of the translated spike protein sequence.

negative: Predicting the Epidemiological Outbreak of the Coronavirus Disease 2019 (COVID-19) in Saudi Arabia The coronavirus diseases 2019 (COVID-19) outbreak continues to spread rapidly across the world and has been declared as pandemic by World Health Organization (WHO). Saudi Arabia was among the countries that was affected by the deadly and contagious virus. Using a real-time data from 2 March 2020 to 15 May 2020 collected from Saudi Ministry of Health, we aimed to give a local prediction of the epidemic in Saudi Arabia. We used two models: the Logistic Growth and the Susceptible-Infected-Recovered for real-time forecasting the confirmed cases of COVID-19 across Saudi Arabia. Our models predicted that the epidemics of COVID-19 will have total cases of 69,000 to 79,000 cases. The simulations also predicted that the outbreak will entering the final-phase by end of June 2020.

negative: Hydroxychloroquine as an aerosol might markedly reduce and even prevent severe clinical symptoms after SARS-CoV-2 infection Abstract Covid-19 is a new coronavirus disease first described in December 2019. This respiratory illness is severe and potentially fatal. Severe cases make up to 15%, lethality ranges between 1.5 and more than 10 %. What is urgently needed is an efficient pharmacological treatment for the treatment of severe cases. During the infection of alveolar epithelial cells of the lung, the ACE2 receptor has a central function. The antimalarial drugs chloroquine phosphate (CQ) and hydroxychloroquine (HCQ) impair in vitro the terminal glycosylation of ACE2 without significant change of cell-surface ACE2 and, therefore, might be potent inhibitors of SARS-CoV-2 infections. Starting inhibition at 0.1 µM, CQ completely prevented in vitro infections at 10 µM, suggesting a prophylactic effect and preventing the virus spread 5 hours after infection. In a first clinical trial, CQ was effective in inhibiting exacerbation of pneumonia, improving lung imaging findings, promotion of virus-negative conversion, and shortening the disease. In addition, HCQ, which is three times more potent than CQ in SARS-CoV-2 infected cells (EC50 0.72 µM), was significantly associated with viral load reduction/disappearance in COVID-19 patients compared to controls. Theoretically, CQ and HCQ could thus be effectively used in the treatment of SARS-CoV pneumonia. From a pharmacological standpoint, however, the major problems of oral treatment with these drugs are possible severe side effects and toxicity. Concretely, this relates to (a) the inconsistent individual bioavailability of these drugs at the alveolar target cells, depending on intestinal resorption, hepatic first-pass metabolism and accumulation in liver, spleen and lung, and (b) the need for a relatively high concentration of 1-5 µM at the alveolar surface. Therefore, we propose in a first dose estimation the use of HCQ as an aerosol in a dosage of 2-4 mg per inhalation in order to reach sufficient therapeutic levels at the alveolar epithelial cells. By using a low-dose non-systemic aerosol, adverse drug reactions will markedly be reduced compared with oral application. This increase in tolerability enables a broader use for prevention and after contact with an infected person, which would be an advantage especially for the high-risk, often multi-morbid and elderly patients. Empirical data on self-medication with a one-week aerosol application by two of the authors is presented. Inhalation was well tolerated without relevant side effects.

negative: First case of Coronavirus Disease 2019 (COVID-19) pneumonia in Taiwan An outbreak of respiratory illness proved to be infected by a 2019 novel coronavirus, officially named Coronavirus Disease 2019 (COVID-19), was notified first in Wuhan, China, and has spread rapidly in China and to other parts of the world. Herein, we reported the first confirmed case of novel coronavirus pneumonia (NCP) imported from China in Taiwan. This case report revealed a natural course of NCP with self-recovery, which may be a good example in comparison with medical treatments.

negative: Identification of murine CD8 T cell epitopes in codon-optimized SARS-associated coronavirus spike protein Abstract The causative agent of severe acute respiratory syndrome (SARS) has been identified as a new type of coronavirus, SARS-associated coronavirus (SARS-CoV). CD8 T cells play an important role in controlling diseases caused by other coronaviruses and in mediating vaccine-induced protective immunity in corresponding animal models. The spike protein, a main surface antigen of SARS-CoV, is one of the most important antigen candidates for vaccine design. Overlapping peptides were used to identify major histocompatibility complex class I-restricted epitopes in mice immunized with vectors encoding codon-optimized SARS-CoV spike protein. CD8 T-cell responses were mapped to two H-2b-restricted epitopes (S436–443 and S525–532) and one H-2d-restricted epitope (S366–374). The identification of these epitopes will facilitate the evaluation of vaccine strategies in murine models of SARS-CoV infection. Furthermore, codon and promoter optimizations can greatly enhance the overall immunogenicity of spike protein in the context of replication-defective human and simian adenoviral vaccine carriers. The optimized recombinant adenoviral vaccine vectors encoding spike can generate robust antigen-specific cellular immunity in mice and may potentially be useful for control of SARS-CoV infection.

negative: Functional Protein Microarray Technology Functional protein microarrays are emerging as a promising new tool for large-scale and high-throughput studies. In this article, we will review their applications in basic proteomics research, where various types of assays have been developed to probe binding activities to other biomolecules, such as proteins, DNA, RNA, small molecules, and glycans. We will also report recent progress of using functional protein microarrays in profiling protein posttranslational modifications, including phosphorylation, ubiquitylation, acetylation, and nitrosylation. Finally, we will discuss potential of functional protein microarrays in biomarker identification and clinical diagnostics. We strongly believe that functional protein microarrays will soon become an indispensible and invaluable tool in proteomics research and systems biology.

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: Effect of mutations in the mouse hepatitis virus 3'(+)42 protein binding element on RNA replication. The mouse hepatitis virus (MHV) genome's 3' untranslated region contains cis-acting sequences necessary for replication. Studies of MHV and other coronaviruses have indicated a role for RNA secondary and tertiary elements in replication. Previous work in our laboratory has identified four proteins which form ribonucleoprotein complexes with the 3'-terminal 42 nucleotides [3'(+)42] of the MHV genome. Defective interfering (DI) RNA replication assays have demonstrated a role for the 3'(+)42 host protein binding element in the MHV life cycle. Using gel mobility shift RNase T1 protection assays and secondary structure modeling, we have characterized a possible role for RNA secondary structure in host protein binding to the 3'-terminal 42-nucleotide element. Additionally we have identified a role for the 3'-terminal 42-nucleotide host protein binding element in RNA replication and transcription using DI RNA replication assays and targeted recombination and by directly constructing mutants in this protein binding element using a recently described MHV reverse genetic system. DI RNA replication assays demonstrated that mutations in the 3'(+)42 host protein binding element had a deleterious effect on the accumulation of DI RNA. When the identical mutations were directly inserted into the MHV genome, most mutant genomes were viable but formed smaller plaques than the wild-type parent virus. One mutant was not viable. This mutant directed the synthesis of genome-sized negative-sense RNA approximately as efficiently as the wild type did but had a defect in subgenomic mRNA synthesis. These results point to a potential role for sequences at the extreme 3' end of the MHV genome in subgenomic RNA synthesis.

negative: Advancing Point-of-Care (PoC) Testing Using Human Saliva as Liquid Biopsy Salivary diagnostics is an emerging field for the encroachment of point of care technology (PoCT). The necessity of the development of point-of-care (PoC) technology, the potential of saliva, identification and validation of biomarkers through salivary diagnostic toolboxes, and a broad overview of emerging technologies is discussed in this review. Furthermore, novel advanced techniques incorporated in devices for the early detection and diagnosis of several oral and systemic diseases in a non-invasive, easily-monitored, less time consuming, and in a personalised way is explicated. The latest technology detection systems and clinical utilities of saliva as a liquid biopsy, electric field-induced release and measurement (EFIRM), biosensors, smartphone technology, microfluidics, paper-based technology, and how their futuristic perspectives can improve salivary diagnostics and reduce hospital stays by replacing it with chairside screening is also highlighted.

negative: A Case-Control Study Assessing the Impact of Nonventilated Hospital-Acquired Pneumonia on Patient Outcomes Background Nonventilated hospital-acquired pneumonia (NVHAP) is a serious nosocomial infection that is increasingly attributed to antibiotic-resistant bacteria. Methods This is a retrospective case-control study comparing patients with and those without NVHAP from January 1, 2014 to December 31, 2014 at Barnes-Jewish Hospital, a 1,300-bed urban academic medical center in St. Louis, Missouri. Results One hundred seventy-four consecutive patients with NVHAP were enrolled. A random sample of 696 control patients matched by age, sex, race, and hospital admission date were selected from a total of 5,322 potential matched control subjects. NVHAP was pathogen-negative in 98 cases (56.3%). Respiratory viruses were identified in 42 patients (24.1%), gram-negative bacteria were seen in 25 patients (14.4%), and gram-positive bacteria were identified in 20 patients (11.5%). Individuals in whom NVHAP developed were more likely to die (15.5% vs 1.6%; P < .01), to require intensive care (56.3% vs 22.8%; P < .01) or mechanical ventilation (19.0% vs 3.9%; P < 0.01), and to have a longer hospital length of stay (15.9 days [range, 9.8-26.3 days] vs 4.4 days [range, 2.9-7.3 days]; P < 0.01). This case-control study identified a strong association between hospital mortality and NVHAP, with patients who acquired NVHAP having an 8.4 times greater odds of death (95% CI, 5.6-12.5). Conclusions The occurrence of NVHAP was associated with significant increases in mortality, the use of intensive care and mechanical ventilation, and hospital length of stay. We also found that respiratory viruses were an important cause of NVHAP. These findings suggest that efforts aimed at the successful prevention of NVHAP could improve patient outcomes and reduce health-care costs.

negative: Evaluation of 19 antiviral drugs against SARS-CoV-2 Infection The global pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV) has prompted multiple clinical trials to jumpstart search for anti-SARS-CoV-2 therapies from existing drugs, including those with reported in vitro efficacies as well as those ones that are not known to inhibit SARS-CoV-2, such as ritonavir/lopinavir and favilavir. Here we report that after screening 19 antiviral drugs that are either in clinical trials or with proposed activity against SARS-CoV-2, remdesivir was the most effective. Chloroquine only effectively protected virus-induced cytopathic effect at around 30 µM with a therapeutic index of 1.5. Our findings also suggest that velpatasvir, ledipasvir, ritonavir, litonavir, lopinavir, favilavir, sofosbuvir, danoprevir, and pocapavir do not have direct antiviral effect.

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

negative: Covid-19 and cancer patients: Choosing wisely is the key

negative: 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).

negative: Immune Biomarkers Predictive of Respiratory Viral Infection in Elderly Nursing Home Residents OBJECTIVE: To determine if immune phenotypes associated with immunosenescence predict risk of respiratory viral infection in elderly nursing home residents. METHODS: Residents ≥65 years from 32 nursing homes in 4 Canadian cities were enrolled in Fall 2009, 2010 and 2011, and followed for one influenza season. Following influenza vaccination, peripheral blood mononuclear cells (PBMCs) were obtained and analysed by flow cytometry for T-regs, CD4+ and CD8+ T-cell subsets (CCR7+CD45RA+, CCR7-CD45RA+ and CD28-CD57+) and CMV-reactive CD4+ and CD8+ T-cells. Nasopharyngeal swabs were obtained and tested for viruses in symptomatic residents. A Cox proportional hazards model adjusted for age, sex and frailty, determined the relationship between immune phenotypes and time to viral infection. RESULTS: 1072 residents were enrolled; median age 86 years and 72% female. 269 swabs were obtained, 87 were positive for virus: influenza (24%), RSV (14%), coronavirus (32%), rhinovirus (17%), human metapneumovirus (9%) and parainfluenza (5%). In multivariable analysis, high T-reg% (HR 0.41, 95% CI 0.20–0.81) and high CMV-reactive CD4+ T-cell% (HR 1.69, 95% CI 1.03–2.78) were predictive of respiratory viral infection. CONCLUSIONS: In elderly nursing home residents, high CMV-reactive CD4+ T-cells were associated with an increased risk and high T-regs were associated with a reduced risk of respiratory viral infection.

negative: Chronic obstructive pulmonary disease subpopulations and phenotyping Information for Category 1 CME Credit Credit can now be obtained, free for a limited time, by reading the review articles in this issue. Please note the following instructions. Method of Physician Participation in Learning Process: The core material for these activities can be read in this issue of the Journal or online at the JACI Web site: www.jacionline.org. The accompanying tests may only be submitted online at www.jacionline.org. Fax or other copies will not be accepted. Date of Original Release: June 2018. Credit may be obtained for these courses until May 31, 2019. Copyright Statement: Copyright © 2018-2019. All rights reserved. Overall Purpose/Goal: To provide excellent reviews on key aspects of allergic disease to those who research, treat, or manage allergic disease. Target Audience: Physicians and researchers within the field of allergic disease. Accreditation/Provider Statements and Credit Designation: The American Academy of Allergy, Asthma & Immunology (AAAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAAAI designates this journal-based CME activity for a maximum of 1.00 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. List of Design Committee Members: Leopoldo N. Segal, MD, MS, and Fernando J. Martinez, MD, MS (authors); Zuhair K. Ballas, MD (editor) Disclosure of Significant Relationships with Relevant Commercial Companies/Organizations: L. N. Segal has received grants from the National Institutes of Health and personal fees from Advanced Inhalation Therapies. F. J. Martinez has received a grant from the National Heart, Lung, and Blood Institute; has received personal fees from Continuing Education, Forest Laboratories, GlaxoSmithKline, Nycomed/Takeda, AstraZeneca, Boehringer Ingelheim, Bellerophon (formerly Ikaria), Genentech, Novartis, Pearl, Roche, Sunovion, Theravance, CME Incite, the Annenberg Center for Health Sciences at Eisenhower, Integritas, InThought, the National Association for Continuing Education, Paradigm Medical Communications, PeerVoice, UpToDate, Haymarket Communications, the Western Society of Allergy and Immunology, Proterixbio, Unity Biotechnology, ConCert Pharmaceuticals, Lucid, Methodist Hospital, Columbia University, Prime Healthcare, WebMD, the PeerView Network, the California Society of Allergy and Immunology, Chiesi, and the Puerto Rico Thoracic Society and is on the COPD advisory board for Janssen. Z. K. Ballas (editor) disclosed no relevant financial relationships. Activity Objectives: 1. To understand the different phenotypes of chronic obstructive pulmonary disease (COPD), including comorbidities, clinical course, and treatment implications. 2. To understand the pathogenesis of COPD. 3. To understand the characteristics of COPD exacerbations. Recognition of Commercial Support: This CME activity has not received external commercial support. List of CME Exam Authors: Ryan Israelsen, MD, Katherine McCormack, MD, Hannah Duffey, MD, Allison Hicks, MD, Joseph Spahn, MD, and Maureen Egan, MD Disclosure of Significant Relationships with Relevant Commercial Companies/Organizations: The exam authors disclosed no relevant financial relationships. The diagnosis and treatment of chronic obstructive pulmonary disease (COPD) has been based largely on a one-size-fits-all approach. Diagnosis of COPD is based on meeting the physiologic criteria of fixed obstruction in forced expiratory flows and treatment focus on symptomatic relief, with limited effect on overall prognosis. However, patients with COPD have distinct features that determine very different evolutions of the disease. In this review we highlight distinct subgroups of COPD characterized by unique pathophysiologic derangements, response to treatment, and disease progression. It is likely that identification of subgroups of COPD will lead to discovery of much needed disease-modifying therapeutic approaches. We argue that a precision approach that integrates multiple dimensions (clinical, physiologic, imaging, and endotyping) is needed to move the field forward in the treatment of this disease.

negative: [Potential antiviral therapeutics for 2019 Novel Coronavirus] The recent outbreak of respiratory illness in Wuhan, China is caused by a novel coronavirus, named 2019-nCoV, which is genetically close to a bat-derived coronavirus. 2019-nCoV is categorized as beta genus coronavirus, same as the two other strains - severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Antiviral drugs commonly used in clinical practice, including neuraminidase inhibitors (oseltamivir, paramivir, zanamivir, etc.), ganciclovir, acyclovir and ribavirin, are invalid for 2019-nCoV and not recommended. Drugs are possibly effective for 2019-nCoV include: remdesivir, lopinavir / ritonavir, lopinavir / ritonavir combined with interferon-ß, convalescent plasma, and monoclonal antibodies. But the efficacy and safety of these drugs for 2019-nCoV pneumonia patients need to be assessed by further clinical trials.

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: Severe Acute Respiratory Syndrome: Clinical Outcome and Prognostic Correlates Severe acute respiratory syndrome (SARS) poses a major threat to the health of people worldwide. We performed a retrospective case series analysis to assess clinical outcome and identify pretreatment prognostic correlates of SARS, managed under a standardized treatment protocol. We studied 127 male and 196 female patients with a mean age of 41±14 (range 18–83). All patients, except two, received ribavirin and steroid combination therapy. In 115 (36%) patients, the course of disease was limited. Pneumonitis progressed rapidly in the remaining patients. Sixty-seven (21%) patients required intensive care, and 42 (13%) required ventilator support. Advanced age, high admission neutrophil count, and high initial lactate dehydrogenase level were independent correlates of an adverse clinical outcome. SARS-associated coronavirus caused severe illnesses in most patients, despite early treatment with ribavirin and steroid. This study has identified three independent pretreatment prognostic correlates.

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: A Review of Salivary Diagnostics and Its Potential Implication in Detection of Covid-19 Saliva is an exocrine secretion produced from the salivary glands and has numerous functions, such as cleansing and protection of the oral cavity, antimicrobial effects and aids in digestion. Due to the speedy development in the field of salivaomics, saliva is now well accepted as a pool of biological markers that vary from changes in biochemicals, nucleic acids and proteins to the microflora. Saliva has an immense potential as a diagnostic fluid and offers an edge over other biological fluids as its collection method does not require invasive procedure, economical and is useful for monitoring systemic health. Development of sensitive and precise salivary diagnostic tools and the formulation of defined guidelines following meticulous testing will allow salivary diagnostics to be utilised as chair side tests for various oral and systemic diseases in the near future. The coronavirus disease (Covid-19) pandemic is the biggest challenge and global health crisis for the world since World War Two. Rapid and accurate diagnosis of Covid-19 is crucial in controlling the outbreak in the community and in hospitals. Nasopharyngeal and oropharyngeal swabs are the recommended specimen types for Covid-19 diagnostic testing. The collection of these specimen types requires close contact between healthcare workers and patients and poses a risk of transmission of the virus, causes discomfort and may cause bleeding, especially in patients with condition such as thrombocytopenia. Hence, nasopharyngeal or oropharyngeal swabs are not desirable for sequential monitoring of viral load. Saliva specimens can be obtained easily as the patient is asked to spit into a sterile bottle. The collection of saliva is non-invasive and greatly minimizes the exposure of healthcare workers to Covid-19. Saliva has a high consistency rate of greater than 90% with nasopharyngeal specimens in the detection of respiratory viruses, including coronaviruses. Saliva has also been used in screening respiratory viruses among hospitalized patients without pyrexia or respiratory symptoms. SARS-CoV can be detected in saliva at high titers. Salivary diagnostics is a dynamic field that is being incorporated as part of disease diagnosis, clinical monitoring of systemic health and to make significant clinical decisions for patient care. More research is required to analyze the potential diagnostic of Covid-19 in saliva to develop rapid chair side tests for the detection of Covid-19 and it is also pivotal to improve and develop successful strategies for prevention, especially for dentists and healthcare professionals who are involved in performing aerosol-generating procedures.

negative: Factors associated with death outcome in patients with severe coronavirus disease-19 (COVID-19): a case-control study Rationale: Up to date, the exploration of clinical features in severe COVID-19 patients were mostly from the same center in Wuhan, China. The clinical data in other centers is limited. This study aims to explore the feasible parameters which could be used in clinical practice to predict the prognosis in hospitalized patients with severe coronavirus disease-19 (COVID-19). Methods: In this case-control study, patients with severe COVID-19 in this newly established isolation center on admission between 27 January 2020 to 19 March 2020 were divided to discharge group and death event group. Clinical information was collected and analyzed for the following objectives: 1. Comparisons of basic characteristics between two groups; 2. Risk factors for death on admission using logistic regression; 3. Dynamic changes of radiographic and laboratory parameters between two groups in the course. Results: 124 patients with severe COVID-19 on admission were included and divided into discharge group (n=35) and death event group (n=89). Sex, SpO2, breath rate, diastolic pressure, neutrophil, lymphocyte, C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), and D-dimer were significantly correlated with death events identified using bivariate logistic regression. Further multivariate logistic regression demonstrated a significant model fitting with C-index of 0.845 (p<0.001), in which SpO2≤89%, lymphocyte≤0.64×109/L, CRP>77.35mg/L, PCT>0.20µg/L, and LDH>481U/L were the independent risk factors with the ORs of 2.959, 4.015, 2.852, 3.554, and 3.185, respectively (p<0.04). In the course, persistently lower lymphocyte with higher levels of CRP, PCT, IL-6, neutrophil, LDH, D-dimer, cardiac troponin I (cTnI), brain natriuretic peptide (BNP), and increased CD4+/CD8+ T-lymphocyte ratio and were observed in death events group, while these parameters stayed stable or improved in discharge group. Conclusions: On admission, the levels of SpO2, lymphocyte, CRP, PCT, and LDH could predict the prognosis of severe COVID-19 patients. Systematic inflammation with induced cardiac dysfunction was likely a primary reason for death events in severe COVID-19 except for acute respiratory distress syndrome.

negative: Structural, glycosylation and antigenic variation between 2019 novel coronavirus (2019-nCoV) and SARS coronavirus (SARS-CoV) The emergence of 2019 novel coronavirus (2019-nCoV) is of global concern and might have emerged from RNA recombination among existing coronaviruses. CoV spike (S) protein which is crucial for receptor binding, membrane fusion via conformational changes, internalization of the virus, host tissue tropism and comprises crucial targets for vaccine development, remain largely uncharacterized. Therefore, the present study has been planned to determine the sequence variation, structural and antigenic divergence of S glycoprotein which may be helpful for the management of 2019-nCoV infection. The sequences of spike glycoprotein of 2019-nCoV and SARS coronavirus (SARS-CoV) were used for the comparison. The sequence variations were determined using EMBOSS Needle pairwise sequence alignment tools. The variation in glycosylation sites was predicted by NetNGlyc 1.0 and validated by N-GlyDE server. Antigenicity was predicted by NetCTL 1.2 and validated by IEDB Analysis Resource server. The structural divergence was determined by using SuperPose Version 1.0 based on cryo-EM structure of the SARS coronavirus spike glycoprotein. Our data suggests that 2019-nCoV is newly spilled coronavirus into humans in China is closely related to SARS-CoV, which has only 12.8% of difference with SARS-CoV in S protein and has 83.9% similarity in minimal receptor-binding domain with SARS-CoV. Addition of a novel glycosylation sites were observed in 2019-nCoV. In addition, antigenic analysis proposes that great antigenic differences exist between both the viral strains, but some of the epitopes were found to be similar between both the S proteins. In spite of the variation in S protein amino acid composition, we found no significant difference in their structures. Collectively, for the first time our results exhibit the emergence of human 2019-nCoV is closely related to predecessor SARS-CoV and provide the evidence that 2019-nCoV uses various novel glycosylation sites as SARS-CoV and may have a potential to become pandemic owing its antigenic discrepancy. Further, demonstration of novel Cytotoxic T lymphocyte epitopes may impart opportunities for the development of peptide based vaccine for the prevention of 2019-nCoV.

negative: The preventive strategy for pandemics in the elderly is to collect in advance samples & data to counteract chronic inflammation (inflammaging) Fighting the current COVID-19 pandemic, we must not forget to prepare for the next. Since elderly and frail people are at high risk, we wish to predict their vulnerability, and intervene if possible. For example, it would take little effort to take additional swabs or dried blood spots. Such minimally-invasive sampling, exemplified here during screening for potential COVID-19 infection, can yield the data to discover biomarkers to better handle this and the next respiratory disease pandemic. Longitudinal outcome data can then be combined with other epidemics and old-age health data, to discover the best biomarkers to predict (i) coping with infection & inflammation and thus hospitalization or intensive care, (ii) long-term health challenges, e.g. deterioration of lung function after intensive care, and (iii) treatment & vaccination response. Further, there are universal triggers of old-age morbidity & mortality, and the elimination of senescent cells improved health in pilot studies in idiopathic lung fibrosis & osteoarthritis patients alike. Biomarker studies are needed to test the hypothesis that resilience of the elderly during a pandemic can be improved by countering chronic inflammation and/or removing senescent cells. Our review suggests that more samples should be taken and saved systematically, following minimum standards, and data be made available, to maximize healthspan & minimize frailty, leading to savings in health care, gains in quality of life, and preparing us better for the next pandemic, all at the same time.

negative: Epidemiological characteristics of an outbreak of Coronavirus Disease 2019 in the Philippines The outbreak of Coronavirus disease 2019 (Covid-2019) is a source of great concern in the Philippines. In this paper, we described the epidemiological characteristics of the laboratory-confirmed patients with Covid-2019 in the Philippines as of April 3, 2020 and provided recommendations on how to limit the spread of the disease. Data from the DOH NCOV tracker and University of the Philippines Covid-2019 tracker were extracted, from its initiation (January 30, 2020) until the most recent situation report (April 3, 2020). The total number of cases and deaths were stratified by sex, age, and region of the Philippines. Descriptive statistics were used to analyze the demographic profile of the confirmed cases. Case fatality rate, in percent, was calculated by dividing the total number of deaths to the total number of confirmed cases. Results revealed that a total of 3,018 cases of Covid-2019 spread were confirmed across 17 regions in the Philippines. These cases occurred over the course of 73 days through person-to-person transmission, highlighting an extremely high infectivity rate. The 144 deaths accounted for, equate to 4.51 case fatality rate, seemingly lower compared to its predecessors, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), but higher compared to that of United States of America, Germany, mainland China, and neighboring Southeast Asian countries such as Malaysia, Singapore, Brunei, and Thailand. Of the 3,018 confirmed cases, majority were male, elderly, and diagnosed in Metro Manila region. Case fatality rates were higher in male and highest among elderly and Filipinos in the Ilocos region. With the surge on the number of cases, precautionary measures should remain a responsibility, and protocols for prevention need to be set. Adherence to infection control guidelines such as but not limited to frequently handwashing for at least 20 seconds, observing coughing etiquette, wearing of masks, and social distancing should be maintained in order to contain the disease.

negative: First Clinical Study Using HCV Protease Inhibitor Danoprevir to Treat Naive and Experienced COVID-19 Patients As coronavirus disease 2019 (COVID-19) outbreak, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), started in China in January, 2020, repurposing approved drugs is emerging as important therapeutic options. We reported here the first clinical study using hepatitis C virus (HCV) protease inhibitor, danoprevir, to treat COVID-19 patients. Danoprevir (Ganovo) is a potent HCV protease (NS3/4A) inhibitor (IC50 = 0.29 nM), which was approved and marketed in China since 2018 to treat chronic hepatitis C patients. Ritonavir is a CYP3A4 inhibitor to enhance plasma concentration of danoprevir while it also acts as a human immunodeficiency virus (HIV) protease inhibitor at high doses. The chymotrypsin-like protease of SARS-CoV-2 shares structure similarity with HCV and HIV proteases. In the current clinical study (NCT04291729) conducted at the Nineth Hospital of Nanchang, we evaluated therapeutic effects of danoprevir, boosted by ritonavir, on treatment naive and experienced COVID-19 patients. The data from this small-sample clinical study showed that danoprevir boosted by ritonavir is safe and well tolerated in all patients. After 4 to 12-day treatment of danoprevir boosted by ritonavir, all eleven patients enrolled, two naive and nine experienced, were discharged from the hospital as they met all four conditions as follows: (1) normal body temperature for at least 3 days; (2) significantly improved respiratory symptoms; (3) lung imaging shows obvious absorption and recovery of acute exudative lesion; and (4) two consecutive RT-PCR negative tests of SARS-CoV-2 nucleotide acid (respiratory track sampling with interval at least one day). Our findings suggest that repurposing danoprevir for COVID-19 is a promising therapeutic option.

negative: Network-based Drug Repurposing for Human Coronavirus Human Coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle east respiratory syndrome coronavirus (MERS-CoV), and 2019 novel coronavirus (2019-nCoV), lead global epidemics with high morbidity and mortality. However, there are currently no effective drugs targeting 2019-nCoV. Drug repurposing, represented as an effective drug discovery strategy from existing drugs, could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we present an integrative, antiviral drug repurposing methodology implementing a systems pharmacology-based network medicine platform, quantifying the interplay between the HCoV-host interactome and drug targets in the human protein-protein interaction network. Phylogenetic analyses of 15 HCoV whole genomes reveal that 2019-nCoV has the highest nucleotide sequence identity with SARS-CoV (79.7%) among the six other known pathogenic HCoVs. Specifically, the envelope and nucleocapsid proteins of 2019-nCoV are two evolutionarily conserved regions, having the sequence identities of 96% and 89.6%, respectively, compared to SARS-CoV. Using network proximity analyses of drug targets and known HCoV-host interactions in the human protein-protein interactome, we computationally identified 135 putative repurposable drugs for the potential prevention and treatment of HCoVs. In addition, we prioritized 16 potential anti-HCoV repurposable drugs (including melatonin, mercaptopurine, and sirolimus) that were further validated by enrichment analyses of drug-gene signatures and HCoV-induced transcriptomics data in human cell lines. Finally, we showcased three potential drug combinations (including sirolimus plus dactinomycin, mercaptopurine plus melatonin, and toremifene plus emodin) captured by the Complementary Exposure pattern: the targets of the drugs both hit the HCoV-host subnetwork, but target separate neighborhoods in the human protein-protein interactome network. In summary, this study offers powerful network-based methodologies for rapid identification of candidate repurposable drugs and potential drug combinations toward future clinical trials for HCoVs.

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: Studying the pathophysiology of coronavirus disease 2019 - a protocol for the Berlin prospective COVID-19 patient cohort (Pa- COVID-19) Purpose Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide causing a global health emergency. Pa-COVID-19 aims to provide comprehensive data on clinical course, pathophysiology, immunology and outcome of COVID-19, in order to identify prognostic biomarkers, clinical scores, and therapeutic targets for improved clinical management and preventive interventions. Methods Pa-COVID-19 is a prospective observational cohort study of patients with confirmed SARS-CoV-2 infection treated at Charite - Universitaetsmedizin Berlin. We collect data on epidemiology, demography, medical history, symptoms, clinical course, pathogen testing and treatment. Systematic, serial blood sampling will allow deep molecular and immunological phenotyping, transcriptomic profiling, and comprehensive biobanking. Longitudinal data and sample collection during hospitalization will be supplemented by long-term follow-up. Results Outcome measures include the WHO clinical ordinal scale on day 15 and clinical, functional and health-related quality of life assessments at discharge and during follow-up. We developed a scalable dataset to (i) suit national standards of care (ii) facilitate comprehensive data collection in medical care facilities with varying resources and (iii) allow for rapid implementation of interventional trials based on the standardized study design and data collection. We propose this scalable protocol as blueprint for harmonized data collection and deep phenotyping in COVID-19 in Germany. Conclusion We established a basic platform for harmonized, scalable data collection, pathophysiological analysis, and deep phenotyping of COVID-19, which enables rapid generation of evidence for improved medical care and identification of candidate therapeutic and preventive strategies. The electronic database accredited for interventional trials allows fast trial implementation for candidate therapeutic agents.

negative: Frequency of diarrhea in novel coronavirus 2019 infection

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: 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.

negative: Protein Microarrays for Personalized Medicine Background: Over the last 10 years, DNA microarrays have achieved a robust analytical performance, enabling their use for analyzing the whole transcriptome or for screening thousands of single-nucleotide polymorphisms in a single experiment. DNA microarrays allow scientists to correlate gene expression signatures with disease progression, to screen for disease-specific mutations, and to treat patients according to their individual genetic profiles; however, the real key is proteins and their manifold functions. It is necessary to achieve a greater understanding of not only protein function and abundance but also their role in the development of diseases. Protein concentrations have been shown to reflect the physiological and pathologic state of an organ, tissue, or cells far more directly than DNA, and proteins can be profiled effectively with protein microarrays, which require only a small amount of sample material. Content: Protein microarrays have become well-established tools in basic and applied research, and the first products have already entered the in vitro diagnostics market. This review focuses on protein microarray applications for biomarker discovery and validation, disease diagnosis, and use within the area of personalized medicine. Summary: Protein microarrays have proved to be reliable research tools in screening for a multitude of parameters with only a minimal quantity of sample and have enormous potential in applications for diagnostic and personalized medicine.

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: Less is more: Intelligent intensive care for SARS-CoV-2 based on the imaging data

negative: A Sequence Homology and Bioinformatic Approach Can Predict Candidate Targets for Immune Responses to SARS-CoV-2 Effective countermeasures against the recent emergence and rapid expansion of the 2019 novel coronavirus (SARS-CoV-2) require the development of data and tools to understand and monitor its spread and immune responses to it. However, little information is available about the targets of immune responses to SARS-CoV-2. We used the Immune Epitope Database and Analysis Resource (IEDB) to catalog available data related to other coronaviruses. This includes SARS-CoV, which has high sequence similarity to SARS-CoV-2 and is the best-characterized coronavirus in terms of epitope responses. We identified multiple specific regions in SARS-CoV-2 that have high homology to the SARS-CoV virus. Parallel bioinformatic predictions identified a priori potential B and T cell epitopes for SARS-CoV-2. The independent identification of the same regions using two approaches reflects the high probability that these regions are promising targets for immune recognition of SARS-CoV-2. These predictions can facilitate effective vaccine design against this virus of high priority.

negative: Effect of changing case definitions for COVID-19 on the epidemic curve and transmission parameters in mainland China: a modelling study BACKGROUND: When a new infectious disease emerges, appropriate case definitions are important for clinical diagnosis and for public health surveillance. Tracking case numbers over time is important to establish the speed of spread and the effectiveness of interventions. We aimed to assess whether changes in case definitions affected inferences on the transmission dynamics of coronavirus disease 2019 (COVID-19) in China. METHODS: We examined changes in the case definition for COVID-19 in mainland China during the first epidemic wave. We used exponential growth models to estimate how changes in the case definitions affected the number of cases reported each day. We then inferred how the epidemic curve would have appeared if the same case definition had been used throughout the epidemic. FINDINGS: From Jan 15 to March 3, 2020, seven versions of the case definition for COVID-19 were issued by the National Health Commission in China. We estimated that when the case definitions were changed, the proportion of infections being detected as cases increased by 7·1 times (95% credible interval [CrI] 4·8–10·9) from version 1 to 2, 2·8 times (1·9–4·2) from version 2 to 4, and 4·2 times (2·6–7·3) from version 4 to 5. If the fifth version of the case definition had been applied throughout the outbreak with sufficient testing capacity, we estimated that by Feb 20, 2020, there would have been 232 000 (95% CrI 161 000–359 000) confirmed cases in China as opposed to the 55 508 confirmed cases reported. INTERPRETATION: The case definition was initially narrow and was gradually broadened to allow detection of more cases as knowledge increased, particularly milder cases and those without epidemiological links to Wuhan, China, or other known cases. These changes should be taken into account when making inferences on epidemic growth rates and doubling times, and therefore on the reproductive number, to avoid bias. FUNDING: Health and Medical Research Fund, Hong Kong.

negative: Predicting ICU admission in community-acquired pneumonia: clinical scores and biomarkers. Community-acquired pneumonia (CAP) remains a common and serious worldwide health problem. Despite all the advances in therapy, significant interest has focused on the identification of patients with CAP who require intensive care unit admission to improve their outcomes. The severity assessment of CAP provides an important guide to clinicians in deciding the site of care and the use of empiric antibiotics and adjuvant therapy. For years, several clinical assessment scores have been suggested and validated to achieve this goal. The recent introduction of biomarkers as prognostic indicators of severe CAP, whether used alone or in conjunction with other clinical severity of illness scores, has been investigated. An objective scoring system with a high level of sensitivity and specificity to predict the severity of CAP and the need for high levels of care do not exist. Today, the addition of clinical scores and biomarkers to clinical judgment is the best approach to optimize the care of severe CAP. Future research will allow validation of these and newer tools to improve the prognosis of patients with CAP.

negative: Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak

negative: Response to the Letter to the Editor: How to Deal with Suspended Oral Treatment during the COVID-19 Epidemic

negative: Preliminary prediction of the basic reproduction number of the Wuhan novel coronavirus 2019‐nCoV OBJECTIVES: To estimate the basic reproduction number of the Wuhan novel coronavirus (2019‐nCoV). METHODS: Based on the susceptible‐exposed‐infected‐removed (SEIR) compartment model and the assumption that the infectious cases with symptoms occurred before 26 January, 2020 are resulted from free propagation without intervention, we estimate the basic reproduction number of 2019‐nCoV according to the reported confirmed cases and suspected cases, as well as the theoretical estimated number of infected cases by other research teams, together with some epidemiological determinants learned from the severe acute respiratory syndrome (SARS). RESULTS: The basic reproduction number fall between 2.8 and 3.3 by using the real‐time reports on the number of 2019‐nCoV‐infected cases from People's Daily in China and fall between 3.2 and 3.9 on the basis of the predicted number of infected cases from international colleagues. CONCLUSIONS: The early transmission ability of 2019‐nCoV is close to or slightly higher than SARS. It is a controllable disease with moderate to high transmissibility. Timely and effective control measures are needed to prevent the further transmissions.

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

negative: Research Advances in Biomarker for Sepsis Sepsis is one of the most common causes of death in severely injured patients worldwide. The early detection of sepsis still has to be solved in clinical practice. The delayed diagnosis often contributes to inappropriate antimicrobial treatment and subsequent high mortality. Sepsis biomarkers are produced during the host response to infection. Traditional biomarkers are polypeptides and/or proteins derived from this response. Omics-based biomarkers are screening out from all kinds of molecules of host response while high-throughout omics technologies are emerging. This review describes traditional and potential omics-based sepsis biomarkers from currently available literatures. The combination of these biomarkers would refine the identification of sepsis for further clinical and experimental sepsis studies.

negative: Thalidomide modulates macrophage-mediated inflammatory innate immune response during Klebsiella pneumoniae B5055 infection in BALB/c mice

negative: COVID-19, a worldwide public health emergency Abstract A new coronavirus outbreak emerged on the 31st of December 2019 in Wuhan, China, causing commotion among the medical community and the rest of the world. This new species of coronavirus has been termed 2019-nCoV and has caused a considerable number of cases of infection and deaths in China and, to a growing degree, beyond China, becoming a worldwide public health emergency. 2019-nCoV has high homology to other pathogenic coronaviruses, such as those originating from bat-related zoonosis (SARS-CoV), which caused approximately 646 deaths in China at the start of the decade. The mortality rate for 2019-nCoV is not as high (approximately 2–3%), but its rapid propagation has resulted in the activation of protocols to stop its spread. This pathogen has the potential to become a pandemic. It is therefore vital to follow the personal care recommendations issued by the World Health Organization.

negative: Proenkephalin, Neutrophil Gelatinase-Associated Lipocalin, and Estimated Glomerular Filtration Rates in Patients With Sepsis BACKGROUND: Proenkephalin (PENK) has been suggested as a novel biomarker for kidney function. We investigated the diagnostic and prognostic utility of plasma PENK in comparison with neutrophil gelatinase-associated lipocalin (NGAL) and estimated glomerular filtration rates (eGFR) in septic patients. METHODS: A total of 167 septic patients were enrolled: 99 with sepsis, 37 with septic shock, and 31 with suspected sepsis. PENK and NGAL concentrations were measured and GFR was estimated by using the isotope dilution mass spectrometry traceable-Modification of Diet in Renal Disease (MDRD) Study and three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations: CKD-EPI(Cr), CDK-EPI(CysC), and CKD-EPI(Cr-CysC). The PENK, NGAL, and eGFR results were compared according to sepsis severity, presence or absence of acute kidney injury (AKI), and clinical outcomes. RESULTS: The PENK, NGAL, and eGFR results were significantly associated with sepsis severity and differed significantly between patients with and without AKI only in the sepsis group (all P<0.05). PENK was superior to NGAL in predicting AKI (P=0.022) and renal replacement therapy (RRT) (P=0.0085). Regardless of the variable GFR category by the different eGFR equations, PENK showed constant and significant associations with all eGFR equations. Unlike NGAL, PENK was not influenced by inflammation and predicted the 30-day mortality. CONCLUSIONS: PENK is a highly sensitive and objective biomarker of AKI and RRT and is useful for prognosis prediction in septic patients. With its diagnostic robustness and predictive power for survival, PENK constitutes a promising biomarker in critical care settings including sepsis.

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

negative: The impact of biosensing in a pandemic outbreak: COVID-19 Abstract COVID-19 pandemic outbreak is the most astounding scene ever experienced in the XXI century. In this opinionated review, we underscore the crucial role of biosensing to handle with such situations. As a matter of fact, testing accelerates life-saving decisions on treatment and isolation of COVID-19 patients in an early stage, and thereby, decelerating or even preventing the spread of such emerging infectious diseases. Meanwhile, it is also proven that a timely and broad application of testing leads to lower mortality rates in countries like Germany or South Korea. Besides, biosensors are also powerful tools for effective assessment of clinical progress and to provide alertness on severity or critical trends of infection. In view hereof, we critically discuss the state-of-the-art biosensing devices for COVID-19 testing. We spot the urgent needs and highlight innovative diagnostic approaches for targeting various COVID-19 related biomarkers. Finally, we outline our recommendations on biosensors and biosensing-related issues towards pandemic outbreaks.

negative: Chapter 15 Biology and Diseases of Ruminants (Sheep, Goats, and Cattle) Ruminants continue to be important in their traditional role in agricultural research and teaching. They are now also extensively used for studies in molecular biology; genetic engineering; and biotechnology for basic science, agricultural and clinical applications. Concern and interest for the welfare for these species and improved understanding of their biology and behavior have continued and are reflected in changing husbandry and management systems. This chapter addresses at high levels basic biology, husbandry, and the more common or important diseases of the three ruminant species used most commonly in the laboratory, namely sheep, goats and cattle.

negative: Application of ProteinChip Array Profiling in Serum Biomarker Discovery for Patients Suffering From Severe Acute Respiratory Syndrome A new strain of coronavirus has caused an outbreak of severe acute respiratory syndrome (SARS) from 2002 to 2003 resulting in 774 deaths worldwide. By protein chip array profiling technology, a number of serum biomarkers that might be useful in monitoring the clinical course of SARS patients were identified. This book chapter describes how the protein chip array profiling was carried out for this study. Briefly, SARS patients’ serum samples were first fractionated in Q Ceramic HyperD ion exchange sorbent beads by buffers at different pH. Serum protein fractions thus obtained were then bound onto a copper (II) immobilized metal affinity capture (IMAC30 Cu [II]) ProteinChip® Array or a weak cation-exchange (CM10) ProteinChip Array. After washing and addition of sinapinic acid, the chips were read in a Protein Biological System (PBS) IIc mass spectrometer. Ions were generated by laser shots and flied in a time of flight mode to the ion detector according to their mass over charge (m/z) ratio. The serum profiling spectra in SARS patients were acquired, baseline subtracted and analyzed in parallel with those from the control subjects by Ciphergen ProteinChip Software 3.0.2 with their peak intensities compared by a nonparametric two sample Mann-Whitney-U test. More than twelve peaks were differentially expressed in SARS patients with one at m/z of 11,695 (later identified to be serum amyloid A protein), which had increase in peak intensity correlating with the extent of SARS-coronavirus induced pneumonia as defined by a serial chest X-ray opacity score. The remaining biomarkers could also be useful in the study of other clinical parameters in SARS patients.

negative: Overview of Protein Microarrays Protein microarray is an emerging technology that provides a versatile platform for characterization of hundreds of thousands of proteins in a highly parallel and high-throughput way. Two major classes of protein microarrays are defined to describe their applications: analytical and functional protein microarrays. In addition, tissue or cell lysates can also be fractionated and spotted on a slide to form a reverse-phase protein microarray. While the fabrication technology is maturing, applications of protein microarrays, especially functional protein microarrays, have flourished during the past decade. Here, we will first review recent advances in the protein microarray technologies, and then present a series of examples to illustrate the applications of analytical and functional protein microarrays in both basic and clinical research. The research areas will include detection of various binding properties of proteins, study of protein posttranslational modifications, analysis of host-microbe interactions, profiling antibody specificity, and identification of biomarkers in autoimmune diseases. As a powerful technology platform, it would not be surprising if protein microarrays will become one of the leading technologies in proteomic and diagnostic fields in the next decade.

negative: Evaluation of organ function in patients with severe COVID-19 infections OBJECTIVE: The purpose of our study was to assess organ function in 102 patients with severe COVID-19 infections, using retrospective clinical analysis. MATERIAL AND METHODS: A retrospective analysis was conducted on 102 patients with severe COVID-19 infections. The patients were divided into a survival group (n=73) and a non-survival group (n=29) according to their prognosis. The age, sex, underlying diseases, clinical laboratory data within 48h (routine blood tests, ALT, AST, TBIL, ALB, BUN, CR, D-Dimer, PT, APTT, FIB, F VIII:C, CK-MB, CK, and LDH), and ventilation status were collected. The organ functions of these severe COVID-19 patients were assessed by comparing the differences between the two groups. RESULTS: AST, BUN, CR, CK-MB, LDH, and CK in the non-survival group were higher than those in the survival group, and the differences were statistically significant (P<0.05). D-Dimer, PT, FIB, and F VIII:C in the non-survival group were higher than the values observed in the survival group, and the differences were statistically significant (P<0.05). PLT, AST, BUN, CR, D-Dimer, PT, FIB, F VIII:C, CK-MB, CK, and LDH predicted the area under the ROC curve (AUC) of the COVID19 endpoint events and were 0.721, 0.854, 0.867, 0.757, 0.699, 0.679, 0.715, 0.811, 0.935, and 0.802, respectively. CONCLUSION: The results showed that there were different degrees of damage to the liver, kidneys, blood coagulation, and heart function in the non-survival group. In addition, PLT, AST, BUN, CR, D-Dimer, PT, FIB, F VIII:C, CK-MB, CK, and LDH had value in evaluating disease prognosis.

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

negative: Lower Respiratory Tract Virus Findings in Mechanically Ventilated Patients With Severe Community-Acquired Pneumonia Background. The role of viral infections in the etiology of severe community-acquired pneumonia (SCAP) was prospectively evaluated from 2008 to 2012 at a university-level intensive care unit. Methods. Clinical data and microbiological tests were assessed: blood cultures, urine pneumococcal and legionella antigens, Mycoplasma pneumoniae and Chlamydia pneumoniae antibodies from paired serums, and respiratory virus detection by multiplex, real-time polymerase chain reaction (PCR) from nasopharyngeal swabs and lower tracheal specimens via intubation tube. Results. Of 49 mechanically ventilated SCAP patients (21 men and 28 women; median age, 54 years), the etiology was identified in 45 cases (92%). There were 21 pure bacterial infections (43%), 5 probably pure viral infections (10%), and 19 mixed bacterial–viral infections (39%), resulting in viral etiology in 24 patients (49%). Of 26 viruses, 21 (81%) were detected from bronchial specimens and 5 (19%) from nasopharyngeal swabs. Rhinovirus (15 cases, 58%) and adenovirus (4 cases, 15%) were the most common viral findings. The bacterial–viral etiology group had the highest peak C-reactive protein levels (median, 356 [25th–75th percentiles, 294–416], P = .05), whereas patients with probably viral etiology had the lowest peak procalcitonin levels (1.7 [25th–75th percentiles, 1.6–1.7]). The clinical characteristics of pure bacterial and mixed bacterial–viral etiologies were comparable. Hospital stay was longest among the bacterial group (17 vs 14 days; P = .02). Conclusions. Viral findings were demonstrated in almost half of the SCAP patients. Clinical characteristics were similar between the pure bacterial and mixed bacterial–viral infections groups. The frequency of viral detection depends on the availability of PCR techniques and lower respiratory specimens.

negative: Lectin-like Intestinal Defensin Inhibits 2019-nCoV Spike binding to ACE2 The burgeoning epidemic caused by novel coronavirus 2019 (2019-nCoV) is currently a global concern. Angiotensin-converting enzyme-2 (ACE2) is a receptor of 2019-nCoV spike 1 protein (S1) and mediates viral entry into host cells. Despite the abundance of ACE2 in small intestine, few digestive symptoms are observed in patients infected by 2019-nCoV. Herein, we investigated the interactions between ACE2 and human defensins (HDs) specifically secreted by intestinal Paneth cells. The lectin-like HD5, rather than HD6, bound ACE2 with a high affinity of 39.3 nM and weakened the subsequent recruitment of 2019-nCoV S1. The cloak of HD5 on the ligand-binding domain of ACE2 was confirmed by molecular dynamic simulation. A remarkable dose-dependent preventive effect of HD5 on 2019-nCoV S1 binding to intestinal epithelial cells was further evidenced by in vitro experiments. Our findings unmasked the innate defense function of lectin-like intestinal defensin against 2019-nCoV, which may provide new insights into the prevention and treatment of 2019-nCoV infection.

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

negative: SEIR Transmission dynamics model of 2019 nCoV coronavirus with considering the weak infectious ability and changes in latency duration Pneumonia patients of 2019-ncov in latent period are not easy to be effectively quarantined, but there is evidence that they have strong infectious ability. Here, the infectious ability of patients during the latent period is slightly less than that of the infected patients was assumed. We established a new SEIR propagation dynamics model, that considered the weak transmission ability of the incubation period, the variation of the incubation period length, and the government intervention measures to track and isolate comprehensively. Based on the raw epidemic data of China from January 23, 2020 to February 10, 2020, the dynamic parameters of the new present SEIR model are fitted. Through the Euler integration algorithm to solve the model, the effect of infectious ability of incubation patients on the theoretical estimation of the present SEIR model was analyzed, and the occurrence time of peak number in China was predicted.

negative: Chronic kidney disease is associated with severe coronavirus disease 2019 (COVID-19) infection

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: Modeling risk of infectious diseases: a case of Coronavirus outbreak in four countries Background The novel coronavirus (2019-nCOV) outbreak has been a serious concern around the globe. Since people are in tremor due to the massive spread of Coronavirus in the major parts of the world, it requires to predict the risk of this infectious disease. In this situation, we develop a model to measure the risk of infectious disease and predict the risk of 2019-nCOV transmission by using data of four countries - United States, Australia, Canada and China. Methods The model underlies that higher the population density, higher the risk of transmission of infectious disease from human to human. Besides, population size, case identification rate and travel of infected passengers in different regions are also incorporated in this model. Results According to the calculated risk index, our study identifies New York State in United States (US) to be the most vulnerable area affected by the novel Coronavirus. Besides, other areas (province/state/territory) such as Hubei (China, 2nd), Massachusetts (US, 3rd), District of Columbia (US, 4th), New Jersey (US, 5th), Quebec (Canada, 20th), Australian Capital Territory (Australia, 29th) are also found as the most risky areas in US, China, Australia and Canada. Conclusion The study suggests avoiding any kind of mass gathering, maintaining recommended physical distances and restricting inbound and outbound flights of highly risk prone areas for tackling 2019-nCOV transmission.

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: Spectroscopy as a tool for detection and monitoring of Coronavirus (COVID-19)

negative: Invasive alien plant species: Their impact on environment, ecosystem services and human health Abstract Ecological perturbations caused by biotic invasion have been identified as a growing threat to global sustainability. Invasive alien plants species (IAPS) are considered to be one of the major drivers of biodiversity loss and thereby altering the ecosystem services and socio-economic conditions through different mechanisms. Although the ecological impacts of IAPS are well documented, there is a dearth of studies regarding their economic quantification, livelihood considerations, biotechnological prospects (phytoremediation, bioenergy, phyto-synthesis of nanoparticles, biomedical, industrial applications etc.) and human health risk assessments of IAPS. In this context, the current panoramic review aimed to investigate the environmental, socio-ecological and health risks posed by IAPS as well as the compounded impact of IAPS with habitat fragmentation, climate and land use changes. To this end, the need of an integrated trans-disciplinary research is emphasized for the sustainable management of IAPS. The management prospects can be further strengthened through their linkage with geo-spatial technologies (remote sensing and GIS) by mapping and monitoring the IAPS spread. Further, the horizon of IAPS management is expanded to ecological indicator perspectives of IAPS, biosecurity, and risk assessment protocols with critical discussion. Moreover, positive as well as negative implications of the IAPS on environment, health, ecosystem services and socio-economy (livelihood) are listed so that a judicious policy framework could be developed for the IAPS management in order to mitigate the human health implications.

negative: The expression and antigenicity of a truncated spike-nucleocapsid fusion protein of severe acute respiratory syndrome-associated coronavirus BACKGROUND: In the absence of effective drugs, controlling SARS relies on the rapid identification of cases and appropriate management of the close contacts, or effective vaccines for SARS. Therefore, developing specific and sensitive laboratory tests for SARS as well as effective vaccines are necessary for national authorities. RESULTS: Genes encoding truncated nucleocapsid (N) and spike (S) proteins of SARSCoV were cloned into the expression vector pQE30 and fusionally expressed in Escherichia coli M15. The fusion protein was analyzed for reactivity with SARS patients' sera and with anti-sera against the two human coronaviruses HCoV 229E and HCoV OC43 by ELISA, IFA and immunoblot assays. Furthermore, to evaluate the antigen-specific humoral antibody and T-cell responses in mice, the fusion protein was injected into 6-week-old BALB/c mice and a neutralization test as well as a T-cell analysis was performed. To evaluate the antiviral efficacy of immunization, BALB/c mice were challenged intranasally with SARSCoV at day 33 post injection and viral loads were determined by fluorescent quantitative RT-PCR. Serological results showed that the diagnostic sensitivity and specificity of the truncated S-N fusion protein derived the SARS virus were > 99% (457/460) and 100.00% (650/650), respectively. Furthermore there was no cross-reactivity with other two human coronaviruses. High titers of antibodies to SRASCoV appeared in the immunized mice and the neutralization test showed that antibodies to the fusion protein could inhibit SARSCoV. The T cell proliferation showed that the fusion protein could induce an antigen-specific T-cell response. Fluorescent quantitative RT-PCR showed that BALB/c mice challenged intranasally with SARSCoV at day 33 post injection were completely protected from virus replication. CONCLUSION: The truncated S-N fusion protein is a suitable immunodiagnostic antigen and vaccine candidate.

negative: Recent advances in nanowires-based field-effect transistors for biological sensor applications Abstract Nanowires (NWs)-based field-effect transistors (FETs) have attracted considerable interest to develop innovative biosensors using NWs of different materials (i.e. semiconductors, polymers, etc.). NWs-based FETs provide significant advantages over the other bulk or non-NWs nanomaterials-based FETs. As the building blocks for FET-based biosensors, one-dimensional NWs offer excellent surface-to-volume ratio and are more suitable and sensitive for sensing applications. During the past decade, FET-based biosensors are smartly designed and used due to their great specificity, sensitivity, and high selectivity. Additionally, they have the advantage of low weight, low cost of mass production, small size and compatible with commercial planar processes for large-scale circuitry. In this respect, we summarize the recent advances of NWs-based FET biosensors for different biomolecule detection i.e. glucose, cholesterol, uric acid, urea, hormone, proteins, nucleotide, biomarkers, etc. A comparative sensing performance, present challenges, and future prospects of NWs-based FET biosensors are discussed in detail.

negative: Critical care management of adults with community-acquired severe respiratory viral infection With the expanding use of molecular assays, viral pathogens are increasingly recognized among critically ill adult patients with community-acquired severe respiratory illness; studies have detected respiratory viral infections (RVIs) in 17–53% of such patients. In addition, novel pathogens including zoonotic coronaviruses like the agents causing Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and the 2019 novel coronavirus (2019 nCoV) are still being identified. Patients with severe RVIs requiring ICU care present typically with hypoxemic respiratory failure. Oseltamivir is the most widely used neuraminidase inhibitor for treatment of influenza; data suggest that early use is associated with reduced mortality in critically ill patients with influenza. At present, there are no antiviral therapies of proven efficacy for other severe RVIs. Several adjunctive pharmacologic interventions have been studied for their immunomodulatory effects, including macrolides, corticosteroids, cyclooxygenase-2 inhibitors, sirolimus, statins, anti-influenza immune plasma, and vitamin C, but none is recommended at present in severe RVIs. Evidence-based supportive care is the mainstay for management of severe respiratory viral infection. Non-invasive ventilation in patients with severe RVI causing acute hypoxemic respiratory failure and pneumonia is associated with a high likelihood of transition to invasive ventilation. Limited existing knowledge highlights the need for data regarding supportive care and adjunctive pharmacologic therapy that is specific for critically ill patients with severe RVI. There is a need for more pragmatic and efficient designs to test different therapeutics both individually and in combination. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-05943-5) contains supplementary material, which is available to authorized users.

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

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

negative: Predicting commercially available antiviral drugs that may act on the novel coronavirus (2019-nCoV), Wuhan, China through a drug-target interaction deep learning model The infection of a novel coronavirus found in Wuhan of China (2019-nCoV) is rapidly spreading, and the incidence rate is increasing worldwide. Due to the lack of effective treatment options for 2019-nCoV, various strategies are being tested in China, including drug repurposing. In this study, we used our pretrained deep learning-based drug-target interaction model called Molecule Transformer-Drug Target Interaction (MT-DTI) to identify commercially available drugs that could act on viral proteins of 2019-nCoV. The result showed that atazanavir, an antiretroviral medication used to treat and prevent the human immunodeficiency virus (HIV), is the best chemical compound, showing a inhibitory potency with Kd of 94.94 nM against the 2019-nCoV 3C-like proteinase, followed by efavirenz (199.17 nM), ritonavir (204.05 nM), and dolutegravir (336.91 nM). Interestingly, lopinavir, ritonavir, and darunavir are all designed to target viral proteinases. However, in our prediction, they may also bind to the replication complex components of 2019-nCoV with an inhibitory potency with Kd < 1000 nM. In addition, we also found that several antiviral agents, such as Kaletra, could be used for the treatment of 2019-nCoV, although there is no real-world evidence supporting the prediction. Overall, we suggest that the list of antiviral drugs identified by the MT-DTI model should be considered, when establishing effective treatment strategies for 2019-nCoV.

negative: Plasma and cerebrospinal fluid-based protein biomarkers for motor neuron disease. Motor neuron diseases (MNDs) and, in particular, amyotrophic lateral sclerosis (ALS), are a heterogeneous group of neurologic disorders characterized by the progressive loss of motor function. In ALS, a selective and relentless degeneration of both upper and lower motor neurons occurs, culminating in mortality typically within 5 years of symptom onset. However, survival rates vary among individual patients and can be from a few months to >10 years from diagnosis. Inadequacies in disease detection and treatment, along with a lack of diagnostic and prognostic tools, have prompted many to turn to proteomics-based biomarker discovery efforts. Proteomics refers to the study of the proteins expressed by a genome at a particular time, and the proteome can respond to and reflect the status of an organism, including health and disease states. Although an emerging field, proteomic applications promise to uncover biomarkers critical for differentiating patients with ALS and other MNDs from healthy individuals and from patients affected by other diseases. Ideally, these studies will also provide mechanistic information to facilitate identification of new drug targets for subsequent therapeutic development. In addition to proper experimental design, standard operating procedures for sample acquisition, preprocessing, and storage must be developed. Biological samples typically analyzed in proteomic studies of neurologic diseases include both plasma and cerebrospinal fluid (CSF). Recent studies have identified individual proteins and/or protein panels from blood plasma and CSF that represent putative biomarkers for ALS, although many of these proteins are not unique to this disease. Continued investigations are required to validate these initial findings and to further pursue the role of these proteins as diagnostic biomarkers or surrogate markers of disease progression. Protein biomarkers specific to ALS will additionally function to evaluate drug efficacy in clinical trials and to identify novel targets for drug design. It is hoped that proteomic technologies will soon integrate the basic biology of ALS with mechanistic disease information to achieve success in the clinical setting.

negative: Aetiological role of viruses in multiple sclerosis: a review.

negative: Measuring multimorbidity beyond counting diseases: systematic review of community and population studies and guide to index choice. OBJECTIVES To identify and summarise existing indices for measuring multimorbidity beyond disease counts, to establish which indices include mental health comorbidities or outcomes, and to develop recommendations based on applicability, performance, and usage. DESIGN Systematic review. DATA SOURCES Seven medical research databases (Medline, Web of Science Core Collection, Cochrane Library, Embase, PsycINFO, Scopus, and CINAHL Plus) from inception to October 2018 and bibliographies and citations of relevant papers. Searches were limited to English language publications. ELIGIBILITY CRITERIA FOR STUDY SELECTION Original articles describing a new multimorbidity index including more information than disease counts and not focusing on comorbidity associated with one specific disease. Studies were of adults based in the community or at population level. RESULTS Among 7128 search results, 5560 unique titles were identified. After screening against eligibility criteria the review finally included 35 papers. As index components, 25 indices used conditions (weighted or in combination with other parameters), five used diagnostic categories, four used drug use, and one used physiological measures. Predicted outcomes included mortality (18 indices), healthcare use or costs (13), hospital admission (13), and health related quality of life (7). 29 indices considered some aspect of mental health, with most including it as a comorbidity. 12 indices are recommended for use. CONCLUSIONS 35 multimorbidity indices are available, with differing components and outcomes. Researchers and clinicians should examine existing indices for suitability before creating new ones. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42017074211.

negative: CT Imaging Features of 2019 Novel Coronavirus (2019-nCoV) In this retrospective case series, chest CT scans of 21 symptomatic patients from China infected with the 2019 novel coronavirus (2019-nCoV) were reviewed, with emphasis on identifying and characterizing the most common findings. Typical CT findings included bilateral pulmonary parenchymal ground-glass and consolidative pulmonary opacities, sometimes with a rounded morphology and a peripheral lung distribution. Notably, lung cavitation, discrete pulmonary nodules, pleural effusions, and lymphadenopathy were absent. Follow-up imaging in a subset of patients during the study time window often demonstrated mild or moderate progression of disease, as manifested by increasing extent and density of lung opacities. © RSNA, 2020

negative: Circulating fibrocytes traffic to the lung in murine acute lung injury and predict outcomes in human acute respiratory distress syndrome: a pilot study BACKGROUND: Fibrosis is an integral component of the pathogenesis of acute lung injury and is associated with poor outcomes in patients with acute respiratory distress syndrome (ARDS). Fibrocytes are bone marrow-derived cells that traffic to injured tissues and contribute to fibrosis; hence their concentration in the peripheral blood has the potential to serve as a biomarker of lung fibrogenesis. We therefore sought to test the hypothesis that the concentration and phenotype of circulating fibrocytes in patients with ARDS predicts clinical outcomes. METHODS: For the animal studies, C57Bl/6 mice were infected with experimental Klebsiella pneumoniae in a model of acute lung injury; one-way ANOVA was used to compare multiple groups and two-way ANOVA was used to compare two groups over time. For the human study, 42 subjects with ARDS and 12 subjects with pneumonia (without ARDS) were compared to healthy controls. Chi-squared or Fisher’s exact test were used to compare binary outcomes. Survival data was expressed using a Kaplan-Meier curve and compared by log-rank test. Univariable and multivariable logistic regression were used to predict death. RESULTS: In mice with acute lung injury caused by Klebsiella pneumonia, there was a time-dependent increase in lung soluble collagen that correlated with sequential expansion of fibrocytes in the bone marrow, blood, and then lung compartments. Correspondingly, when compared via cross-sectional analysis, the initial concentration of blood fibrocytes was elevated in human subjects with ARDS or pneumonia as compared to healthy controls. In addition, fibrocytes from subjects with ARDS displayed an activated phenotype and on serial measurements, exhibited intermittent episodes of markedly elevated concentration over a median of 1 week. A peak concentration of circulating fibrocytes above a threshold of > 4.8 × 10(6) cells/mL cells correlated with mortality that was independent of age, ratio of arterial oxygen concentration to the fraction of inspired oxygen, and vasopressor requirement. CONCLUSIONS: Circulating fibrocytes increase in a murine model of acute lung injury and elevation in the number of these cells above a certain threshold is correlated with mortality in human ARDS. Therefore, these cells may provide a useful and easily measured biomarker to predict outcomes in these patients.

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

negative: Recommendations on diagnosis and treatment in hepatobiliary surgery under 2019-nCoV epidemic 2019 novel coronavirus pneumonia is a serious life-threatening disease and it has affected many people globally, especially the people who live in China. A high prevalence of hepatobiliary diseases has been observed in 2019-nCoV patients and some may require emergency surgery. In the context of the novel coronavirus pneumonia, new challenges have arisen for surgeons in terms of ways to effectively treat outpatients, safety of medical staffs in performing surgery treatment, and the lack of efficient postoperative management and follow-up procedure. It is hoped that through this article, surgeons will have a better system in hepatobiliary diseases classification, treatment selection, and protective measures to improve the clinical practice in accordance with the guidelines for the diagnosis and treatment of the novel coronavirus pneumonia.

negative: The epidemiologic parameters for COVID-19: A Systematic Review and Meta-Analysis Introduction: The World Health Organization (WHO) declared the outbreak to be a public health emergency and international concern and recognized it as a pandemic. The aim of this study was to estimate the epidemiologic parameters of novel coronavirus (COVID-19) pandemic for clinical and epidemiological help. Methods: Four electronic databases including Web of Science, Medline (PubMed), Scopus and Google Scholar were searched for literature published from early December 2019 up to 23 March 2020. The "metan" command was used to perform a fixed or random effects analysis. Cumulative meta-analysis was performed using the "metacum" command. Results: Totally 76 observational studies were included in the analysis. The pooled estimate for R0 was 2.99 (95% CI: 2.71-3.27) for COVID-19. The overall R0 was 3.23, 1.19, 3.6 and 2.35 for China, Singapore, Iran and Japan, respectively. The overall Serial Interval, doubling time, incubation period were 4.45, 4.14 and 4.24 days for COVID-19. In addition, the overall estimation for growth rate and case fatality rate for COVID-19 were 0.38% and 3.29%, respectively. Conclusion: Calculating the pooled estimate of the epidemiological parameters of COVID-19 as an emerging disease, could reveal epidemiological features of the disease that consequently pave the way for health policy makers to think more about control strategies. Keywords: Epidemiologic Parameters; R0; Serial Interval; Doubling Time; Case Fatality Rate;COVID-19

negative: Atrial Arrhythmias in a Patient Presenting With Coronavirus Disease-2019 (COVID-19) Infection The coronavirus disease-2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) that has significant potential cardiovascular implications for patients. These include myocarditis, acute coronary syndromes, cardiac arrhythmias, cardiomyopathies with heart failure and cardiogenic shock, and venous thromboembolic events. We describe a Caribbean-Black gentleman with COVID-19 infection presenting with atrial arrhythmias, namely, atrial flutter and atrial fibrillation, which resolved with rate and rhythm control strategies, and supportive care.

negative: Analysis of angiotensin-converting enzyme 2 (ACE2) from different species sheds some light on cross-species receptor usage of a novel coronavirus 2019-nCoV

negative: Inorganic Complexes and Metal-Based Nanomaterials for Infectious Disease Diagnostics [Image: see text] Infectious diseases claim millions of lives each year. Robust and accurate diagnostics are essential tools for identifying those who are at risk and in need of treatment in low-resource settings. Inorganic complexes and metal-based nanomaterials continue to drive the development of diagnostic platforms and strategies that enable infectious disease detection in low-resource settings. In this review, we highlight works from the past 20 years in which inorganic chemistry and nanotechnology were implemented in each of the core components that make up a diagnostic test. First, we present how inorganic biomarkers and their properties are leveraged for infectious disease detection. In the following section, we detail metal-based technologies that have been employed for sample preparation and biomarker isolation from sample matrices. We then describe how inorganic- and nanomaterial-based probes have been utilized in point-of-care diagnostics for signal generation. The following section discusses instrumentation for signal readout in resource-limited settings. Next, we highlight the detection of nucleic acids at the point of care as an emerging application of inorganic chemistry. Lastly, we consider the challenges that remain for translation of the aforementioned diagnostic platforms to low-resource settings.

negative: Case fatality rate in COVID-19: a systematic review and meta-analysis Background: Estimating the prevalence of severe or critical illness and case fatality of COVID-19 outbreak in December, 2019 remains a challenge due to biases associated with surveillance, data synthesis and reporting. We aimed to address this limitation in a systematic review and meta-analysis and to examine the clinical, biochemical and radiological risk factors in a meta-regression. Methods: PRISMA guidelines were followed. PubMed, Scopus and Web of Science were searched using pre-specified keywords on March 07, 2020. Peer-reviewed empirical studies examining rates of severe illness, critical illness and case fatality among COVID-19 patients were examined. Numerators and denominators to compute the prevalence rates and risk factors were extracted. Random-effects meta-analyses were performed. Results were corrected for publication bias. Meta-regression analyses examined the moderator effects of potential risk factors. Results: The meta-analysis included 29 studies representing 2,090 individuals. Pooled rates of severe illness, critical illness and case fatality among COVID-19 patients were 15%, 5% and 0.8% respectively. Adjusting for potential underreporting and publication bias, increased these estimates to 26%, 16% and 7.4% respectively. Increasing age and elevated LDH consistently predicted severe / critical disease and case fatality. Hypertension; fever and dyspnea at presentation; and elevated CRP predicted increased severity. Conclusions: Risk factors that emerged in our analyses predicting severity and case fatality should inform clinicians to define endophenotypes possessing a greater risk. Estimated case fatality rate of 7.4% after correcting for publication bias underscores the importance of strict adherence to preventive measures, case detection, surveillance and reporting.

negative: Maladies respiratoires, allergies et infections à COVID-19. Premières nouvelles de Wuhan

negative: Host Factors in Coronavirus Replication Coronaviruses are pathogens with a serious impact on human and animal health. They mostly cause enteric or respiratory disease, which can be severe and life threatening, e.g., in the case of the zoonotic coronaviruses causing severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) in humans. Despite the economic and societal impact of such coronavirus infections, and the likelihood of future outbreaks of additional pathogenic coronaviruses, our options to prevent or treat coronavirus infections remain very limited. This highlights the importance of advancing our knowledge on the replication of these viruses and their interactions with the host. Compared to other +RNA viruses, coronaviruses have an exceptionally large genome and employ a complex genome expression strategy. Next to a role in basic virus replication or virus assembly, many of the coronavirus proteins expressed in the infected cell contribute to the coronavirus-host interplay. For example, by interacting with the host cell to create an optimal environment for coronavirus replication, by altering host gene expression or by counteracting the host’s antiviral defenses. These coronavirus–host interactions are key to viral pathogenesis and will ultimately determine the outcome of infection. Due to the complexity of the coronavirus proteome and replication cycle, our knowledge of host factors involved in coronavirus replication is still in an early stage compared to what is known for some other +RNA viruses. This review summarizes our current understanding of coronavirus–host interactions at the level of the infected cell, with special attention for the assembly and function of the viral RNA-synthesising machinery and the evasion of cellular innate immune responses.

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: Recent advances in the detection of respiratory virus infection in humans Respiratory tract viral infection caused by viruses or bacteria is one of the most common diseases in human worldwide, while those caused by emerging viruses, such as the novel coronavirus, 2019‐nCoV that caused the pneumonia outbreak in Wuhan, China most recently, have posed great threats to global public health. Identification of the causative viral pathogens of respiratory tract viral infections is important to select an appropriate treatment, save people's lives, stop the epidemics, and avoid unnecessary use of antibiotics. Conventional diagnostic tests, such as the assays for rapid detection of antiviral antibodies or viral antigens, are widely used in many clinical laboratories. With the development of modern technologies, new diagnostic strategies, including multiplex nucleic acid amplification and microarray‐based assays, are emerging. This review summarizes currently available and novel emerging diagnostic methods for the detection of common respiratory viruses, such as influenza virus, human respiratory syncytial virus, coronavirus, human adenovirus, and human rhinovirus. Multiplex assays for simultaneous detection of multiple respiratory viruses are also described. It is anticipated that such data will assist researchers and clinicians to develop appropriate diagnostic strategies for timely and effective detection of respiratory virus infections.

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

negative: Could COVID-19 represent a negative prognostic factor in patients with stroke?

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

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

negative: A MULTINATIONAL REPORT TO CHARACTERISE SARS-CoV-2 INFECTION IN PEOPLE WITH CYSTIC FIBROSIS Abstract Information is lacking on the clinical impact of the novel coronavirus, SARS-CoV-2 on people with cystic fibrosis (CF). Our aim was to characterize SARS-CoV-2 infection in people with cystic fibrosis. Methods: Anonymised data submitted by each participating country to their National CF Registry was reported using a standardised template, then collated and summarised. Results: 40 cases have been reported across 8 countries. Of the 40 cases, 31 (78%) were symptomatic for SARS-CoV-2 at presentation, with 24 (60%) having a fever. 70% have recovered, 30% remain unresolved at time of reporting, and no deaths have been submitted. Conclusions: This early report shows good recovery from SARS-CoV-2 in this heterogeneous CF cohort. The disease course does not seem to differ from the general population, but the current numbers are too small to draw firm conclusions and people with CF should continue to strictly follow public health advice to protect themselves from infection.

negative: The utility of peripheral blood leucocyte ratios as biomarkers in infectious diseases: A systematic review and meta-analysis Summary Objectives To assess the utility of the neutrophil:lymphocyte (NLR), lymphocyte:monocyte (LMR) and platelet:lymphocyte ratios (PLR) as infection biomarkers. Methods PubMed/MEDLINE, Embase and Cochrane databases were searched to identify eligible articles. Studies of diagnosis, severity or outcome were included. PROSPERO systematic review registration CRD42017075032. Results Forty studies were included, reporting on bacterial and viral infections, malaria, and critical illness due to sepsis. Ten studies reported an association of higher NLR with bacteraemia, supported by meta-analysis of patient-level data (five studies, n = 3320; AUC 0.72, p<0.0001) identifying a cut-off of >12.65. Two studies reported an association with lower LMR and diagnosis of influenza virus infection in patients with respiratory tract infection. Meta-analysis of patient-level data (n = 85; AUC 0.66, p = 0.01) identified a cut-off of ≤2.06. The directionality of associations between NLR and outcomes in heterogeneous cohorts of critically ill adults with sepsis varied. Potential clinical utility was also demonstrated in pneumonia (NLR), pertussis (NLR), urinary tract infection (NLR), diabetic foot infections (NLR) and Crimean Congo Haemorrhagic Fever (PLR). Longitudinal measurement of LMR during respiratory virus infection reflected symptoms and NLR during sepsis and bacteraemia predicted mortality. Conclusions Peripheral blood leucocyte ratios are useful infection biomarkers, with the most evidence related to diagnosis of bacteraemia and influenza virus infection. In critical illness due to sepsis, a signal towards an association with NLR and outcomes exists, and NLR should be evaluated in future stratification models. Longitudinal measurement of ratios during infection could be informative. Overall, these biomarkers warrant further recognition and study in infectious diseases.

negative: 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.

negative: Computational Prediction of the Comprehensive SARS-CoV-2 vs. Human Interactome to Guide the Design of Therapeutics Understanding the disease pathogenesis of the novel coronavirus, denoted SARS-CoV-2, is critical to the development of anti-SARS-CoV-2 therapeutics. The global propagation of the viral disease, denoted COVID-19 (“coronavirus disease 2019”), has unified the scientific community in searching for possible inhibitory small molecules or polypeptides. Given the known interaction between the human ACE2 (“Angiotensin-converting enzyme 2”) protein and the SARS-CoV virus (responsible for the coronavirus outbreak circa. 2003), considerable focus has been directed towards the putative interaction between the SARS-CoV-2 Spike protein and ACE2. However, a more holistic understanding of the SARS-CoV-2 vs. human inter-species interactome promises additional putative protein-protein interactions (PPI) that may be considered targets for the development of inhibitory therapeutics. To that end, we leverage two state-of-the-art, sequence-based PPI predictors (PIPE4 & SPRINT) capable of generating the comprehensive SARS-CoV-2 vs. human interactome, comprising approximately 285,000 pairwise predictions. Of these, we identify the high-scoring subset of human proteins predicted to interact with each of the 14 SARS-CoV-2 proteins by both methods, comprising 279 high-confidence putative interactions involving 225 human proteins. Notably, the Spike-ACE2 interaction was the highest ranked for both the PIPE4 and SPRINT predictors, corroborating existing evidence for this PPI. Furthermore, the PIPE-Sites algorithm was used to predict the putative subsequence that might mediate each interaction and thereby inform the design of inhibitory polypeptides intended to disrupt the corresponding host-pathogen interactions. We hereby publicly release the comprehensive set of PPI predictions and their corresponding PIPE-Sites landscapes in the following DataVerse repository: 10.5683/SP2/JZ77XA. All data and metadata are released under a CC-BY 4.0 licence. The information provided represents theoretical modeling only and caution should be exercised in its use. It is intended as a resource for the scientific community at large in furthering our understanding of SARS-CoV-2.

negative: Can routine laboratory tests discriminate 2019 novel coronavirus infected pneumonia from other community-acquired pneumonia? Background. The clinical presentation of 2019 Novel Coronavirus (2019-nCov) infected pneumonia (NCIP) resembles that of other etiologies of community-acquired pneumonia (CAP). We aimed to identify clinical laboratory features to distinguish NCIP from CAP. Methods. We compared the ability of the hematological and biochemical features of 84 patients with NCIP at hospital admission and 316 patients with CAP. Parameters independently predictive of NCIP were calculated by multivariate logistic regression. The receiver operating characteristic (ROC) curves were generated and the area under the ROC curve (AUC) was measured to evaluate the discriminative ability. Results. Most hematological and biochemical indexes of patients with NCIP were significantly different from patients with CAP. Nine laboratory parameters were identified to be highly predictive of a diagnosis of NCIP by multivariate analysis. The AUCs demonstrated good discriminatory ability for red cell distribution width (RDW) with an AUC of 0.88 and Hemoglobin (HGB) with an AUC of 0.82. Red blood cell (RBC), albumin (ALB), eosinophil (EO), hematocrit (HCT), alkaline phosphatase (ALP), and white blood cell (WBC) had fair discriminatory ability. Combinations of any two parameters performed better than did the RDW alone. Conclusions. Routine laboratory examinations may be helpful for the diagnosis of NCIP. Application of laboratory tests may help to optimize the use of isolation rooms for patients when they present with unexplained febrile respiratory illnesses.

negative: Chapter 24 Nanosensor networks for health-care applications Abstract Functionalized transistors provide effective sensors for a variety of viruses (Zika, severe acute respiratory syndrome), toxins (botulinum), cancers (breast and prostate), and disease or injury biomarkers (troponin, cerebrospinal fluid). A hallmark of this approach is high specificity, rapid response (<5minutes), and ability to be integrated with wireless data transmission capabilities. The ultimate goal is hand-held point-of-care detection that can streamline patient diagnosis.

negative: HIGH LIVER FAT ASSOCIATES WITH HIGHER RISK OF DEVELOPING SYMPTOMATIC COVID-19 INFECTION - INITIAL UK BIOBANK OBSERVATIONS Background A high proportion of COVID-19 patients develop acute liver dysfunction. Early research has suggested that pre-existing fatty liver disease may be a significant risk factor for hospitalisation. Liver fat, in particular, is a modifiable parameter and can be a target for public health policy and individual patient plans. In this study we aimed to assess pre-existing liver disease as a risk factor for developing symptomatic COVID-19. Methods From 502,506 participants from the UK Biobank, 42,146 underwent MRI (aged 45-82), and had measures of liver fat, liver fibroinflammatory disease and liver iron. Patients were censored on May 28th to determine how many had tested for COVID-19 with symptomatic disease. UK testing was restricted to those with symptoms in hospital. COVID-19 symptoms included fever, dry cough, sore throat, diarrhoea and fatigue. Univariate analysis was performed on liver phenotypic biomarkers to determine if these variables increased risk of symptomatic COVID-19, and compared to previously described risk factors associated with severe COVID-19, including to age, ethnicity, gender and obesity, Findings Increased liver fat was associated with a higher risk for symptomatic confirmed COVID-19 in this population in univariate analysis(OR:1.85, p=0.03). In obese participants, only those with concomitant fatty liver([≥]10%) were at increased risk(OR:2.96, p=0.02), with those having normal liver fat (<5%) showing no increased risk(OR:0.36, p=0.09). Conclusions UK Biobank data demonstrated an association between pre-existing liver disease and obesity with severe COVID-19, with higher proportions of liver fat in obese individuals a likely risk factor for symptomatic disease and severity. Public policy measures to protect patients with liver disease who may have almost double the risk of the general population should be considered, especially as dietary and pharmacological strategies to reduce body weight and liver fat already exist. Funding University of Oxford, Innovate UK, UK Biobank. Authors are employees of Perspectum Ltd.

negative: Chapter 6 Involvement and Roles of Long Noncoding RNAs in the Molecular Mechanisms of Emerging and Reemerging Viral Infections Abstract The studies on the mechanisms of viral–host interactions in infections have been focusing on protein-coding sequences of the genome. Although it is essential to consider the nonprotein-coding part that represents approximately 80% of the human genome. Thus advances in sequencing techniques have led to the discovery of thousands of RNAs with low or no capacity to encode proteins but are exhibiting crucial biological functions. Long noncoding RNAs (ncRNAs) (lncRNAs) are a heterogeneous class of these ncRNAs that are longer than 200nt. Accumulating evidences have demonstrated the involvement of these molecules in development and physiological processes, especially through their regulation of gene expression. LncRNAs are encoded in mammalian cells as well as in microorganisms and viruses. Several studies have found differential expressions of lncRNAs in response to viral infection of emerging viruses, which suggest important roles. In fact, they are involved in promoting viral replication, evading host immunity and regulating the host response to the infection. In addition, lncRNAs do not induce immune response compared to viral proteins; thus viruses might employ them as an effective strategy to invade their hosts. In this chapter, we discuss particularly the emerging virus–host interaction associated lncRNAs through addressing their involvement in the mechanisms underlying emerging viral infections as well as in the pathways of immune system in response to these infections. We also discuss the promising role of these noncoding transcripts as biomarkers for diagnosing viral pathologies.

negative: Modern approaches to understanding stress and disease susceptibility: A review with special emphasis on respiratory disease Studies in animals and humans link both physical and psychological stress with an increased incidence and severity of respiratory infections. For this manuscript we define stress as the physiological responses an individual undergoes while adjusting to a continually changing environment. It is known that stressors of various types (psychological/physical) can alter the physiological levels of certain hormones, chemokines and cytokines. These alterations send information to the central nervous system to take necessary action which then sends messages to appropriate organs/tissues/cells to respond. These messages can either activate or suppress the immune system as needed and failure to compensate for this by the body can lead to serious health-related problems. Little is known how stress affects disease susceptibility, yet understanding this mechanism is important for developing effective treatments, and for improving health and food quality. The current review focuses on (a) the effects of psychological stressors in humans and animals, (b) various methodologies employed to understand stress responses and their outcomes, and (c) the current status of the attempts to correlate stress and disease with respiratory disease as model system. The methodologies included in this review span traditional epidemiological, behavioral and immunological studies to current high throughput genomic, proteomic, metabolomic/metabonomic approaches. With the advent of various newer omics and bioinformatics methodologies we postulate that it will become feasible to understand the mechanisms through which stress can influence disease onset. Although the literature in this area is limited because of the infancy of this research area, the objective of this review is to illustrate the power of new approaches to address complex biological questions. These new approaches will also aid in our understanding how these processes are related to the dynamics and kinetics of changes in expression of multiple genes at various levels.

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

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: ECR 2013 Book of Abstracts - A - Postgraduate Educational Programme

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: Evaluating new evidence in the early dynamics of the novel coronavirus COVID-19 outbreak in Wuhan, China with real time domestic traffic and potential asymptomatic transmissions The novel coronavirus (COVID-19), first detected in Wuhan, China in December 2019, has spread to 28 countries/regions with over 43,000 confirmed cases. Much about this outbreak is still unknown. At this early stage of the epidemic, it is important to investigate alternative sources of information to understand its dynamics and spread. With updated real time domestic traffic, this study aims to integrate recent evidence of international evacuees extracted from Wuhan between Jan. 29 and Feb. 2, 2020 to infer the dynamics of the COVD-19 outbreak in Wuhan. In addition, a modified SEIR model was used to evaluate the empirical support for the presence of asymptomatic transmissions. Based on the data examined, this study found little evidence for the presence of asymptomatic transmissions. However, it is still too early to rule out its presence conclusively due to sample size and other limitations. The updated basic reproductive number was found to be 2.12 on average with a 95% credible interval of [2.04, 2.18]. It is smaller than previous estimates probably because the new estimate factors in the social and non-pharmaceutical mitigation implemented in Wuhan through the evacuee dataset. Detailed predictions of infected individuals exported both domestically and internationally were produced. The estimated case confirmation rate has been low but has increased steadily to 23.37% on average. The findings of this study depend on the validity of the underlying assumptions, and continuing work is needed, especially in monitoring the current infection status of Wuhan residents.

negative: Impact of coronavirus outbreak on psychological health

negative: Novel Coronavirus Disease 2019 (COVID-19): An Emerging Infectious Disease in the 21st Century Background: At the beginning of the New Year 2020, China alerted the world health organization (WHO) to a cluster of unusual pneumonia cases in Wuhan After extensive speculation, eventually a new species of coronavirus introduced as the causative pathogen of the disease Coronavirus disease 2019 (COVID-19) is a name for the disease, and the virus that causes it is known SARS-CoV-2 The very rapid spread of the COVID-19 in China and in many other countries has caused fear among people across the world The novel coronavirus outbreak declared a Public Health Emergency of International Concern on 30 January 2020 Materials and Methods: Several databases such as PubMed, Scopus, Google scholar, and BioRxiv were searched for publications reporting on the novel coronavirus up to 29 February 2020 Literature searches were performed using keywords including “Coronavirus 2019”, “2019-nCoV”, “COVID-19”, and “SARS-CoV-2” Moreover, websites such as the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) were searched to retrieve updated data and statistics regarding the novel coronavirus We extracted data on the epidemiology, pathogenesis, virology, clinical manifestations, transmission routes, diagnosis, treatment, and prevention measures Results: From the 1416 articles identified in the initial search, 53 were remained after title and abstract screening After full-text review, 37 articles were eligible to include in our study Incubation period for COVID-19 is between 2-10 days, according to the World Health Organization (WHO) The case fatality rate in patients infected with SARC-CoV-2 is 4 3%, and the results indicate that the mortality is higher in elderly individuals and patients with chronic conditions including patients with coronary artery disease, diabetes, chronic pulmonary disease, and hypertension The mortality rate in healthy subjects is less than 1% Conclusion: The outbreak caused by the novel coronavirus is larger than the previous human coronaviruses, showing that the SARS-CoV-2 is an extremely contagious virus However, the mortality rate of COVID-19 is lower than that of other coronaviruses diseases such as SARS or MERS and other viruses like HIV and Ebola Currently, due to the lack of an effective treatment and vaccine, the best way to deal with the COVID-19 disease is to prevent transmission and spread of the virus and to execute personal protective measures

negative: Calprotectin, a new biomarker for diagnosis of acute respiratory infections Respiratory tract infections require early diagnosis and adequate treatment. With the antibiotic overuse and increment in antibiotic resistance there is an increased need to accurately distinguish between bacterial and viral infections. We investigated the diagnostic performance of calprotectin in respiratory tract infections and compared it with the performance of heparin binding protein (HBP) and procalcitonin (PCT). Biomarkers were analyzed in patients with viral respiratory infections and patients with bacterial pneumonia, mycoplasma pneumonia and streptococcal tonsillitis (n = 135). Results were compared with values obtained from 144 healthy controls. All biomarkers were elevated in bacterial and viral infections compared to healthy controls. Calprotectin was significantly increased in patients with bacterial infections; bacterial pneumonia, mycoplasma pneumonia and streptococcal tonsillitis compared with viral infections. PCT was significantly elevated in patients with bacterial pneumonia compared to viral infections but not in streptococcal tonsillitis or mycoplasma caused infections. HBP was not able to distinguish between bacterial and viral causes of infections. The overall clinical performance of calprotectin in the distinction between bacterial and viral respiratory infections, including mycoplasma was greater than performance of PCT and HBP. Rapid determination of calprotectin may improve the management of respiratory tract infections and allow more precise diagnosis and selective use of antibiotics.

negative: Neurological Complications in Critically Ill Patients

negative: Nucleocapsid protein of SARS-CoV activates interleukin-6 expression through cellular transcription factor NF-κB Abstract High levels of interleukin-6 (IL-6) in the acute stage associated with lung lesions were found in SARS patients. To evaluate the mechanisms behind this event, we investigated the roles of SARS-CoV proteins in the regulation of IL-6. Results showed that the viral nucleocapsid (N) protein activated IL-6 expression in a concentration-dependent manner. Promoter analyses suggested that NF-κB binding element was required for IL-6 expression regulated by N protein. Further studies demonstrated that N protein bound directly to NF-κB element on the promoter. We also showed that N protein activated IL-6 expression through NF-κB by facilitating the translocation of NF-κB from cytosol to nucleus. Mutational analyses revealed that two regions of N protein were essential for its function in the activation of IL-6. These results provided new insights into understanding the mechanism involved in the function of SARS-CoV N protein and pathogenesis of the virus.

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

negative: In Vitro Diagnostic Assays for COVID-19: Recent Advances and Emerging Trends There have been tremendous advances in in vitro diagnostic (IVD) assays for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The main IVD assays used for COVID-19 employ real-time reverse transcriptase polymerase chain reaction (RT-PCR) that takes a few hours. But the assay duration has been shortened to 45 min by Cepheid. Of interest is the point-of-care (POC) molecular assay by Abbott that decreased the assay duration to just 5 min. Most molecular tests have been approved by the United States Food and Drug Administration (FDA) under emergency use authorization (EUA) and are Conformité Européenne (CE) marked. A wide range of serology immunoassays (IAs) have also been developed that complement the molecular assays for the diagnosis of COVID-19. The most prominent IAs are automated chemiluminescent IA (CLIA), manual ELISA, and rapid lateral flow IA (LFIA), which detect the immunoglobulin M (IgM) and immunoglobulin G (IgG) produced in persons in response to SARS-CoV-2 infection. The ongoing research efforts and advances in complementary technologies will pave the way to new POC IVD assays in the coming months. However, the performance of IVD assays needs to be critically evaluated before they are employed for the clinical diagnosis of COVID-19.

negative: Status of Cellular Rather Than Humoral Immunity is Correlated with Clinical Outcome of Enterovirus 71 We valuated specific cellular and humoral immune response of cases of enterovirus 71 (EV71) infection and correlated immune response with clinical outcome. After obtaining informed consent, we enrolled 30 EV71 cases including 7 cases with brainstem encephalitis plus pulmonary edema, 12 cases of CNS (CNS) involvement and 11 uncomplicated cases. We measured antibodies specific to EV71, lymphocyte proliferation response and EV71-stimulated cellular response of Th1/Th2 cytokines and chemokines. The 7 EV71 cases involving brainstem encephalitis plus pulmonary edema had a significantly lower phytohemagglutinin stimulation index than other cases (p = 0.04). After EV71 stimulation of peripheral mononuclear cells, there was a significant increase in cellular Th1 cytokine (γ-interferon) and proinflammatroy cytokines. However, cases with pulmonary edema had significantly lower cellular γ-interferon (p = 0.04), lower cellular IL-1β (p = 0.04), lower cellular IL-6 (p = 0.04), lower cellular tumor necrosis factor-α response (p = 0.04), and lower cellular macrophage inflammatory protein-1α (p = 0.04) response compared with other cases. Their titers of EV71 neutralizing antibodies demonstrated no difference among cases. These results suggest lower EV71-specific cellular response may be associated with immunopathogenesis of EV71-related pulmonary edema.

negative: Overcoming Barriers: The Endothelium As a Linchpin of Coronavirus Disease 2019 Pathogenesis? OBJECTIVE Coronavirus disease 2019 (COVID-19) is a global pandemic involving >5 500 000 cases worldwide as of May 26, 2020. The culprit is the severe acute respiratory syndrome coronavirus-2, which invades cells by binding to angiotensin-converting enzyme 2. While the majority of patients mount an appropriate antiviral response and recover at home, others progress to respiratory distress requiring hospital admission for supplemental oxygen. In severe cases, deterioration to acute respiratory distress syndrome necessitating mechanical ventilation, development of severe thrombotic events, or cardiac injury and dysfunction occurs. In this review, we highlight what is known to date about coronavirus disease 2019 and cardiovascular risk, focusing in on the putative role of the endothelium in disease susceptibility and pathogenesis. Approach and Results: Cytokine-driven vascular leak in the lung alveolar-endothelial interface facilitates acute lung injury in the setting of viral infection. Given that the virus affects multiple organs, including the heart, it likely gains access into systemic circulation by infecting or passing from the respiratory epithelium to the endothelium for viral dissemination. Indeed, cardiovascular complications of coronavirus disease 2019 are highly prevalent and include acute cardiac injury, myocarditis, and a hypercoagulable state, all of which may be influenced by altered endothelial function. Notably, the disease course is worse in individuals with preexisting comorbidities that involve endothelial dysfunction and may be linked to elevated ACE2 (angiotensin-converting enzyme 2) expression, such as diabetes mellitus, hypertension, and cardiovascular disease. CONCLUSIONS Rapidly emerging data on coronavirus disease 2019, together with results from studies on severe acute respiratory syndrome coronavirus-1, are providing insight into how endothelial dysfunction may contribute to the pandemic that is paralyzing the globe. This may, in turn, inform the design of biomarkers predictive of disease course, as well as therapeutics targeting pathogenic endothelial responses.

negative: Improved Algorithmic Complexity for the 3SEQ Recombination Detection Algorithm Identifying recombinant sequences in an era of large genomic databases is challenging as it requires an efficient algorithm to identify candidate recombinants and parents, as well as appropriate statistical methods to correct for the large number of comparisons performed. In 2007, a computation was introduced for an exact nonparametric mosaicism statistic that gave high-precision P values for putative recombinants. This exact computation meant that multiple-comparisons corrected P values also had high precision, which is crucial when performing millions or billions of tests in large databases. Here, we introduce an improvement to the algorithmic complexity of this computation from O(mn(3)) to O(mn(2)), where m and n are the numbers of recombination-informative sites in the candidate recombinant. This new computation allows for recombination analysis to be performed in alignments with thousands of polymorphic sites. Benchmark runs are presented on viral genome sequence alignments, new features are introduced, and applications outside recombination analysis are discussed.

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: Public responses to the novel 2019 coronavirus (2019‐nCoV) in Japan: Mental health consequences and target populations

negative: Infección por coronavirus (COVID-19) en Anales de Pediatría

negative: Evolving status of the 2019 novel coronavirus infection: Proposal of conventional serologic assays for disease diagnosis and infection monitoring The novel coronavirus (nCoV-2019) outbreak in Wuhan, China has spread rapidly nationwide, with some cases occurring in other parts of the world. Although most patients present with mild febrile illness with patchy pulmonary inflammation, a significant portion develop severe acute respiratory distress syndrome (ARDS), with a current case fatality of 2.3-3%. Diagnosis is based on clinical history and laboratory and chest radiographic findings, but confirmation currently relies on nucleic acid-based assays. The latter are playing an important role in facilitating patient isolation, treatment and assessment of infectious activities. However, due to their limited capacity to handle an epidemic of the current scale and insufficient supply of assay kits, only a portion of suspected cases can be tested, leading to incompleteness and inaccuracy in updating new cases, as well as delayed diagnosis. Furthermore, there has not been enough time to assess specificity and sensitivity. Conventional serological assays, such as enzyme-linked immunoassay (ELISA) for specific IgM and IgG antibodies, should offer a high-throughput alternative, which allows for uniform tests for all suspected patients, and can facilitate more complete identification of infected cases and avoidance of unnecessary cross infection among unselected patients. This article is protected by copyright. All rights reserved.

negative: The role of procalcitonin as a guide for the diagnosis, prognosis, and decision of antibiotic therapy for lower respiratory tract infections Abstract Objectives To assess the value of PCT as a rapid and sensitive marker for diagnosis, prognosis, and therapy of lower respiratory tract bacterial infections necessitating antimicrobial treatment and comparing this marker with other markers of infections including C-reactive protein (CRP) and total white-blood cell counts (WBCs). Patients and methods Sixty Patients were enrolled in the study, they were subjected to complete history taking, physical examination, laboratory investigations including complete blood count, blood gases, blood chemistry, bacteriological culture for sputum and blood, serology for atypicals, and PCR for respiratory viruses, serum C-reactive protein (CRP) and PCT levels were measured. The patients were divided into two groups, group 1 included 26 patients who were culture negative for bacterial infection and group 2 included 34 patients who were culture positive. Group 2 patients were given antibiotic therapy according to the culture sensitivity. Result The results revealed that, there was no significant difference between group 1 and group 2 patients as regards age, sex, clinical manifestations, final diagnosis, white blood cell counts, blood gases, number of admitted patients, intensive care unit admission and length of hospital stay. A significant increase of PCT and CRP levels was detected in group 2 compared to group 1 at initial diagnosis. At cutoff value >0.5ng/ml, PCT gave a sensitivity of 94.1%, specificity of 88.4%, positive predictive value (PPV) of 91.4%, negative predictive value (NPV) of 92% and diagnostic efficiency of 91.6% for diagnosis of respiratory tract bacterial infections. However, at a cutoff value >8mg/L, CRP gave a sensitivity of 85.2%, specificity of 76.9%, PPV of 82.8%, NPV of 80% and diagnostic efficiency of 81.7%. After antibiotic therapy PCT and CRP levels dropped in group 2 patients as compared to their pre-treatment levels. Conclusion Serum PCT level could be used as a novel marker of lower respiratory tract bacterial infections for diagnosis, prognosis and follow up of therapy. This reduces side-effects of an unnecessary antibiotic use, lowers costs, and in the long-term, leads to diminishing drug resistance.

negative: 15 What factors predispose patients to acute respiratory distress syndrome? Abstract: Sepsis, pneumonia, and shock are the most common conditions predisposing to acute respiratory distress syndrome (ARDS) and certain host genetic variants have been associated with the development of ARDS. Risk modifiers include abuse of alcohol and tobacco, malnutrition, and obesity. The Lung Injury Prediction Score (LIPS) and the simplified Early Acute Lung Injury Score predict ARDS based on clinical and investigational criteria. Hospital-acquired ARDS may result from a medley factors of which high tidal volume ventilation, high oxygen concentration, and plasma transfusion are most commonly implicated. The Checklist for Lung Injury Prevention (CLIP) has been developed to ensure compliance with evidence-based practice that may affect ARDS occurrence. To date, no pharmacologic intervention has been shown to prevent ARDS

negative: Unraveling virus relationships by structure-based phylogenetic classification Delineation of the intricacies of protein function from macromolecular structure constitutes a continual obstacle in the study of cell and pathogen biology. Structure-based phylogenetic analysis has emerged as a powerful tool for addressing this challenge, allowing the detection and quantification of conserved architectural properties between proteins, including those with low or no detectable sequence homology. With a focus on viral protein structure, we highlight how a number of investigations have utilized this powerful method to infer common functionality and ancestry.

negative: Discovery of pharmaceutically-targetable pathways and prediction of survivorship for pneumonia and sepsis patients from the view point of ensemble gene noise Finding novel biomarkers for human pathologies and predicting clinical outcomes for patients is rather challenging. This stems from the heterogenous response of individuals to disease which is also reflected in the inter-individual variability of gene expression responses. This in turn obscures differential gene expression analysis (DGE). In the midst of the COVID-19 pandemic, we wondered whether an alternative to DGE approaches could be applied to dissect the molecular nature of a host-response to infection exemplified here by an analysis of H1N1 influenza, community/hospital acquired pneumonia (CAP) and sepsis. To this end, we turned to the analysis of ensemble gene noise. Ensemble gene noise, as we defined it here, represents a variance within an individual for a collection of genes encoding for either members of known biological pathways or subunits of annotated protein complexes. From the law of total variance, ensemble gene noise depends on the stoichiometry of the ensemble genes’ expression and on their average noise (variance). Thus, rather than focusing on specific genes, ensemble gene noise allows for the holistic identification and interpretation of gene expression disbalance on the level of gene networks and systems. Comparing H1N1, CAP and sepsis patients we spotted common disturbances in a number of pathways/protein complexes relevant to the sepsis pathology which lead to an increase in the ensemble gene noise. Among others, these include mitochondrial respiratory chain complex I and peroxisomes which could be readily targeted for adjuvant treatment by methylene blue and 4-phenylbutyrate respectively. Finally, we showed that ensemble gene noise could be successfully applied for the prediction of clinical outcome, namely mortality, of CAP and sepsis patients. Thus, we conclude that ensemble gene noise represents a promising approach for the investigation of molecular mechanisms of a pathology through a prism of alterations in coherent expression of gene circuits.

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: Comment on “Should COVID-19 Concern Nephrologists? Why and to What Extent? The Emerging Impasse of Angiotensin Blockade”

negative: Retrospective Analysis of 2019-nCov-Infected Cases in Dongyang, Southeastern China The 2019 novel coronavirus (2019-nCov) has caused increasing number of infected cases globally. This study was performed to analyze information regarding the transmission route and presence of viral nucleic acids on several clinical samples. Confirmed 2019-nCov-infected cases were identified in Dongyang and were treated according to guidelines for the diagnosis of 2019-nCov infection released by the National Health Commission. Information regarding the contacts that the infected people had was collected to determine whether it caused clustered cases. A series of successive nucleic acid examination of feces, oropharyngeal swabs, and sputum was also performed, and the results were analyzed. A total of 19 confirmed cases of 2019-nCov infection were identified in Dongyang, Zhejiang Province, China. Five cases showed severe symptoms, and the remaining ones showed mild manifestations. Ten cases infected from two asymptomatic individuals were clustered into two groups. Among 14 cases with consecutive nucleic acid test results, four patients showed positive results in feces after their negative conversion in oropharyngeal swabs. Asymptomatic individuals with the virus could cause 2019-nCov clustered cases, and the clustered cases may differ from sporadic cases on age and length of hospitalization. In addition, nucleic acids in feces last longer than those in oropharyngeal swabs.

negative: Serum cytokines and clinical features in patients with fever and thrombocytopenia syndrome Abstract Purpose To explore the clinical, microbiological and immunological features of patients with fever and thrombocytopenia. Methods Patients with unexplained fever and thrombocytopenia were enrolled. Viruses were detected using real-time PCR, and bacteria were measured by culturing methods. Serum cytokines, platelet antibody IgG (PA-IgG) and Helicobacter pylori (HP) were detected using ELISA. Results Pathogens were detected in 74.68% of patients, which included single fungal/viral/bacterial infection and multiple infection. The pathogens could not be unidentified in 25.32% of cases. Cytokines including Interleukin (IL)-6, IL-10, interferon-γ(IFN-γ), platelet activating factor (PAF) and PA-IgG were significantly higher in patients as compared to healthy controls (P < .01 or P < .05). Principal component analyses extracted four groups of parameters that have a strong positive predicting value, revealing that disease status evaluation would be more accurate if we combined the platelet parameters and inflammatory biomarkers. While event-free survival (EFS) that indicates the time of platelet elevated after therapy was the highest in patients with single bacterial or fungal infection, EFS was affected by the levels of cytokines and PA-IgG. Conclusions Differences in immune function may be the main factors affecting the prognosis of patients with fever and thrombocytopenia, while treatment based on precise etiological diagnosis is important for therapeutic efficacy.

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: 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.

negative: Treatment to prevent the development of severe COVID-19 The respiratory virus infection COVID-19 caused by the new coronavirus SARS-CoV2 has been reported in China since December 2019 It has been reported that COVID-19 tends to be more severe in the elderly and in patients with underlying diseases including diabetes, heart disease, and chronic lung disease In severe cases, patients require intensive cares including mechanical ventilation in the ICUs So far, no biomarker that predicts the severity, or no therapeutic strategies to prevent the development of severe diseases has been established Pathology of severe COVID-19 has two aspects: viral overgrowth and excess pulmonary inflammation For the former, clinical trials using existing drugs such as remdesivir (nucleic acid drug), lopinavir/ritonavir combination drug (protease inhibitor), favipravir (polymerase inhibitor), and interferon (antiviral drugs) are being conducted in patients with severe COVID-19 in China Furthermore the interest has been focused on immune globulin preparations enriched with pathogen-specific antibodies collected from the plasma of recovered patients For the latter, clinical studies using tocilizumab (IL-6 receptor antibody) and ACE2 protein have been conducted with the purpose of reducing excessive inflammation of the lung In addition, single cell analysis of immune cells and comprehensive repertoire analysis of TCR/BCR using patient blood are in progress overseas, which are useful to elucidate the mechanism of the severe disease progression and identify the useful biomarkers for it

negative: Hospitalization and Mortality among Black Patients and White Patients with Covid-19 BACKGROUND: Many reports on coronavirus disease 2019 (Covid-19) have highlighted age- and sex-related differences in health outcomes. More information is needed about racial and ethnic differences in outcomes from Covid-19. METHODS: In this retrospective cohort study, we analyzed data from patients seen within an integrated-delivery health system (Ochsner Health) in Louisiana between March 1 and April 11, 2020, who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the virus that causes Covid-19) on qualitative polymerase-chain-reaction assay. The Ochsner Health population is 31% black non-Hispanic and 65% white non-Hispanic. The primary outcomes were hospitalization and in-hospital death. RESULTS: A total of 3626 patients tested positive, of whom 145 were excluded (84 had missing data on race or ethnic group, 9 were Hispanic, and 52 were Asian or of another race or ethnic group). Of the 3481 Covid-19–positive patients included in our analyses, 60.0% were female, 70.4% were black non-Hispanic, and 29.6% were white non-Hispanic. Black patients had higher prevalences of obesity, diabetes, hypertension, and chronic kidney disease than white patients. A total of 39.7% of Covid-19–positive patients (1382 patients) were hospitalized, 76.9% of whom were black. In multivariable analyses, black race, increasing age, a higher score on the Charlson Comorbidity Index (indicating a greater burden of illness), public insurance (Medicare or Medicaid), residence in a low-income area, and obesity were associated with increased odds of hospital admission. Among the 326 patients who died from Covid-19, 70.6% were black. In adjusted time-to-event analyses, variables that were associated with higher in-hospital mortality were increasing age and presentation with an elevated respiratory rate; elevated levels of venous lactate, creatinine, or procalcitonin; or low platelet or lymphocyte counts. However, black race was not independently associated with higher mortality (hazard ratio for death vs. white race, 0.89; 95% confidence interval, 0.68 to 1.17). CONCLUSIONS: In a large cohort in Louisiana, 76.9% of the patients who were hospitalized with Covid-19 and 70.6% of those who died were black, whereas blacks comprise only 31% of the Ochsner Health population. Black race was not associated with higher in-hospital mortality than white race, after adjustment for differences in sociodemographic and clinical characteristics on admission.

negative: IFN-γ–induced protein 10 is a novel biomarker of rhinovirus-induced asthma exacerbations Background Rhinovirus-induced acute asthma is the most frequent trigger for asthma exacerbations. Objective We assessed which inflammatory mediators were released from bronchial epithelial cells (BECs) after infection with rhinovirus and then determined whether they were also present in subjects with acute virus-induced asthma, with the aim to identify a biomarker or biomarkers for acute virus-induced asthma. Methods BECs were obtained from bronchial brushings of steroid-naive asthmatic subjects and healthy nonatopic control subjects. Cells were infected with rhinovirus 16. Inflammatory mediators were measured by means of flow cytometry with a cytometric bead array. Subjects with acute asthma and virus infection were recruited; they were characterized clinically by using lung function tests and had blood taken to measure the inflammatory mediators identified as important by the BEC experiments. Results IFN-γ–induced protein 10 (IP-10) and RANTES were released in the greatest quantities, followed by IL-6, IL-8, and TNF-α. Dexamethasone treatment of BECs only partially suppressed IP-10 and TNF-α but was more effective at suppressing RANTES, IL-6, and IL-8. In acute clinical asthma serum IP-10 levels were increased to a greater extent in those with acute virus-induced asthma (median of 604 pg/mL compared with 167 pg/mL in those with non–virus-induced acute asthma, P < .01). Increased serum IP-10 levels were predictive of virus-induced asthma (odds ratio, 44.3 [95% CI, 3.9-100.3]). Increased serum IP-10 levels were strongly associated with more severe airflow obstruction (r = −0.8; P < .01). Conclusions IP-10 release is specific to acute virus-induced asthma. Clinical implications Measurement of serum IP-10 could be used to predict a viral trigger to acute asthma.

negative: 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

negative: Markers and Biomarkers of Endothelium: When Something Is Rotten in the State Endothelium is a community of endothelial cells (ECs), which line the blood and lymphatic vessels, thus forming an interface between the tissues and the blood or lympha. This strategic position of endothelium infers its indispensable functional role in controlling vasoregulation, haemostasis, and inflammation. The state of endothelium is simultaneously the cause and effect of many diseases, and this is coupled with modifications of endothelial phenotype represented by markers and with biochemical profile of blood represented by biomarkers. In this paper, we briefly review data on the functional role of endothelium, give definitions of endothelial markers and biomarkers, touch on the methodological approaches for revealing biomarkers, present an implicit role of endothelium in some toxicological mechanistic studies, and survey the role of reactive oxygen species (ROS) in modulation of endothelial status.

negative: Biomarkers for Acute Respiratory Distress syndrome and prospects for personalised medicine Acute lung injury (ALI) affects over 10% of patients hospitalised in critical care, with acute respiratory distress syndrome (ARDS) being the most severe form of ALI and having a mortality rate in the region of 40%. There has been slow but incremental progress in identification of biomarkers that contribute to the pathophysiology of ARDS, have utility in diagnosis and monitoring, and that are potential therapeutic targets (Calfee CS, Delucchi K, Parsons PE, Thompson BT, Ware LB, Matthay MA, Thompson T, Ware LB, Matthay MA, Lancet Respir Med 2014, 2:611–-620). However, a major issue is that ARDS is such a heterogeneous, multi-factorial, end-stage condition that the strategies for “lumping and splitting” are critical (Prescott HC, Calfee CS, Thompson BT, Angus DC, Liu VX, Am J Respir Crit Care Med 2016, 194:147–-155). Nevertheless, sequencing of the human genome, the availability of improved methods for analysis of transcription to mRNA (gene expression), and development of sensitive immunoassays has allowed the application of network biology to ARDS, with these biomarkers offering potential for personalised or precision medicine (Sweeney TE, Khatri P, Toward precision medicine Crit Care Med; 2017 45:934-939). Biomarker panels have potential applications in molecular phenotyping for identifying patients at risk of developing ARDS, diagnosis of ARDS, risk stratification and monitoring. Two subphenotypes of ARDS have been identified on the basis of blood biomarkers: hypo-inflammatory and hyper-inflammatory. The hyper-inflammatory subphenotype is associated with shock, metabolic acidosis and worst clinical outcomes. Biomarkers of particular interest have included interleukins (IL-6 and IL-8), interferon gamma (IFN-γ), surfactant proteins (SPD and SPB), von Willebrand factor antigen, angiopoietin 1/2 and plasminogen activator inhibitor-1 (PAI-1). In terms of gene expression (mRNA) in blood there have been found to be increases in neutrophil-related genes in sepsis-induced and influenza-induced ARDS, but whole blood expression does not give a robust diagnostic test for ARDS. Despite improvements in management of ARDS on the critical care unit, this complex disease continues to be a major life-threatening event. Clinical trials of β(2)-agonists, statins, surfactants and keratinocyte growth factor (KGF) have been disappointing. In addition, monoclonal antibodies (anti-TNF) and TNFR fusion protein have also been unconvincing. However, there have been major advances in methods of mechanical ventilation, a neuromuscular blocker (cisatracurium besilate) has shown some benefit, and stem cell therapy is being developed. In the future, by understanding the role of biomarkers in the pathophysiology of ARDS and lung injury, it is hoped that this will provide rational therapeutic targets and ultimately improve clinical care (Seymour CW, Gomez H, Chang CH, Clermont G, Kellum JA, Kennedy J, Yende S, Angus DC, Crit Care 2017, 21:257).

negative: Do chronic respiratory diseases or their treatment affect the risk of SARS-CoV-2 infection?

negative: [Potential antiviral therapeutics for 2019 Novel Coronavirus]. The recent outbreak of respiratory illness in Wuhan, China is caused by a novel coronavirus, named 2019-nCoV, which is genetically close to a bat-derived coronavirus. 2019-nCoV is categorized as beta genus coronavirus, same as the two other strains - severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Antiviral drugs commonly used in clinical practice, including neuraminidase inhibitors (oseltamivir, paramivir, zanamivir, etc.), ganciclovir, acyclovir and ribavirin, are invalid for 2019-nCoV and not recommended. Drugs are possibly effective for 2019-nCoV include: remdesivir, lopinavir / ritonavir, lopinavir / ritonavir combined with interferon-β, convalescent plasma, and monoclonal antibodies. But the efficacy and safety of these drugs for 2019-nCoV pneumonia patients need to be assessed by further clinical trials.

negative: The Risk of Diabetes on Clinical Outcomes in Patients with Coronavirus Disease 2019: A Retrospective Cohort Study BACKGROUND: To determine the role of diabetes mellitus (DM) in the coronavirus disease 2019 (COVID-19), we explored the clinical characteristics of patients with DM and compared risk factors such as age, glycemic control, and medications to those without DM. METHODS: This was a retrospective cohort study of 117 confirmed patients with COVID-19 which conducted at a tertiary hospital in Daegu, South Korea. The primary outcome was defined as the severe and critical outcome (SCO), of which the composite outcomes of acute respiratory distress syndrome, septic shock, intensive care unit care, and 28-day mortality. We analyzed what clinical features and glycemic control-related factors affect the prognosis of COVID-19 in the DM group. RESULTS: After exclusion, 110 participants were finally included. DM patients (n=29) was older, and showed higher blood pressure compared to non-DM patients. DM group showed higher levels of inflammation-related biomarkers and severity score, and highly progressed to SCO. After adjustment with other risk factors, DM increased the risk of SCO (odds ratio [OR], 10.771; P<0.001). Among the DM patients, SCO was more prevalent in elderly patients of ≥70 years old and age was an independent risk factor for SCO in patients with DM (OR, 1.175; P=0.014), while glycemic control was not. The use of medication did not affect the SCO, but the renin-angiotensin system inhibitors showed protective effects against acute cardiac injury (OR, 0.048; P=0.045). CONCLUSION: The COVID-19 patients with DM had higher severity and resulted in SCO. Intensive and aggressive monitoring of COVID-19 clinical outcomes in DM group, especially in elderly patients is warranted.

negative: Predictions for the binding domain and potential new drug targets of 2019-nCoV An outbreak of new SARS-like viral in Wuhan, China has been named 2019-nCoV. The current state of the epidemic is increasingly serious, and there has been the urgent necessity to develop an effective new drug. In previous studies, it was found that the conformation change in CTD1 was the region where SARS-CoV bound to human ACE2. Although there are mutations of the 2019-nCoV, the binding energy of ACE2 remains high. The surface glycoprotein of 2019-nCoV was coincident with the CTD1 region of the S-protein by comparing the I-TASSER prediction model with the actual SARS model, which suggests that 2019-nCoV may bind to the ACE2 receptor through conformational changes. Furthermore, site prediction on the surface glycoprotein of 2019-nCoV suggests some core amino acid area may be a novel drug target against 2019-nCoV.

negative: Viral pneumonia Summary About 200 million cases of viral community-acquired pneumonia occur every year—100 million in children and 100 million in adults. Molecular diagnostic tests have greatly increased our understanding of the role of viruses in pneumonia, and findings indicate that the incidence of viral pneumonia has been underestimated. In children, respiratory syncytial virus, rhinovirus, human metapneumovirus, human bocavirus, and parainfluenza viruses are the agents identified most frequently in both developed and developing countries. Dual viral infections are common, and a third of children have evidence of viral-bacterial co-infection. In adults, viruses are the putative causative agents in a third of cases of community-acquired pneumonia, in particular influenza viruses, rhinoviruses, and coronaviruses. Bacteria continue to have a predominant role in adults with pneumonia. Presence of viral epidemics in the community, patient's age, speed of onset of illness, symptoms, biomarkers, radiographic changes, and response to treatment can help differentiate viral from bacterial pneumonia. However, no clinical algorithm exists that will distinguish clearly the cause of pneumonia. No clear consensus has been reached about whether patients with obvious viral community-acquired pneumonia need to be treated with antibiotics. Apart from neuraminidase inhibitors for pneumonia caused by influenza viruses, there is no clear role for use of specific antivirals to treat viral community-acquired pneumonia. Influenza vaccines are the only available specific preventive measures. Further studies are needed to better understand the cause and pathogenesis of community-acquired pneumonia. Furthermore, regional differences in cause of pneumonia should be investigated, in particular to obtain more data from developing countries.

negative: Analysis of clinical characteristics and laboratory findings of 95 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a retrospective analysis BACKGROUND: Since December 2019, 2019 novel coronavirus pneumonia emerged in Wuhan city and rapidly spread throughout China and even the world. We sought to analyse the clinical characteristics and laboratory findings of some cases with 2019 novel coronavirus pneumonia . METHODS: In this retrospective study, we extracted the data on 95 patients with laboratory-confirmed 2019 novel coronavirus pneumonia in Wuhan Xinzhou District People’s Hospital from January 16th to February 25th, 2020. Cases were confirmed by real-time RT-PCR and abnormal radiologic findings. Outcomes were followed up until March 2th, 2020. RESULTS: Higher temperature, blood leukocyte count, neutrophil count, neutrophil percentage, C-reactive protein level, D-dimer level, alanine aminotransferase activity, aspartate aminotransferase activity, α - hydroxybutyrate dehydrogenase activity, lactate dehydrogenase activity and creatine kinase activity were related to severe 2019 novel coronavirus pneumonia and composite endpoint, and so were lower lymphocyte count, lymphocyte percentage and total protein level. Age below 40 or above 60 years old, male, higher Creatinine level, and lower platelet count also seemed related to severe 2019 novel coronavirus pneumonia and composite endpoint, however the P values were greater than 0.05, which mean under the same condition studies of larger samples are needed in the future. CONCLUSION: Multiple factors were related to severe 2019 novel coronavirus pneumonia and composite endpoint, and more related studies are needed in the future.

negative: Interleukin-1 receptor antagonist anakinra in association with remdesivir in severe Coronavirus disease 2019: A case report Abstract We report the first successful treatment with the IL-1 receptor antagonist anakinra, in association with the most promising and available antiviral therapy, of a severe case of novel coronavirus disease 2019 (COVID-19). We describe the diagnosis, clinical course, and management of the case, including the respiratory failure at presentation, the progression to a scenario characterized by profound inflammatory dysregulation similar to that observed during macrophage activation syndrome, and the clinical improvement after treatment with the IL-1 receptor antagonist anakinra. This case highlights the high tolerability and the interesting immunomodulatory profile of the IL-1 receptor antagonist anakinra in the setting of severe COVID-19 associated with remdesivir therapy. Further studies are needed to confirm the safety and efficacy of this combination strategy in the treatment of this emerging infection.

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

negative: Inflammation and Inflammatory Diseases, Markers, and Mediators: Role of CRP in Some Inflammatory Diseases The knowledge of inflammation records dates back in first century AD. Initially discovered with features of rubor, tumor, calor, and dolor, scientific investigations have revealed chemical components, cells, and pathways involved in the process of inflammation. The body’s initial defense in response to infection, trauma, or inflammation is through the acute-phase response (APR). APR is a multifaceted set of systemic reactions seen shortly after the experience of a triggering event. One of the many aspects of an APR is the increased hepatic synthesis of positive acute-phase proteins (APPs) leading to increased serum concentration of these proteins. The serum level of these APPs returns to base concentration when the stimulating factor is not anymore present. Today a plethora of inflammatory diseases are causing concern to global health. All the key players and mediators of inflammation change its role with the change in setup of disease and patients. The biomarkers of inflammation and inflammatory mediators are also used as therapeutic targets in under-trial animal models. Even in clinical diagnosis of an inflammatory patient, some broad-spectrum markers were analyzed without individual dissection of each mediator or biomarker. This chapter also provides a review of the acute-phase protein C-reactive protein and its possible use as inflammatory biomarker in diseases. We have highlighted case studies of some patients from Kolkata, India, revealing inflammation from disease together with their clinical history. The question which we probe in here is that whether there is a correlation with the clinical history, C-reactive protein, and inflammation and whether CRP can act as a unique diagnostic and prognostic biomarker in some diseases. The future course of this chapter lies in identifying clinical markers for inflammation, the sequential flow of inflammatory responses for a wide spectrum of diseases and its diagnostic, and therapeutic application to screen out pro-inflammatory diseases vs. anti-inflammatory conditions.

negative: Potentially highly potent drugs for 2019-nCoV The World Health Organization (WHO) has declared the 2019 novel coronavirus (2019-nCoV) infection outbreak a global health emergency. Currently, there is no effective anti-2019-nCoV medication. The sequence identity of the 3CL proteases of 2019-nCoV and SARS is 96%, which provides a sound foundation for structural-based drug repositioning (SBDR). Based on a SARS 3CL protease X-ray crystal structure, we construct a 3D homology structure of 2019-nCoV 3CL protease. Based on this structure and existing experimental datasets for SARS 3CL protease inhibitors, we develop an SBDR model based on machine learning and mathematics to screen 1465 drugs in the DrugBank that have been approved by the U.S. Food and Drug Administration (FDA). We found that many FDA approved drugs are potentially highly potent to 2019-nCoV.

negative: Method of regulatory network that can explore protein regulations for disease classification Abstract Objective To develop regulatory network to explore and model the regulatory relationships of protein biomarkers and classify different disease groups. Methods Regulatory network is constructed to be a hopfield-like network with nodes representing biomarkers and directional connections to be regulations in between. The input to the network is the measured expression levels of biomarkers, and the output is the summation of regulatory strengths from other biomarkers. The network is optimized towards minimizing the energy function that is defined as the measure of the disagreement between the input and output of the network. To simulate more complicated regulations, a sigmoid kernel function is imposed on each node to construct a non-linear regulatory network. Results Two datasets have been used as test beds, one dataset includes patients of nasopharyngeal carcinoma with different responses to chemotherapy drug, and the other consists of patients of severe acute respiratory syndrome, influenza, and control normals. The regulatory networks among protein biomarkers were reconstructed for different disease conditions in each dataset. We demonstrated our methods have better classification capability when comparing with conventional methods including Fisher linear discriminant (FLD), K-nearest neighborhood (KNN), linear support vector machines (linSVM) and radial basis function based support vector machines (rbfSVM). Conclusion The derived networks can effectively capture the unique regulatory patterns of protein markers associated with different patient groups and hence can be used for disease classification. The discovered regulation relationships can potentially provide insights to revealing the molecular signaling pathways. In this paper, a novel technique of regulatory network is proposed on purpose of modeling biomarker regulations and classifying different disease groups. The network is composed of a certain number of nodes that are directionally connected in between in which nodes denote predictors and connections to be the regulation relationship. The network is optimized towards minimizing its energy function with biomarker expression data acquired from a specific patient group, thus the optimized network can model the regulatory relationship of biomarkers under the same circumstance. To simulate more complicated regulations, a sigmoid kernel function is imposed on each node to construct a non-linear regulatory network. The regulatory network can extract unique features of each disease condition, thus one immediate application of regulatory network is to classifying different diseases. We demonstrated that regulatory network is capable of performing disease classification through comparing with conventional methods including FLD, KNN, linSVM and rbfSVM on two protein datasets. We believe our method is promising in mining knowledge of protein regulations and be powerful for disease classification.

negative: Biomarkers for Late-Onset Neonatal Sepsis: Cytokines and Beyond Acute phase reactants, pro and antiinflammatory mediators including chemokines and cytokines, and cell-surface antigens are nonspecific biomarkers that have been extensively studied for the diagnosis and management of late-onset neonatal sepsis (LONS) and necrotizing enterocolitis. It is expected that the next generation of biomarkers and tests will be more specific, will pinpoint the precise disease entity, and will provide crucial information on the exact pathogen or category of microorganism and its antibiotic profile within hours of clinical presentation. Research on molecular pathogen detection and proteomic profiling has shown promising results. Academic-industry partnerships are vital for successful development of new diagnostic biomarkers for LONS, which are sensitive, inexpensive, fully automated, and easy to measure, allowing a quick turnaround time for clinical decision making.

negative: Voice from China: nomenclature of the novel coronavirus and related diseases

negative: Risk factors for adverse clinical outcomes in patients with COVID-19: A systematic review and meta-analysis Importance: COVID-19 is a clinically heterogeneous disease of varying severity and prognosis. Clinical characteristics that impact disease course could offer guidance for clinical decision making and future research endeavors and unveil disease pathways. Objective: To examine risk factors associated with adverse clinical outcomes in patients with COVID-19. Data sources: We performed a systematic review in PubMed from January 1 until April 19, 2020. Study selection: Observational studies that examined the association of any clinical characteristic with an adverse clinical outcome were considered eligible. We scrutinized studies for potential overlap. Data extraction and synthesis: Information on the effect of clinical factors on clinical endpoints of patients with COVID-19 was independently extracted by two researchers. When an effect size was not reported, crude odds ratios were calculated based on the available information from the eligible articles. Study-specific effect sizes from non-overlapping studies were synthesized applying the random-effects model. Main outcome and measure: The examined outcomes were severity and progression of disease, admission to ICU, need for mechanical ventilation, mortality, or a composite outcome. Results: We identified 88 eligible articles, and we performed a total of 256 meta-analyses on the association of 98 unique risk factors with five clinical outcomes. Seven meta-analyses presented the strongest epidemiological evidence in terms of statistical significance (P-value <0.005), between-study heterogeneity (I2 <50%), sample size (more than 1000 COVID-19 patients), 95% prediction interval excluded the null value, and absence of small-study effects. Elevated C-reactive protein (OR, 6.46; 95% CI, 4.85 - 8.60), decreased lymphocyte count (OR, 4.16; 95% CI, 3.17 - 5.45), cerebrovascular disease (OR, 2.84; 95% CI, 1.55 - 5.20), chronic obstructive pulmonary disease (OR, 4.44; 95% CI, 2.46 - 8.02), diabetes mellitus (OR, 2.04; 95% CI, 1.54 - 2.70), hemoptysis (OR, 7.03; 95% CI, 4.57 - 10.81), and male sex (OR, 1.51; 95% CI, 1.30 - 1.75) were associated with risk of severe COVID-19. Conclusions and relevance: Our results highlight factors that could be useful for prognostic model building, help guide patients' selection for randomized clinical trials, as well as provide alternative treatment targets by shedding light to disease pathophysiology.

negative: Identification and characterization of Coronaviridae genomes from Vietnamese bats and rats based on conserved protein domains The Coronaviridae family of viruses encompasses a group of pathogens with a zoonotic potential as observed from previous outbreaks of the severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus. Accordingly, it seems important to identify and document the coronaviruses in animal reservoirs, many of which are uncharacterized and potentially missed by more standard diagnostic assays. A combination of sensitive deep sequencing technology and computational algorithms is essential for virus surveillance, especially for characterizing novel- or distantly related virus strains. Here, we explore the use of profile Hidden Markov Model-defined Pfam protein domains (Pfam domains) encoded by new sequences as a Coronaviridae sequence classification tool. The encoded domains are used first in a triage to identify potential Coronaviridae sequences and then processed using a Random Forest method to classify the sequences to the Coronaviridae genus level. The application of this algorithm on Coronaviridae genomes assembled from agnostic deep sequencing data from surveillance of bats and rats in Dong Thap province (Vietnam) identified thirty-four Alphacoronavirus and eleven Betacoronavirus genomes. This collection of bat and rat coronaviruses genomes provided essential information on the local diversity of coronaviruses and substantially expanded the number of coronavirus full genomes available from bat and rats and may facilitate further molecular studies on this group of viruses.

negative: Risk perception and behavioral change during epidemics: Comparing models of individual and collective learning Modern societies are exposed to a myriad of risks ranging from disease to natural hazards and technological disruptions. Exploring how the awareness of risk spreads and how it triggers a diffusion of coping strategies is prominent in the research agenda of various domains. It requires a deep understanding of how individuals perceive risks and communicate about the effectiveness of protective measures, highlighting learning and social interaction as the core mechanisms driving such processes. Methodological approaches that range from purely physics-based diffusion models to data-driven environmental methods rely on agent-based modeling to accommodate context-dependent learning and social interactions in a diffusion process. Mixing agent-based modeling with data-driven machine learning has become popularity. However, little attention has been paid to the role of intelligent learning in risk appraisal and protective decisions, whether used in an individual or a collective process. The differences between collective learning and individual learning have not been sufficiently explored in diffusion modeling in general and in agent-based models of socio-environmental systems in particular. To address this research gap, we explored the implications of intelligent learning on the gradient from individual to collective learning, using an agent-based model enhanced by machine learning. Our simulation experiments showed that individual intelligent judgement about risks and the selection of coping strategies by groups with majority votes were outperformed by leader-based groups and even individuals deciding alone. Social interactions appeared essential for both individual learning and group learning. The choice of how to represent social learning in an agent-based model could be driven by existing cultural and social norms prevalent in a modeled society.

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

negative: Transplantation of ACE2(-) Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia A coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak in Wuhan, China. Preventing and reversing the cytokine storm may be the key to save the patients with severe COVID-19 pneumonia. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate whether MSC transplantation improves the outcome of 7 enrolled patients with COVID-19 pneumonia in Beijing YouAn Hospital, China, from Jan 23, 2020 to Feb 16, 2020. The clinical outcomes, as well as changes of inflammatory and immune function levels and adverse effects of 7 enrolled patients were assessed for 14 days after MSC injection. MSCs could cure or significantly improve the functional outcomes of seven patients without observed adverse effects. The pulmonary function and symptoms of these seven patients were significantly improved in 2 days after MSC transplantation. Among them, two common and one severe patient were recovered and discharged in 10 days after treatment. After treatment, the peripheral lymphocytes were increased, the C-reactive protein decreased, and the overactivated cytokine-secreting immune cells CXCR3+CD4+ T cells, CXCR3+CD8+ T cells, and CXCR3+ NK cells disappeared in 3-6 days. In addition, a group of CD14+CD11c+CD11b(mid) regulatory DC cell population dramatically increased. Meanwhile, the level of TNF-α was significantly decreased, while IL-10 increased in MSC treatment group compared to the placebo control group. Furthermore, the gene expression profile showed MSCs were ACE2(-) and TMPRSS2(-) which indicated MSCs are free from COVID-19 infection. Thus, the intravenous transplantation of MSCs was safe and effective for treatment in patients with COVID-19 pneumonia, especially for the patients in critically severe condition.

negative: ESICM LIVES 2016: part one: Milan, Italy. 1-5 October 2016

negative: Diagnosis of Parasitic Diseases: Old and New Approaches Methods for the diagnosis of infectious diseases have stagnated in the last 20–30 years. Few major advances in clinical diagnostic testing have been made since the introduction of PCR, although new technologies are being investigated. Many tests that form the backbone of the “modern” microbiology laboratory are based on very old and labour-intensive technologies such as microscopy for malaria. Pressing needs include more rapid tests without sacrificing sensitivity, value-added tests, and point-of-care tests for both high- and low-resource settings. In recent years, research has been focused on alternative methods to improve the diagnosis of parasitic diseases. These include immunoassays, molecular-based approaches, and proteomics using mass spectrometry platforms technology. This review summarizes the progress in new approaches in parasite diagnosis and discusses some of the merits and disadvantages of these tests.

negative: Immunoglobulins in the treatment of COVID-19 infection: Proceed with caution!() The COVID-19 pandemic is one of the greatest infectious challenges in recent history. Presently, few treatment options exist and the availability of effective vaccines is at least one year away. There is an urgent need to find currently available, effective therapies in the treatment of patients with COVID-19 infection. In this review, we compare and contrast the use of intravenous immunoglobulin and hyperimmune globulin in the treatment of COVID-19 infection.

negative: A Note on COVID-19 Diagnosis Number Prediction Model in China Importance: To predict the diagnosed COVID-19 patients and the trend of the epidemic in China. It may give the public some scientific information to ease the fear of the epidemic. Objective: In December 2019, pneumonia infected with the novel coronavirus burst in Wuhan, China. We aimed to use a mathematical model to predict number of diagnosed patients in future to ease anxiety on the emergent situation. Design: According to all diagnosis number from WHO website and combining with the transmission mode of infectious diseases, the mathematical model was fitted to predict future trend of outbreak. Setting: Our model was based on the epidemic situation in China, which could provide referential significance for disease prediction in other countries, and provide clues for prevention and intervention of relevant health authorities. Participants: In this retrospective, all diagnosis number from Jan 21 to Feb 10, 2020 reported from China was included and downloaded from WHO website. Main Outcome(s) and Measure(s): We develop a simple but accurate formula to predict the next day diagnosis number:N_i/N_(i-1) =[(N_(i-1)/N_(i-2) )]^α，where Ni is the total diagnosed patient till the ith day, and α was estimated as 0.904 at Feb 10. Results: Based on this model, it is predicted that the rate of disease infection will decrease exponentially. The total number of infected people is limited; thus, the disease will have limited impact. However, new diagnosis will last to March. Conclusions and Relevance: Through the establishment of our model, we can better predict the trend of the epidemic in China.

negative: Optimize Clinical Laboratory Diagnosis of COVID-19 from Suspect Cases by Likelihood Ratio of SARS-CoV-2 IgM and IgG antibody Objective: To optimize clinical laboratory diagnosis of COVID-19 from suspect cases by Likelihood Ratio of SARS-CoV-2 IgM and IgG antibody. Methods: By reinterpreting the data in the article "Diagnostic Value of Combined Detection of Serum 2019 novel coronavirus IgM and IgG Antibodies in novel coronavirusin Infection", the positive likelihood ratio of IgM and IgG antibody in diagnosis of COVID-19 (nucleic acid positive patients) was calculated, and the posterior probability of IgM and IgG antibodies and their tandem detection to diagnose was finally calculated. Results: The positive likelihood ratios of single IgM and IgG antibody were 18.50 and 12.65 respectively, and the posterior probabilities were 90.18% and 86.26% respectively. However, the posterior probability of the two antibodies tandem detection is 99.15%, which can give clinicians quantitative confidence in the diagnosis of COVID-19 from suspected cases. According to the results of this study, combining the advantages and disadvantages of nucleic acid detection and antibody detection, the clinical pathway for clinicians to diagnose COVID-19 is found. Conclusion: For suspected cases, IgM and IgG antibody tests should be firstly done at the same time. If the antibody tests are all positive, COVID-19 can be confirmed. If not, nucleic acid detection (one or more times) is performed, and in extreme cases, high-throughput viral genome sequencing is performed.

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

negative: [Pregnant women with new coronavirus infection: a clinical characteristics and placental pathological analysis of three cases]. Objective: To investigate the clinical characteristics and placental pathology of 2019-nCoV infection in pregnancy, and to evaluate intrauterine vertical transmission potential of 2019-nCoV infection. Methods: The placentas delivered from pregnant women with confirmed 2019-nCoV infection which were received in the Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology collected by February 4th, 2020 and retrospectively studied. Their clinical material including placental tissue and lung CT, and laboratory results were collected, meanwhile, nucleic acid detection of 2019-nCoV of the placentas were performed by RT-PCR. Results: Three placentas delivered from pregnant women with confirmed 2019-nCoV infection, who were all in their third trimester with emergency caesarean section. All of the three patients presented with fever (one before caesarean and two in postpartum), and had no significant leukopenia and lymphopenia. Neonatal throat swabs from three newborns were tested for 2019-nCoV, and all samples were negative for the nucleic acid of 2019-nCoV. One premature infant was transferred to Department of Neonatology due to low birth weight. By the end of February 25, 2020, none of the three patients developed severe 2019-nCoV pneumonia or died(two patients had been cured and discharged, while another one had been transferred to a square cabin hospital for isolation treatment). There were various degrees of fibrin deposition inside and around the villi with local syncytial nodule increases in all three placentas. One case of placenta showed the concomitant morphology of chorionic hemangioma and another one with massive placental infarction. No pathological change of villitis and chorioamnionitis was observed in our observation of three cases. All samples from three placentas were negative for the nucleic acid of 2019-nCoV. Conclusions: The clinical characteristics of pregnant women with 2019-nCoV infection in late pregnancy are similar to those of non-pregnant patients, and no severe adverse pregnancy outcome is found in the 3 cases of our observation. Pathological study suggests that there are no morphological changes related to infection in the three placentas. Currently no evidence for intrauterine vertical transmission of 2019-nCoV is found in the three women infected by 2019-nCoV in their late pregnancy.

negative: Circulating microRNAs in malaria infection: bench to bedside Severe malaria has a poor prognosis with a morbidity rate of 80% in tropical areas. The early parasite detection is one of the effective means to prevent severe malaria of which specific treatment strategies are limited. Many clinical characteristics and laboratory testings have been used for the early diagnosis and prediction of severe disease. However, a few of these factors could be applied to clinical practice. MicroRNAs (miRNAs) were demonstrated as useful biomarkers in many diseases such as malignant diseases and cardiovascular diseases. Recently it was found that plasma miR-451 and miR-16 were downregulated in malaria infection at parasitic stages or with multi-organ failure involvement. MiR-125b, -27a, -23a, -150, 17–92 and -24 are deregulated in malaria patients with multiple organ failures. Here, the current findings of miRNAs were reviewed in relation to clinical severity of malaria infection and emphasized that miRNAs are potential biomarkers for severe malaria infection.

negative: Community-acquired Pseudomonas aeruginosa-pneumonia in a previously healthy man occupationally exposed to metalworking fluids Although the Pseudomonas aeruginosa infection is well known and frequently found in hospitals and nursing care facilities, many cases are also reported outside these boundaries. In general, this pathogen infects debilitated patients either by comorbidities or by any form of immunodeficiency. In cases of respiratory infection, tobacco abuse seems to play an important role as a risk factor. In previously healthy patients, community-acquired pneumonia (CAP) with P. aeruginosa as the etiological agent is extremely rare, and unlike the cases involving immunocompromised or hospitalized patients, the outcome is severe, and is fatal in up to 61.1% of cases. Aerosolized contaminated water or solutions are closely linked to the development of respiratory tract infection. In this setting, metalworking fluids used in factories may be implicated in CAP involving previously healthy people. The authors report the case of a middle-aged man who worked in a metalworking factory and presented a right upper lobar pneumonia with a rapid fatal outcome. P. aeruginosa was cultured from blood and tracheal aspirates. The autopsy findings confirmed a hemorrhagic necrotizing pneumonia with bacteria-invading vasculitis and thrombosis. A culture of the metalworking fluid of the factory was also positive for P. aeruginosa. The pulsed-field gel electrophoresis showed that both strains (blood culture and metalworking fluid) were genetically indistinguishable. The authors highlight the occupational risk for the development of this P. aeruginosa-infection in healthy people.

negative: Driving forces for COVID-19 clinical trials using chloroquine: the need to choose the right research questions and outcomes

negative: Emergence of Novel Coronavirus 2019-nCoV: Need for Rapid Vaccine and Biologics Development Novel Coronavirus (2019-nCoV) is an emerging pathogen that was first identified in Wuhan, China in late December 2019. This virus is responsible for the ongoing outbreak that causes severe respiratory illness and pneumonia-like infection in humans. Due to the increasing number of cases in China and outside China, the WHO declared coronavirus as a global health emergency. Nearly 35,000 cases were reported and at least 24 other countries or territories have reported coronavirus cases as early on as February. Inter-human transmission was reported in a few countries, including the United States. Neither an effective anti-viral nor a vaccine is currently available to treat this infection. As the virus is a newly emerging pathogen, many questions remain unanswered regarding the virus’s reservoirs, pathogenesis, transmissibility, and much more is unknown. The collaborative efforts of researchers are needed to fill the knowledge gaps about this new virus, to develop the proper diagnostic tools, and effective treatment to combat this infection. Recent advancements in plant biotechnology proved that plants have the ability to produce vaccines or biopharmaceuticals rapidly in a short time. In this review, the outbreak of 2019-nCoV in China, the need for rapid vaccine development, and the potential of a plant system for biopharmaceutical development are discussed.

negative: Clinical presentation and virological assessment of hospitalized cases of coronavirus disease 2019 in a travel-associated transmission cluster Background: In coronavirus disease 2019 (COVID-19), current case definitions presume mainly lower respiratory tract infection. However, cases seen outside the epicenter of the epidemic may differ in their overall clinical appearance due to more sensitive case finding. Methods: We studied viral load courses by RT-PCR in oro- and nasopharyngeal swabs, sputum, stool, blood, and urine in nine hospitalized cases. Infectious virus was detected by cell culture. Active replication was demonstrated by analysis of viral subgenomic replicative intermediates. Serology including neutralization testing was done to characterize immune response. Results: Seven cases had upper respiratory tract disease. Lower respiratory tract symptoms seen in two cases were limited. Clinical sensitivity of RT-PCR on swabs taken on days 1-5 of symptoms was 100%, with no differences comparing swab and sputum samples taken simultaneously. Average viral load was 6.76x10E5 copies per swab during the first 5 days. Live virus isolates were obtained from swabs during the first week of illness. Proof of active viral replication in upper respiratory tract tissues was obtained by detection of subgenomic viral RNA. Shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after about one week. Conclusions: The present study shows that COVID-19 can often present as a common cold-like illness. SARS-CoV-2 can actively replicate in the upper respiratory tract, and is shed for a prolonged time after symptoms end, including in stool. These findings suggest adjustments of current case definitions and re-evaluation of the prospects of outbreak containment.

negative: New approach to identifying proper thresholds for a heat warning system using health risk increments Abstract Background A critical adaptation strategy for reducing heat-related health risk under climate change is to establish a heat warning system with a proper threshold that requires evaluation of heat-health relationships using empirical data. Objectives This work presents a new approach to selecting proper health-based thresholds for a heat warning system which are different from thresholds of heat-health relationship. Methods The proposed approach examined heat-health relationships through analyzing 15 years of health records with a modified generalized additive model (GAM), compared risk ratio increments (RRIs) of threshold candidates against a reference, assessed frequency of days above these candidates, and presented results graphically for easy communication. The candidate with the maximum RRI and proper occurring frequency is potentially the best threshold. Three heat indicators, including wet-bulb globe temperature (WBGT), temperature (T), and apparent temperature (AT), as well as three health outcomes, including all-cause mortality, heat-related hospital admissions, and heat-related emergency visits were evaluated. Results Risk ratios for all three health outcomes showed a consistent rising trend with increasing threshold candidates for all three heat indicators among different age and gender groups. WBGT had the most obvious increasing trend of RRIs with the three health outcomes. The maximum RRI was observed in heat-related emergency visits (242%), followed by heat-related hospital admissions (73%), and all-cause mortality (9%). The RRIs assessed for the three health outcomes pointed to the same thresholds, 33.0 °C, 34.0 °C, and 37.5 °C for WBGT, T, and AT, respectively. The number of days above these thresholds and for warning to be issued ranged between 0 and 7 days during 2000–2014. Discussion This study demonstrated a new approach to determining heat-warning thresholds with different heat indicators and health outcomes. The proposed approach provides a straightforward, feasible, and flexible scientific tool that assists the authorities around the world in selecting a proper threshold for a heat warning system.

negative: Point-of-Care Microdevices for Blood Plasma Analysis in Viral Infectious Diseases Each year, outbreaks of viral infections cause illness, disability, death, and economic loss. As learned from past incidents, the detrimental impact grows exponentially without effective quarantine. Therefore, rapid on-site detection and analysis are highly desired. In addition, for high-risk areas of viral contamination, close monitoring should be provided during the potential disease incubation period. As the epidemic progresses, a response protocol needs tobe rapidly implemented and the virus evolution fully tracked. For these scenarios, point-of-care microdevices can provide sensitive, accurate, rapid and low-cost analysis for a large population, especially in handling complex patient samples, such as blood, urine and saliva. Blood plasma can be considered as a mine of information containing sources and clues of biomarkers, including nucleic acids, immunoglobulin and other proteins, as well as pathogens for clinical diagnosis. However, blood plasma is also the most complicated body fluid. For targeted plasma biomarker detection or untargeted plasma biomarker discovery, the challenges can be as difficult as identifying a needle in a haystack. A useful platform must not only pursue single performance characteristics, but also excel at multiple performance parameters, such as speed, accuracy, sensitivity, selectivity, cost, portability, reliability, and user friendliness. Throughout the decades, tremendous progress has been made in point-of-care microdevices for viral infectious diseases. In this paper, we review fully integrated lab-on-chip systems for blood analysis of viral infectious disease.

negative: In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus Abstract Objective In this study we execute a rational screen to identify Chinese medical herbs that are commonly used in treating viral respiratory infections and also contain compounds that might directly inhibit 2019 novel coronavirus (2019-nCoV), an ongoing novel coronavirus that causes pneumonia. Methods There were two main steps in the screening process. In the first step we conducted a literature search for natural compounds that had been biologically confirmed as against sever acute respiratory syndrome coronavirus or Middle East respiratory syndrome coronavirus. Resulting compounds were cross-checked for listing in the Traditional Chinese Medicine Systems Pharmacology Database. Compounds meeting both requirements were subjected to absorption, distribution, metabolism and excretion (ADME) evaluation to verify that oral administration would be effective. Next, a docking analysis was used to test whether the compound had the potential for direct 2019-nCoV protein interaction. In the second step we searched Chinese herbal databases to identify plants containing the selected compounds. Plants containing 2 or more of the compounds identified in our screen were then checked against the catalogue for classic herbal usage. Finally, network pharmacology analysis was used to predict the general in vivo effects of each selected herb. Results Of the natural compounds screened, 13 that exist in traditional Chinese medicines were also found to have potential anti-2019-nCoV activity. Further, 125 Chinese herbs were found to contain 2 or more of these 13 compounds. Of these 125 herbs, 26 are classically catalogued as treating viral respiratory infections. Network pharmacology analysis predicted that the general in vivo roles of these 26 herbal plants were related to regulating viral infection, immune/inflammation reactions and hypoxia response. Conclusion Chinese herbal treatments classically used for treating viral respiratory infection might contain direct anti-2019-nCoV compounds.

negative: Management of infections in critically ill returning travellers in the intensive care unit—II: clinical syndromes and special considerations in immunocompromised patients Summary This position paper is the second ESCMID Consensus Document on this subject and aims to provide intensivists, infectious disease specialists, and emergency physicians with a standardized approach to the management of serious travel-related infections in the intensive care unit (ICU) or the emergency department. This document is a cooperative effort between members of two European Society of Clinical Microbiology and Infectious Diseases (ESCMID) study groups and was coordinated by Hakan Leblebicioglu and Jordi Rello for ESGITM (ESCMID Study Group for Infections in Travellers and Migrants) and ESGCIP (ESCMID Study Group for Infections in Critically Ill Patients), respectively. A relevant expert on the subject of each section prepared the first draft which was then edited and approved by additional members from both ESCMID study groups. This article summarizes considerations regarding clinical syndromes requiring ICU admission in travellers, covering immunocompromised patients.

negative: Phylogenetic study of 2019-nCoV by using alignment-free method The origin and early spread of 2019-nCoV is studied by phylogenetic analysis using IC-PIC alignment-free method based on DNA/RNA sequence information correlation (IC) and partial information correlation (PIC). The topology of phylogenetic tree of Betacoronavirus is remarkably consistent with biologist's systematics, classifies 2019-nCoV as Sarbecovirus of Betacoronavirus and supports the assumption that these novel viruses are of bat origin with pangolin as one of the possible intermediate hosts. The novel virus branch of phylogenetic tree shows location-virus linkage. The placement of root of the early 2019-nCoV tree is studied carefully in Neighbor Joining consensus algorithm by introducing different out-groups (Bat-related coronaviruses, Pangolin coronaviruses and HIV viruses etc.) and comparing with UPGMA consensus trees. Several oldest branches (lineages) of the 2019-nCoV tree are deduced that means the COVID-19 may begin to spread in several regions in the world before its outbreak in Wuhan.

negative: Diagnosis and clinical management of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection: an operational recommendation of Peking Union Medical College Hospital (V2.0) Since December 2019, China has been experiencing an outbreak of a new infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical features include fever, coughing, shortness of breath, and inflammatory lung infiltration. China rapidly listed SARS-CoV-2-related pneumonia as a statutory infectious disease. To standardize the diagnosis and treatment of this new infectious disease, an operational recommendation for the diagnosis and management of SARS-CoV-2 infection is developed by Peking Union Medical College Hospital.

negative: Proteome-wide analysis of differentially-expressed SARS-CoV-2 antibodies in early COVID-19 infection Rapid and accurate tests that detect IgM and IgG antibodies to SARS-CoV-2 proteins are essential in slowing the spread of COVID-19 by identifying patients who are infected with COVID-19. Using a SARS-CoV-2 proteome microarray developed in our lab, we comprehensively profiled both IgM and IgG antibodies in forty patients with early-stage COVID-19, influenza, or non-influenza who had similar symptoms. The results revealed that the SARS-CoV-2 N protein is not an ideal biomarker for COVID-19 diagnosis because of its low immunogenicity, thus tests that rely on this marker alone will have a high false negative rate. Our data further suggest that the S protein subunit 1 receptor binding domain (S1-RBD) might be the optimal antigen for IgM antibody detection, while the S protein extracellular domain (S1+S2ECD) would be the optimal antigen for both IgM and IgG antibody detection. Notably, the combination of all IgM and IgG biomarkers can identify 87% and 73.3% COVID-19 patients, respectively. Finally, the COVID-19-specific antibodies are significantly correlated with the clinical indices of viral infection and acute myocardial injury (p≤0.05). Our data may help understand the function of anti-SARS-CoV-2 antibodies and improve serology tests for rapid COVID-19 screening.

negative: Research progress in SELDI-TOF MS and its clinical applications Abstract Proteinchip profiling is a powerful and innovative proteomic technology for the discovery of biomarkers and the development of diagnostic/prognostic assays. On the basis of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), Ciphergen’s proteinchip system offers a single, unified, and high throughput platform for a multitude of proteomic research applications. Proteins are the major functional components of the cell. The study of proteomics helps to better understand the mechanism of a disease. Remarkable findings in disease biomarkers have shed light on the early diagnosis, monitoring, and prognosis of various diseases, especially for cancer. In this paper, the development and technology of SELDI-TOF MS are introduced. The research progress and encouraging research results in malignancies, infectious diseases, neurological diseases, and diabetes mellitus using SELDI-TOF MS are reviewed. This paper concludes by evaluating the pros and cons, and the future perspectives are also expounded.

negative: A comprehensive review on drug repositioning against coronavirus disease 2019 (COVID19) Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is the reason for this ongoing pandemic infection diseases termed coronavirus disease 2019 (COVID-19) that has emerged since early December 2019 in Wuhan City, Hubei Province, China. In this century, it is the worst threat to international health and the economy. After 4 months of COVID-19 outbreak, there is no certain and approved medicine against it. In this public health emergency, it makes sense to investigate the possible effects of old drugs and find drug repositioning that is efficient, economical, and riskless process. Old drugs that may be effective are from different pharmacological categories, antimalarials, anthelmintics, anti-protozoal, anti-HIVs, anti-influenza, anti-hepacivirus, antineoplastics, neutralizing antibodies, immunoglobulins, and interferons. In vitro, in vivo, or preliminary trials of these drugs in the treatment of COVID-19 have been encouraging, leading to new research projects and trials to find the best drug/s. In this review, we discuss the possible mechanisms of these drugs against COVID-19. Also, it should be mentioned that in this manuscript, we discuss preliminary rationales; however, clinical trial evidence is needed to prove them. COVID-19 therapy must be based on expert clinical experience and published literature and guidelines from major health organizations. Moreover, herein, we describe current evidence that may be changed in the future.

negative: Megapneumonia Coinfection: pneumococcus, Mycoplasma pneumoniae, and Metapneumovirus We report a young girl who died of Streptococcus pneumoniae 19A pneumonia, septic shock, and hemolytic uremic syndrome despite prior pneumococcal vaccination, appropriate antibiotics, and aggressive intensive care support. Serotype 19A is not covered by the 7- or 10-valent pneumococcal vaccines. Mycoplasma pneumoniae and metapneumovirus were simultaneously detected by PCR in the nasopharyngeal and tracheal aspirates. The pneumococcus is penicillin sensitive. Although infections with each of these pathogens alone are typically mild, this case highlights that co-infection with the triple respiratory pathogens possibly contributed to the fatal outcome of this child. Also, the new policy in Hong Kong to use PCV13 may help prevent further cases of serotype 19A infections.

negative: Can glypican-3 be a disease-specific biomarker? BACKGROUND: Glypican-3 (GPC3) is a cell surface-bound proteoglycan which has been identified as a potential biomarker candidate in hepatocellular carcinoma, lung carcinoma, severe pneumonia, and acute respiratory distress syndrome (ARDS). The aim of our review is to evaluate whether GPC3 has utility as a disease-specific biomarker, to discuss the potential involvement of GPC3 in cell biology, and to consider the changes of GPC3 gene and protein expression and regulation in hepatocellular carcinoma, lung cancer, severe pneumonia, and ARDS. RESULTS: Immunohistochemical studies have suggested that over-expression of GPC3 is associated with a poorer prognosis for hepatocellular carcinoma patients. Expression of GPC3 leads to an increased apoptosis response in human lung carcinoma tumor cells, and is considered to be a candidate lung tumor suppressor gene. Increased serum levels of GPC3 have been demonstrated in ARDS patients with severe pneumonia. CONCLUSIONS: Glypican-3 could be considered as a clinically useful biomarker in hepatocellular carcinoma, lung carcinoma, and ARDS, but further research is needed to confirm and expand on these findings.

negative: Molecular mechanism of evolution and human infection with the novel coronavirus (2019-nCoV) Since December, 2019, an outbreak of pneumonia caused by the new coronavirus (2019-nCoV) has hit the city of Wuhan in the Hubei Province. With the continuous development of the epidemic, it has become a national public health crisis and calls for urgent antiviral treatments or vaccines. The spike protein on the coronavirus envelope is critical for host cell infection and virus vitality. Previous studies showed that 2019-nCoV is highly homologous to human SARS-CoV and attaches host cells though the binding of the spike receptor binding domain (RBD) domain to the angiotensin-converting enzyme II (ACE2). However, the molecular mechanisms of 2019-nCoV binding to human ACE2 and evolution of 2019-nCoV remain unclear. In this study, we have extensively studied the RBD-ACE2 complex, spike protein, and free RBD systems of 2019-nCoV and SARS-CoV using protein-protein docking and molecular dynamics (MD) simulations. It was shown that the RBD-ACE2 binding free energy for 2019-nCoV is significantly lower than that for SARS-CoV, which is consistent with the fact that 2019-nCoV is much more infectious than SARS-CoV. In addition, the spike protein of 2019-nCoV shows a significantly lower free energy than that of SARS-CoV, suggesting that 2019-nCoV is more stable and able to survive a higher temperature than SARS-CoV. This may also provide insights into the evolution of 2019-nCoV because SARS-like coronaviruses are thought to have originated in bats that are known to have a higher body-temperature than humans. It was also revealed that the RBD of 2019-nCoV is much more flexible especially near the binding site and thus will have a higher entropy penalty upon binding ACE2, compared to the RBD of SARS-CoV. That means that 2019-nCoV will be much more temperature-sensitive in terms of human infection than SARS-CoV. With the rising temperature, 2019-nCoV is expected to decrease its infection ability much faster than SARS-CoV, and get controlled more easily. The present findings are expected to be helpful for the disease prevention and control as well as drug and vaccine development of 2019-nCoV.

negative: Relevant Cytokines in the Management of Community-Acquired Pneumonia Community-acquired pneumonia (CAP) is the leading cause of infectious death in the world. Immune dysregulation during acute lung infection plays a role in lung injury and the systemic inflammatory response. Cytokines seem to be major players in severe lung infection cases. Here, we present a review of published papers in the last 3 years regarding this topic. The cytokine response during pneumonia is different in bacterial vs viral infections; some of these cytokines correlate with clinical severity scales such as CURB65 or SOFA. Treatment focused in the cytokine environment is an interesting area that could impact the prognosis of CAP. Some of the agents that have been studied as co-adjuvant therapy are corticosteroids, macrolides, and linezolid, but anyone of those have shown a clear or proven efficacy or have been recommended as a part of the standard of care for CAP. More studies designed to define the role of immunomodulatory agents, such as co-adjuvant therapy in pneumonia, are needed.

negative: 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: Diagnostic Testing for Severe Acute Respiratory Syndrome–Related Coronavirus-2: A Narrative Review Diagnostic testing to identify persons infected with severe acute respiratory syndrome–related coronavirus-2 (SARS–CoV-2) infection is central to control the global pandemic of COVID-19 that began in late 2019. In a few countries, the use of diagnostic testing on a massive scale has been a cornerstone of successful containment strategies. In contrast, the United States, hampered by limited testing capacity, has prioritized testing for specific groups of persons. Real-time reverse transcriptase polymerase chain reaction–based assays performed in a laboratory on respiratory specimens are the reference standard for COVID-19 diagnostics. However, point-of-care technologies and serologic immunoassays are rapidly emerging. Although excellent tools exist for the diagnosis of symptomatic patients in well-equipped laboratories, important gaps remain in screening asymptomatic persons in the incubation phase, as well as in the accurate determination of live viral shedding during convalescence to inform decisions to end isolation. Many affluent countries have encountered challenges in test delivery and specimen collection that have inhibited rapid increases in testing capacity. These challenges may be even greater in low-resource settings. Urgent clinical and public health needs currently drive an unprecedented global effort to increase testing capacity for SARS–CoV-2 infection. Here, the authors review the current array of tests for SARS–CoV-2, highlight gaps in current diagnostic capacity, and propose potential solutions.

negative: Trends and prediction in daily incidence of novel coronavirus infection in China, Hubei Province and Wuhan City: an application of Farr law Background: The recent outbreak of novel coronavirus (2019-nCoV) has infected tens of thousands of patients in China. Studies have forecasted future trends of the incidence of 2019-nCoV infection, but appeared unsuccessful. Farr law is a classic epidemiology theory/practice for predicting epidemics. Therefore, we used and validated a model based on Farr law to predict the daily-incidence of 2019-nCoV infection in China and 2 regions of high-incidence. Methods: We extracted the 2019-nCoV incidence data of China, Hubei Province and Wuhan City from websites of the Chinese and Hubei health commissions. A model based on Farr law was developed using the data available on Feb. 8, 2020, and used to predict daily-incidence of 2019-nCoV infection in China, Hubei Province and Wuhan City afterward. Results: We observed 50,995 (37001 on or before Feb. 8) incident cases in China from January 16 to February 15, 2020. The daily-incidence has peaked in China, Hubei Providence and Wuhan City, but with different downward slopes. If no major changes occur, our model shows that the daily-incidence of 2019-nCoV will drop to single-digit by February 25 for China and Hubei Province, but by March 8 for Wuhan city. However, predicted 75% confidence intervals of daily-incidence in all 3 regions of interest had an upward trend. The predicted trends overall match the prospectively-collected data, confirming usefulness of these models. Conclusions: This study shows the daily-incidence of 2019-nCoV in China, Hubei Province and Wuhan City has reached the peak and was decreasing. However, there is a possibility of upward trend.

negative: The potential of wastewater-based epidemiology as surveillance and early warning of infectious disease outbreaks Infectious diseases caused by pathogens have become one of the main threats to public health. Efficient monitoring of infectious disease transmission is critical to prevent and manage infectious disease epidemics. Wastewater-based epidemiology (WBE) is an efficient approach with great potential for early warning of infectious disease transmission and outbreaks. By analysing infectious disease biomarkers in wastewater taken from wastewater collection points, the transmission of infectious diseases in certain areas can be comprehensively monitored in near real time. This short review presents WBE as a surveillance and early warning system for infectious disease outbreaks regarding pathogens with pandemic potential. We also discuss the challenges and perspective of WBE in infectious disease surveillance and early warning.

negative: Clinical usefulness of serum procalcitonin level in distinguishing between Kawasaki disease and other infections in febrile children PURPOSE: The aims of this study were to compare serum procalcitonin (PCT) levels between febrile children with Kawasaki disease (KD) and those with bacterial or viral infections, and assess the clinical usefulness of PCT level in predicting KD. METHODS: Serum PCT levels were examined in febrile pediatric patients admitted between August 2013 and August 2014. The patients were divided into 3 groups as follows: 49 with KD, 111 with viral infections, and 24 with bacterial infections. RESULTS: The mean PCT level in the KD group was significantly lower than that in the bacterial infection group (0.82±1.73 ng/mL vs. 3.11±6.10 ng/mL, P=0.002) and insignificantly different from that in the viral infection group (0.23±0.34 ng/mL,P=0.457). The mean erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level in the KD group were significantly higher than those in the viral and bacterial infection groups (P<0.001 and P<0.001 for ESR, P<0.001 and P=0.005 for CRP, respectively). The proportion of patients in the KD group with PCT levels of >1.0 ng/mL was significantly higher in the nonresponders to the initial intravenous immunoglobulin treatment than in the responders (36% vs. 8%, P=0.01). CONCLUSION: PCT levels may help to differentiate KD from bacterial infections. A combination of disease markers, including ESR, CRP, and PCT, may be useful for differentiating between KD and viral/bacterial infections.

negative: Plasma Erythropoietin, IL-17A, and IFNÎ³ as Potential Biomarkers of Motor Function Recovery in a Canine Model of Spinal Cord Injury Traumatic spinal cord injury (SCI) is a devastating neurological disease for which an accurate, cost-effective prediction of motor function recovery is in pressing need. A plethora of neurochemical changes involved in the pathophysiological process of SCI may serve as a new source of biomarkers for patient outcomes. Five dogs were included in this study. We characterized the plasma cytokine profiles in acute phase (0, 1, and 3 days after SCI) and subacute phase (7, 14, and 21 days after SCI) with microarray analysis. The motor function recovery following SCI was monitored by Olby scores. The expression level of differentially expressed proteins (DEPs) was measured with enzyme-linked immunosorbent assay (ELISA). Then, correlations with the Olby scores and receiver operating characteristic curve (ROC) analysis were performed. We identified 12 DEPs including 10 pro-inflammatory and 2 anti-inflammatory cytokines during the 21-day study period. Among those, the expression levels of erythropoietin (EPO), IL-17A, and IFNÎ³ significantly correlated with the Olby scores with R2 values of 0.870, 0.740, and 0.616, respectively. The results of the ROC analysis suggested that plasma EPO, IL-17A, and IFNÎ³ exhibited a significant predictive power with an area under the curve (AUC) of 0.656, 0.848, and 0.800 for EPO, IL-17A, and IFNÎ³, respectively. Our results provide a longitudinal description of the changes in plasma cytokine expression in the acute and subacute stages of canine SCI. These data reveal novel panels of inflammation-related cytokines which have the potential to be evaluated as biomarkers for predicting motor function prognosis after SCI.

negative: COVID-19, hypercoagulation and what it could mean for patients with psychotic disorders

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

negative: Potential inhibitors against 2019-nCoV coronavirus M protease from clinically approved medicines

negative: Proteomic analysis of serum, plasma, and lymph for the identification of biomarkers Probably no topic has generated more excitement in the world of proteomics than the search for biomarkers. This excitement has been generated by two realities: the constant need for better biomarkers that can be used for disease diagnosis and prognosis, and the recent developments in proteomic technologies that are capable of scanning the individual proteins within varying complex clinical samples. Ideally a biomarker would be assayable from a noninvasively collected sample, therefore, much of the focus in proteomics has been on the analysis of biofluids such as serum, plasma, urine, cerebrospinal fluid, lymph, etc. While the discovery of biomarkers has been elusive, there have been many advances made in the understanding of the proteome content of various biofluids, and in the technologies used for their analysis, that continues to point the research community toward new methods for achieving the ultimate goal of identifying novel disease‐specific biomarkers. In this review, we will describe and discuss many of the proteomic approaches taken in an attempt to find novel biomarkers in serum, plasma, and lymph.

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: IL-33 and ST2 as predictors of disease severity in children with viral acute lower respiratory infection Abstract Background Mechanisms influencing severity of acute lower respiratory infection (ALRI) in children are not established. We aimed to assess the role of inflammatory markers and respiratory viruses in ALRI severity. Methods Concentrations of interleukin(IL)-33, soluble suppression of tumorigenicity (sST)2, IL-1ß, tumor necrosis factor α, IL-4, IL-6 and IL- 8 and types of respiratory viruses were evaluated in children at the first and fifth days after hospital admission. Disease severity was defined as need for mechanical ventilation. Results Seventy-nine children <5 years-old were included; 33(41.8%) received mechanical ventilation. No associations between virus type, viral load or co-detections and severity of disease were observed. Detection of IL-33 and sST2 in nasopharyngeal aspirates (NPA) on admission were associated with higher risk for mechanical ventilation (RR = 2.89 and RR = 4.57, respectively). IL-6 and IL-8 concentrations were higher on Day 5 in mechanically ventilated children. IL-6 NPA concentrations decreased from Day 1 to Day 5 in children who did not receive mechanical ventilation. Increase in sST2 NPA concentrations from Day 1 to Day 5 was associated with longer hospital length of stay (p < 0.01). Conclusions An exacerbated local activation of the IL-33/ST2 axis and persistently high sST2 concentrations over time were associated with severity of viral ALRI in children.

negative: Biomarkers for Chronic Kidney Disease Associated with High Salt Intake High salt intake has been related to the development to chronic kidney disease (CKD) as well as hypertension. In its early stages, symptoms of CKD are usually not apparent, especially those that are induced in a “silent” manner in normotensive individuals, thereby providing a need for some kind of urinary biomarker to detect injury at an early stage. Because traditional renal biomarkers such as serum creatinine are insensitive, it is difficult to detect kidney injury induced by a high-salt diet, especially in normotensive individuals. Recently, several new biomarkers for damage of renal tubular epithelia such as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (Kim-1) have been identified. Previously, we found a novel renal biomarker, urinary vanin-1, in several animal models with renal tubular injury. However, there are few studies about early biomarkers of the progression to CKD associated with a high-salt diet. This review presents some new insights about these novel biomarkers for CKD in normotensives and hypertensives under a high salt intake. Interestingly, our recent reports using spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) fed a high-salt diet revealed that urinary vanin-1 and NGAL are earlier biomarkers of renal tubular damage in SHR and WKY, whereas urinary Kim-1 is only useful as a biomarker of salt-induced renal injury in SHR. Clinical studies will be needed to clarify these findings.

negative: Diabetes and metabolic syndrome as risk factors for COVID-19 BACKGROUND AND AIMS: Clinical evidence exists that patients with diabetes are at higher risk for Coronavirus disease 2019 (COVID-19). We investigated the physiological origins of this clinical observation linking diabetes with severity and adverse outcome of COVID-19. METHODS: Publication mining was applied to reveal common physiological contexts in which diabetes and COVID-19 have been investigated simultaneously. Overall, we have acquired 1,121,078 publications from PubMed in the time span between 01-01-2000 and 17-04-2020, and extracted knowledge graphs interconnecting the topics related to diabetes and COVID-19. RESULTS: The Data Mining revealed three pathophysiological pathways linking diabetes and COVID-19. The first pathway indicates a higher risk for COVID-19 because of a dysregulation of Angiotensin-converting enzyme 2. The other two important physiological links between diabetes and COVID-19 are liver dysfunction and chronic systemic inflammation. A deep network analysis has suggested clinical biomarkers predicting the higher risk: Hypertension, elevated serum Alanine aminotransferase, high Interleukin-6, and low Lymphocytes count. CONCLUSIONS: The revealed biomarkers can be applied directly in clinical practice. For newly infected patients, the medical history needs to be checked for evidence of a long-term, chronic dysregulation of these biomarkers. In particular, patients with diabetes, but also those with prediabetic state, deserve special attention.

negative: Knowledge and Beliefs towards Universal Safety Precautions to flatten the curve during Novel Coronavirus Disease (nCOVID-19) Pandemic among general Public in India: Explorations from a National Perspective Background: The novel Coronavirus disease (COVID-19) is being considered as the most serious health threat that the world has never witnessed in the recent times and significantly affecting the daily routine of mankind by emerging as a global pandemic. Yet, as there is no treatment nor a vaccine that was approved so far, universal safety precautions (USPs) and mitigating strategies are the only way to deal with this emergency crisis. However, knowledge and beliefs towards USPs among the general public in countries such as India with a large population are lacking. Methods: A prospective, cross-sectional, web-based online survey was conducted among the general public in India during March 2020. A 20-items self-administered survey questionnaire was developed and randomly distributed among the public using google document forms through social media networks. Descriptive statistics were used in representing the study characteristics, and the Chi-square test was used in assessing the associations among the study variables with a p-value of < 0.05 was considered as statistically significant. Results: Of 1287 participants, 1117 have given their consent of willingness and completed the questionnaire with a response rate of 86.8%. The mean age of the study participants was 28.8 ± 10.9 years, where the majority of them belong to the age category <25 years, and sex was equally distributed. Based upon the socio-demographic information, the majority were post-graduates (32.9%), professional job holders (45%) and belonged to the upper-middle (40%) economic class. Overall, the knowledge and beliefs towards USPs and mitigating strategies among participants varied between moderate to high, with statistically significant associations with their socio-demographic characteristics. Conclusions: Although the knowledge and beliefs of the general public in India towards USPs are encouraging, there is a need for long-term educational interventions as the dynamics and severity of COVID-19 have been changing day-by-day rapidly. The findings of this study could guide the public health authorities in making and implementing decisions to combat this pandemic. Keywords: Coronavirus, COVID-19, outbreak, Pandemic, universal precautions, SARS-CoV-2.

negative: CSF neopterin, a useful biomarker in children presenting with influenza associated encephalopathy? Abstract Purpose Neurological complications of influenza cause significant disease in children. Central nervous system inflammation, the presumed mechanism of influenza-associated encephalopathy, is difficult to detect. Characteristics of children presenting with severe neurological complications of influenza, and potential biomarkers of influenza-associated encephalopathy are described. Methods A multi-center, retrospective case-series of children with influenza and neurological complications during 2017 was performed. Enrolled cases met criteria for influenza-associated encephalopathy or had status epilepticus. Functional outcome at discharge was compared between groups using the Modified Rankin Scale (mRS). Results There were 22 children with influenza studied of whom 11/22 had encephalopathy and 11/22 had status epilepticus. Only one child had a documented influenza immunization. The biomarker CSF neopterin was tested in 10/11 children with encephalopathy and was elevated in 8/10. MRI was performed in all children with encephalopathy and was abnormal in 8 (73%). Treatment of children with encephalopathy was with corticosteroids or intravenous immunoglobulin in 9/11 (82%). In all cases oseltamivir use was low (59%) while admission to the intensive care unit was frequent (14/22, 66%). Clinical outcome at discharge was moderate to severe disability (mRS score > 2) in the majority of children with encephalopathy (7/11, 64%), including one child who died. Children with status epilepticus recovered to near-baseline function in all cases. Conclusion Raised CSF neopterin was present in most cases of encephalopathy, and along with diffusion restriction on MRI, is a useful diagnostic biomarker. Lack of seasonal influenza vaccination represents a missed opportunity to prevent illness in children, including severe neurological disease.

negative: New markers in pneumonia Abstract Pneumonia is one of the most common causes of death from infectious diseases worldwide, and the most common fatal infection acquired in hospitals. Despite advances in prevention strategies, such as antibiotic therapies and intensive care, significant improvement in the mortality rate is still lacking. This high mortality is largely due to the limitations in current clinical practices and laboratory tests, which delay the timing of adequate antibiotic therapy. In recent years, many indicators (biomarkers) are present in scenarios where infectious pathogens invade into the body. These biomarkers, as reflected in specific biological responses to infections, have been reported to demonstrate the ability to facilitate the diagnosis, risk stratification, and management of pneumonia. This review provides a schematic overview of these new potential biomarkers based on the categories of (1) microorganisms and their derivatives, (2) inflammation mediators, (3) inflammation response proteins, and (4) stress-sensing proteins. In addition, approaches to identifying new biomarkers are also briefly introduced. Although no current biomarker can solely achieve a definitive diagnosis, many of them can be complemented, rather than replaced outright, in routine clinical practices to improve decision-making processes regarding pneumonia.

negative: Pathogen–Host Defense in the Evolution of Depression: Insights into Epidemiology, Genetics, Bioregional Differences and Female Preponderance Significant attention has been paid to the potential adaptive value of depression as it relates to interactions with people in the social world. However, in this review, we outline the rationale of why certain features of depression including its environmental and genetic risk factors, its association with the acute phase response and its age of onset and female preponderance appear to have evolved from human interactions with pathogens in the microbial world. Approaching the relationship between inflammation and depression from this evolutionary perspective yields a number of insights that may reveal important clues regarding the origin and epidemiology of the disorder as well as the persistence of its risk alleles in the modern human genome.

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: Application of recombinant severe fever with thrombocytopenia syndrome virus nucleocapsid protein for the detection of SFTSV-specific human IgG and IgM antibodies by indirect ELISA BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging disease that was first reported in China in 2011. It is caused by SFTS virus (SFTSV) which is a member of the Phlebovirus genus in the Bunyaviridae family. SFTSV has been classified as a BSL3 pathogen. There is a need to develop safe and affordable serodiagnostic methods for proper clinical management of infected patients. METHODS: The full length nucleocapsid (N) gene of SFTSV Yamaguchi strain was amplified by RT-PCR and cloned to an expression vector pQE30. The recombinant (r) SFTSV-N protein was expressed by using Escherichia coli (E. coli) expression system and purified under native conditions. rSFTSV-N protein based indirect IgG and IgM enzyme linked immunosorbent assay (ELISA) systems were established to detect specific human IgG and IgM antibodies, respectively. One hundred fifteen serum samples from clinically suspected-SFTS patients were used to evaluate the newly established systems and the results were compared with the total antibody detecting sandwich ELISA system. RESULTS: The native form of recombinant (r) SFTSV-N protein was expressed and purified. Application of the rSFTSV-N protein based indirect IgG ELISA to the 115 serum samples showed results that perfectly matched those of the total antibody sandwich ELISA with a sensitivity and specificity of 100 %. The rSFTSV-N protein based indirect IgM ELISA missed 8 positive samples that were detected by the total antibody sandwich ELISA. The sensitivity and specificity of rSFTSV-N-IgM capture ELISA were 90.59 and 100 %, respectively. CONCLUSIONS: The rSFTSV-N protein is highly immunoreactive and a good target for use as an assay antigen in laboratory diagnosis. Its preparation is simpler in comparison with that used for the total antibody sandwich system. Our rSFTSV-N protein-based IgG and IgM ELISA systems have the advantage of distinguishing two types of antibodies and require small volume of serum sample only. They are safe to use for diagnosis of SFTS virus infection and especially fit in large-scale epidemiological investigations.

negative: A systematic review of biomarkers multivariately associated with acute respiratory distress syndrome development and mortality BACKGROUND: Heterogeneity of acute respiratory distress syndrome (ARDS) could be reduced by identification of biomarker-based phenotypes. The set of ARDS biomarkers to prospectively define these phenotypes remains to be established. OBJECTIVE: To provide an overview of the biomarkers that were multivariately associated with ARDS development or mortality. DATA SOURCES: We performed a systematic search in Embase, MEDLINE, Web of Science, Cochrane CENTRAL, and Google Scholar from inception until 6 March 2020. STUDY SELECTION: Studies assessing biomarkers for ARDS development in critically ill patients at risk for ARDS and mortality due to ARDS adjusted in multivariate analyses were included. DATA EXTRACTION AND SYNTHESIS: We included 35 studies for ARDS development (10,667 patients at risk for ARDS) and 53 for ARDS mortality (15,344 patients with ARDS). These studies were too heterogeneous to be used in a meta-analysis, as time until outcome and the variables used in the multivariate analyses varied widely between studies. After qualitative inspection, high plasma levels of angiopoeitin-2 and receptor for advanced glycation end products (RAGE) were associated with an increased risk of ARDS development. None of the biomarkers (plasma angiopoeitin-2, C-reactive protein, interleukin-8, RAGE, surfactant protein D, and Von Willebrand factor) was clearly associated with mortality. CONCLUSIONS: Biomarker data reporting and variables used in multivariate analyses differed greatly between studies. Angiopoeitin-2 and RAGE in plasma were positively associated with increased risk of ARDS development. None of the biomarkers independently predicted mortality. Therefore, we suggested to structurally investigate a combination of biomarkers and clinical parameters in order to find more homogeneous ARDS phenotypes. PROSPERO IDENTIFIER: PROSPERO, CRD42017078957

negative: Modeling pathogenesis of emergent and pre-emergent human coronaviruses in mice The emergence of highly pathogenic human coronaviruses (hCoVs) in the last two decades has illuminated their potential to cause high morbidity and mortality in human populations and disrupt global economies. Global pandemic concerns stem from their high mortality rates, capacity for human-to-human spread by respiratory transmission, and complete lack of approved therapeutic countermeasures. Limiting disease may require the development of virus-directed and host-directed therapeutic strategies due to the acute etiology of hCoV infections. Therefore, understanding how hCoV–host interactions cause pathogenic outcomes relies upon mammalian models that closely recapitulate the pathogenesis of hCoVs in humans. Pragmatism has largely been the driving force underpinning mice as highly effective mammalian models for elucidating hCoV–host interactions that govern pathogenesis. Notably, tractable mouse genetics combined with hCoV reverse genetic systems has afforded the concomitant manipulation of virus and host genetics to evaluate virus–host interaction networks in disease. In addition to assessing etiologies of known hCoVs, mouse models have clinically predictive value as tools to appraise potential disease phenotypes associated with pre-emergent CoVs. Knowledge of CoV pathogenic potential before it crosses the species barrier into the human population provides a highly desirable preclinical platform for addressing global pathogen preparedness, an overarching directive of the World Health Organization. Although we recognize that results obtained in robust mouse models require evaluation in non-human primates, we focus this review on the current state of hCoV mouse models, their use as tractable complex genetic organisms for untangling complex hCoV–host interactions, and as pathogenesis models for preclinical evaluation of novel therapeutic interventions.

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: 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: Composition of human-specific slow codons and slow di-codons in SARS-CoV and 2019-nCoV are lower than other coronaviruses suggesting a faster protein synthesis rate of SARS-CoV and 2019-nCoV Translation of a genetic codon without a cognate tRNA gene is affected by both the cognate tRNA availability and the interaction with non-cognate isoacceptor tRNAs. Moreover, two consecutive slow codons (slow di-codons) lead to a much slower translation rate. Calculating the composition of host specific slow codons and slow di-codons in the viral protein coding sequences can predict the order of viral protein synthesis rates between different virus strains. Comparison of human-specific slow codon and slow di-codon compositions in the genomes of 590 coronaviruses infect humans revealed that the protein synthetic rates of 2019 novel coronavirus (2019-nCoV) and severe acute respiratory syndrome-related coronavirus (SARS-CoV) may be much faster than other coronaviruses infect humans. Analysis of host-specific slow codon and di-codon compositions provides links between viral genomic sequences and capability of virus replication in host cells that may be useful for surveillance of the transmission potential of novel viruses.

negative: SARS-CoV-2 and Coronavirus Disease 2019: What We Know So Far In December 2019, a cluster of fatal pneumonia cases presented in Wuhan, China. They were caused by a previously unknown coronavirus. All patients had been associated with the Wuhan Wholefood market, where seafood and live animals are sold. The virus spread rapidly and public health authorities in China initiated a containment effort. However, by that time, travelers had carried the virus to many countries, sparking memories of the previous coronavirus epidemics, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and causing widespread media attention and panic. Based on clinical criteria and available serological and molecular information, the new disease was called coronavirus disease of 2019 (COVID-19), and the novel coronavirus was called SARS Coronavirus-2 (SARS-CoV-2), emphasizing its close relationship to the 2002 SARS virus (SARS-CoV). The scientific community raced to uncover the origin of the virus, understand the pathogenesis of the disease, develop treatment options, define the risk factors, and work on vaccine development. Here we present a summary of current knowledge regarding the novel coronavirus and the disease it causes.

negative: Deep learning for classification and localization of COVID-19 markers in point-of-care lung ultrasound. Deep learning (DL) has proved successful in medical imaging and, in the wake of the recent COVID-19 pandemic, some works have started to investigate DLbased solutions for the assisted diagnosis of lung diseases. While existing works focus on CT scans, this paper studies the application of DL techniques for the analysis of lung ultrasonography (LUS) images. Specifically, we present a novel fully-annotated dataset of LUS images collected from several Italian hospitals, with labels indicating the degree of disease severity at a frame-level, videolevel, and pixel-level (segmentation masks). Leveraging these data, we introduce several deep models that address relevant tasks for the automatic analysis of LUS images. In particular, we present a novel deep network, derived from Spatial Transformer Networks, which simultaneously predicts the disease severity score associated to a input frame and provides localization of pathological artefacts in a weakly-supervised way. Furthermore, we introduce a new method based on uninorms for effective frame score aggregation at a video-level. Finally, we benchmark state of the art deep models for estimating pixel-level segmentations of COVID-19 imaging biomarkers. Experiments on the proposed dataset demonstrate satisfactory results on all the considered tasks, paving the way to future research on DL for the assisted diagnosis of COVID-19 from LUS data.

negative: Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, double-blinded, phase IIb clinical trial (CloroCovid-19 Study) Background There is no specific antiviral therapy recommended for the disease caused by SARS-CoV-2 (COVID-19). Recent publications have drawn attention to the possible benefit of chloroquine (CQ). Our study aimed to comprehensively evaluate the safety and efficacy of two different CQ dosages in patients with established severe COVID-19. Methods We performed a parallel, double-blinded, randomized, phase IIb clinical trial, aiming to assess safety and efficacy of two different CQ dosages as adjunctive therapy of hospitalized patients with SARS in Manaus, Brazilian Amazon. Eligible participants were allocated to receive orally or via nasogastric tube high dose CQ (600mg CQ twice daily for 10 days or total dose 12g); or low dose CQ (450mg for 5 days, twice daily only on the first day, or total dose 2.7g). In addition, all patients received ceftriaxone and azithromycin. This study was registered with ClinicalTrials.gov, number NCT04323527. Findings Out of a pre-defined 440 patients sample size, 81 patients were enrolled. The high dose CQ arm presented more QTc>500ms (25%), and a trend toward higher lethality (17%) than the lower dosage. Fatality rate was 13.5% (95%CI=6.9-23.0%), overlapping with the CI of historical data from similar patients not using CQ (95%CI=14.5-19.2%). In 14 patients with paired samples, respiratory secretion at day 4 was negative in only one patient. Interpretation Preliminary findings suggest that the higher CQ dosage (10-day regimen) should not be recommended for COVID-19 treatment because of its potential safety hazards. Such results forced us to prematurely halt patient recruitment to this arm. Given the enormous global push for the use of CQ for COVID-19, results such as the ones found in this trial can provide robust evidence for updated COVID-19 patient management recommendations.

negative: Coronavirus envelope protein: current knowledge BACKGROUND: Coronaviruses (CoVs) primarily cause enzootic infections in birds and mammals but, in the last few decades, have shown to be capable of infecting humans as well. The outbreak of severe acute respiratory syndrome (SARS) in 2003 and, more recently, Middle-East respiratory syndrome (MERS) has demonstrated the lethality of CoVs when they cross the species barrier and infect humans. A renewed interest in coronaviral research has led to the discovery of several novel human CoVs and since then much progress has been made in understanding the CoV life cycle. The CoV envelope (E) protein is a small, integral membrane protein involved in several aspects of the virus’ life cycle, such as assembly, budding, envelope formation, and pathogenesis. Recent studies have expanded on its structural motifs and topology, its functions as an ion-channelling viroporin, and its interactions with both other CoV proteins and host cell proteins. MAIN BODY: This review aims to establish the current knowledge on CoV E by highlighting the recent progress that has been made and comparing it to previous knowledge. It also compares E to other viral proteins of a similar nature to speculate the relevance of these new findings. Good progress has been made but much still remains unknown and this review has identified some gaps in the current knowledge and made suggestions for consideration in future research. CONCLUSIONS: The most progress has been made on SARS-CoV E, highlighting specific structural requirements for its functions in the CoV life cycle as well as mechanisms behind its pathogenesis. Data shows that E is involved in critical aspects of the viral life cycle and that CoVs lacking E make promising vaccine candidates. The high mortality rate of certain CoVs, along with their ease of transmission, underpins the need for more research into CoV molecular biology which can aid in the production of effective anti-coronaviral agents for both human CoVs and enzootic CoVs.

negative: Overlapping and discrete aspects of the pathology and pathogenesis of the emerging human pathogenic coronaviruses SARS‐CoV, MERS‐CoV, and 2019‐nCoV First reported from Wuhan, The People's Republic of China, on 31 December 2019, the ongoing outbreak of a novel coronavirus (2019‐nCoV) causes great global concerns. Based on the advice of the International Health Regulations Emergency Committee and the fact that to date 24 other countries also reported cases, the WHO Director‐General declared that the outbreak of 2019‐nCoV constitutes a Public Health Emergency of International Concern on 30 January 2020. Together with the other two highly pathogenic coronaviruses, the severe acute respiratory syndrome coronavirus (SARS‐CoV) and Middle East respiratory syndrome coronavirus (MERS‐CoV), 2019‐nCov and other yet to be identified coronaviruses pose a global threat to public health. In this mini‐review, we provide a brief introduction to the pathology and pathogenesis of SARS‐CoV and MERS‐CoV and extrapolate this knowledge to the newly identified 2019‐nCoV.

negative: Estimates of the severity of coronavirus disease 2019: a model-based analysis BACKGROUND: In the face of rapidly changing data, a range of case fatality ratio estimates for coronavirus disease 2019 (COVID-19) have been produced that differ substantially in magnitude. We aimed to provide robust estimates, accounting for censoring and ascertainment biases. METHODS: We collected individual-case data for patients who died from COVID-19 in Hubei, mainland China (reported by national and provincial health commissions to Feb 8, 2020), and for cases outside of mainland China (from government or ministry of health websites and media reports for 37 countries, as well as Hong Kong and Macau, until Feb 25, 2020). These individual-case data were used to estimate the time between onset of symptoms and outcome (death or discharge from hospital). We next obtained age-stratified estimates of the case fatality ratio by relating the aggregate distribution of cases to the observed cumulative deaths in China, assuming a constant attack rate by age and adjusting for demography and age-based and location-based under-ascertainment. We also estimated the case fatality ratio from individual line-list data on 1334 cases identified outside of mainland China. Using data on the prevalence of PCR-confirmed cases in international residents repatriated from China, we obtained age-stratified estimates of the infection fatality ratio. Furthermore, data on age-stratified severity in a subset of 3665 cases from China were used to estimate the proportion of infected individuals who are likely to require hospitalisation. FINDINGS: Using data on 24 deaths that occurred in mainland China and 165 recoveries outside of China, we estimated the mean duration from onset of symptoms to death to be 17·8 days (95% credible interval [CrI] 16·9–19·2) and to hospital discharge to be 24·7 days (22·9–28·1). In all laboratory confirmed and clinically diagnosed cases from mainland China (n=70 117), we estimated a crude case fatality ratio (adjusted for censoring) of 3·67% (95% CrI 3·56–3·80). However, after further adjusting for demography and under-ascertainment, we obtained a best estimate of the case fatality ratio in China of 1·38% (1·23–1·53), with substantially higher ratios in older age groups (0·32% [0·27–0·38] in those aged <60 years vs 6·4% [5·7–7·2] in those aged ≥60 years), up to 13·4% (11·2–15·9) in those aged 80 years or older. Estimates of case fatality ratio from international cases stratified by age were consistent with those from China (parametric estimate 1·4% [0·4–3·5] in those aged <60 years [n=360] and 4·5% [1·8–11·1] in those aged ≥60 years [n=151]). Our estimated overall infection fatality ratio for China was 0·66% (0·39–1·33), with an increasing profile with age. Similarly, estimates of the proportion of infected individuals likely to be hospitalised increased with age up to a maximum of 18·4% (11·0–7·6) in those aged 80 years or older. INTERPRETATION: These early estimates give an indication of the fatality ratio across the spectrum of COVID-19 disease and show a strong age gradient in risk of death. FUNDING: UK Medical Research Council.

negative: Chapter 11 Detection of Biomarkers for Different Diseases on Biosensor Surfaces Part II Abstract In this chapter the authors analyze the binding and dissociation kinetics (if applicable) of (1) interferon-gamma as a function of aptamer variants and inclusion of spacer, (2) GST-N protein in PBS and GST-N protein in 10-fold diluted serum to a localized surface plasmon resonance coupled fluorescence biosensor, (3) cytochrome c mutant to a superoxide biosensor, (4) Carbonic Anhydrase-II to an 4-(2-aminoethyl)-benzene sulfonamide ligand on an surface plasmon resonance biosensor surface, (5) glycerol secretion from differentiated (murine 3T3-L1) adipocytes to a microfluidic platform for fluorescence-based assay, and (6) different concentrations of C-reactive protein in solution to a sandwich-type assay using reflectometric interference spectroscopy (label-free detection method).

negative: Dataset on the COVID-19 Pandemic Situation in Tunisia with application to SIR Model April 9, 2020 marks 100 days since first cases of the Coronavirus Disease 2019 in China. In this crucial day with 1 436 198 confirmed infected cases in the world (New confirmed infected cases 82 837) and 85 521 deaths (6286 New daily deaths), the Global Level of the Covid-19 pandemic is evaluated at very high according to the World Health Organization (WHO) situation report. For most people, COVID-19 infection will cause mild illness (fever and at least one sign/symptom of respiratory disease), however for more than 3.4% of people, it can be fatal. Older people and those with pre-existing medical conditions (such as cardiovascular disease, chronic respiratory disease or diabetes) are at risk for severe disease and mortality. The incubation period of the virus is estimated to be between 2 and 14 days but longer incubation are reported. Furthermore, Data published by world authorities shows that statistics are different for different geographical regions and depends on many social and environmental factors. The sad reality of the COVID-19 is that there are currently no medications or vaccines proven to be effective for the treatment or prevention of the disease. The pandemic spread is consequenctly followed by a worldwide panic. Facing this dramatic uncertain situation, implementing a country wide strategy for social distancing and a general logistic policy for critical and life-saving supplies is an urgency for governomental and sanitaire authorities. Several mathematical models have been proposed for developed countries to predict the epidemic spread. However these models can't be adapted to developing countries due to the major differences in geographic, societal, economic and political adopted strategies. Here, we propose the application of the well known SIR model to the case study of Tunisia where Data are collected from three official databases showing differences in reporting methods. The proposed data could be useful to predict the spread of COVID-2019 and design a more reliable model that can estimate the finale size of the spread and help in monitoring infection control.

negative: 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.

negative: Molecular Distance to Health Transcriptional Score and Disease Severity in Children Hospitalized With Community-Acquired Pneumonia Background: Community-acquired pneumonia (CAP) is a leading cause of hospitalization and mortality in children. Diagnosis remains challenging and there are no reliable tools to objectively risk stratify patients or predict clinical outcomes. Molecular distance to health (MDTH) is a genomic score that measures the global perturbation of the transcriptional profile and may help classify patients by disease severity. We evaluated the value of MDTH to assess disease severity in children hospitalized with CAP. Methods: Children hospitalized with CAP and matched healthy controls were enrolled in a prospective observational study. Blood samples were obtained for transcriptome analyses within 24 h of hospitalization. MDTH scores were calculated to assess disease severity and correlated with laboratory markers, such as white blood cell count, c-reactive protein (CRP), and procalcitonin (PCT), and clinical outcomes, including duration of fever and duration of hospitalization (LOS). Univariate and multivariable logistic regression were applied to assess factors associated with LOS and duration of fever after hospitalization. Results: Among children hospitalized with CAP (n = 152), pyogenic bacteria (PB) were detected in 16 (11%), Mycoplasma pneumoniae was detected in 41 (28%), respiratory viruses (RV) alone were detected in 78 (51%), and no pathogen was detected in 17 (11%) children. Statistical group comparisons identified 6,726 genes differentially expressed in patients with CAP vs. healthy controls (n = 39). Children with confirmed PB had higher MDTH scores than those with RV (p < 0.05) or M. pneumoniae (p < 0.01) detected alone. CRP (r = 0.39, p < 0.0001), PCT (r = 0.39, p < 0.0001), and MDTHs (r = 0.24, p < 0.01) correlated with duration of fever, while only MDTHs correlated with LOS (r = 0.33, p < 0.0001). Unadjusted analyses showed that both higher CRP and MDTHs were associated with longer LOS (OR 1.04 [1–1.07] and 1.12 [1.04–1.20], respectively), however, only MDTH remained significant when adjusting for other covariates (aOR 1.11 [1.01–1.22]). Conclusions: In children hospitalized with CAP MDTH score measured within 24 h of admission was independently associated with longer duration of hospitalization, regardless of the pathogen detected. This suggests that transcriptional biomarkers may represent a promising approach to assess disease severity in children with CAP.

negative: SELDI-TOF-MS Proteomic Profiling of Serum, Urine, and Amniotic Fluid in Neural Tube Defects Neural tube defects (NTDs) are common birth defects, whose specific biomarkers are needed. The purpose of this pilot study is to determine whether protein profiling in NTD-mothers differ from normal controls using SELDI-TOF-MS. ProteinChip Biomarker System was used to evaluate 82 maternal serum samples, 78 urine samples and 76 amniotic fluid samples. The validity of classification tree was then challenged with a blind test set including another 20 NTD-mothers and 18 controls in serum samples, and another 19 NTD-mothers and 17 controls in urine samples, and another 20 NTD-mothers and 17 controls in amniotic fluid samples. Eight proteins detected in serum samples were up-regulated and four proteins were down-regulated in the NTD group. Four proteins detected in urine samples were up-regulated and one protein was down-regulated in the NTD group. Six proteins detected in amniotic fluid samples were up-regulated and one protein was down-regulated in the NTD group. The classification tree for serum samples separated NTDs from healthy individuals, achieving a sensitivity of 91% and a specificity of 97% in the training set, and achieving a sensitivity of 90% and a specificity of 97% and a positive predictive value of 95% in the test set. The classification tree for urine samples separated NTDs from controls, achieving a sensitivity of 95% and a specificity of 94% in the training set, and achieving a sensitivity of 89% and a specificity of 82% and a positive predictive value of 85% in the test set. The classification tree for amniotic fluid samples separated NTDs from controls, achieving a sensitivity of 93% and a specificity of 89% in the training set, and achieving a sensitivity of 90% and a specificity of 88% and a positive predictive value of 90% in the test set. These suggest that SELDI-TOF-MS is an additional method for NTDs pregnancies detection.

negative: Immune defects and cardiovascular risk in X chromosome monosomy mosaicism mediated by loss of chromosome Y. A risk factor for SARS-CoV-2 vulnerability in elderly men? The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) has an estimated overall case fatality ratio of 1.38% in China, being 53% higher in males and increasing exponentially with age. Mosaicism for X chromosome monosomy (XCM) shows a similar increase in aging population mostly driven by loss of chromosome Y in males (LOY), and is associated with a raise in all-cause mortality. Using comparative transcriptomic data, we have defined that XCM/LOY is associated with abnormal peripheral blood cell counts with decreased progenitor cells and multiple biomarkers of immune system dysfunction, pro-coagulation activity and increased cardiovascular risk. Several differentially down-regulated genes in XCM/LOY individuals are involved in the initial immune response to SARS-CoV-2 (OR of enrichment=7.23, p=1.5x10-7), mainly interferon-induced genes that code for inhibitors of viral processes. Thus, our data suggest that XCM mosaicism underlies at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential relevance for modulating prognosis and therapeutic response, we propose that evaluation of LOY and XCM by currently established methods should be implemented as biomarkers in infected patients, including currently ongoing clinical trials with different medications and vaccines for COVID-19. Testing for LOY/XCM at large scale among elderly people may also be helpful to identify still unexposed people who may be especially vulnerable to severe Covid-19 disease.

negative: Therapeutic Drugs Targeting 2019-nCoV Main Protease by High-Throughput Screening 2019 Novel Coronavirus (2019-nCoV) is a virus identified as the cause of the outbreak of pneumonia first detected in Wuhan, China. Investigations on the transmissibility, severity, and other features associated with this virus are ongoing. Currently, there is no vaccine or therapeutic antibody to prevent the infection, and more time is required to develop an effective immune strategy against the pathogen. In contrast, specific inhibitors targeting the key protease involved in replication and proliferation of the virus are the most effective means to alleviate the epidemic. The main protease of SARS-CoV is essential for the life cycle of the virus, which showed 96.1% of similarity with the main proteaseof 2019-nCoV, is considered to be an attractive target for drug development. In this study, we have identified 4 small molecular drugs with high binding capacity with SARS-CoV main protease by high-throughput screening based on the 8,000 clinical drug libraries, all these drugs have been widely used in clinical applications with guaranteed safety, which may serve as promising candidates to treat the infection of 2019-nCoV.

negative: 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.

negative: Potential Maternal and Infant Outcomes from Coronavirus 2019-nCoV (SARS-CoV-2) Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections In early December 2019 a cluster of cases of pneumonia of unknown cause was identified in Wuhan, a city of 11 million persons in the People’s Republic of China. Further investigation revealed these cases to result from infection with a newly identified coronavirus, initially termed 2019-nCoV and subsequently SARS-CoV-2. The infection moved rapidly through China, spread to Thailand and Japan, extended into adjacent countries through infected persons travelling by air, eventually reaching multiple countries and continents. Similar to such other coronaviruses as those causing the Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS), the new coronavirus was reported to spread via natural aerosols from human-to-human. In the early stages of this epidemic the case fatality rate is estimated to be approximately 2%, with the majority of deaths occurring in special populations. Unfortunately, there is limited experience with coronavirus infections during pregnancy, and it now appears certain that pregnant women have become infected during the present 2019-nCoV epidemic. In order to assess the potential of the Wuhan 2019-nCoV to cause maternal, fetal and neonatal morbidity and other poor obstetrical outcomes, this communication reviews the published data addressing the epidemiological and clinical effects of SARS, MERS, and other coronavirus infections on pregnant women and their infants. Recommendations are also made for the consideration of pregnant women in the design, clinical trials, and implementation of future 2019-nCoV vaccines.

negative: Chapter 28 Asthma Abstract Asthma is a common respiratory disease with a complex etiology involving a combination of genetic and environmental components. Current asthma management involves a step-up and step-down approach based on asthma control with a large degree of heterogeneity in responses to the main drug classes currently in use: β2-adrenergic receptor agonists, corticosteroids, and leukotriene modifiers. Importantly, asthma is heterogeneous with respect to clinical presentation and the inflammatory mechanisms that underlie it. This heterogeneity likely contributes to variable results in clinical trials, particularly when targeting specific inflammatory mediators. These factors have motivated a drive toward stratified medicine in asthma based on clinical/cellular outcomes or genetics (i.e., pharmacogenetics). Significant progress has been made in identifying genetic polymorphisms that influence the efficacy and potential for adverse effects of all main classes of asthma drugs. Importantly an emerging role for genetics in phase II development of newer therapies has been demonstrated (e.g., anti-IL4). Similarly, the stratification of patients based on clinical characteristics (e.g., blood and sputum eosinophil levels) has been critical in evaluating newer therapies (e.g., anti-IL5). As a proof of concept, anti-IgE is the latest therapy to be introduced into clinical practice, although only for severe, allergic patients (i.e., in a stratified manner). As new asthma genes are identified using genome-wide association, among other technologies, new targets (e.g., IL33/IL33 receptor (IL1RL1)) will emerge and pharmacogenetics in these development programs will be essential. In this chapter we review the current understanding of asthma pathobiology and its clinical presentation, as well as the use of stratified medicine, which holds great promise for maximizing clinical outcomes and minimizing adverse effects in existing and new therapies.

negative: SARS and MERS: recent insights into emerging coronaviruses The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second introduction of a highly pathogenic coronavirus into the human population in the twenty-first century. The continuing introductions of MERS-CoV from dromedary camels, the subsequent travel-related viral spread, the unprecedented nosocomial outbreaks and the high case-fatality rates highlight the need for prophylactic and therapeutic measures. Scientific advancements since the 2002–2003 severe acute respiratory syndrome coronavirus (SARS-CoV) pandemic allowed for rapid progress in our understanding of the epidemiology and pathogenesis of MERS-CoV and the development of therapeutics. In this Review, we detail our present understanding of the transmission and pathogenesis of SARS-CoV and MERS-CoV, and discuss the current state of development of measures to combat emerging coronaviruses. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrmicro.2016.81) contains supplementary material, which is available to authorized users.

negative: Cats, coronaviruses and coronavirus antibody tests Feline infectious peritonitis and other coronavirus infections of cats are briefly reviewed. Interpretation and applications of feline coronavirus antibody tests are described, and general recommendations are provided for practitioners. Some of the major unresolved questions regarding coronavirus infections of cats are delineated.

negative: Effective containment explains sub-exponential growth in confirmed cases of recent COVID-19 outbreak in Mainland China The recent outbreak of COVID-19 in Mainland China is characterized by a distinctive algebraic, sub-exponential increase of confirmed cases with time during the early phase of the epidemic, contrasting an initial exponential growth expected for an unconstrained outbreak with sufficiently large reproduction rate. Although case counts vary significantly between affected provinces in Mainland China, the scaling law t^μ is surprisingly universal, with a range of exponents μ = 2.1 ± 0.3. The universality of this behavior indicates that, in spite of social, regional, demographical, geographical, and socio-economical heterogeneities of affected Chinese provinces, this outbreak is dominated by fundamental mechanisms that are not captured by standard epidemiological models. We show that the observed scaling law is a direct consequence of containment policies that effectively deplete the susceptible population. To this end we introduce a parsimonious model that captures both, quarantine of symptomatic infected individuals as well as population wide isolation in response to mitigation policies or behavioral changes. For a wide range of parameters, the model reproduces the observed scaling law in confirmed cases and explains the observed exponents. Quantitative fits to empirical data permit the identification of peak times in the number of asymptomatic or oligo-symptomatic, unidentified infected individuals, as well as estimates of local variations in the basic reproduction number. The model implies that the observed scaling law in confirmed cases is a direct signature of effective contaiment strategies and/or systematic behavioral changes that affect a substantial fraction of the susceptible population. These insights may aid the implementation of containment strategies in potential export induced COVID-19 secondary outbreaks elsewhere or similar future outbreaks of other emergent infectious diseases.

negative: Shifting emphasis from pharmacogenomics to theragnostics What will be the role of theragnostic patents in upstream and downstream biomarker research?

negative: Should scientists infect healthy people with the coronavirus to test vaccines?

negative: The course of clinical diagnosis and treatment of a case infected with coronavirus disease 2019 A pneumonia outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was first identified in Wuhan, present a major threat to public health since December 2019. There are more than 50,000 confirmed cases and 1300 dead cases worldwide for the past month or more, because of the occurrence of a highly contagious performance. Patients had clinical manifestations of fever, cough, shortness of breath, diarrhea, vomiting and so on. We herein report a case of SARS-CoV-2, describe the epidemic history, clinical diagnosis and the changes of clinical parameters during the combination therapy. This article is protected by copyright. All rights reserved.

negative: Vitamin D and SARS-CoV-2 virus/COVID-19 disease

negative: Heparin‐binding protein, lysozyme, and inflammatory cytokines in bronchoalveolar lavage fluid as diagnostic tools for pulmonary infection in lung transplanted patients Pulmonary infection is a common complication after lung transplantation, and early detection is crucial for outcome. However, the condition can be clinically difficult to diagnose and to distinguish from rejection. The aim of this prospective study was to evaluate heparin‐binding protein (HBP), lysozyme, and the cytokines interleukin (IL)‐1β, IL‐6, IL‐8, IL‐10 and tumor necrosis factor (TNF) in bronchoalveolar lavage fluid (BALF) as potential biomarkers for pulmonary infection in lung‐transplanted patients. One hundred thirteen BALF samples from 29 lung transplant recipients were collected at routine scheduled bronchoscopies at 3 and 6 months, or on clinical indication. Samples were classified into no, possible, probable, or definite infection at the time of sampling. Rejection was defined by biopsy results. HBP, lysozyme, and cytokines were analyzed in BALF and correlated to likelihood of infection and rejection. All biomarkers were significantly increased in BALF during infection, whereas patients with rejection presented low levels that were comparable to noninfection samples. HBP, IL‐1β, and IL‐8 were the best diagnostic markers of infection with area under the receiver‐operating characteristic curve values of 0.88, 0.91, and 0.90, respectively. In conclusion, HBP, IL‐1β, and IL‐8 could be useful diagnostic markers of pulmonary infection in lung‐transplanted patients.

negative: Potential T-cell and B-cell Epitopes of 2019-nCoV As of early March, 2019-nCoV has infected more than one hundred thousand people and claimed thousands of lives. 2019-nCoV is a novel form of coronavirus that causes COVID-19 and has high similarity with SARS-CoV. No approved vaccine yet exists for any form of coronavirus. Here we use computational tools from structural biology and machine learning to identify 2019-nCoV T-cell and B-cell epitopes based on viral protein antigen presentation and antibody binding properties. These epitopes can be used to develop more effective vaccines and identify neutralizing antibodies. We identified 405 viral peptides with good antigen presentation scores for both human MHC-I and MHC-II alleles, and two potential neutralizing B-cell epitopes near the 2019-nCoV spike protein receptor binding domain (440-460 and 494-506). Analyzing mutation profiles of 68 viral genomes from four continents, we identified 96 coding-change mutations. These mutations are more likely to occur in regions with good MHC-I presentation scores (p=0.02). No mutations are present near the spike protein receptor binding domain. Based on these findings, the spike protein is likely immunogenic and a potential vaccine candidate. We validated our computational pipeline with SARS-CoV experimental data. The novel coronavirus 2019-nCoV has affected more than 100 countries and continues to spread. There is an immediate need for effective vaccines that contain antigens which trigger responses from human T-cells and B-cells (known as epitopes). Here we identify potential T-cell epitopes through an analysis of human antigen presentation, as well as B-cell epitopes through an analysis of protein structure. We identify a list of top candidates, including an epitope located on 2019-nCoV spike protein that potentially triggers both T-cell and B-cell responses. Analyzing 68 samples, we observe that viral mutations are more likely to happen in regions with strong antigen presentation, a potential form of immune evasion. Our computational pipeline is validated with experimental data from SARS-CoV.

negative: Perceptions and behavioural responses of the general public during the COVID-19 pandemic: A cross-sectional survey of UK Adults Objective: To examine risk perceptions and behavioural responses of the UK adult population during the early phase of the COVID-19 epidemic in the UK. Design: A cross-sectional survey Setting: Conducted with a nationally representative sample of UK adults within 48 hours of the UK Government advising the public to stop non-essential contact with others and all unnecessary travel. Participants: 2,108 adults living in the UK aged 18 years and over. Data were collected between March 17 and 18 2020. Main outcome measures: Descriptive statistics for all survey questions, including the number of respondents and the weighted percentages. Logistic regression was used to identify sociodemographic variation in: (1) adoption of social-distancing measures, (2) ability to work from home, and (3) willingness and (4) ability to self-isolate. Results Overall, 1,992 (94.2%) respondents reported taking at least one preventive measure: 85.8% washed their hands with soap more frequently; 56.5% avoided crowded areas and 54.5% avoided social events. Adoption of social-distancing measures was higher in those aged over 70 compared to younger adults aged 18 to 34 years (aOR:1.9; 95% CI:1.1 to 3.4). Those with the lowest household income were six times less likely to be able to work from home (aOR:0.16; 95% CI:0.09 to 0.26) and three times less likely to be able to self-isolate (aOR:0.31; 95% CI:0.16 to 0.58). Ability to self-isolate was also lower in black and minority ethnic groups (aOR:0.47; 95% CI:0.27 to 0.82). Willingness to self-isolate was high across all respondents. Conclusions The ability to adopt and comply with certain NPIs is lower in the most economically disadvantaged in society. Governments must implement appropriate social and economic policies to mitigate this. By incorporating these differences in NPIs among socio-economic subpopulations into mathematical models of COVID-19 transmission dynamics, our modelling of epidemic outcomes and response to COVID-19 can be improved.

negative: Genomics, Other “Omic” Technologies, Personalized Medicine, and Additional Biotechnology-Related Techniques The products resulting for biotechnologies continue to grow at an exponential rate, and the expectations are that an even greater percentage of drug development will be in the area of the biologics. In 2011, worldwide there were over 800 new biotech drugs and treatments in development including 23 antisense, 64 cell therapy, 50 gene therapy, 300 monoclonal antibodies, 78 recombinant proteins, and 298 vaccines (PhRMA 2012). Pharmaceutical biotechnology techniques are at the core of most methodologies used today for drug discovery and development of both biologics and small molecules. While recombinant DNA technology and hybridoma techniques were the major methods utilized in pharmaceutical biotechnology through most of its historical timeline, our ever-widening understanding of human cellular function and disease processes and a wealth of additional and innovative biotechnologies have been, and will continue to be, developed in order to harvest the information found in the human genome. These technological advances will provide a better understanding of the relationship between genetics and biological function, unravel the underlying causes of disease, explore the association of genomic variation and drug response, enhance pharmaceutical research, and fuel the discovery and development of new and novel biopharmaceuticals. These revolutionary technologies and additional biotechnology-related techniques are improving the very competitive and costly process of drug development of new medicinal agents, diagnostics, and medical devices. Some of the technologies and techniques described in this chapter are both well established and commonly used applications of biotechnology producing potential therapeutic products now in development including clinical trials. New techniques are emerging at a rapid and unprecedented pace and their full impact on the future of molecular medicine has yet to be imagined.

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: SARS-CoV-2 proteome microarray for mapping COVID-19 antibody interactions at amino acid resolution COVID-19 has quickly become a worldwide pandemic, which has significantly impacted the economy, education, and social interactions. Understanding the humoral antibody response to SARS-CoV-2 proteins may help identify biomarkers that can be used to detect and treat COVID-19 infection. However, no immuno-proteomics platform exists that can perform such proteome-wide analysis. To address this need, we created a SARS-CoV-2 proteome microarray to analyze antibody interactions at amino acid resolution by spotting peptides 15 amino acids long with 5-amino acid offsets representing full-length SARS-CoV-2 proteins. Moreover, the array processing time is short (1.5 hours), the dynamic range is ~2 orders of magnitude, and the lowest limit of detection is 94 pg/mL. Here, the SARS-CoV-2 proteome array reveals that antibodies commercially available for SARS-CoV-1 proteins can also target SARS-CoV-2 proteins. These readily available reagents could be used immediately in COVID-19 research. Second, IgM and IgG immunogenic epitopes of SARS-CoV-2 proteins were profiled in the serum of ten COVID-19 patients. Such epitope biomarkers provide insight into the immune response to COVID-19 and are potential targets for COVID-19 diagnosis and vaccine development. Finally, serological antibodies that may neutralize viral entry into host cells via the ACE2 receptor were identified. Further investigation into whether these antibodies can inhibit the propagation of SARS-CoV-2 is warranted. Antibody and epitope profiling in response to COVID-19 is possible with our peptide-based SARS-COV-2 proteome microarray. The data gleaned from the array could provide invaluable information to the scientific community to understand, detect, and treat COVID-19.

negative: Prediction of the Epidemic of COVID-19 Based on Quarantined Surveillance in China Background and Objective: To predict the epidemic of COVID-19 based on quarantined surveillance from real world in China by modified SEIR model different from the previous simply mathematical model. Design and Methods: We forecasted the epidemic of COVID-19 based on current clinical and epidemiological data and built a modified SEIR model to consider both the infectivity during incubation period and the influence on the epidemic from strict quarantined measures. Results: The peak time of the curve for the infected newly diagnosed as COVID-19 should substantially present on Feb.5,2020(in non-Hubei areas) and Feb.19,2020(in Hubei. It is estimated that the peak of the curve of the cumulative confirmed cases will appear in non-Hubei areas on Mar.3,2020 and in Hubei province on Mar.10,2020,and the total number of the patients diagnosed as COVID-19 is 18,000 in non-Hubei areas and 78,000-96,000 in Hubei.The Chinese COVID-19 epidemic can be completely controlled in May,2020. Conclusions: COVID-19 is only a local outbreak in Hubei Province,China.It can be probably avoided the pandemic of global SARS-CoV-2 cases rise with the great efforts by Chinese government and its people.

negative: 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.

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: microRNAs in viral acute respiratory infections: immune regulation, biomarkers, therapy, and vaccines MicroRNAs (miRNAs) are single-stranded RNAs of 17–24 nt. These molecules regulate gene expression at the post-transcriptional level and are differentially expressed in viral acute respiratory infections (ARIs), which are responsible for high morbidity and mortality around the world. In recent years, miRNAs have been studied in order to discover anti-viral ARI drug targets as well as biomarkers for diagnosis, severity, and prognosis. This review presents an analysis of the regulatory response to viral ARIs of miRNAs, including their participation in the innate immune response, their utility as biomarkers, and their potential for future therapies and vaccine development.

negative: 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.

negative: Association of Interleukin-8 and Neutrophils with Nasal Symptom Severity During Acute Respiratory Infection Using a large data set (n = 811), the relationship between acute respiratory infection illness severity and inflammatory biomarkers was investigated to determine whether certain symptoms are correlated more closely than others with the inflammatory biomarkers, interleukin-8 (IL-8) and nasal neutrophils. Participants with community acquired acute respiratory infection underwent nasal lavage for IL-8 and neutrophil testing, in addition to multiplex polymerase chain reaction (PCR) methods for the detection and identification of respiratory viruses. Information about symptoms was obtained throughout the duration of the illness episode using the well-validated Wisconsin Upper Respiratory Symptom Survey (WURSS-21). Global symptom severity was calculated by the area under the curve (AUC) plotting duration versus WURSS total. Of the specimens tested, 56% were positively identified for one or more of nine different respiratory viruses. During acute respiratory infection illness, both IL-8 and neutrophils positively correlate with AUC (r(s) = 0.082, P = 0.022; r(s) = 0.080, P = 0.030). IL-8 and neutrophils correlate with nasal symptom severity: runny nose (r = 0.13, P = <0.00001; r = 0.18, P = <0.003), plugged nose (r = 0.045, P = 0.003; r = 0.14, P = 0.058), and sneezing (r = −0.02, P = <0.0001; r = −0.0055, P = 0.31). Neutrophils correlate with some quality of life measures such as sleeping well (r = 0.15, P = 0.026). Thus, the study demonstrates that IL-8 and neutrophils are correlated with severity of nasal symptoms during acute respiratory infection. Further research is necessary to determine if the concentration of these or other biomarkers can predict the overall duration and severity of acute respiratory infection illness.

negative: Inferring Infection Patterns Based on a Connectivity Map of Host Transcriptional Responses Host responses to infections represent an important pathogenicity determiner, and delineation of host responses can elucidate pathogenesis processes and inform the development of anti-infection therapies. Low cost, high throughput, easy quantitation, and rich descriptions have made gene expression profiling generated by DNA microarrays an optimal approach for describing host transcriptional responses (HTRs). However, efforts to characterize the landscape of HTRs to diverse pathogens are far from offering a comprehensive view. Here, we developed an HTR Connectivity Map based on systematic assessment of pairwise similarities of HTRs to 50 clinically important human pathogens using 1353 gene-expression profiles generated from >60 human cells/tissues. These 50 pathogens were further partitioned into eight robust “HTR communities” (i.e., groups with more consensus internal HTR similarities). These communities showed enrichment in specific infection attributes and differential gene expression patterns. Using query signatures of HTRs to external pathogens, we demonstrated four distinct modes of HTR associations among different pathogens types/class, and validated the reliability of the HTR community divisions for differentiating and categorizing pathogens from a host-oriented perspective. These findings provide a first-generation HTR Connectivity Map of 50 diverse pathogens, and demonstrate the potential for using annotated HTR community to detect functional associations among infectious pathogens.

negative: Elevated thrombopoietin and platelet indices confirm active thrombopoiesis but fail to predict clinical severity of puumala hantavirus infection We evaluated the mechanisms of thrombocytopenia and procoagulant changes in relation with clinical variables in a cohort of patients with acute hantavirus disease. Blood samples of 33 prospectively recruited, consecutive, hospitalized patients with acute Puumala virus–induced hemorrhagic fever with renal syndrome (HFRS) were collected acutely and at the recovery visit (control). Serum thrombopoietin (TPO) and activity of plasma microparticles (MPs) from various cell sources were measured with enzyme-linked immunosorbent assay-based methods. The results were related to data on platelet indices and functions, coagulation variables, and clinical disease. Serum TPO was nearly 4-fold higher acutely compared with the control (median 207 pg/mL, range 56–1258 pg/mL vs. median 58 pg/mL, range 11–241 pg/mL, P < 0.001) and coincided with high mean platelet volume (MPV) and immature platelet fraction (IPF%). Prothrombin fragments and D-dimer were high acutely compared with the control (F1 + 2 median 704 pmol/L, range 284–1875 pmol/L vs. median 249 pmol/L, range 118–556 pmol/L, P < 0.001; d-dimer median 2.8 mg/L, range 0.6–34.0 mg/L vs. median 0.4 mg/L, range 0.2–1.1 mg/L, P < 0.001), and associated with low platelet count and severe acute kidney injury (AKI). MPs’ procoagulant activity was high acutely only among patients with mild AKI (plasma creatinine below the median at the time of the measurement). Upregulated TPO together with high MPV and IPF% confirm active thrombopoiesis, but do not predict severity of HFRS. Simultaneously, elevated prothrombin fragments and d-dimer suggest increased consumption of platelets in patients with severe AKI. Activity of platelet-derived MPs in HFRS should be studied with flow cytometry in a larger cohort of patients.

negative: COVID-19 and hypertension-evidence and practical management: Guidance from the HOPE Asia Network There are several risk factors for worse outcomes in patients with coronavirus 2019 disease (COVID-19). Patients with hypertension appear to have a poor prognosis, but there is no direct evidence that hypertension increases the risk of new infection or adverse outcomes independent of age and other risk factors. There is also concern about use of renin-angiotensin system (RAS) inhibitors due to a key role of angiotensin-converting enzyme 2 receptors in the entry of the SARS-CoV-2 virus into cells. However, there is little evidence that use of RAS inhibitors increases the risk of SARS-CoV-2 virus infection or worsens the course of COVID-19. Therefore, antihypertensive therapy with these agents should be continued. In addition to acute respiratory distress syndrome, patients with severe COVID-19 can develop myocardial injury and cytokine storm, resulting in heart failure, arteriovenous thrombosis, and kidney injury. Troponin, N-terminal pro-B-type natriuretic peptide, D-dimer, and serum creatinine are biomarkers for these complications and can be used to monitor patients with COVID-19 and for risk stratification. Other factors that need to be incorporated into patient management strategies during the pandemic include regular exercise to maintain good health status and monitoring of psychological well-being. For the ongoing management of patients with hypertension, telemedicine-based home blood pressure monitoring strategies can facilitate maintenance of good blood pressure control while social distancing is maintained. Overall, multidisciplinary management of COVID-19 based on a rapidly growing body of evidence will help ensure the best possible outcomes for patients, including those with risk factors such as hypertension.

negative: Use of cardiac biomarkers in neonatology. Cardiac biomarkers are used to identify cardiac disease in term and preterm infants. This review discusses the roles of natriuretic peptides and cardiac troponins. Natriuretic peptide levels are elevated during atrial strain (atrial natriuretic peptide (ANP)) or ventricular strain (B-type natriuretic peptide (BNP)). These markers correspond well with cardiac function and can be used to identify cardiac disease. Cardiac troponins are used to assess cardiomyocyte compromise. Affected cardiomyocytes release troponin into the bloodstream, resulting in elevated levels of cardiac troponin. Cardiac biomarkers are being increasingly incorporated into clinical trials as indicators of myocardial strain. Furthermore, cardiac biomarkers can possibly be used to guide therapy and improve outcome. Natriuretic peptides and cardiac troponins are potential tools in the diagnosis and treatment of neonatal disease that is complicated by circulatory compromise. However, clear reference ranges need to be set and validation needs to be carried out in a population of interest.

negative: Inflammatory response in mixed viral-bacterial community-acquired pneumonia BACKGROUND: The role of mixed pneumonia (virus + bacteria) in community-acquired pneumonia (CAP) has been described in recent years. However, it is not known whether the systemic inflammatory profile is different compared to monomicrobial CAP. We wanted to investigate this profile of mixed viral-bacterial infection and to compare it to monomicrobial bacterial or viral CAP. METHODS: We measured baseline serum procalcitonin (PCT), C reactive protein (CRP), and white blood cell (WBC) count in 171 patients with CAP with definite etiology admitted to a tertiary hospital: 59 (34.5%) bacterial, 66 (39.%) viral and 46 (27%) mixed (viral-bacterial). RESULTS: Serum PCT levels were higher in mixed and bacterial CAP compared to viral CAP. CRP levels were higher in mixed CAP compared to the other groups. CRP was independently associated with mixed CAP. CRP levels below 26 mg/dL were indicative of an etiology other than mixed in 83% of cases, but the positive predictive value was 45%. PCT levels over 2.10 ng/mL had a positive predictive value for bacterial-involved CAP versus viral CAP of 78%, but the negative predictive value was 48%. CONCLUSIONS: Mixed CAP has a different inflammatory pattern compared to bacterial or viral CAP. High CRP levels may be useful for clinicians to suspect mixed CAP.

negative: Partial RdRp sequences offer a robust method for Coronavirus subgenus classification The recent reclassification of the Riboviria, and the introduction of multiple new taxonomic categories including both subfamilies and subgenera for coronaviruses (family Coronaviridae, subfamily Orthocoronavirinae) represents a major shift in how official classifications are used to designate specific viral lineages. While the newly defined subgenera provide much-needed standardisation for commonly cited viruses of public health importance, no method has been proposed for the assignment of subgenus based on partial sequence data, or for sequences that are divergent from the designated holotype reference genomes. Here, we describe the genetic variation of a partial region of the coronavirus RNA-dependent RNA polymerase (RdRp), which is one of the most used partial sequence loci for both detection and classification of coronaviruses in molecular epidemiology. We infer Bayesian phylogenies from more than 7000 publicly available coronavirus sequences and examine clade groupings relative to all subgenus holotype sequences. Our phylogenetic analyses are largely coherent with genome-scale analyses based on designated holotype members for each subgenus. Distance measures between sequences form discrete clusters between taxa, offering logical threshold boundaries that can attribute subgenus or indicate sequences that are likely to belong to unclassified subgenera both accurately and robustly. We thus propose that partial RdRp sequence data of coronaviruses is sufficient for the attribution of subgenus-level taxonomic classifications and we supply the R package, “MyCoV”, which provides a method for attributing subgenus and assessing the reliability of the attribution. The analysis of polymerase chain reaction amplicons derived from biological samples is the most common modern method for detection and classification of infecting viral agents, such as Coronaviruses. Recent updates to the official standard for taxonomic classification of Coronaviruses, however, may leave researchers unsure as to whether the viral sequences they obtain by these methods can be classified into specific viral taxa due to variations in the sequences when compared to type strains. Here, we present a plausible method for defining genetic dissimilarity cut-offs that will allow researchers to state which taxon their virus belongs to and with what level of certainty. To assist in this, we also provide the R package ‘MyCoV’ which classifies user generated sequences.

negative: Role of Biomarkers in Health Care Study of biomarkers of various diseases will help to improve the management in three ways: 1. By providing a better understanding of the disease pathomechanism 2. By improving the diagnosis and determining the prognosis 3. By providing a basis for development of therapeutics and monitoring the effect of therapeutics on the disease

negative: Mutations, Recombination and Insertion in the Evolution of 2019-nCoV The 2019 novel coronavirus (2019-nCoV or SARS-CoV-2) has spread more rapidly than any other betacoronavirus including SARS-CoV and MERS-CoV. However, the mechanisms responsible for infection and molecular evolution of this virus remained unclear. We collected and analyzed 120 genomic sequences of 2019-nCoV including 11 novel genomes from patients in China. Through comprehensive analysis of the available genome sequences of 2019-nCoV strains, we have tracked multiple inheritable SNPs and determined the evolution of 2019-nCoV relative to other coronaviruses. Systematic analysis of 120 genomic sequences of 2019-nCoV revealed co-circulation of two genetic subgroups with distinct SNPs markers, which can be used to trace the 2019-nCoV spreading pathways to different regions and countries. Although 2019-nCoV, human and bat SARS-CoV share high homologous in overall genome structures, they evolved into two distinct groups with different receptor entry specificities through potential recombination in the receptor binding regions. In addition, 2019-nCoV has a unique four amino acid insertion between S1 and S2 domains of the spike protein, which created a potential furin or TMPRSS2 cleavage site. Our studies provided comprehensive insights into the evolution and spread of the 2019-nCoV. Our results provided evidence suggesting that 2019-nCoV may increase its infectivity through the receptor binding domain recombination and a cleavage site insertion. Novel 2019-nCoV sequences revealed the evolution and specificity of betacoronavirus with possible mechanisms of enhanced infectivity.

negative: Serum inflammatory biomarkers and clinical outcomes of COPD exacerbation caused by different pathogens. BACKGROUND AND OBJECTIVE COPD exacerbation is characterized by worsening of symptoms, warranting change in treatment. Systemic and airway inflammation play roles in the pathogenesis of COPD exacerbation. We hypothesized whether increased serum inflammatory biomarkers are associated with the clinical outcomes of COPD exacerbation caused by different infectious pathogens. METHODS COPD patients with exacerbation were recruited from a hospital emergency department during 2014-2015. Serum procalcitonin (PCT) and C-reactive protein (CRP) were measured. Dyspnea, eosinopenia, consolidation, acidemia, and atrial fibrillation (DECAF) score was calculated for predicting mortality. Multiplex polymerase chain reaction was carried out for respiratory viral assay from nasopharyngeal swabs, and sputum bacterial culture was also performed. Hospital mortality, invasive mechanical ventilation requirement, and length of hospital stay (LOS) were evaluated, and their associations with clinical characteristics, DECAF score, and serum biomarkers were examined. RESULTS A total of 62 COPD patients were enrolled. These patients were classified as Global Initiative for Obstructive Lung Disease (GOLD) stage 2, 3, and 4 in 12.9%, 6.4%, and 80.7% of cases, respectively. Isolated bacterial exacerbation was recovered in 30.6% of exacerbation episodes: Klebsiella pneumoniae was the most commonly identified bacteria. Viral pathogens and coinfections were noted in 9.6% and 16.1% of exacerbated patients, respectively. Influenza was the most commonly detected viral pathogen. Serum biomarkers and DECAF score for viruses, bacteria, coinfection, and noninfectious causes of exacerbations were similar. Neither DECAF score nor serum biomarkers were able to differentiate patients with and without mortality or requiring mechanical ventilation. Increased serum PCT was noted in patients with LOS ≥7 days when compared with those with LOS <7 days (0.38 ng/mL vs 0.1 ng/mL; P=0.035). CONCLUSION Increased serum PCT is associated with longer LOS in COPD exacerbation. However, CRP and DECAF score play limited roles in predicting clinical outcome and lack an association with causes of exacerbation.

negative: [Clinical feature changes of a COVID-19 patient from mild to critical condition and cardiopulmonary pathological results]. Objective: To analyse the clinical history, laboratory tests and pathological data of a patient who suffered from novel coronavirus pneumonia(COVID-19) and provide reference for the clinical treatment of similar cases. Methods: Data of clinical manifestation, laboratory examination, bronchoscopy, echocardiography and cardiopulmonary pathological results were retrospectively reviewed in a case of COVID-19 with rapid exacerbation from mild to critical condition. Results: This patient hospitalized at day 9 post 2019 novel coronavirus(2019-nCoV) infection, experienced progressive deterioration from mild to severe at day 11, severe to critical at day 18 and underwent extracorporeal membrane oxygenation(ECMO) and continuous renal replacement therapy(CRRT) as well as heart lung transplantation during day 28-45 day post infection, and died on the second day post heart and lung transplantation. The patient had suffered from hypertension for 8 years. At the early stage of the disease, his symptoms were mild and the inflammatory indices increased and the lymphocyte count decreased continuously. The patient's condition exacerbated rapidly with multi-organ infections, and eventually developed pulmonary hemorrhage and consolidation, pulmonary hypertension, right heart failure, malignant ventricular arrhythmias, liver dysfunction, etc. His clinical manifestations could not be improved despite viral RNAs test results became negative. The patient underwent lung and heart transplantation and finally died of multi organ failure at the second day post lung and heart transplantation. Pathological examination indicated massive mucus, dark red secretions and blood clots in bronchus. The pathological changes were mainly diffused pulmonary hemorrhagic injuries and necrosis, fibrosis, small vessel disease with cardiac edema and lymphocyte infiltration. Conclusions: The clinical course of COVID-19 can exacerbate rapidly from mild to critical with lung, liver and heart injuries. Steadily increased inflammation indices are suggestive of irreversible disease progression and worse outcome. In the early stages of the disease, the progress of the disease should be closely observed and evaluated, and the factors related to the progress of the disease should be identified and managed.

negative: Characterization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia. Despite extensive laboratory investigations in patients with respiratory tract infections, no microbiological cause can be identified in a significant proportion of patients. In the past 3 years, several novel respiratory viruses, including human metapneumovirus, severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), and human coronavirus NL63, were discovered. Here we report the discovery of another novel coronavirus, coronavirus HKU1 (CoV-HKU1), from a 71-year-old man with pneumonia who had just returned from Shenzhen, China. Quantitative reverse transcription-PCR showed that the amount of CoV-HKU1 RNA was 8.5 to 9.6 x 10(6) copies per ml in his nasopharyngeal aspirates (NPAs) during the first week of the illness and dropped progressively to undetectable levels in subsequent weeks. He developed increasing serum levels of specific antibodies against the recombinant nucleocapsid protein of CoV-HKU1, with immunoglobulin M (IgM) titers of 1:20, 1:40, and 1:80 and IgG titers of <1:1,000, 1:2,000, and 1:8,000 in the first, second and fourth weeks of the illness, respectively. Isolation of the virus by using various cell lines, mixed neuron-glia culture, and intracerebral inoculation of suckling mice was unsuccessful. The complete genome sequence of CoV-HKU1 is a 29,926-nucleotide, polyadenylated RNA, with G+C content of 32%, the lowest among all known coronaviruses with available genome sequence. Phylogenetic analysis reveals that CoV-HKU1 is a new group 2 coronavirus. Screening of 400 NPAs, negative for SARS-CoV, from patients with respiratory illness during the SARS period identified the presence of CoV-HKU1 RNA in an additional specimen, with a viral load of 1.13 x 10(6) copies per ml, from a 35-year-old woman with pneumonia. Our data support the existence of a novel group 2 coronavirus associated with pneumonia in humans.

negative: 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.

negative: New immunization strategies: adapting to global challenges Immunization has made an enormous contribution to global health. Global vaccination coverage has dramatically improved and mortality rates among children due to vaccine-preventable diseases have been significantly reduced since the creation of the Expanded Programme of Immunization in 1974, the formation of Gavi, the Vaccine Alliance, in 2000, and the development of the Global Vaccine Action Plan in 2012. However, challenges remain and persisting inequities in vaccine uptake contribute to the continued occurrence and outbreaks of vaccine-preventable diseases. Inequalities in immunization coverage by geography, urban-rural, and socio-economic status jeopardize the achievement of global immunization goals and call for renewed immunization strategies. These should take into account emerging opportunities for building better immunization systems and services, as well as the development of new vaccine products and delivery technologies. Such strategies need to achieve equity in vaccination coverage across and within countries. This will require the participation of communities, a better understanding of vaccine acceptance and hesitancy, the expansion of vaccination across the life course, approaches to improve immunization in middle-income countries, enhanced use of data and possible financial and non-financial incentives. Vaccines also have an important role to play in comprehensive disease control, including the fight against antimicrobial resistance. Lessons learned from disease eradication and elimination efforts of polio, measles and maternal and neonatal tetanus are instrumental in further enhancing global immunization strategies in line with the revised goals and targets of the new Immunization Agenda 2030, which is currently being developed.

negative: Prognostic and predictive enrichment in sepsis Sepsis is a heterogeneous disease state that is both common and consequential in critically ill patients. Unfortunately, the heterogeneity of sepsis at the individual patient level has hindered advances in the field beyond the current therapeutic standards, which consist of supportive care and antibiotics. This complexity has prompted attempts to develop a precision medicine approach, with research aimed towards stratifying patients into more homogeneous cohorts with shared biological features, potentially facilitating the identification of new therapies. Several investigators have successfully utilized leukocyte-derived mRNA and discovery-based approaches to subgroup patients on the basis of biological similarities defined by transcriptomic signatures. A critical next step is to develop a consensus sepsis subclassification system, which includes transcriptomic signatures as well as other biological and clinical data. This goal will require collaboration among various investigative groups, and validation in both existing data sets and prospective studies. Such studies are required to bring precision medicine to the bedside of critically ill patients with sepsis.

negative: Acute phase proteins as local biomarkers of respiratory infection in calves BACKGROUND: Cumulating reports suggest that acute phase proteins (APPs) do not only play a role as systemic inflammatory mediators, but are also expressed in different tissues as local reaction to inflammatory stimuli. The present study aimed to evaluate presence and changes in luminal lung concentrations of the APPs haptoglobin (Hp), lipopolysaccharide binding protein (LBP), C-reactive protein (CRP), and lactoferrin (Lf) in calves with an acute respiratory disease experimentally induced by Chlamydia (C.) psittaci. RESULTS: Intra-bronchial inoculation of the pathogen resulted in a consistent respiratory illness. In venous blood of the infected calves (n = 13), concentrations of plasma proteins and serum LBP were assessed (i) before exposure and (ii) 8 times within 14 days after inoculation (dpi). Increasing clinical illness correlated significantly with increasing LBP—and decreasing albumin concentrations in blood, both verifying a systemic acute phase response. Broncho-alveolar lavage fluid (BALF) was obtained from all 13 calves experimentally infected with C. psittaci at 4, 9 and 14 dpi, and from 6 uninfected healthy calves. Concentrations of bovine serum albumin (BSA), Hp, LBP, CRP and Lf in BALF were determined by ELISA. In infected animals, absolute concentrations of LBP and Hp in BALF correlated significantly with the respiratory score. The quotient [LBP]/[BSA] in BALF peaked significantly in acutely infected animals (4 dpi), showed a time-dependent decrease during the recovery phase (9-14 dpi), and was significantly higher compared to healthy controls. Concentrations of Hp and Lf in BALF as well as [Hp]/[BSA]—and [Lf]/[BSA]-quotients decreased during the study in infected animals, but were never higher than in healthy controls. CRP concentrations and [CRP]/[BSA]-quotient did not express significant differences between infected and healthy animals or during the course of infection. CONCLUSION: In conclusion, absolute concentrations of LBP in blood and BALF as well as the quotient [LBP]/[BSA] in BALF perfectly paralleled the clinical course of respiratory illness after infection. Beside LBP, the suitability of Hp and Lf as local biomarkers of respiratory infections in cattle and their role in the local response to pathogens is worth further investigation, while CRP does not seem to play a role in local defense mechanisms of the bovine lung.

negative: New approaches to sepsis: molecular diagnostics and biomarkers. Sepsis is among the most common causes of death in hospitals. It arises from the host response to infection. Currently, diagnosis relies on nonspecific physiological criteria and culture-based pathogen detection. This results in diagnostic uncertainty, therapeutic delays, the mis- and overuse of antibiotics, and the failure to identify patients who might benefit from immunomodulatory therapies. There is a need for new sepsis biomarkers that can aid in therapeutic decision making and add information about screening, diagnosis, risk stratification, and monitoring of the response to therapy. The host response involves hundreds of mediators and single molecules, many of which have been proposed as biomarkers. It is, however, unlikely that one single biomarker is able to satisfy all the needs and expectations for sepsis research and management. Among biomarkers that are measurable by assays approved for clinical use, procalcitonin (PCT) has shown some usefulness as an infection marker and for antibiotic stewardship. Other possible new approaches consist of molecular strategies to improve pathogen detection and molecular diagnostics and prognostics based on transcriptomic, proteomic, or metabolic profiling. Novel approaches to sepsis promise to transform sepsis from a physiologic syndrome into a group of distinct biochemical disorders and help in the development of better diagnostic tools and effective adjunctive sepsis therapies.

negative: 1583. The Utility of the Immunodeficiency Scoring Index (ISI) to Predict Outcomes of Coronavirus (HCoV) Infections in Hematopietic Cell Transplant (HCT) Recipients BACKGROUND: Respiratory viral infections in HCT recipients are associated with high morbidity and mortality, especially after progression from upper respiratory tract infection (URI) to lower respiratory tract infections (LRI). Data on risk factors (RF) for LRI and mortality is lacking for HCoV infections after HCT. We aimed to validate our ISI in HCoV infections. METHODS: All adult HCT recipients with HCoV infection from 2015 to 2017 were evaluated. An ISI based on RF was used to classify patients as low (0–2), moderate (3–6), or high (7 or higher) risk for progression to LRI or death. We defined LRI as HCoV detected in nasal wash and/or bronchoalveolar lavage and new lung infiltrates on diagnostic imaging. Clinical parameters were collected and ISI were calculated for comparison. RESULTS: A total of 144 adult HCT recipients with 166 episodes of HCoV infections were analyzed. The most common HCoV serotype for LRI and URI was 229E (42.4%) and OC43 (37.6%), respectively, and most patients were infected between November and March each year (Figures 1 and 2). When compared with URI, patients with LRI were more likely in the pre-engraftment period, had multiple respiratory viruses infections, had nosocomially acquired HCoV, required hospitalization, ICU transfer, and mechanical ventilation (all, P < 0.05). Overall mortality rate was 4% at Day 30 from diagnosis and all patients who died had LRI with an 18% mortality. Among those who died, 33% had nosocomial infection, 67% were co-infected with another respiratory virus and 67% required mechanical ventilation. Using an ISI cut off of <4, the negative predictive value (NPV) for progression to LRI was 86% with a specificity of 76%. CONCLUSION: HCT recipients with HCoV LRI were more likely to have a fatal outcome. The NPV of the ISI for progression to LRI was high and could be used as a prognostic tool for future studies and for therapeutic clinical trials. DISCLOSURES: All authors: No reported disclosures.

negative: Immunological characterizations of the nucleocapsid protein based SARS vaccine candidates The recombinant nucleocapsid (rN) protein of the coronavirus (CoV) responsible for severe acute respiratory syndrome (SARS) was cloned and expressed in Escherichia coli, extracted from cell lysates containing 6 M urea, then purified by Ni(2+)-affinity chromatography. In animal immunogenicity studies, we found that most anti-rN protein antibodies were IgG2a in BALB/c mice vaccinated with rN emulsified in Montanide ISA-51 containing the synthetic oligodeoxynucleotide, CpG. In contrast, anti-rN protein antibodies of mice immunized with rN protein in PBS were found to mainly be IgG1. These results indicated that ISA-51/CpG-formulated rN protein was dramatically biased toward a Th1 immune response. To identify the B-cell immunodominant epitopes of the rN protein in the mouse and monkey, the reactivities of antisera raised against purified rN proteins formulated in ISA-51/CpG were tested with a panel of overlapping synthetic peptides covering the entire N protein sequence. Three immunodominant linear B-cell epitope regions were mapped to residues 166–180, 356–375, and 396–410 of the rN protein. When the reactivities of these peptides were screened with human sera from five SARS patients, peptides corresponding to residues 156–175 reacted strongly with sera from two of the SARS patients. These results indicated that the region around residues 156–175 of the N protein is immunogenic in the mouse, monkey, and human. We found that peptides corresponding to residues 1–30, 86–100, 306–320, and 351–365 contained murine immunodominant T-cell epitopes. To identify functional CTL epitopes of the N protein, BALB/c mice were immunized with peptides containing the H-2K(d) CTL motif emulsified in adjuvant ISA-51/CpG. Using an IFN-γ secretion cell assay and analysis by flow cytometry, peptides containing residues 81–95 were found to be capable of stimulating both CD4(+) and CD8(+) cell proliferation in vitro. We also only observed that peptides corresponding to residues 336–350 were capable of stimulating IFN-γ production in T-cell cultures derived from peripheral blood mononuclear cells (PBMCs) of macaques immunized with the rN protein emulsified in ISA/CpG adjuvant. Our current results together with those of others suggest that some immunodominant B-cell and T-cell epitopes are conserved in the mouse, monkey, and human. This information is very important for the development SARS diagnostic kits and a vaccine.

negative: Hospitalized Patients with Acute Pneumonia Pneumonia is one of the leading causes of mortality and hospitalization among US adults. The decision to admit patients from the emergency department is a major one because of its impact on patients and the hospital. The diagnosis of pneumonia is often clinical and based on symptoms and signs combined with radiographic findings. There are multiple severity assessments available that can guide treatment, prognosis, and disposition. Viruses are an important cause of pneumonia and require early recognition and treatment. The recommended treatment for community-acquired pneumonia includes a beta lactam plus a macrolide or a respiratory fluoroquinolone.

negative: IL-21 optimizes T cell and humoral responses in the central nervous system during viral encephalitis Acute coronavirus encephalomyelitis is controlled by T cells while humoral responses suppress virus persistence. This study defines the contribution of interleukin (IL)-21, a regulator of T and B cell function, to central nervous system (CNS) immunity. IL-21 receptor deficiency did not affect peripheral T cell activation or trafficking, but dampened granzyme B, gamma interferon and IL-10 expression by CNS T cells and reduced serum and intrathecal humoral responses. Viral control was already lost prior to humoral CNS responses, but demyelination remained comparable. These data demonstrate a critical role of IL-21 in regulating CNS immunity, sustaining viral persistence and preventing mortality.

negative: Norwegian Coronavirus Disease 2019 (NO COVID-19) Pragmatic Open label Study to assess early use of hydroxychloroquine sulphate in moderately severe hospitalised patients with coronavirus disease 2019: A structured summary of a study protocol for a randomised controlled trial OBJECTIVES: The hypothesis of the study is that treatment with hydroxychloroquine sulphate in hospitalised patients with coronavirus disease 2019 (Covid-19) is safe and will accelerate the virological clearance rate for patients with moderately severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) when compared to standard care. Furthermore, we hypothesize that early treatment with hydroxychloroquine sulphate is associated with more rapid resolve of clinical symptoms as assessed by the National Early Warning Score 2 (NEWS2), decreased admission rate to intensive care units and mortality, and improvement in protein biomarker profiles (C-reactive protein, markers of renal and hepatic injury, and established cardiac biomarkers like cardiac troponin and B-type natriuretic peptide). TRIAL DESIGN: The study is a two-arm, open label, pragmatic randomised controlled group sequential adaptive trial designed to assess the effect on viral loads and clinical outcome of hydroxychloroquine sulphate therapy in addition to standard care compared to standard care alone in patients with established Covid-19. By utilizing resources already paid for by the hospitals (physicians and nurses in daily clinical practice), this pragmatic trial can include a larger number of patients over a short period of time and at a lower cost than studies utilizing traditional randomized controlled trial designs with an external study organization. The pragmatic approach will enable swift initiation of randomisation and allocation to treatment. PARTICIPANTS: Patients will be recruited from all inpatients at Akershus University Hospital, Lørenskog, Norway. Electronic real-time surveillance of laboratory reports from the Department of Microbiology will be examined regularly for SARS-CoV-2 positive subjects. All of the following conditions must apply to the prospective patient at screening prior to inclusion: (1) Hospitalisation; (2) Adults 18 years or older; (3) Moderately severe Covid-19 disease (NEWS2 of 6 or less); (4) SARS-CoV-2 positive nasopharyngeal swab; (5) Expected time of hospitalisation > 48 hours; and (6) Signed informed consent must be obtained and documented according to Good Clinical Practice guidelines of the International Conference on Harmonization, and national/local regulations. Patients will be excluded from participation in the study if they meet any of the following criteria: (1) Requiring intensive care unit admission at screening; (2) History of psoriasis; (3) Known adverse reaction to hydroxychloroquine sulphate; (4) Pregnancy; or (5) Prolonged corrected QT interval (>450 ms). Clinical data, including standard hospital biochemistry, medical therapy, vital signs, NEWS2, and microbiology results (including blood culture results and reverse transcriptase polymerase chain reaction [RT-PCR] for other upper airway viruses), will be automatically extracted from the hospital electronic records and merged with the study specific database. INTERVENTION AND COMPARATOR: Included patients will be randomised in a 1:1 ratio to (1) standard care with the addition of 400 mg hydroxychloroquine sulphate (PlaquenilTM) twice daily for seven days or (2) standard care alone. MAIN OUTCOMES: The primary endpoint of the study is the rate of decline in SARS-CoV-2 viral load in oropharyngeal samples as assessed by RT-PCR in samples collected at baseline, 48 and 96 hours after randomization and administration of drug for the intervention arm. Secondary endpoints include change in NEWS2 at 96 hours after randomisation, admission to intensive care unit, mortality (in-hospital, and at 30 and 90 days), duration of hospital admission, clinical status on a 7-point ordinal scale 14 days after randomization ([1] Death [2] Hospitalised, on invasive mechanical ventilation or extracorporeal membrane oxygenation [3] Hospitalised, on non-invasive ventilation or high flow oxygen devices [4] Hospitalized, requiring supplemental oxygen [5] Hospitalised, not requiring supplemental oxygen [6] Not hospitalized, but unable to resume normal activities [7] Not hospitalised, with resumption of normal activities), and improvement in protein biomarker profiles (C-reactive protein, markers of renal and hepatic injury, and established cardiac biomarkers like cardiac troponin and B-type natriuretic peptide) at 96 hours after randomization. RANDOMISATION: Eligible patients will be allocated in a 1:1 ratio, using a computer randomisation procedure. The allocation sequence has been prepared by an independent statistician. BLINDING (MASKING): Open label randomised controlled pragmatic trial without blinding, no active or placebo control. The virologist assessing viral load in the oropharyngeal samples and the statistician responsible for analysis of the data will be blinded to the treatment allocation for the statistical analyses. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): This is a group sequential adaptive trial where analyses are planned after 51, 101, 151 and 202 completed patients, with a maximum sample size of 202 patients (101 patients allocated to intervention and standard care and 101 patients allocated to standard care alone). TRIAL STATUS: Protocol version 1.3 (March 26, 2020). Recruitment of first patient on March 26, 2020, and 51 patients were included as per April 28, 2020. Study recruitment is anticipated to be completed by July 2020. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT04316377. Trial registered March 20, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

negative: Implications of COVID-19 for the management of patients with inflammatory rheumatic diseases

negative: Mouse Hepatitis Virus This chapter attempts to provide an overview of the important aspects of mouse hepatitis virus (MHV) experimental biology while emphasizing the virus as a naturally occurring mouse pathogen. Even this is complicated, as it is impossible to generalize with this virus, due to marked differences in the biologic behavior of the myriad virus strains, plus the marked effects of a large number of host factors. It is now known that the MHV group is represented by numerous variants that are constantly mutating, and that these viruses can be biologically separated into respiratory (polytropic) MHVs and enterotropic MHVs, with distinctly different patterns of tissue tropism. This dichotomy is emphasized for discussion, but biology is never absolute. Many of the early MHV isolations are made as a result of contamination of biological materials that correlated with their polytropic biologic behavior. Their stated tropisms frequently were the result of the investigators' research interests and many have therefore been subjected to selective passage that favors a particular tissue tropism. All MHV isolates are related genetically and antigenically, but isolates can be differentiated by genetic sequencing, cross-serum neutralization, or with monoclonal antibodies. Genetic and antigenic relationships are not predictive of biologic behavior.

negative: 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.

negative: The Use of Adjuvant Therapy in Preventing Progression to Severe Pneumonia in Patients with Coronavirus Disease 2019: A Multicenter Data Analysis ABSTRACT IMPORTANCE Coronavirus disease 2019 (COVID-19) is a global pandemic associated with high mortality and effective treatment to prevent clinical deterioration to severe pneumonia has not yet been well clarified. OBJECTIVE To investigate the role of several adjuvant treatments in preventing severe pneumonia in patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS Multicenter, retrospective cohort study of 564 consecutively hospitalized patients with confirmed COVID-19 at Third Xiangya Hospital of Central South University, Changsha Public Health Treatment Center, First Hospital of Yueyang, Junshan People's Hospital of Yueyang, Central Hospital of Shaoyang, Central Hospital of Xiangtan, Second Hospital of Changde, Central Hospital of Loudi, and First Affiliated Hospital of University of South China in Hunan province from January 17, 2020 to February 28, 2020; The final date of follow-up was March 15, 2020. EXPOSURES Nonspecific antivirals (arbidol, lopinavir/ritonavir, and interferon α), antihypertensives, and chloroquine. MAIN OUTCOMES AND MEASURES The development of severe COVID-19 pneumonia; Demographic, epidemiological, clinical, laboratory, radiological, and treatment data were collected and analyzed. RESULTS Of 564 patients, the median age was 47 years (interquartile range, 36-58 years), and 284 (50.4%) patients were men. Sixty-nine patients (12.2%) developed severe pneumonia. Patients who developed severe pneumonia were older (median age of 59 and 45 years, respectively), and more patients had comorbidities including hypertension (30.4% and 12.3%, respectively), diabetes (17.4% and 6.7%, respectively), and cardiovascular disease (8.7% and 3.2%, respectively) and presented with fever (84.1% and 60.4%, respectively) and shortness of breath (10.1% and 3.8%, respectively) compared with those who did not. Nonspecific antiviral therapy did not prevent clinical progression to severe pneumonia, although fewer hypertensive patients on angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers (ACEI/ARB) therapy developed severe pneumonia in contrast with those on non-ACEI/ARB antihypertensive therapy (1 of 16 [6.3%] patients and 16 of 49 [32.7%] patients, respectively [difference, 26.4%; 95% CI, 1.5% to 41.3%]). Multivariate logistic regression analysis showed that hypertension without receiving ACEI/ARB therapy was an independent risk factor (odds ratio [OR], 2.07; 95% CI, 1.07 to 4.00) for developing severe pneumonia irrespective of age. Besides, none of patients treated with chloroquine developed severe pneumonia, though without significance (difference, 12.0%; 95% CI, -3.5% to 30.0%) by propensity score matching. CONCLUSIONS AND RELEVANCE Hypertensive patients on ACEI or ARB may be protective from severe pneumonia in COVID-19 and hence these therapies should not be ceased unless there is a strong indication or further epidemiological evidence. Though none of the current antiviral and immunoregulation therapy showed benefit in preventing COVID-19 progression, chloroquine deserved further investigation.

negative: Diagnostic accuracy of C-reactive protein and procalcitonin in suspected community-acquired pneumonia adults visiting emergency department and having a systematic thoracic CT scan INTRODUCTION: Community-acquired pneumonia (CAP) requires prompt treatment, but its diagnosis is complex. Improvement of bacterial CAP diagnosis by biomarkers has been evaluated using chest X-ray infiltrate as the CAP gold standard, producing conflicting results. We analyzed the diagnostic accuracy of biomarkers in suspected CAP adults visiting emergency departments for whom CAP diagnosis was established by an adjudication committee which founded its judgment on a systematic multidetector thoracic CT scan. METHODS: In an ancillary study of a multi-center prospective study evaluating the impact of systematic thoracic CT scan on CAP diagnosis, sensitivity and specificity of C-reactive protein (CRP) and procalcitonin (PCT) were evaluated. Systematic nasopharyngeal multiplex respiratory virus PCR was performed at inclusion. An adjudication committee classified CAP diagnostic probability on a 4-level Likert scale, based on all available data. RESULTS: Two hundred patients with suspected CAP were analyzed. The adjudication committee classified 98 patients (49.0 %) as definite CAP, 8 (4.0 %) as probable, 23 (11.5 %) as possible and excluded in 71 (35.5 %, including 29 patients with pulmonary infiltrates on chest X-ray). Among patients with radiological pulmonary infiltrate, 23 % were finally classified as excluded. Viruses were identified by PCR in 29 % of patients classified as definite. Area under the curve was 0.787 [95 % confidence interval (95 % CI), 0.717 to 0.857] for CRP and 0.655 (95 % CI, 0.570 to 0.739) for PCT to detect definite CAP. CRP threshold at 50 mg/L resulted in a positive predictive value of 0.76 and a negative predictive value of 0.75. No PCT cut-off resulted in satisfactory positive or negative predictive values. CRP and PCT accuracy was not improved by exclusion of the 25 (25.5 %) definite viral CAP cases. CONCLUSIONS: For patients with suspected CAP visiting emergency departments, diagnostic accuracy of CRP and PCT are insufficient to confirm the CAP diagnosis established using a gold standard that includes thoracic CT scan. Diagnostic accuracy of these biomarkers is also insufficient to distinguish bacterial CAP from viral CAP. TRIAL REGISTRATION: ClinicalTrials.gov registry NCT01574066 (February 7, 2012) ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-1083-6) contains supplementary material, which is available to authorized users.

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: Disease control of 2019-novel coronavirus infection in hospital: West China urgent recommendation/ 新型冠状病毒感染医院内防控的华西紧急推荐 China is facing the serious situation of 2019-novel coronavirus (2019-nCoV) infection. The health care institutions have actively participated in the prevention, diagnosis, and treatment of the disease. Proper regulation of in-hospital policy may help control virus spreading. We developed seven key clinical questions about the prevention and control of 2019-novel coronavirus infection in a hospital, and provided recommendations based on the best available evidence and expert experience. We interpret the recommendations for better feasibility in Chinese hospital. We hope to provide evidence and reference for the domestic medical institutions to reasonably adjust the hospital workflow during 2019-nCoV infection period.

negative: Main factors influencing recovery in MERS Co-V patients using machine learning Abstract Background Middle East Respiratory Syndrome (MERS) is a major infectious disease which has affected the Middle Eastern countries, especially the Kingdom of Saudi Arabia (KSA) since 2012. The high mortality rate associated with this disease has been a major cause of concern. This paper aims at identifying the major factors influencing MERS recovery in KSA. Methods The data used for analysis was collected from the Ministry of Health website, KSA. The important factors impelling the recovery are found using machine learning. Machine learning models such as support vector machine, conditional inference tree, naïve Bayes and J48 are modelled to identify the important factors. Univariate and multivariate logistic regression analysis is also carried out to identify the significant factors statistically. Result The main factors influencing MERS recovery rate are identified as age, pre-existing diseases, severity of disease and whether the patient is a healthcare worker or not. In spite of MERS being a zoonotic disease, contact with camels is not a major factor influencing recovery. Conclusion The methods used were able to determine the prime factors influencing MERS recovery. It can be comprehended that awareness about symptoms and seeking medical intervention at the onset of development of symptoms will make a long way in reducing the mortality rate.

negative: Novel translational approaches to the search for precision therapies for acute respiratory distress syndrome Summary In the 50 years since acute respiratory distress syndrome (ARDS) was first described, substantial progress has been made in identifying the risk factors for and the pathogenic contributors to the syndrome and in characterising the protein expression patterns in plasma and bronchoalveolar lavage fluid from patients with ARDS. Despite this effort, however, pharmacological options for ARDS remain scarce. Frequently cited reasons for this absence of specific drug therapies include the heterogeneity of patients with ARDS, the potential for a differential response to drugs, and the possibility that the wrong targets have been studied. Advances in applied biomolecular technology and bioinformatics have enabled breakthroughs for other complex traits, such as cardiovascular disease or asthma, particularly when a precision medicine paradigm, wherein a biomarker or gene expression pattern indicates a patient's likelihood of responding to a treatment, has been pursued. In this Review, we consider the biological and analytical techniques that could facilitate a precision medicine approach for ARDS.

negative: Coronaviruses: An Overview of Their Replication and Pathogenesis Coronaviruses (CoVs), enveloped positive-sense RNA viruses, are characterized by club-like spikes that project from their surface, an unusually large RNA genome, and a unique replication strategy. Coronaviruses cause a variety of diseases in mammals and birds ranging from enteritis in cows and pigs and upper respiratory disease chickens to potentially lethal human respiratory infections. Here we provide a brief introduction to coronaviruses discussing their replication and pathogenicity, and current prevention and treatment strategies. We will also discuss the outbreaks of the highly pathogenic Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the recently identified Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV).

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: Procalcitonin as a prognostic marker for sepsis based on SEPSIS‐3 BACKGROUND: The revised definition of sepsis is life‐threatening organ dysfunction caused by a dysregulated host response to infection (SEPSIS‐3). The objective of this study was to evaluate procalcitonin (PCT) for the diagnosis and prognosis of sepsis using SEPSIS‐3. METHODS: We enrolled 248 patients, who were admitted to the emergency department with suspected bacterial infection from June 2016 to February 2017. Definite bacterial infection was defined by proven culture results, and probable bacterial infection was based on diagnostic modalities other than culture. The sequential organ failure assessment (SOFA) score of 2 points or more from the baseline was diagnosed as sepsis. PCT was measured by the AFIAS‐6 immunoassay system (Boditech Med Inc.) using whole blood. White blood cell (WBC), C‐reactive protein (CRP), and erythrocyte sedimentation rate (ERS) were evaluated. RESULTS: The final diagnosis was sepsis in 185 patients with infection of respiratory and genitourinary tract constituted 84.6%. The area under the receiver operating characteristic curve (AUROC) with 95% confidence interval (CI) was as follows: PCT, 0.682 (0.589‐0.765); CRP, 0.583 (0.487‐0.673); ESR, 0.540 (0.515‐0.699); and WBC, 0.611 (0.455‐0.633), respectively. In multivariate analysis, age, SOFA, and PCT (log scale) predicted non‐survivors with an odds ratio with 95% confidence interval of 1.055 (1.008‐1.105), 1.303 (1.142‐1.486), and 2.004 (1.240‐3.238), respectively. Among sepsis group, initial PCT was increased in non‐survivor (23.2 ng/dL) compared to survivor group (8.1 ng/dL) with statistical significance (P = .005). CONCLUSIONS: PCT could support and predict the unfavorable prognosis of sepsis based on SEPSIS‐3, whereas diagnostic potential of PCT requires further evaluations.

negative: Fatal outcome in a liver transplant recipient with COVID-19 Liver injury is common in patients with COVID-19, but little is known about its clinical presentation and severity in the context of liver transplant. We describe a case of COVID-19 in a patient who underwent transplant 3 years ago for hepatocellular carcinoma. The patient came to clinic with symptoms of respiratory disease; pharyngeal swabs for severe acute respiratory syndrome coronavirus 2 were positive. His disease progressed rapidly from mild to critical illness and was complicated by several nosocomial infections and multiorgan failure. Despite multiple invasive procedures and rescue therapies, he died from the disease. The management of COVID-19 in the posttransplant setting presents complex challenges, emphasizing the importance of strict prevention strategies.

negative: Machine learning in predicting respiratory failure in patients with COVID-19 pneumonia - challenges, strengths, and opportunities in a global health emergency Background Machine learning can assist clinicians in forecasting patients with COVID-19 who develop respiratory failure requiring mechanical ventilation. This analysis aimed to determine a 48 hours prediction of moderate to severe respiratory failure, as assessed with PaO2/FiO2 < 150 mmHg, in hospitalized patients with COVID-19 pneumonia. Methods This was an observational study that comprised all consecutive adult patients with COVID-19 pneumonia admitted to the Infectious Diseases Clinic of the University Hospital of Modena, Italy from 21 February to 6 April 2020. COVID-19 was confirmed with PCR positive nasopharyngeal swabs while the presence of pneumonia was radiologically confirmed. Patients received standard of care according to national guidelines for clinical management of SARS-CoV-2 infection. The patients' full medical history, demographic and epidemiological features, clinical data, complete blood count, coagulation, inflammatory and biochemical markers were routinely collected and aggregated in a clinically-oriented logical framework in order to build different datasets. The dataset was used to train a learning framework relying on Microsoft LightGBM and leveraging a hybrid approach, where clinical expertise is applied alongside a data-driven analysis. Shapley Additive exPlanations (SHAP) values were used to quantify the positive or negative impact of each variable included in the model on the predicted outcome. The study outcome was the onset of moderate to severe respiratory failure defined as PaO2/FiO2 ratio < 150 mmHg ([≥] 13.3 kPa) in at least one of two consecutive arterial blood gas analyses in the following 48 hours. Results A total of 198 patients contributed to generate 1068 valuable observations which allowed to build 3 prediction models based respectively on 31-variables signs and symptoms, 39-variables laboratory biomarkers and 91-variables as a composition of the two. A fourth boosted mixed model which included 20 variables was selected from the model 3, achieved the best predictive performance (AUC=0.84). Its clinical performance was applied in a narrative case report as an example. Conclusion This study developed a machine learning algorithm, with a 84% prediction accuracy, which is potentially able to assist clinicians in decision making process with therapeutic implications.

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: Recent advances in the understanding and management of cystic fibrosis pulmonary exacerbations Pulmonary exacerbations are common events in cystic fibrosis and have a profound impact on quality of life, morbidity, and mortality. Pulmonary exacerbation outcomes remain poor and a significant proportion of patients fail to recover their baseline lung function despite receiving aggressive treatment with intravenous antibiotics. This focused review provides an update on some of the recent advances that have taken place in our understanding of the epidemiology, pathophysiology, diagnosis, and management of pulmonary exacerbations in cystic fibrosis as well as direction for future study.

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

negative: Metagenomic Sequencing Detects Respiratory Pathogens in Hematopoietic Cellular Transplant Patients Current microbiologic diagnostics often fail to identify the etiology of lower respiratory tract infections (LRTI) in hematopoietic cellular transplant recipients (HCT), which precludes the implementation of targeted therapies. To address the need for improved LRTI diagnostics, we evaluated the utility of metagenomic next generation sequencing (mNGS) of bronchoalveolar lavage (BAL) to detect microbial pathogens in HCT patients with acute respiratory illnesses. We enrolled 22 post-HCT adults ages 19-69 years with acute respiratory illnesses who underwent BAL at the University of Michigan between January 2012 and May 2013. mNGS was performed on BAL fluid to detect microbes and simultaneously assess the host transcriptional response. Results were compared against conventional microbiologic assays. mNGS demonstrated 100% sensitivity for detecting respiratory microbes (human metapneumovirus, respiratory syncytial virus, Stenotrophomonas maltophilia, human herpesvirus 6 and cytomegalovirus) when compared to standard testing. Previously unrecognized LRTI pathogens were identified in six patients for whom standard testing was negative (human coronavirus 229E, human rhinovirus A, Corynebacterium propinquum and Streptococcus mitis); findings were confirmed by independent PCR and 16S rRNA sequencing. Relative to patients without infection, patients with infection had increased expression of immunity related genes (p=0.022) and significantly lower diversity of their respiratory microbiome (p=0.017). Compared to conventional diagnostics, mNGS enhanced detection of pathogens in BAL fluid from HCT patients. Furthermore, our results suggest that combining unbiased microbial pathogen detection with assessment of host gene biomarkers of immune response may hold promise for enhancing the diagnosis of post-HCT respiratory infections.

negative: Coronavirus Disease 2019 and Cardiovascular System: A Narrative Review At the end of 2019, a viral pneumonia disease called coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), emerged in Wuhan, China. This novel disease rapidly spread at an alarming rate that as a result, it has now been declared pandemic by the World Health Organization. Although this infective disease is mostly characterized by respiratory tract symptoms, increasing numbers of evidence had shown considerable amounts of patients with cardiovascular involvements and these were associated with higher mortality among COVID-19 patients. Cardiac involvement as a possible late phenomenon of the viral respiratory infection is an issue that should be anticipated in patients with COVID-19. Cardiovascular manifestation in COVID-19 patients include myocardial injury (MI), arrhythmias, cardiac arrests, heart failure and coagulation abnormality, ranging from 7.2% up to 33%. The mechanism of cardiac involvement in COVID-19 patients involves direct injury to myocardial cells mediated by angiotensin-converting enzyme 2 (ACE2) receptors as suggested by some studies, while the other studies suggest that systemic inflammation causing indirect myocyte injury may also play a role. Combination of proper triage, close monitoring, and avoidance of some drugs that have cardiovascular toxicity are important in the management of cardiovascular system involvement in COVID-19 patients. The involvement of the cardiovascular system in COVID-19 patients is prevalent, variable, and debilitating. Therefore, it requires our attention and comprehensive management.

negative: COVID‐19 hypothesis: Activated protein C for therapy of virus‐induced pathologic thromboinflammation Seriously ill patients with coronavirus disease 2019 (COVID‐19) at risk for death exhibit elevated cytokine and chemokine levels and D‐dimer, and they often have comorbidities related to vascular dysfunctions. In preclinical studies, activated protein C (APC) provides negative feedback downregulation of excessive inflammation and thrombin generation, attenuates damage caused by ischemia‐reperfusion in many organs including lungs, and reduces death caused by bacterial pneumonia. APC exerts both anticoagulant activities and direct cell‐signaling activities. Preclinical studies show that its direct cell‐signaling actions mediate anti‐inflammatory and anti‐apoptotic actions, mortality reduction for pneumonia, and beneficial actions for ischemia‐reperfusion injury. The APC mutant 3K3A‐APC, which was engineered to have diminished anticoagulant activity while retaining cell‐signaling actions, was safe in phase 1 and phase 2 human trials. Because of its broad spectrum of homeostatic effects in preclinical studies, we speculate that 3K3A‐APC merits consideration for clinical trial studies in appropriately chosen, seriously ill patients with COVID‐19.

negative: COVID-19: room for treating T cell exhaustion?

negative: Developing Bioinformatic Resources for Coronaviruses

negative: Cardiovascular Implications and Therapeutic Considerations in COVID-19 Infection The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has profoundly impacted all fields of medicine. Infection with SARS-CoV-2 and the resulting coronavirus of 2019 (COVID-19) syndrome has multiorgan effects. The pandemic has united researchers from bench to bedside in attempts to understand the pathophysiology of the disease and define optimal treatment strategies. Cardiovascular disease is highly prevalent and a leading cause of death across gender, race, and ethnic groups. As the pandemic spreads, there is increasing concern about the cardiovascular effects of the viral infection and the interaction of infection with existing cardiovascular disease. Additionally, there are concerns about the cardiac effects of the numerous treatment agents under study. It will be essential for cardiologists to understand the interplay between underlying cardiac comorbidities, acute cardiovascular effects of COVID-19 disease, and adverse effects of new treatments. Here we describe emerging evidence of the epidemiology of SARS-CoV-2 infection and underlying cardiovascular disease, the evidence for direct myocardial injury in SARS-CoV-2 infection, the specific presentations of cardiovascular involvement by SARS-CoV-2, and the cardiac effects of emerging treatments.

negative: Aminopeptidase N Knockout Pigs Are Not Resistant to Porcine Epidemic Diarrhea Virus Infection

negative: Chapter Four Free Circulating miRNAs Measurement in Clinical Settings The Still Unsolved Issue of the Normalization Abstract Circulating molecules that are released into the circulation in response to specific stimuli are considered potential biomarkers for physiological or pathological processes. Their effective usefulness as biomarkers resides in their stability and high availability in all the biological fluids, combined with the limited invasiveness of intervention. Among the circulating molecules, miRNAs represent a novel class of biomarkers as they possess all the required characteristics such as sensitivity, predictivity, specificity, robustness, translatability, and noninvasiveness. miRNAs are small non-coding RNAs, that act as inhibitors of protein translation, and intervene in the complex network of the post-transcriptional mechanisms finely regulating gene expression. The emerging role of miRNAs as potential biomarkers for clinical applications (e.g., cancer and cardiovascular diseases diagnosis and prediction, musculoskeletal disease diagnosis and bone fracture risk prediction), however, requires the standardization of miRNA processing, from sample collection and sample storage, to RNA isolation, RNA reverse-transcription, and data analyses. Normalization is one of the most controversial issues related to quantitative Real-Time PCR data analysis since no universally accepted normalization strategies and reference genes exist, even more importantly, for circulating miRNA quantification. As it is widely demonstrated that the choice of different normalization strategies influences the results of gene expression analysis, it is important to select the most appropriate normalizers for each experimental set. This review discloses on the different strategies adopted in RT-qPCR miRNA normalization and the concerning issues to highlight on the need of a universally accepted methodology to make comparable the results produced by different studies.

negative: Primary biliary cirrhosis Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease with a slowly progressive course. Without treatment, most patients eventually develop fibrosis and cirrhosis of the liver and may need liver transplantation in the late stage of disease. PBC primarily affects women (female preponderance 9–10:1) with a prevalence of up to 1 in 1,000 women over 40 years of age. Common symptoms of the disease are fatigue and pruritus, but most patients are asymptomatic at first presentation. The diagnosis is based on sustained elevation of serum markers of cholestasis, i.e., alkaline phosphatase and gamma-glutamyl transferase, and the presence of serum antimitochondrial antibodies directed against the E2 subunit of the pyruvate dehydrogenase complex. Histologically, PBC is characterized by florid bile duct lesions with damage to biliary epithelial cells, an often dense portal inflammatory infiltrate and progressive loss of small intrahepatic bile ducts. Although the insight into pathogenetic aspects of PBC has grown enormously during the recent decade and numerous genetic, environmental, and infectious factors have been disclosed which may contribute to the development of PBC, the precise pathogenesis remains enigmatic. Ursodeoxycholic acid (UDCA) is currently the only FDA-approved medical treatment for PBC. When administered at adequate doses of 13–15 mg/kg/day, up to two out of three patients with PBC may have a normal life expectancy without additional therapeutic measures. The mode of action of UDCA is still under discussion, but stimulation of impaired hepatocellular and cholangiocellular secretion, detoxification of bile, and antiapoptotic effects may represent key mechanisms. One out of three patients does not adequately respond to UDCA therapy and may need additional medical therapy and/or liver transplantation. This review summarizes current knowledge on the clinical, diagnostic, pathogenetic, and therapeutic aspects of PBC.

negative: The cardiovascular burden of coronavirus disease 2019 (COVID-19) with a focus on congenital heart disease Abstract Coronavirus disease 2019 (COVID-19), caused by a novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first described in a cluster of patients presenting with pneumonia symptoms in Wuhan, China, in December of 2019. Over the past few months, COVID-19 has developed into a worldwide pandemic, with over 400,000 documented cases globally as of March 24, 2020. The SARS-CoV-2 virus is most likely of zoonotic origin, but has been shown to have effective human-to-human transmission. COVID-19 results in mild symptoms in the majority of infected patients, but can cause severe lung injury, cardiac injury, and death. Given the novel nature of COVID-19, no established treatment beyond supportive care exists currently, but extensive public-health measures to reduce person-to-person transmission of COVID-19 have been implemented globally to curb the spread of disease, reduce the burden on healthcare systems, and protect vulnerable populations, including the elderly and those with underlying medical comorbidities. Since this is an emerging infectious disease, there is, as of yet, limited data on the effects of this infection on patients with cardiovascular disease, particularly so for those with congenital heart disease. We summarize herewith the early experience with COVID-19 and consider the potential applicability to and implications for patients with cardiovascular disease in general and congenital heart disease in particular.

negative: Shotgun Transcriptome and Isothermal Profiling of SARS-CoV-2 Infection Reveals Unique Host Responses, Viral Diversification, and Drug Interactions The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused thousands of deaths worldwide, including >18,000 in New York City (NYC) alone. The sudden emergence of this pandemic has highlighted a pressing clinical need for rapid, scalable diagnostics that can detect infection, interrogate strain evolution, and identify novel patient biomarkers. To address these challenges, we designed a fast (30-minute) colorimetric test (LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs, plus a large-scale shotgun metatranscriptomics platform (total-RNA-seq) for host, bacterial, and viral profiling. We applied both technologies across 857 SARS-CoV-2 clinical specimens and 86 NYC subway samples, providing a broad molecular portrait of the COVID-19 NYC outbreak. Our results define new features of SARS-CoV-2 evolution, nominate a novel, NYC-enriched viral subclade, reveal specific host responses in interferon, ACE, hematological, and olfaction pathways, and examine risks associated with use of ACE inhibitors and angiotensin receptor blockers. Together, these findings have immediate applications to SARS-CoV-2 diagnostics, public health, and new therapeutic targets.

negative: Sugar-Binding Profiles of Chitin-Binding Lectins from the Hevein Family: A Comprehensive Study Chitin-binding lectins form the hevein family in plants, which are defined by the presence of single or multiple structurally conserved GlcNAc (N-acetylglucosamine)-binding domains. Although they have been used as probes for chito-oligosaccharides, their detailed specificities remain to be investigated. In this study, we analyzed six chitin-binding lectins, DSA, LEL, PWM, STL, UDA, and WGA, by quantitative frontal affinity chromatography. Some novel features were evident: WGA showed almost comparable affinity for pyridylaminated chitotriose and chitotetraose, while LEL and UDA showed much weaker affinity, and DSA, PWM, and STL had no substantial affinity for the former. WGA showed selective affinity for hybrid-type N-glycans harboring a bisecting GlcNAc residue. UDA showed extensive binding to high-mannose type N-glycans, with affinity increasing with the number of Man residues. DSA showed the highest affinity for highly branched N-glycans consisting of type II LacNAc (N-acetyllactosamine). Further, multivalent features of these lectins were investigated by using glycoconjugate and lectin microarrays. The lectins showed substantial binding to immobilized LacNAc as well as chito-oligosaccharides, although the extents to which they bound varied among them. WGA showed strong binding to heavily sialylated glycoproteins. The above observations will help interpret lectin-glycoprotein interactions in histochemical studies and glyco-biomarker investigations.

negative: Quantitative analysis of rutin, quercetin, naringenin, and gallic acid by validated RP- and NP-HPTLC methods for quality control of anti-HBV active extract of Guiera senegalensis Context:Guiera senegalensis J.F. Gmel (Combretaceae) is a folk medicinal plant used in various metabolic and infectious diseases. In addition to its antiviral activities against herpes and fowlpox, the anti-HBV efficacy is very recently reported. Objective: To develop and validate simple, sensitive RP-/NP-HPTLC methods for quantitative determination of biomarkers rutin, quercetin, naringenin, and gallic acid in the anti-HBV active G. senegalensis leaves ethanol-extract. Materials and methods: RP-HPTLC (rutin & quercetin; phase- acetonitrile:water, 4:6) and NP-HPTLC (naringenin & gallic acid; phase- toluene:ethyl acetate:formic acid, 6:4:0.8) were performed on glass-backed silica gel plates 60F(254)-RP18 and 60F(254), respectively. The methods were validated according to the ICH guidelines. Results: Well-separated and compact spots (R(f)) of rutin (0.52 ± 0.006), quercetin (0.23 ± 0.005), naringenin (0.56 ± 0.009) and gallic acid (0.28 ± 0.006) were detected. The regression equations (Y) were 12.434x + 443.49, 10.08x + 216.85, 11.253x + 973.52 and 11.082x + 446.41 whereas the coefficient correlations (r(2)) were 0.997 ± 0.0004, 0.9982 ± 0.0001, 0.9974 ± 0.0004 and 0.9981 ± 0.0001, respectively. The linearity ranges (ng/spot) were 200–1400 (RP-HPTLC) and 100–1200 (NP-HPTLC). The LOD/LOQ (ng/band) were 33.03/100.1 (rutin), 9.67/29.31 (quercetin), 35.574/107.8 (naringenin), and 12.32/37.35 (gallic acid). Gallic acid (7.01 μg/mg) was the most abundant biomarker compared to rutin (2.42 μg/mg), quercetin (1.53 μg/mg) and naringenin (0.14 μg/mg) in the extract. Conclusion: The validated NP-/RP-HPTLC methods were simple, accurate, and sensitive for separating and quantifying antiviral biomarkers in G. senegalensis, and endorsed its anti-HBV activity. The developed methods could be further employed in the standardization and quality-control of herbal formulations.

negative: The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus Antiviral drugs for managing infections with human coronaviruses are not yet approved, posing a serious challenge to current global efforts aimed at containing the outbreak of severe acute respiratory syndrome–coronavirus 2 (CoV-2). Remdesivir (RDV) is an investigational compound with a broad spectrum of antiviral activities against RNA viruses, including severe acute respiratory syndrome–CoV and Middle East respiratory syndrome (MERS–CoV). RDV is a nucleotide analog inhibitor of RNA-dependent RNA polymerases (RdRps). Here, we co-expressed the MERS–CoV nonstructural proteins nsp5, nsp7, nsp8, and nsp12 (RdRp) in insect cells as a part a polyprotein to study the mechanism of inhibition of MERS–CoV RdRp by RDV. We initially demonstrated that nsp8 and nsp12 form an active complex. The triphosphate form of the inhibitor (RDV-TP) competes with its natural counterpart ATP. Of note, the selectivity value for RDV-TP obtained here with a steady-state approach suggests that it is more efficiently incorporated than ATP and two other nucleotide analogs. Once incorporated at position i, the inhibitor caused RNA synthesis arrest at position i + 3. Hence, the likely mechanism of action is delayed RNA chain termination. The additional three nucleotides may protect the inhibitor from excision by the viral 3′–5′ exonuclease activity. Together, these results help to explain the high potency of RDV against RNA viruses in cell-based assays.

negative: Microarray Analysis of Gene Expression of Cancer to Guide the Use of Chemotherapeutics Summary The beauty of microarray analysis of gene expression (MAGE) is that it can be used to discover some genes that were previously thought to be unrelated to a physiologic or pathologic event. During the period from 1999 to 2007, applications of MAGE in cancer investigation have shifted from molecular profiling, identifying previously undiscovered cancer types, predicting outcomes of cancer patients, revealing metastasis signatures of solid tumors, to guiding the use of therapeutics. The roles of cancer genomic signatures have evolved through three phases. In the first phase, genomic signatures were described in stored cancer specimens and dubbed as molecular portraits of cancer. When gene expression profiles were carefully correlated with sufficient clinical information of cancer patients, new subgroups of cancers with distinct outcomes were revealed. In studies of the second phase, validation of cancer signatures was emphasized and commonly performed with independent groups of cancer specimens or independent data set. In the third phase, cancer genomic signatures have been further expanded beyond depicting the molecular portrait of cancer to predicting patient outcomes and guiding the use of cancer therapeutics. Cancer genomic signatures have become an essential part of a new generation of cancer clinical trials. It is advocated that, in future clinical trials of cancer therapy, the cancer specimens of each participant should be tested for currently available predictor genomic signatures, so that the most effective treatment with the least adverse effects for each patient can be identified. Then, participants can be triaged to an appropriate study group.

negative: An Invited Commentary on ‘ Evidence Based Management Guideline for the COVID-19 Pandemic- Review article’ Abstract COVID 19 been declared recently as a pandemic, to date has affected over 1,8881,365 with over 119,403 deaths in accordance to the global pandemic Real-Time Report. In this paper, the prime motive is to enlighten the key variables to the public on the pandemic and essential key points to note and practice in accordance to standard regulation to curb the aggressive COVID-19 pandemic. Author Summary To date over one(1) million persons have been affected indicating exponential spread of the disease and more rigorous implementation and adherence to more strengthen restrictions of social distancing would mitigate the spread of the pandemic disease and may prove to be even tedious.

negative: Pentraxin 3 as a clinical marker in children with lower respiratory tract infection BACKGROUND: Pentraxin 3 (PTX‐3) is an acute‐phase protein that increases in the plasma during inflammation. OBJECTIVE: We aimed to evaluate the usefulness of PTX‐3 as a clinical marker in children with lower respiratory tract infection (LRTI) and examine the correlation of PTX‐3 with other biomarkers such as C‐reactive protein (CRP) and procalcitonin (PCT). METHODS: We enrolled 117 consecutive patients admitted to Seoul St. Mary's Hospital with LRTI using the WHO criteria. We recorded data on fever duration and peak temperature before admission, duration of fever after admission, respiratory rate, heart rate, oxygen saturation upon admission, duration of oxygen supplementation, and duration of hospital stay. Upon admission, white blood cell (WBC) count, erythrocyte sedimentation rate, CRP level were measured. Multiplex respiratory virus polymerase chain reaction was performed using nasal swabs. PTX‐3, PCT, and various cytokines were measured after the study had been completed. RESULTS: We found that there was no significant difference in the level of PTX‐3 according to the type of viral infection. PTX‐3 levels showed a significant correlation with PCT levels, but not with levels of CRP. The level of PTX‐3 showed a significant correlation with peak temperature and duration of fever before admission as well as interleukin (IL)‐6 levels. PCT levels showed a significant correlation with IL‐6 and granulocyte‐colony stimulating factor levels, peak temperature, and duration of fever before admission, and duration of hospital stay. CRP levels showed a significant correlation with duration of fever before admission, total WBC count, and neutrophil count. PCT levels significantly predicted a hospital stay of 7 days or more. PTX‐3, PCT, and CRP levels showed no correlation with any other clinical features. CONCLUSION: PTX‐3 reflected disease severity but failed to predict length of hospital stay. Further studies evaluating the use of PTX‐3 as a biomarker in mild LRTI would be useful. Pediatr Pulmonol. 2016;51:42–48. © 2015 Wiley Periodicals, Inc.

negative: Exosome Function: From Tumor Immunology to Pathogen Biology Exosomes are the newest family member of ‘bioactive vesicles’ that function to promote intercellular communication. Exosomes are derived from the fusion of multi-vesicular bodies with the plasma membrane and extracellular release of the intraluminal vesicles. Recent studies have focused on the biogenesis and composition of exosomes as well as regulation of exosome release. Exosomes have been shown to be released by cells of hematopoietic and non-hematopoietic origin, yet their function remains enigmatic. Much of the prior work has focused on exosomes as a source of tumor antigens and in presentation of tumor antigens to T cells. However, new studies have shown that exosomes might also promote cell-to-cell spread of infectious agents. Moreover, exosomes isolated from cells infected with various intra-cellular pathogens, including Mycobacterium tuberculosis and Toxoplasma gondii, have been shown to contain microbial components and can promote antigen presentation and macrophage activation, suggesting that exosomes may function in immune surveillance. In this review, we summarize our understanding of exosome biogenesis but focus primarily on new insights into exosome function. We also discuss their possible use as disease biomarkers and vaccine candidates.

negative: Transmission routes of 2019-nCoV and controls in dental practice A novel β-coronavirus (2019-nCoV) caused severe and even fetal pneumonia explored in a seafood market of Wuhan city, Hubei province, China, and rapidly spread to other provinces of China and other countries. The 2019-nCoV was different from SARS-CoV, but shared the same host receptor the human angiotensin-converting enzyme 2 (ACE2). The natural host of 2019-nCoV may be the bat Rhinolophus affinis as 2019-nCoV showed 96.2% of whole-genome identity to BatCoV RaTG13. The person-to-person transmission routes of 2019-nCoV included direct transmission, such as cough, sneeze, droplet inhalation transmission, and contact transmission, such as the contact with oral, nasal, and eye mucous membranes. 2019-nCoV can also be transmitted through the saliva, and the fetal–oral routes may also be a potential person-to-person transmission route. The participants in dental practice expose to tremendous risk of 2019-nCoV infection due to the face-to-face communication and the exposure to saliva, blood, and other body fluids, and the handling of sharp instruments. Dental professionals play great roles in preventing the transmission of 2019-nCoV. Here we recommend the infection control measures during dental practice to block the person-to-person transmission routes in dental clinics and hospitals.

negative: Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System? Respiratory viruses infect the human upper respiratory tract, mostly causing mild diseases. However, in vulnerable populations, such as newborns, infants, the elderly and immune-compromised individuals, these opportunistic pathogens can also affect the lower respiratory tract, causing a more severe disease (e.g., pneumonia). Respiratory viruses can also exacerbate asthma and lead to various types of respiratory distress syndromes. Furthermore, as they can adapt fast and cross the species barrier, some of these pathogens, like influenza A and SARS-CoV, have occasionally caused epidemics or pandemics, and were associated with more serious clinical diseases and even mortality. For a few decades now, data reported in the scientific literature has also demonstrated that several respiratory viruses have neuroinvasive capacities, since they can spread from the respiratory tract to the central nervous system (CNS). Viruses infecting human CNS cells could then cause different types of encephalopathy, including encephalitis, and long-term neurological diseases. Like other well-recognized neuroinvasive human viruses, respiratory viruses may damage the CNS as a result of misdirected host immune responses that could be associated with autoimmunity in susceptible individuals (virus-induced neuro-immunopathology) and/or viral replication, which directly causes damage to CNS cells (virus-induced neuropathology). The etiological agent of several neurological disorders remains unidentified. Opportunistic human respiratory pathogens could be associated with the triggering or the exacerbation of these disorders whose etiology remains poorly understood. Herein, we present a global portrait of some of the most prevalent or emerging human respiratory viruses that have been associated with possible pathogenic processes in CNS infection, with a special emphasis on human coronaviruses.

negative: COVID-19 coronavirus vaccine design using reverse vaccinology and machine learning To ultimately combat the emerging COVID-19 pandemic, it is desired to develop an effective and safe vaccine against this highly contagious disease caused by the SARS-CoV-2 coronavirus. Our literature and clinical trial survey showed that the whole virus, as well as the spike (S) protein, nucleocapsid (N) protein, and membrane protein, have been tested for vaccine development against SARS and MERS. We further used the Vaxign reverse vaccinology tool and the newly developed Vaxign-ML machine learning tool to predict COVID-19 vaccine candidates. The N protein was found to be conserved in the more pathogenic strains (SARS/MERS/COVID-19), but not in the other human coronaviruses that mostly cause mild symptoms. By investigating the entire proteome of SARS-CoV-2, six proteins, including the S protein and five non-structural proteins (nsp3, 3CL-pro, and nsp8–10) were predicted to be adhesins, which are crucial to the viral adhering and host invasion. The S, nsp3, and nsp8 proteins were also predicted by Vaxign-ML to induce high protective antigenicity. Besides the commonly used S protein, the nsp3 protein has not been tested in any coronavirus vaccine studies and was selected for further investigation. The nsp3 was found to be more conserved among SARS-CoV-2, SARS-CoV, and MERS-CoV than among 15 coronaviruses infecting human and other animals. The protein was also predicted to contain promiscuous MHC-I and MHC-II T-cell epitopes, and linear B-cell epitopes localized in specific locations and functional domains of the protein. Our predicted vaccine targets provide new strategies for effective and safe COVID-19 vaccine development.

negative: Zoonotic origins of human coronaviruses Mutation and adaptation have driven the co-evolution of coronaviruses (CoVs) and their hosts, including human beings, for thousands of years. Before 2003, two human CoVs (HCoVs) were known to cause mild illness, such as common cold. The outbreaks of severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) have flipped the coin to reveal how devastating and life-threatening an HCoV infection could be. The emergence of SARS-CoV-2 in central China at the end of 2019 has thrusted CoVs into the spotlight again and surprised us with its high transmissibility but reduced pathogenicity compared to its sister SARS-CoV. HCoV infection is a zoonosis and understanding the zoonotic origins of HCoVs would serve us well. Most HCoVs originated from bats where they are non-pathogenic. The intermediate reservoir hosts of some HCoVs are also known. Identifying the animal hosts has direct implications in the prevention of human diseases. Investigating CoV-host interactions in animals might also derive important insight on CoV pathogenesis in humans. In this review, we present an overview of the existing knowledge about the seven HCoVs, with a focus on the history of their discovery as well as their zoonotic origins and interspecies transmission. Importantly, we compare and contrast the different HCoVs from a perspective of virus evolution and genome recombination. The current CoV disease 2019 (COVID-19) epidemic is discussed in this context. In addition, the requirements for successful host switches and the implications of virus evolution on disease severity are also highlighted.

negative: CT Manifestations of Two Cases of 2019 Novel Coronavirus (2019-nCoV) Pneumonia

negative: Lipoteichoic acid from Staphylococcus aureus exacerbates respiratory disease in porcine respiratory coronavirus-infected pigs The objective of this study was to assess if lipoteichoic acid (LTA), produced by Staphylococcus aureus, exacerbates respiratory disease in porcine respiratory coronavirus (PRCV)-infected pigs, as has previously been shown with lipopolysaccharide. Piglets were inoculated with PRCV and 24 h later with S. aureus LTA. Clinical signs, lung virus titres, inflammatory cells and cytokines in bronchoalveolar lavage fluid (BALF) were compared with those of animals in PRCV- and LTA- inoculated control groups. All PRCV-LTA inoculated pigs except one developed severe respiratory disease, whereas clinical signs in the control groups were minimal or absent. Virus titres and grossly visible pulmonary lesions were similar in the PRCV-LTA- and PRCV-inoculated groups and were not detected in the LTA-group. Neutrophil percentages in BALF were higher in the PRCV-LTA than in the PRCV group. There was no significant difference in interferon (IFN)-γ, interleukin (IL)-1, IL-6, IL-12/IL-23 and tumour necrosis factor (TNF)-α concentrations in BALF between the PRCV-LTA and PRCV groups, but levels of IL-6, IL-12/IL-23 and IFN-γ were higher in the PRCV-LTA-inoculated than in the LTA-inoculated controls. The findings suggest that the experimentally-induced respiratory disease was not mediated by cytokine over-production, but rather reflected the concerted action of particular cytokine interactions and/or as yet unidentified mediators. This is the first in vivo study to report the synergistic interaction between a virus and LTA in enhancing the severity of respiratory disease in the pig. Given that Gram-positive bacteria, capable of producing LTA, are commonly found in pig accommodation, the role of this compound in the development of the porcine respiratory disease complex requires further investigation.

negative: Using the spike protein feature to predict infection risk and monitor the evolutionary dynamic of coronavirus BACKGROUND: Coronavirus can cross the species barrier and infect humans with a severe respiratory syndrome. SARS-CoV-2 with potential origin of bat is still circulating in China. In this study, a prediction model is proposed to evaluate the infection risk of non-human-origin coronavirus for early warning. METHODS: The spike protein sequences of 2666 coronaviruses were collected from 2019 Novel Coronavirus Resource (2019nCoVR) Database of China National Genomics Data Center on Jan 29, 2020. A total of 507 human-origin viruses were regarded as positive samples, whereas 2159 non-human-origin viruses were regarded as negative. To capture the key information of the spike protein, three feature encoding algorithms (amino acid composition, AAC; parallel correlation-based pseudo-amino-acid composition, PC-PseAAC and G-gap dipeptide composition, GGAP) were used to train 41 random forest models. The optimal feature with the best performance was identified by the multidimensional scaling method, which was used to explore the pattern of human coronavirus. RESULTS: The 10-fold cross-validation results showed that well performance was achieved with the use of the GGAP (g = 3) feature. The predictive model achieved the maximum ACC of 98.18% coupled with the Matthews correlation coefficient (MCC) of 0.9638. Seven clusters for human coronaviruses (229E, NL63, OC43, HKU1, MERS-CoV, SARS-CoV, and SARS-CoV-2) were found. The cluster for SARS-CoV-2 was very close to that for SARS-CoV, which suggests that both of viruses have the same human receptor (angiotensin converting enzyme II). The big gap in the distance curve suggests that the origin of SARS-CoV-2 is not clear and further surveillance in the field should be made continuously. The smooth distance curve for SARS-CoV suggests that its close relatives still exist in nature and public health is challenged as usual. CONCLUSIONS: The optimal feature (GGAP, g = 3) performed well in terms of predicting infection risk and could be used to explore the evolutionary dynamic in a simple, fast and large-scale manner. The study may be beneficial for the surveillance of the genome mutation of coronavirus in the field.

negative: Serum phosphorylated neurofilament heavy-chain levels reflect phenotypic heterogeneity and are an independent predictor of survival in motor neuron disease To investigate the prognostic role and the major determinants of serum phosphorylated neurofilament heavy -chain (pNfH) concentration across a large cohort of motor neuron disease (MND) phenotypes. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum pNfH concentration in 219 MND patients consecutively enrolled in our tertiary MND clinic. A multifactorial analysis was carried out to investigate the major clinical determinants of serum pNfH. Kaplan–Meier survival curves and Cox regression analysis were performed to explore the prognostic value of serum pNfH. Serum pNfH levels were not homogenous among MND phenotypes; higher concentrations in pyramidal, bulbar, and classic phenotypes were observed. C9orf72-MND exhibited higher pNfH concentrations compared to non-C9orf72 MND. Multiple linear regression analysis revealed mean MEP/cMAP and disease progression rate as the two major predictors of serum pNfH levels (R(2) = 0.188; p ≤ 0.001). Kaplan–Meier curves showed a significant difference of survival among MND subgroups when divided into quartiles based on pNfH concentrations, log-rank X(2) = 53.0, p ≤ 0.0001. Our study evidenced that higher serum pNfH concentration is a negative independent prognostic factor for survival. In Cox multivariate model, pNfH concentration showed the highest hazard ratio compared to the other factors influencing survival included in the analysis. pNfH differs among the MND phenotypes and is an independent prognostic factor for survival. This study provides supporting evidence of the role of pNfH as useful prognostic biomarker for MND patients. Neurofilament measurements should be considered in the future prognostic models and in clinical trials for biomarker-based stratification, and to evaluate treatment response. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00415-020-09838-9) contains supplementary material, which is available to authorized users.

negative: Serum Metabolomics Revealed the Differential Metabolic Pathway in Calves with Severe Clinical Diarrhea Symptoms SIMPLE SUMMARY: The present study focuses on the metabolic changes in the diarrhea of calves, which are manifested with the following symptoms: a thin water-like stool, cold ears and nose, throbbing bowels, oliguria, a pale or yellowish complexion, a smooth mouth, and a slow pulse. The differential metabolic pathways in calves with diarrhea were screened by metabolomics. There were nine biomarkers in the serum of healthy calves and calves with diarrhea. On the basis of these biomarkers, their associated mineral absorption, protein digestion and absorption, and other metabolic pathways, the targeted regulation of the metabolic differences of calves with diarrhea may contribute to the diagnosis, treatment, and discussion of the mechanism of calf diarrhea. ABSTRACT: The complex etiology, higher morbidity and mortality, poor prognosis, and expensive cost of calf diarrhea have made it a catastrophic disease in the dairy industry. This study aims to assess the biomarkers in calves with diarrhea and to predict the biomarkers related to the pathway. As subjects, nine calves with diarrhea and nine healthy calves were enrolled, according to strict enrollment criteria. The serum metabolites were detected by a liquid chromatographic tandem mass spectrometry (LC-MS/MS), and then analyzed by online multivariate statistical analysis software to further screen the biomarkers. In addition, the biomarkers involved in the metabolic pathways of calves with diarrhea and healthy calves were analyzed. In the serum of calves with diarrhea, nine biomarkers were found to which several biomarkers exhibited a certain relation. Moreover, these biomarkers were involved in important metabolic pathways, including protein digestion and absorption, ABC transporters, aminoacyl-tRNA biosynthesis, mineral absorption, and fatty acid biosynthesis. All these findings suggested that the imbalance of these markers was closely related to the occurrence and development of calf diarrhea. The targeted regulation of metabolic pathways involved in these biomarkers may facilitate the diagnosis, treatment, and discussion of the mechanism of calf diarrhea.

negative: [Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia] Objective: To analyze the clinical characteristics of 2019 novel coronavirus (2019-nCoV) pneumonia and to investigate the correlation between serum inflammatory cytokines and severity of the disease. Methods: 29 patients with 2019-ncov admitted to the isolation ward of Tongji hospital affiliated to Tongji medical college of Huazhong University of Science and Technology in January 2020 were selected as the study subjects. Clinical data were collected and the general information, clinical symptoms, blood test and CT imaging characteristics were analyzed. According to the relevant diagnostic criteria, the patients were divided into three groups: mild (15 cases), severe (9 cases) and critical (5 cases). The expression levels of inflammatory cytokines and other markers in the serum of each group were detected, and the changes of these indicators of the three groups were compared and analyzed, as well as their relationship with the clinical classification of the disease. Results: (1) The main symptoms of 2019-nCoV pneumonia was fever (28/29) with or without respiratory and other systemic symptoms. Two patients died with underlying disease and co-bacterial infection, respectively. (2) The blood test of the patients showed normal or decreased white blood cell count (23/29), decreased lymphocyte count (20/29), increased hypersensitive C reactive protein (hs-CRP) (27/29), and normal procalcitonin. In most patients,serum lactate dehydrogenase (LDH) was significantly increased (20/29), while albumin was decreased(15/29). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Tbil), serum creatinine (Scr) and other items showed no significant changes. (3) CT findings of typical cases were single or multiple patchy ground glass shadows accompanied by septal thickening. When the disease progresses, the lesion increases and the scope expands, and the ground glass shadow coexists with the solid shadow or the stripe shadow. (4) There were statistically significant differences in the expression levels of interleukin-2 receptor (IL-2R) and IL-6 in the serum of the three groups (P<0.05), among which the critical group was higher than the severe group and the severe group was higher than the mildgroup. However, there were no statistically significant differences in serum levels of tumor necrosis factor-alpha (TNF-α), IL-1, IL-8, IL-10, hs-CRP, lymphocyte count and LDH among the three groups (P>0.05). Conclusion: The clinical characteristics of 2019-nCoV pneumonia are similar to those of common viral pneumonia. High resolution CT is of great value in the differential diagnosis of this disease. The increased expression of IL-2R and IL-6 in serum is expected to predict the severity of the 2019-nCoV pneumonia and the prognosis of patients.

negative: Gut microbiota may underlie the predisposition of healthy individuals to COVID-19 The COVID-19 pandemic is spreading globally with high disparity in the susceptibility of the disease severity. Identification of the key underlying factors for this disparity is highly warranted. Here we describe constructing a proteomic risk score based on 20 blood proteomic biomarkers which predict the progression to severe COVID-19. We demonstrate that in our own cohort of 990 individuals without infection, this proteomic risk score is positively associated with proinflammatory cytokines mainly among older, but not younger, individuals. We further discovered that a core set of gut microbiota could accurately predict the above proteomic biomarkers among 301 individuals using a machine learning model, and that these gut microbiota features are highly correlated with proinflammatory cytokines in another set of 366 individuals. Fecal metabolomic analysis suggested potential amino acid-related pathways linking gut microbiota to inflammation. This study suggests that gut microbiota may underlie the predisposition of normal individuals to severe COVID-19.

negative: Rapid community-driven development of a SARS-CoV-2 tissue simulator The 2019 novel coronavirus, SARS-CoV-2, is an emerging pathogen of critical significance to international public health. Knowledge of the interplay between molecular-scale virus-receptor interactions, single-cell viral replication, intracellular-scale viral transport, and emergent tissue-scale viral propagation is limited. Moreover, little is known about immune system-virus-tissue interactions and how these can result in low-level (asymptomatic) infections in some cases and acute respiratory distress syndrome (ARDS) in others, particularly with respect to presentation in different age groups or pre-existing inflammatory risk factors like diabetes. Given the nonlinear interactions within and among each of these processes, multiscale simulation models can shed light on the emergent dynamics that lead to divergent outcomes, identify actionable “choke points” for pharmacologic interactions, screen potential therapies, and identify potential biomarkers that differentiate patient outcomes. Given the complexity of the problem and the acute need for an actionable model to guide therapy discovery and optimization, we introduce and iteratively refine a prototype of a multiscale model of SARS-CoV-2 dynamics in lung tissue. The first prototype model was built and shared internationally as open source code and an online interactive model in under 12 hours, and community domain expertise is driving rapid refinements with a two-to-four week release cycle. In a sustained community effort, this consortium is integrating data and expertise across virology, immunology, mathematical biology, quantitative systems physiology, cloud and high performance computing, and other domains to accelerate our response to this critical threat to international health.

negative: 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.

negative: Analysis of Serologic Cross-Reactivity Between Common Human Coronaviruses and SARS-CoV-2 Using Coronavirus Antigen Microarray The current practice for diagnosis of SARS-CoV-2 infection relies on PCR testing of nasopharyngeal or respiratory specimens in a symptomatic patient at high epidemiologic risk. This testing strategy likely underestimates the true prevalence of infection, creating the need for serologic methods to detect infections missed by the limited testing to date. Here, we describe the development of a coronavirus antigen microarray containing immunologically significant antigens from SARS-CoV-2, in addition to SARS-CoV, MERS-CoV, common human coronavirus strains, and other common respiratory viruses. A preliminary study of human sera collected prior to the SARS-CoV-2 pandemic demonstrates overall high IgG reactivity to common human coronaviruses and low IgG reactivity to epidemic coronaviruses including SARS-CoV-2, with some cross-reactivity of conserved antigenic domains including S2 domain of spike protein and nucleocapsid protein. This array can be used to answer outstanding questions regarding SARS-CoV-2 infection, including whether baseline serology for other coronaviruses impacts disease course, how the antibody response to infection develops over time, and what antigens would be optimal for vaccine development.

negative: Histopathologic Evaluation and Scoring of Viral Lung Infection Emergent coronaviruses such as MERS-CoV and SARS-CoV can cause significant morbidity and mortality in infected individuals. Lung infection is a common clinical feature and contributes to disease severity as well as viral transmission. Animal models are often required to study viral infections and therapies, especially during an initial outbreak. Histopathology studies allow for identification of lesions and affected cell types to better understand viral pathogenesis and clarify effective therapies. Use of immunostaining allows detection of presumed viral receptors and viral tropism for cells can be evaluated to correlate with lesions. In the lung, lesions and immunostaining can be qualitatively described to define the cell types, microanatomic location, and type of changes seen. These features are important and necessary, but this approach can have limitations when comparing treatment groups. Semiquantitative and quantitative tissue scores are more rigorous as these provide the ability to statistically compare groups and increase the reproducibility and rigor of the study. This review describes principles, approaches, and resources that can be useful to evaluate coronavirus lung infection, focusing on MER-CoV infection as the principal example.

negative: Innate immune response of human alveolar type II cells infected with severe acute respiratory syndrome-coronavirus. Severe acute respiratory syndrome (SARS)-coronavirus (CoV) produces a devastating primary viral pneumonia with diffuse alveolar damage and a marked increase in circulating cytokines. One of the major cell types to be infected is the alveolar type II cell. However, the innate immune response of primary human alveolar epithelial cells infected with SARS-CoV has not been defined. Our objectives included developing a culture system permissive for SARS-CoV infection in primary human type II cells and defining their innate immune response. Culturing primary human alveolar type II cells at an air-liquid interface (A/L) improved their differentiation and greatly increased their susceptibility to infection, allowing us to define their primary interferon and chemokine responses. Viral antigens were detected in the cytoplasm of infected type II cells, electron micrographs demonstrated secretory vesicles filled with virions, virus RNA concentrations increased with time, and infectious virions were released by exocytosis from the apical surface of polarized type II cells. A marked increase was evident in the mRNA concentrations of interferon-β and interferon-λ (IL-29) and in a large number of proinflammatory cytokines and chemokines. A surprising finding involved the variability of expression of angiotensin-converting enzyme-2, the SARS-CoV receptor, in type II cells from different donors. In conclusion, the cultivation of alveolar type II cells at an air-liquid interface provides primary cultures in which to study the pulmonary innate immune responses to infection with SARS-CoV, and to explore possible therapeutic approaches to modulating these innate immune responses.

negative: Can a Paper-Based Device Trace COVID-19 Sources with Wastewater-Based Epidemiology?

negative: Applications of Functional Protein Microarrays in Basic and Clinical Research The protein microarray technology provides a versatile platform for characterization of hundreds of thousands of proteins in a highly parallel and high-throughput manner. It is viewed as a new tool that overcomes the limitation of DNA microarrays. On the basis of its application, protein microarrays fall into two major classes: analytical and functional protein microarrays. In addition, tissue or cell lysates can also be directly spotted on a slide to form the so-called “reverse-phase” protein microarray. In the last decade, applications of functional protein microarrays in particular have flourished in studying protein function and construction of networks and pathways. In this chapter, we will review the recent advancements in the protein microarray technology, followed by presenting a series of examples to illustrate the power and versatility of protein microarrays in both basic and clinical research. As a powerful technology platform, it would not be surprising if protein microarrays will become one of the leading technologies in proteomic and diagnostic fields in the next decade.

negative: Insights into the Recent 2019 Novel Coronavirus (SARS-CoV-2) in Light of Past Human Coronavirus Outbreaks Coronaviruses (CoVs) are RNA viruses that have become a major public health concern since the Severe Acute Respiratory Syndrome-CoV (SARS-CoV) outbreak in 2002. The continuous evolution of coronaviruses was further highlighted with the emergence of the Middle East Respiratory Syndrome-CoV (MERS-CoV) outbreak in 2012. Currently, the world is concerned about the 2019 novel CoV (SARS-CoV-2) that was initially identified in the city of Wuhan, China in December 2019. Patients presented with severe viral pneumonia and respiratory illness. The number of cases has been mounting since then. As of late February 2020, tens of thousands of cases and several thousand deaths have been reported in China alone, in addition to thousands of cases in other countries. Although the fatality rate of SARS-CoV-2 is currently lower than SARS-CoV, the virus seems to be highly contagious based on the number of infected cases to date. In this review, we discuss structure, genome organization, entry of CoVs into target cells, and provide insights into past and present outbreaks. The future of human CoV outbreaks will not only depend on how the viruses will evolve, but will also depend on how we develop efficient prevention and treatment strategies to deal with this continuous threat.

negative: Host resilience to emerging coronaviruses Recently, two coronaviruses, severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus, have emerged to cause unusually severe respiratory disease in humans. Currently, there is a lack of effective antiviral treatment options or vaccine available. Given the severity of these outbreaks, and the possibility of additional zoonotic coronaviruses emerging in the near future, the exploration of different treatment strategies is necessary. Disease resilience is the ability of a given host to tolerate an infection, and to return to a state of health. This review focuses on exploring various host resilience mechanisms that could be exploited for treatment of severe acute respiratory syndrome coronavirus, Middle East respiratory syndrome coronavirus and other respiratory viruses that cause acute lung injury and acute respiratory distress syndrome.

negative: Human coronaviruses: Viral and cellular factors involved in neuroinvasiveness and neuropathogenesis Abstract Among the various respiratory viruses infecting human beings, coronaviruses are important pathogens, which usually infect the upper respiratory tract, where they are mainly associated with common colds. However, in more vulnerable populations, such as newborns, infants, the elderly and immune-compromised individuals, these opportunistic pathogens can also affect the lower respiratory tract, leading to pneumonia, exacerbations of asthma, and various types of respiratory distress syndrome. The respiratory involvement of human coronaviruses has been clearly established since the 1960s. Nevertheless, for almost three decades now, data reported in the scientific literature has also demonstrated that, like it was described for other human viruses, coronaviruses have neuroinvasive capacities since they can spread from the respiratory tract to the central nervous system (CNS). Once there, infection of CNS cells (neurotropism) could lead to human health problems, such as encephalitis and long-term neurological diseases. Neuroinvasive coronaviruses could damage the CNS as a result of misdirected host immune responses that could be associated with autoimmunity in susceptible individuals (virus-induced neuroimmunopathology) and/or viral replication, which directly induces damage to CNS cells (virus-induced neuropathology). Given all these properties, it has been suggested that these opportunistic human respiratory pathogens could be associated with the triggering or the exacerbation of neurologic diseases for which the etiology remains poorly understood. Herein, we present host and viral factors that participate in the regulation of the possible pathogenic processes associated with CNS infection by human coronaviruses and we try to decipher the intricate interplay between virus and host target cells in order to characterize their role in the virus life cycle as well as in the capacity of the cell to respond to viral invasion.

negative: Coronavirus disease 2019 (COVID-19): update for anesthesiologists and intensivists March 2020 The current outbreak of coronavirus disease (COVID-19) has reached Germany. The majority of people infected present with mild disease, but there are severe cases that need intensive care. Unlike other acute infectious diseases progressing to sepsis, the severe courses of COVID19 seemingly show prolonged progression from onset of first symptoms to life-threatening deterioration of (primarily) lung function. Diagnosis relies on PCR using specimens from the respiratory tract. Severe ARDS reflects the hallmark of a critical course of the disease. Preventing nosocomial infections (primarily by correct use of personal protective equipment) and maintenance of hospitals’ operational capability are of utmost importance. Departments of Anaesthesia, Intensive Care and emergency medicine will envisage major challenges.

negative: Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore. Importance Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in December 2019 and has spread globally with sustained human-to-human transmission outside China. Objective To report the initial experience in Singapore with the epidemiologic investigation of this outbreak, clinical features, and management. Design, Setting, and Participants Descriptive case series of the first 18 patients diagnosed with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection at 4 hospitals in Singapore from January 23 to February 3, 2020; final follow-up date was February 25, 2020. Exposures Confirmed SARS-CoV-2 infection. Main Outcomes and Measures Clinical, laboratory, and radiologic data were collected, including PCR cycle threshold values from nasopharyngeal swabs and viral shedding in blood, urine, and stool. Clinical course was summarized, including requirement for supplemental oxygen and intensive care and use of empirical treatment with lopinavir-ritonavir. Results Among the 18 hospitalized patients with PCR-confirmed SARS-CoV-2 infection (median age, 47 years; 9 [50%] women), clinical presentation was an upper respiratory tract infection in 12 (67%), and viral shedding from the nasopharynx was prolonged for 7 days or longer among 15 (83%). Six individuals (33%) required supplemental oxygen; of these, 2 required intensive care. There were no deaths. Virus was detectable in the stool (4/8 [50%]) and blood (1/12 [8%]) by PCR but not in urine. Five individuals requiring supplemental oxygen were treated with lopinavir-ritonavir. For 3 of the 5 patients, fever resolved and supplemental oxygen requirement was reduced within 3 days, whereas 2 deteriorated with progressive respiratory failure. Four of the 5 patients treated with lopinavir-ritonavir developed nausea, vomiting, and/or diarrhea, and 3 developed abnormal liver function test results. Conclusions and Relevance Among the first 18 patients diagnosed with SARS-CoV-2 infection in Singapore, clinical presentation was frequently a mild respiratory tract infection. Some patients required supplemental oxygen and had variable clinical outcomes following treatment with an antiretroviral agent.

negative: Studying the pathophysiology of coronavirus disease 2019: a protocol for the Berlin prospective COVID-19 patient cohort (Pa-COVID-19) PURPOSE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide causing a global health emergency. Pa-COVID-19 aims to provide comprehensive data on clinical course, pathophysiology, immunology and outcome of COVID-19, to identify prognostic biomarkers, clinical scores, and therapeutic targets for improved clinical management and preventive interventions. METHODS: Pa-COVID-19 is a prospective observational cohort study of patients with confirmed SARS-CoV-2 infection treated at Charité - Universitätsmedizin Berlin. We collect data on epidemiology, demography, medical history, symptoms, clinical course, and pathogen testing and treatment. Systematic, serial blood sampling will allow deep molecular and immunological phenotyping, transcriptomic profiling, and comprehensive biobanking. Longitudinal data and sample collection during hospitalization will be supplemented by long-term follow-up. RESULTS: Outcome measures include the WHO clinical ordinal scale on day 15 and clinical, functional, and health-related quality-of-life assessments at discharge and during follow-up. We developed a scalable dataset to (i) suit national standards of care, (ii) facilitate comprehensive data collection in medical care facilities with varying resources, and (iii) allow for rapid implementation of interventional trials based on the standardized study design and data collection. We propose this scalable protocol as blueprint for harmonized data collection and deep phenotyping in COVID-19 in Germany. CONCLUSION: We established a basic platform for harmonized, scalable data collection, pathophysiological analysis, and deep phenotyping of COVID-19, which enables rapid generation of evidence for improved medical care and identification of candidate therapeutic and preventive strategies. The electronic database accredited for interventional trials allows fast trial implementation for candidate therapeutic agents. TRIAL REGISTRATION: Registered at the German registry for clinical studies (DRKS00021688) ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s15010-020-01464-x) contains supplementary material, which is available to authorized users.

negative: Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding BACKGROUND: In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. METHODS: We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. FINDINGS: The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. INTERPRETATION: 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. FUNDING: National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.

negative: Synergistic Learning of Lung Lobe Segmentation and Hierarchical Multi-Instance Classification for Automated Severity Assessment of COVID-19 in CT Images Understanding chest CT imaging of the coronavirus disease 2019 (COVID-19) will help detect infections early and assess the disease progression. Especially, automated severity assessment of COVID-19 in CT images plays an essential role in identifying cases that are in great need of intensive clinical care. However, it is often challenging to accurately assess the severity of this disease in CT images, due to variable infection regions in the lungs, similar imaging biomarkers, and large inter-case variations. To this end, we propose a synergistic learning framework for automated severity assessment of COVID-19 in 3D CT images, by jointly performing lung lobe segmentation and multi-instance classification. Considering that only a few infection regions in a CT image are related to the severity assessment, we first represent each input image by a bag that contains a set of 2D image patches (with each cropped from a specific slice). A multi-task multi-instance deep network (called M$^2$UNet) is then developed to assess the severity of COVID-19 patients and also segment the lung lobe simultaneously. Our M$^2$UNet consists of a patch-level encoder, a segmentation sub-network for lung lobe segmentation, and a classification sub-network for severity assessment (with a unique hierarchical multi-instance learning strategy). Here, the context information provided by segmentation can be implicitly employed to improve the performance of severity assessment. Extensive experiments were performed on a real COVID-19 CT image dataset consisting of 666 chest CT images, with results suggesting the effectiveness of our proposed method compared to several state-of-the-art methods.

negative: Risk for Transportation of 2019 Novel Coronavirus (COVID-19) from Wuhan to Cities in China On January 23, 2020, China quarantined Wuhan to contain an emerging coronavirus (COVID-19). We estimated the probability of transportation of COVID-19 from Wuhan to 369 cities in China before the quarantine. The expected risk is >50% in 130 (95% CI 89–190) cities and >99% in the 4 largest metropolitan areas of China.

negative: 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: Associations between media use and health information-seeking behavior on vaccinations in South Korea BACKGROUND: Although vaccinations are critical for preventing emerging infectious diseases, scant research has been conducted on risk communication. With socio-economic characteristics, health behavior, and underlying diseases under control, we investigated associations between media use, health information-seeking behavior, health information type, and vaccination in the population. METHODS: This study relied on a national survey of Korean adults (n = 1367). Participants were adult males and females age 20 and older. Web and face-to-face surveys were conducted throughout July 2014. The main outcome was vaccination (categorized as yes or no). Independent variables were time spent on media, frequency of health information-seeking behavior, and types of health information sought. RESULTS: Controlling for co-variates, logistic regression analysis was conducted to identify factors that influence Korean adults being vaccinated. Results revealed that accessible information about emerging infectious diseases, listening to the radio, and reading the newspaper were associated with increased odds of being vaccinated. Active seeking health information as well as being female and of higher socio-economic status were positively correlated with Korean adults being vaccinated. CONCLUSION: It is critical to promote health information-seeking behavior and use diverse media channels to increase acceptance and awareness of emerging infectious diseases and vaccinations. Because there are differences in vaccination awareness depending on social class, it is critical to reduce communication inequality, strengthen accessibility to vaccinations, and devise appropriate risk communication strategies that ensure Korean adults receive vaccinations.

negative: Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China BACKGROUND: Studies have reminded that cardiovascular metabolic comorbidities made patients more susceptible to suffer 2019 novel corona virus (2019-nCoV) disease (COVID-19), and exacerbated the infection. The aim of this analysis is to determine the association of cardiovascular metabolic diseases with the development of COVID-19. METHODS: A meta-analysis of eligible studies that summarized the prevalence of cardiovascular metabolic diseases in COVID-19 and compared the incidences of the comorbidities in ICU/severe and non-ICU/severe patients was performed. Embase and PubMed were searched for relevant studies. RESULTS: A total of six studies with 1527 patients were included in this analysis. The proportions of hypertension, cardia-cerebrovascular disease and diabetes in patients with COVID-19 were 17.1%, 16.4% and 9.7%, respectively. The incidences of hypertension, cardia-cerebrovascular diseases and diabetes were about twofolds, threefolds and twofolds, respectively, higher in ICU/severe cases than in their non-ICU/severe counterparts. At least 8.0% patients with COVID-19 suffered the acute cardiac injury. The incidence of acute cardiac injury was about 13 folds higher in ICU/severe patients compared with the non-ICU/severe patients. CONCLUSION: Patients with previous cardiovascular metabolic diseases may face a greater risk of developing into the severe condition and the comorbidities can also greatly affect the prognosis of the COVID-19. On the other hand, COVID-19 can, in turn, aggravate the damage to the heart.

negative: Impact of cardiovascular disease and cardiac injury on in-hospital mortality in patients with COVID-19: a systematic review and meta-analysis BACKGROUND: Coronavirus disease 2019 (COVID-19) has produced a significant health burden worldwide, especially in patients with cardiovascular comorbidities. The aim of this systematic review and meta-analysis was to assess the impact of underlying cardiovascular comorbidities and acute cardiac injury on in-hospital mortality risk. METHODS: PubMed, Embase and Web of Science were searched for publications that reported the relationship of underlying cardiovascular disease (CVD), hypertension and myocardial injury with in-hospital fatal outcomes in patients with COVID-19. The ORs were extracted and pooled. Subgroup and sensitivity analyses were performed to explore the potential sources of heterogeneity. RESULTS: A total of 10 studies were enrolled in this meta-analysis, including eight studies for CVD, seven for hypertension and eight for acute cardiac injury. The presence of CVD and hypertension was associated with higher odds of in-hospital mortality (unadjusted OR 4.85, 95% CI 3.07 to 7.70; I(2)=29%; unadjusted OR 3.67, 95% CI 2.31 to 5.83; I(2)=57%, respectively). Acute cardiac injury was also associated with a higher unadjusted odds of 21.15 (95% CI 10.19 to 43.94; I(2)=71%). CONCLUSION: COVID-19 patients with underlying cardiovascular comorbidities, including CVD and hypertension, may face a greater risk of fatal outcomes. Acute cardiac injury may act as a marker of mortality risk. Given the unadjusted results of our meta-analysis, future research are warranted.

negative: Recent advances and perspectives of nucleic acid detection for coronavirus The recent pneumonia outbreak caused by a novel coronavirus (SARS-CoV-2) is posing a great threat to global public health. Therefore, rapid and accurate identification of pathogenic viruses plays a vital role in selecting appropriate treatments, saving people’s lives and preventing epidemics. It is important to establish a quick standard diagnostic test for the detection of the infectious disease (COVID-19) to prevent subsequent secondary spread. Polymerase chain reaction (PCR) is regarded as a gold standard test for the molecular diagnosis of viral and bacterial infections with high sensitivity and specificity. Isothermal nucleic acid amplification is considered to be a highly promising candidate method due to its fundamental advantage in quick procedure time at constant temperature without thermocycler operation. A variety of improved or new approaches also have been developed. This review summarizes the currently available detection methods for coronavirus nucleic acid. It is anticipated that this will assist researchers and clinicians in developing better techniques for timely and effective detection of coronavirus infection.

negative: Integrative Bioinformatics Analysis Provides Insight into the Molecular Mechanisms of 2019-nCoV The 2019-nCoV is reported to share the same entry (ACE2) as SARS-CoV according to the updated findings. Analyzing the distribution and expression level of the route of coronavirus may help reveal underlying mechanisms of viral susceptibility and post-infection modulation. In this study, we found that the expression of ACE2 in healthy populations and patients with underlying diseases was not significantly different, suggesting relatively similar susceptibility, which was consistent with current clinical observations. Moreover, based on the expression of ACE2 in smoking individuals, we inferred that long-term smoking might be a risk factor for 2019-nCoV. Analyzing the ACE2 in SARS-CoV infected cells suggested that ACE2 was more than just a receptor but also participated in post-infection regulation, including immune response, cytokine secretion, and viral genome replication. We also constructed Protein-protein interaction (PPI) networks and identified hub genes in viral activity and cytokine secretion. Our findings could explain the clinical symptoms so far and help clinicians and researchers understand the pathogenesis and design therapeutic strategies for 2019-nCoV.

negative: Utility of massive open online courses (MOOCs) concerning outbreaks of emerging and reemerging diseases The emergence and re-emergence of infectious diseases such as Ebola, chikungunya, and Zika increase the necessity of knowledgeable and skilled health professionals. Massive open online courses (MOOCs) arise as opportunities that allow people around the world to participate in higher education courses. A search was conducted on specialized MOOC platforms to find courses related to outbreaks, using terms included in the list of the WHO disease outbreaks from January 1st to December 31 (st), 2016. We found seven courses about Ebola, two about Zika, three about the dynamics of epidemics and pandemics, and only one course about dengue, chikungunya, and malaria. Most of the courses were conducted in English. The courses on Ebola, Zika and chikungunya were released after their last outbreak. MOOCs could be used to learn about health issues of global relevance, and with the necessity of fast divulgation of knowledge and skills. Translating the courses into more languages could give these courses more traction, and allow participation of professionals in regions affected by these outbreaks.

negative: Detection and analysis of nucleic acid in various biological samples of COVID-19 patients Abstract COVID-19 (corona virus disease 2019) is a kind of acute severe pneumonia caused by 2019-nCoV (2019-nCoV) infection. Since December 2019, it has been found in Wuhan, Hubei Province, and then spread to the whole country. Some parts of the world also showed an outbreak trend [1–3]. Real-time fluorescence quantitative reverse transcriptase polymerase chain reaction (reverse transcriptase-polymerase chain reaction,RT-PCR) and viral gene sequencing are the gold standard for the diagnosis of COVID-19. At present, upper respiratory tract nasopharyngeal swabs are mostly used as nucleic acid detection samples in China, but the positive rate is low. However, there are few reports on clinical application of 2019-nCoV nucleic acid detection in other biological samples. Methods | The East Section of Renmin Hospital of Wuhan University is a designated COVID-19 hospital in Wuhan City, Hubei Province, China. This observation study included 132 patients diagnosed with COVID-19 in the infectious disease areas of the East Section of Renmin Hospital of Wuhan University from 2020.1.31 to 2020.2.29. COVID-19 diagnostic criteria: according to China's 《pneumonia diagnosis and treatment Program of novel coronavirus infection (trial version 7) 》, in accordance with the relevant epidemiological and clinical manifestations, nasopharyngeal swabs real-time fluorescence RT-PCR detection of 2019-nCoV nucleic acid positive, COVID-19 cases were divided into mild, ordinary, severe and severe [4]. The nasopharyngeal swabs of 132 cases of COVID-19 were positive for 2019-nCoV nucleic acid on admission, including 72 males and 60 females, with an average age of 66.7 ± 9.1 years, including 80 cases of common type, 44 cases of severe type and 8 cases of critical type. During the period of admission, under the condition of tertiary protection, nasopharyngeal swabs, sputum, blood, feces and anal swabs of COVID-19 cases were collected many times in the isolation ward for 2019-nCoV nucleic acid detection. All biological samples are sealed and transferred to the laboratory in strict accordance with the standard process. The RT-PCR test kits (BioGerm) were recommended by the Chinese Center for Disease Control and Prevention. The same technician and brand of test kit was used for all RT-PCR testing reported; both internal controls and negative controls were routinely performed with each batch of tests. Results | 132 the results of 2019-nCoV nucleic acid test of various biological samples during the treatment of confirmed COVID-19 cases are as follows: the positive rate of 2019-nCoV nucleic acid test of nasopharyngeal swab is 38.13% (180/472 times), the positive rate of 2019-nCoV nucleic acid test of sputum is 48.68% (148/304 times), the positive rate of blood 2019-nCoV nucleic acid test is 3.03% (4/132 times), and the positive rate of 2019-nCoV nucleic acid test of feces is 9.83% (24/244 times). The positive rate of 2019-nCoV nucleic acid detection in anal swabs is 10.00% (12/120 times). Discussion| In this study, it was found that the positive rate of 2019-nCoV nucleic acid in sputum of 132 patients with COVID-19 was higher than that of nasopharyngeal swabs, and viral nucleic acids were also detected in blood and digestive tract (fecal/anal swabs). Simple detection of nasopharyngeal swab 2019-nCoV nucleic acid detection positive rate is not high, multi-sample 2019-nCoV nucleic acid detection can improve the accuracy, reduce the false negative rate, better guide clinical treatment and evaluate the therapeutic effect.

negative: 2019-NCoV: What Every Neurologist Should Know? The 2019 novel Corona Virus pandemic beginning from Wuhan, China primarily affects the respiratory tract but its has impacted clinical practice across a range of specialities including neurology. We review the bearing of the 2019 NCoV infection on neurological practice. Neurological manifestations are less common than respiratory manifestations, yet conspicuous, affecting nearly over a third of hospitalized individuals. These may be classified in to early – headache, dizziness, hyposmia and hypogeusia and late – encephalopathy. Rarely but surely, a very small proportion of infected individuals might present with stroke. Certain neurological conditions, including cerebrovascular disease in both China and Italy and dementia in Italy predispose to infection and more severe manifestations, requiring intensive care unit admission. There is no convincing evidence that the manifestations, course and outcome of various neurological disorders is impacted by 2019 nCoV infection. Concerns of an increased risk of febrile seizures offset by a reduced frequency of infection in the paediatric age group. Individuals with multiple sclerosis might potentially experience both true and pseudorelapses. Besides a direct effect, 2019 nCoV has tremendously affected neurological care by disrupting the continuity of care and the availability of neurological medicines worldwide. Neurologists should respond to this challenge by developing and sustaining innovative methods of providing care as well as alerting the society at large to adopt measures to contain the spread of 2019 nCoV.

negative: Single-cell Analysis of ACE2 Expression in Human Kidneys and Bladders Reveals a Potential Route of 2019-nCoV Infection Since December 2019, a novel coronavirus named 2019 coronavirus (2019-nCoV) has emerged in Wuhan of China and spread to several countries worldwide within just one month. Apart from fever and respiratory complications, acute kidney injury has been observed in some patients with 2019-nCoV. In a short period of time, angiotensin converting enzyme II (ACE2), have been proposed to serve as the receptor for the entry of 2019-nCoV, which is the same for severe acute respiratory syndrome coronavirus (SARS). To investigate the possible cause of kidney damage in 2019-nCoV patients, we used both published kidney and bladder cell atlas data and an independent unpublished kidney single cell RNA-Seq data generated in-house to evaluate ACE2 gene expressions in all cell types in healthy kidneys and bladders. Our results showed the enriched expression of all subtypes of proximal tubule cells of kidney and low but detectable levels of expression in bladder epithelial cells. These results indicated the urinary system is a potential route for 2019-nCoV infection, along with the respiratory system and digestion system. Our findings suggested the kidney abnormalities of SARS and 2019-nCoV patients may be due to proximal tubule cells damage and subsequent systematic inflammatory response induced kidney injury. Beyond that, laboratory tests of viruses and related indicators in urine may be needed in some special patients of 2019-nCoV.

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: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan A mysterious outbreak of atypical pneumonia in late 2019 was traced to a seafood wholesale market in Wuhan of China. Within a few weeks, a novel coronavirus tentatively named as 2019 novel coronavirus (2019-nCoV) was announced by the World Health Organization. We performed bioinformatics analysis on a virus genome from a patient with 2019-nCoV infection and compared it with other related coronavirus genomes. Overall, the genome of 2019-nCoV has 89% nucleotide identity with bat SARS-like-CoVZXC21 and 82% with that of human SARS-CoV. The phylogenetic trees of their orf1a/b, Spike, Envelope, Membrane and Nucleoprotein also clustered closely with those of the bat, civet and human SARS coronaviruses. However, the external subdomain of Spike’s receptor binding domain of 2019-nCoV shares only 40% amino acid identity with other SARS-related coronaviruses. Remarkably, its orf3b encodes a completely novel short protein. Furthermore, its new orf8 likely encodes a secreted protein with an alpha-helix, following with a beta-sheet(s) containing six strands. Learning from the roles of civet in SARS and camel in MERS, hunting for the animal source of 2019-nCoV and its more ancestral virus would be important for understanding the origin and evolution of this novel lineage B betacoronavirus. These findings provide the basis for starting further studies on the pathogenesis, and optimizing the design of diagnostic, antiviral and vaccination strategies for this emerging infection.

negative: Annexin A2 on lung epithelial cell surface is recognized by severe acute respiratory syndrome-associated coronavirus spike domain 2 antibodies Abstract Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infection causes lung failure characterized by atypical pneumonia. We previously showed that antibodies against SARS-CoV spike domain 2 (S2) in the patient sera can cross-react with human lung epithelial cells; however, the autoantigen is not yet identified. In this study, we performed proteomic studies and identified several candidate autoantigens recognized by SARS patient sera in human lung type II epithelial cell A549. Among the candidate proteins, annexin A2, which was identified by mass spectrometry analysis and had the highest score by Mascot data search, was further characterized and investigated for its role as an autoantigen. By confocal microscopic observation, SARS patient sera and anti-S2 antibodies were co-localized on A549 cells and both of them were co-localized with anti-annexin A2 antibodies. Anti-annexin A2 antibodies bound to purified S2 proteins, and anti-S2 bound to immunoprecipitated annexin A2 from A549 cell lysate in a dose-dependent manner. Furthermore, an increased surface expression and raft-structure distribution of annexin A2 was present in A549 cells after stimulation with SARS-induced cytokines interleukin-6 and interferon-γ. Cytokine stimulation increased the binding capability of anti-S2 antibodies to human lung epithelial cells. Together, the upregulated expression of annexin A2 by SARS-associated cytokines and the cross-reactivity of anti-SARS-CoV S2 antibodies to annexin A2 may have implications in SARS disease pathogenesis.

negative: Spread and control of COVID-19 in China and their associations with population movement, public health emergency measures, and medical resources ABSTRACT BACKGROUND The COVID-19 epidemic, first emerged in Wuhan during December 2019, has spread globally. While the mass population movement for Chinese New Year has significantly influenced spreading the disease, little direct evidence exists about the relevance to epidemic and its control of population movement from Wuhan, local emergency response, and medical resources in China. METHODS Spearman's correlation analysis was performed between official data of confirmed COVID-19 cases from Jan 20th to Feb 19th, 2020 and real-time travel data and health resources data. RESULTS There were 74,675 confirmed COVID-19 cases in China by Feb 19th, 2020. The overall fatality rate was 2.84%, much higher in Hubei than in other regions (3.27% vs 0.73%). The index of population inflow from Hubei was positively correlated with total (Provincial r=0.9159, p<0.001; City r=0.6311, p<0.001) and primary cases (Provincial r=0.8702, p<0.001; City r=0.6358, p<0.001). The local health emergency measures (eg, city lockdown and traffic control) were associated with reduced infections nationwide. Moreover, the number of public health employees per capita was inversely correlated with total cases (r=-0.6295, p<0.001) and infection rates (r=-0.4912, p<0.01). Similarly, cities with less medical resources had higher fatality (r=-0.4791, p<0.01) and lower cure rates (r=0.5286, p<0.01) among the confirmed cases. CONCLUSIONS The spread of the COVID-19 in China in its early phase was attributed primarily to population movement from Hubei, and effective governmental health emergency measures and adequate medical resources played important roles in subsequent control of epidemic and improved prognosis of affected individuals.

negative: SARS-CoV-2 and viral sepsis: observations and hypotheses Summary Since the outbreak of coronavirus disease 2019 (COVID-19), clinicians have tried every effort to understand the disease, and a brief portrait of its clinical features have been identified. In clinical practice, we noticed that many severe or critically ill COVID-19 patients developed typical clinical manifestations of shock, including cold extremities and weak peripheral pulses, even in the absence of overt hypotension. Understanding the mechanism of viral sepsis in COVID-19 is warranted for exploring better clinical care for these patients. With evidence collected from autopsy studies on COVID-19 and basic science research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV, we have put forward several hypotheses about SARS-CoV-2 pathogenesis after multiple rounds of discussion among basic science researchers, pathologists, and clinicians working on COVID-19. We hypothesise that a process called viral sepsis is crucial to the disease mechanism of COVID-19. Although these ideas might be proven imperfect or even wrong later, we believe they can provide inputs and guide directions for basic research at this moment.

negative: 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.

negative: Novel coronavirus 2019-nCoV: early estimation of epidemiological parameters and epidemic predictions Since first identified, the epidemic scale of the recently emerged novel coronavirus (2019-nCoV) in Wuhan, China, has increased rapidly, with cases arising across China and other countries and regions. using a transmission model, we estimate a basic reproductive number of 3.11 (95%CI, 2.39-4.13); 58-76% of transmissions must be prevented to stop increasing; Wuhan case ascertainment of 5.0% (3.6-7.4); 21022 (11090-33490) total infections in Wuhan 1 to 22 January.

negative: Quantitative real time polymerase chain reaction in drug development Measurements of the number of copies of DNA or mRNA with the quantitative polymerase chain reaction (qPCR) have transformed the drug development process. This transformation is driven by the information these measurements have contributed for a better understanding of the molecular definition of disease and of the mechanisms of efficacy and toxicity for new drugs. As this information is translated into accurate genomic biomarkers of efficacy and toxicity, drug development processes supported by these measurements are becoming more efficient. This transformation is exemplified in the conversion of P450 enzyme activity measurements to gene expression in drug metabolism studies, the measurement of cytokine and chemokine genomic expression levels as clinical markers, and the identification and evaluation of genomic biomarkers of nephrotoxicity. A good understanding of factors affecting qPCR measurements can simplify their implementation, as will high‐throughput platforms for these assays. Drug Dev. Res. 62:151–158, 2004. © 2004 Wiley‐Liss, Inc.

negative: ISG56/IFIT1 is primarily responsible for interferon-induced changes to patterns of parainfluenza virus type 5 transcription and protein synthesis Interferon (IFN) induces an antiviral state in cells that results in alterations of the patterns and levels of parainfluenza virus type 5 (PIV5) transcripts and proteins. This study reports that IFN-stimulated gene 56/IFN-induced protein with tetratricopeptide repeats 1 (ISG56/IFIT1) is primarily responsible for these effects of IFN. It was shown that treating cells with IFN after infection resulted in an increase in virus transcription but an overall decrease in virus protein synthesis. As there was no obvious decrease in the overall levels of cellular protein synthesis in infected cells treated with IFN, these results suggested that ISG56/IFIT1 selectively inhibits the translation of viral mRNAs. This conclusion was supported by in vitro translation studies. Previous work has shown that ISG56/IFIT1 can restrict the replication of viruses lacking a 2′-O-methyltransferase activity, an enzyme that methylates the 2′-hydroxyl group of ribose sugars in the 5′-cap structures of mRNA. However, the data in the current study strongly suggested that PIV5 mRNAs are methylated at the 2′-hydroxyl group and thus that ISG56/IFIT1 selectively inhibits the translation of PIV5 mRNA by some as yet unrecognized mechanism. It was also shown that ISG56/IFIT1 is primarily responsible for the IFN-induced inhibition of PIV5.

negative: A study of non-prescription usage of antibiotics in the upper respiratory tract infections in the urban population

negative: Sustained Viremia and High Viral Load in Respiratory Tract Secretions Are Predictors for Death in Immunocompetent Adults with Adenovirus Pneumonia The predictors for fatal adenovirus (AdV) pneumonia among immunocompetent adults are unclear. Laboratory-confirmed, hospitalized AdV pneumonia adults were prospectively enrolled in Beijing Chao-Yang hospital from March to June 2013. Clinical data and serial whole blood and respiratory tract secretions from such patients were collected. Quantitative real-time polymerase chain reaction was performed to quantify the viral load. A total of 14 AdV pneumonia cases were consecutively enrolled, and four of them were fatal. Ten cases were caused by AdV-55, three by AdV-7 and one by AdV-3. There were no differences in age, gender or underlying diseases between the patients in the fatal cases and surviving cases. At admission (on day 5–7 after illness onset), the patients in fatal cases presented higher initial viral loads in respiratory tract secretions (8.578 ± 2.115 vs 6.263 ± 1.225 Log(10) copies/ml, p = 0.023). All patients in fatal cases presented with viremia on day 12–14 (100% vs 66.7%, p = 0.017). A higher initial viral load in the respiratory tract and sustained viremia (more than 2 weeks) may be predictors for fatal clinical outcomes.

negative: 2019 Novel-coronavirus: Cardiovascular Insights about Risk Factors, Myocardial Injury, Therapy and Clinical Implications From December 31th, 2019, a novel highly pathogenic coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide, reaching at present the dimension of a pandemic. In addition to damaging the lungs, SARS-CoV-2 may also damage the heart and this is corroborated by the evidence that cardiovascular comorbidities are associated with a higher mortality and poor clinical outcomes in patient infected by the virus. During the infection myocardial injury, myocarditis and arrhythmias have also been reported, but the pathophysiological mechanisms of these complications are yet to be understood. Great attention is also being posed on the potential beneficial/harmful role of angiotensin converting enzyme (ACE) inhibitors, as far as the virus binds to angiotensin converting enzyme 2 (ACE2) to infect cells, but evidences lack. Furthermore, SARS-CoV-2 can also affect the aspect of acute coronary syndromes, not only because these two distinct pathological entities share pathogenic aspects (such as the systemic inflammatory state and cytokine release), but also and above all for the consequences that the need to contain the infection has on the management of cardiological urgencies. Aim of this review is therefore to summarize the relationship between the virus and the cardiovascular system.

negative: Improving vaccine-induced immunity: Can Baseline Predict Outcome? Abstract Immune signatures measured at baseline and immediately prior to vaccination, may predict the immune response to vaccination. Such pre-vaccine assessment might allow not only population-based, but also more personalized vaccination strategies (‘precision vaccination’). If baseline immune signatures are predictive, the underlying mechanism they reflect may also determine vaccination outcome. Thus, baseline signatures might contribute to identifying interventional targets to be modulated prior to vaccination in order to improve vaccination responses. This concept has the potential to transform vaccination strategies and usher in a new approach to improve global health.

negative: Review and Prospect of Pathological Features of Corona Virus Disease. Abstract Since 2003, coronavirus has caused multiple major public health events that resulted in global epidemics such as, severe acute respiratory syndrome （SARS）, Middle East respiratory syndrome （MERS） and corona virus disease 2019 （COVID-19）. Especially since COVID-19 has outbroken in Wuhan, Hubei, in December 2019, coronavirus has had a significant impact on people's health and lives. But so far, the pathological diagnosis of COVID-19 has been relatively deficient： it is still confined to the pathological findings of punctured organs, and the majority of medical workers have poor awareness of its pathological characteristics. The COVID-19, as same as SARS and MERS, is caused by coronaviruses and can cause viral pneumonia. They have certain similarities. This article comprehensively reviews the pathological features observed in the autopsies of the aforementioned three diseases, in order to provide reference to the analysis of pathological changes of COVID-19.

negative: Features, Evaluation and Treatment Coronavirus (COVID-19) According to the World Health Organization (WHO), viral diseases continue to emerge and represent a serious issue to public health In the last twenty years, several viral epidemics such as the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 to 2003, and H1N1 influenza in 2009, have been recorded Most recently, the Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia in 2012 In a timeline that reaches the present day, an epidemic of cases with unexplained low respiratory infections detected in Wuhan, the largest metropolitan area in China's Hubei province, was first reported to the WHO Country Office in China, on December 31, 2019 Published literature can trace the beginning of symptomatic individuals back to the beginning of December 2019 As they were unable to identify the causative agent, these first cases were classified as "pneumonia of unknown etiology " The Chinese Center for Disease Control and Prevention (CDC) and local CDCs organized an intensive outbreak investigation program The etiology of this illness is now attributed to a novel virus belonging to the coronavirus (CoV) family, COVID-19 On February 11, 2020, the WHO Director-General, Dr Tedros Adhanom Ghebreyesus, announced that the disease caused by this new CoV was a "COVID-19," which is the acronym of "coronavirus disease 2019" In the past twenty years, two additional coronavirus epidemics have occurred SARS-CoV provoked a large-scale epidemic beginning in China and involving two dozen countries with approximately 8000 cases and 800 deaths, and the MERS-CoV that began in Saudi Arabia and has approximately 2,500 cases and 800 deaths and still causes as sporadic cases This new virus seems to be very contagious and has quickly spread globally In a meeting on January 30, 2020, per the International Health Regulations (IHR, 2005), the outbreak was declared by the WHO a Public Health Emergency of International Concern (PHEIC) as it had spread to 18 countries with four countries reporting human-to-human transmission An additional landmark occurred on February 26, 2020, as the first case of the disease, not imported from China, was recorded in the United States Initially, the new virus was called 2019-nCoV Subsequently, the task of experts of the International Committee on Taxonomy of Viruses (ICTV) termed it the SARS-CoV-2 virus as it is very similar to the one that caused the SARS outbreak (SARS-CoVs) The CoVs have become the major pathogens of emerging respiratory disease outbreaks They are a large family of single-stranded RNA viruses (+ssRNA) that can be isolated in different animal species For reasons yet to be explained, these viruses can cross species barriers and can cause, in humans, illness ranging from the common cold to more severe diseases such as MERS and SARS Interestingly, these latter viruses have probably originated from bats and then moving into other mammalian hosts — the Himalayan palm civet for SARS-CoV, and the dromedary camel for MERS-CoV — before jumping to humans The dynamics of SARS-Cov-2 are currently unknown, but there is speculation that it also has an animal origin The potential for these viruses to grow to become a pandemic worldwide seems to be a serious public health risk Concerning COVID-19, the WHO raised the threat to the CoV epidemic to the "very high" level, on February 28, 2020 Probably, the effects of the epidemic caused by the new CoV has yet to emerge as the situation is quickly evolving World governments are at work to establish countermeasures to stem possible devastating effects Health organizations coordinate information flows and issues directives and guidelines to best mitigate the impact of the threat At the same time, scientists around the world work tirelessly, and information about the transmission mechanisms, the clinical spectrum of disease, new diagnostics, and prevention and therapeutic strategies are rapidly developing Many uncertainties remain with regard to both the virus-host interac ion and the evolution of the epidemic, with specific reference to the times when the epidemic will reach its peak At the moment, the therapeutic strategies to deal with the infection are only supportive, and prevention aimed at reducing transmission in the community is our best weapon Aggressive isolation measures in China have led to a progressive reduction of cases in the last few days In Italy, in geographic regions of the north of the peninsula, political and health authorities are making incredible efforts to contain a shock wave that is severely testing the health system In the midst of the crisis, the authors have chosen to use the "Statpearls" platform because, within the PubMed scenario, it represents a unique tool that may allow them to make updates in real-time The aim, therefore, is to collect information and scientific evidence and to provide an overview of the topic that will be continuously updated

negative: The role of CXCL10 in the pathogenesis of experimental septic shock INTRODUCTION: The chemokine CXCL10 is produced during infection and inflammation to activate the chemokine receptor CXCR3, an important regulator of lymphocyte trafficking and activation. The goal of this study was to assess the contributions of CXCL10 to the pathogenesis of experimental septic shock in mice. METHODS: Septic shock was induced by cecal ligation and puncture (CLP) in mice resuscitated with lactated Ringer’s solution and, in some cases, the broad spectrum antibiotic Primaxin. Studies were performed in CXCL10 knockout mice and mice treated with anti-CXCL10 immunoglobulin G (IgG). Endpoints included leukocyte trafficking and activation, core body temperature, plasma cytokine concentrations, bacterial clearance and survival. RESULTS: CXCL10 was present at high concentrations in plasma and peritoneal cavity during CLP-induced septic shock. Survival was significantly improved in CXCL10 knockout (CXCL10KO) mice and mice treated with anti-CXCL10 IgG compared to controls. CXCL10KO mice and mice treated with anti-CXCL10 IgG showed attenuated hypothermia, lower concentrations of interleukin-6 (IL-6) and macrophage inhibitory protein-2 (MIP-2) in plasma and lessened natural killer (NK) cell activation compared to control mice. Compared to control mice, bacterial burden in blood and lungs was lower in CXCL10-deficient mice but not in mice treated with anti-CXCL10 IgG. Treatment of mice with anti-CXCL10 IgG plus fluids and Primaxin at 2 or 6 hours after CLP significantly improved survival compared to mice treated with non-specific IgG under the same conditions. CONCLUSIONS: CXCL10 plays a role in the pathogenesis of CLP-induced septic shock and could serve as a therapeutic target during the acute phase of septic shock.

negative: COVID-19 and pneumonia: a role for the uPA/uPAR system Here, we highlight recent findings on the urokinase plasminogen activator (uPA)/uPA receptor (uPAR) system that suggest its potential role as a main orchestrator of fatal progression to pulmonary, kidney, and heart failure in patients with coronavirus. Patients with prolonged background inflammation can present with aberrant inflammatory reactions, well recognized as the main factors that can result in death and probably sustained by a dysregulated uPA/uPAR system. SuPAR, the soluble form of uPAR, represents a biomarker of disease progression, and its levels correlate well with comorbidities associated with the death of patients with coronavirus. New drugs that regulate the uPA/uPAR system could help treat the severe complications of highly pathogenic human coronaviruses (hCoVs), including pandemic coronavirus 2019 (COVID-19).

negative: Predicting Outcomes After Blunt Chest Trauma—Utility of Thoracic Trauma Severity Score, Cytokines (IL-1β, IL-6, IL-8, IL-10, and TNF-α), and Biomarkers (vWF and CC-16) Thoracic trauma severity score (TTSS) has been used to assess severity and risk of pulmonary complications in patients with chest trauma. The role of cytokines and biomarkers in patients with chest trauma and its association with TTSS is not well elucidated. The aim of the study was to assess the cytokines (IL-1β, IL-6, IL-8, IL-10, and TNF-α) and biomarkers (vWF, CC-16) in patients of thoracic trauma and correlate it with TTSS and patient’s outcome. This was a prospective observational study. Serum and bronchoalveolar lavage fluid samples were collected from chest trauma patients. TTSS was calculated in all patients. Suitable controls for serum and bronchoalveolar lavage (BAL) sample were selected. The outcome parameters included patient discharge or death, duration of hospital, and intensive care unit (ICU) stay. Forty-three patients were included. There was no significant correlation between the measured cytokines and biomarkers and TTSS. The mean TTSS of patients who had a fatal outcome was significantly higher than the patients who recovered. Patients with a high TTSS score had a significant prolonged ICU stay. Patients with a prolonged hospital stay had lower values of CC-16. TTSS is a useful tool to predict severity of chest trauma and prolonged ICU stay. Lower levels of CC-16 in BAL fluid of chest trauma patients were associated with prolonged hospital stay suggestive of its protective role in the airway. Longer prospective studies are required to determine the role of cytokines and biomarkers in patients with thoracic trauma in predicting the patient’s outcome.

negative: Access to Care for Dementia patients suffering from COVID-19

negative: A Melting Curve-Based Multiplex RT-qPCR Assay for Simultaneous Detection of Four Human Coronaviruses Human coronaviruses HCoV-OC43, HCoV-229E, HCoV-NL63 and HCoV-HKU1 are common respiratory viruses associated with acute respiratory infection. They have a global distribution. Rapid and accurate diagnosis of HCoV infection is important for the management and treatment of hospitalized patients with HCoV infection. Here, we developed a melting curve-based multiplex RT-qPCR assay for simultaneous detection of the four HCoVs. In the assay, SYTO 9 was used to replace SYBR Green I as the fluorescent dye, and GC-modified primers were designed to improve the melting temperature (Tm) of the specific amplicon. The four HCoVs were clearly distinguished by characteristic melting peaks in melting curve analysis. The detection sensitivity of the assay was 3 × 10(2) copies for HCoV-OC43, and 3 × 10(1) copies for HCoV-NL63, HCoV-229E and HCoV-HKU1 per 30 μL reaction. Clinical evaluation and sequencing confirmation demonstrated that the assay was specific and reliable. The assay represents a sensitive and reliable method for diagnosis of HCoV infection in clinical samples.

negative: Serological detection of 2019-nCoV respond to the epidemic: A useful complement to nucleic acid testing Corona Virus Disease 2019 (COVID-19) has spread rapidly to more than 70 countries and regions overseas and over 80000 cases have been infected, resulting in more than three thousand deaths. Rapid diagnosis of patients remains a bottleneck in containing the progress of the epidemic. We used automated chemiluminescent immunoassay to detect serum IgM and IgG antibodies to 2019-nCoV of 736 subjects. COVID-19 patients were becoming reactive(positive) for specific antibodies from 7-12 days after the onset of morbidity. Specific IgM and IgG increased with the progression of the disease. The areas under the ROC curves of IgM and IgG were 0.988 and 1.000, respectively. Specific antibody detection has good sensitivity and specificity. Detection of specific antibodies in patients with fever can be a good distinction between COVID-19 and other diseases, so as to be a complement to nucleic acid diagnosis to early diagnosis of suspected cases.

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: Guidelines for the management of adult lower respiratory tract infections - Full version This document is an update of Guidelines published in 2005 and now includes scientific publications through to May 2010. It provides evidence-based recommendations for the most common management questions occurring in routine clinical practice in the management of adult patients with LRTI. Topics include management outside hospital, management inside hospital (including community-acquired pneumonia (CAP), acute exacerbations of COPD (AECOPD), acute exacerbations of bronchiectasis) and prevention. Background sections and graded evidence tables are also included. The target audience for the Guideline is thus all those whose routine practice includes the management of adult LRTI.

negative: Current Understanding of COVID-19 Clinical Course and Investigational Treatments Importance: Currently, there is no unified framework linking disease progression to established viral levels, clinical tests, inflammatory markers, and investigational treatment options. Objective: It may take many weeks or months to establish a standard treatment approach. Given the growing morbidity and mortality with respect to COVID-19, we present a treatment approach based on a thorough review of scholarly articles and clinical reports. Our focus is on staged progression, clinical algorithms, and individualized treatment. Evidence Review: We followed the protocol for a quality review article proposed by Heyn et. al.1 A literature search was conducted to find all relevant studies related to COVID-19. The search was conducted between April 1, 2020 and April 13, 2020 using the following electronic databases: PubMed (1809 to present), Google Scholar (1900 to present), MEDLINE (1946 to present), CINAHL (1937 to present), and Embase (1980 to present). Keywords used included COVID-19, 2019-nCov, SARS-CoV-2, SARS-CoV, and MERS-CoV, with terms such as efficacy, seroconversion, microbiology, pathophysiology, viral levels, inflammation, survivability, and treatment and pharmacology. No language restriction was placed on the search. Reference lists were manually scanned for additional studies. Findings: Of the articles found in the literature search, 70 were selected for inclusion in this study (67 cited in the body of the manuscript and 3 additional unique references in the Figures). The articles represent work from China, Japan, Taiwan, Vietnam, Rwanda, Israel, France, the United Kingdom, the Netherlands, Canada, and the United States. Most of the articles were cohort or case studies, but we also drew upon information found in guidelines from hospitals and clinics instructing their staff on procedures to follow. In addition, we based some decisions on data collected by agencies such as the CDC, FDA, IHME, ISDA, and Worldometer. None of the case studies or cohort studies used a large number of participants. The largest group of participants numbered less than 500 and some case studies had fewer than 30 patients. However, the review of the literature revealed the need for individualized treatment protocols due to the variability of patient clinical presentation and survivability. A number of factors appear to influence mortality: the stage at which the patient first presented for care, pre-existing health conditions, age, and the viral load the patient carried. Conclusion and Relevance: COVID-19 can be divided into three distinct Stages, beginning at the time of infection (Stage I), sometimes progressing to pulmonary involvement (Stage II, with or without hypoxemia) and less frequently to systemic inflammation (Stage III). In addition to modeling the stages of disease progression, we have also created a treatment algorithm which considers age, comorbidities, clinical presentation, and disease progression to suggest drug classes or treatment modalities. This paper presents the first evidence-based recommendations for individualized treatment for COVID-19.

negative: 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: The Role of Interferon-λ Locus Polymorphisms in Hepatitis C and Other Infectious Diseases Since its discovery in 2003, the type III interferon-λ (IFN-λ) family has been found to contribute significantly to the host response to infection. Whilst IFN-λ shares many features with type I IFN induction and signalling pathways, the tissue-specific restricted expression of its receptor, IL28RA, makes IFN-λ a major mediator of host innate immunity in tissues and organs with a high epithelial cell content. Host susceptibility and responses to infection are known to be heterogeneous, and the identification of common genetic variants linked to disease outcome by genome-wide association studies (GWAS) has underscored the significance of host polymorphisms in responses to infection. Several such GWAS have highlighted the IFN-λ locus on chromosome 19q13 as an area of genetic variation significantly associated with hepatitis C virus (HCV) infection, and the rs12979860 genotype can be used in clinical practice as a biomarker for predicting a successful response to treatment with pegylated IFN and ribavarin. Here, we discuss IFN-λ genetic polymorphisms and their role in HCV and other infectious diseases as well as their potential impact on clinical diagnostics, patient stratification and therapy. Finally, the broader role of IFN-λ in the immunopathogenesis of non-infectious inflammatory diseases is considered.

negative: HIV and SARS‐CoV‐2 co‐infection: A case report from Uganda There are no reports of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and HIV co‐infection from sub‐Saharan Africa where 70% of people living with HIV are found. We report a case of HIV/SARS‐CoV‐2 co‐infection from Uganda. A 34 year old HIV‐positive female on antiretroviral therapy (tenofovir disoproxil fumarate, lamivudine and efavirenz) for 5 years, tested positive for SARS‐CoV‐2, the causative agent for coronavirus disease 19 (COVID‐19). She was asymptomatic at presentation but subsequently developed headache, chest pain, diarrhoea, anorexia and fatigue on day 3 of isolation without cough, fever or shortness of breath. Her CD4 count was 965 cells/mm(3), the HIV viral load was undetectable (<1,000 cells/mm(3)) and other laboratory work up was normal. She was successfully managed with hydroxychloroquine and broad spectrum antibiotics, and was discharged after 24 days. This case demonstrates an atypical clinical presentation of COVID – 19 in an HIV infected patient without other co‐morbidity. This article is protected by copyright. All rights reserved.

negative: Clinical and epidemiological predictors of transmission in Severe Acute Respiratory Syndrome (SARS) BACKGROUND: Only a minority of probable SARS cases caused transmission. We assess if any epidemiological or clinical factors in SARS index patients were associated with increased probability of transmission. METHODS: We used epidemiological and clinical data on probable SARS patients admitted to Tan Tock Seng Hospital. Using a case-control approach, index patients who had probable SARS who subsequently transmitted the disease to at least one other patient were analysed as "cases" against patients with no transmission as "controls", using multivariate logistic regression analysis. RESULTS: 98 index patients were available for analysis (22 with transmission, 76 with no transmission). Covariates positively associated with transmission in univariate analysis at p < 0.05 included delay to isolation (Day 7 of illness or later), admission to a non-isolation facility, pre-existing chronic respiratory disease and immunosuppressive disease, need for oxygen, shortness of breath, vomiting, and higher lactate dehydrogenase levels and higher neutrophil counts. In the multivariate analysis, only three factors were significant: delay to isolation, admission to a non-isolation facility and higher lactate dehydrogenase levels of >650 IU/L (OR 6.4, 23.8 and 4.7 respectively). CONCLUSION: Clinical and epidemiological factors can help us to explain why transmission was observed in some instances but not in others.

negative: Sepsis biomarkers: an omics perspective Sepsis is a common cause of death in hospitalized patients worldwide. The early detection of sepsis remains a great challenge for clinicians, and delayed diagnosis frequently undermines treatment efforts, thereby contributing to high mortality. Omics technologies allow high-throughput screening of sepsis biomarkers. This review describes currently available and novel sepsis biomarkers in the context of genomics, transcriptomics, proteomics, and metabolomics. The combination of these technologies can help refine the diagnosis of sepsis. This review paper serves as a reference for future studies that employ an integrated, multi-omics approach to disease identification.

negative: Prospective observational study in two Dutch hospitals to assess the performance of inflammatory plasma markers to determine disease severity of viral respiratory tract infections in children INTRODUCTION: Respiratory viruses causing lower respiratory tract infections (LRTIs) are a major cause of hospital admissions in children. Since the course of these infections is unpredictable with potential fast deterioration into respiratory failure, infants are easily admitted to the hospital for observation. The aim of this study was to examine whether systemic inflammatory markers can be used to predict severity of disease in children with respiratory viral infections. METHODS: Blood and nasopharyngeal washings from children <3 years of age with viral LRTI attending a hospital were collected within 24 hours (acute) and after 4–6 weeks (recovery). Patients were assigned to a mild (observation only), moderate (supplemental oxygen and/or nasogastric feeding) or severe (mechanical ventilation) group. Linear regression analysis was used to design a prediction rule using plasma levels of C reactive protein (CRP), serum amyloid A (SAA), pentraxin 3 (PTX3), serum amyloid P component and properdin. This rule was tested in a validation cohort. RESULTS: One hundred and four children (52% male) were included. A combination of CRP, SAA, PTX3 and properdin was a better indicator of severe disease compared with any of the individual makers and age (69% sensitivity (95% CI 50 to 83), 90% specificity (95% CI 80 to 96)). Validation in 141 patients resulted in 71% sensitivity (95% CI 53 to 85), 87% specificity (95% CI 79 to 92), negative predictive value of 64% (95% CI 47 to 78) and positive predictive value of 90% (95% CI 82 to 95). The prediction rule was not able to identify patients with a mild course of disease. CONCLUSION: A combination of CRP, SAA, PTX3 and properdin was able to identify children with a severe course of viral LRTI disease, even in children under 2 months of age. To assess the true impact on clinical management, these results should be validated in a prospective randomised control study.

negative: Human coronavirus NL-63 infections in children: a 1-year study. Human coronavirus NL63 (HCoV-NL63), a newly discovered coronavirus, has been associated with acute respiratory tract infections (ARI). Important questions pertaining to the contribution of HCoV-NL63 to ARI and its impact on public health remain. We reviewed HCoV-NL63 in specimens collected from 13 November 2002 to 31 December 2003 from the Stollery Children's Hospital on patients of <17 years of age to assess the role of this virus in ARI in children. Twenty-six of 1,240 specimens (2.1%) from seven outpatients and 19 inpatients aged 7 days to 9.5 years tested positive for HCoV-NL63 by reverse transcription-PCR. The majority of outpatients (86%) had upper respiratory tract infections, while the majority of inpatients (58%) had bronchiolitis. Peak HCoV-NL63 activity occurred in March. These results provide further evidence of the importance of HCoV-NL63 in ARI in children.

negative: Disease-specific B cell epitopes for serum antibodies from patients with severe acute respiratory syndrome (SARS) and serologic detection of SARS antibodies by epitope-based peptide antigens Severe acute respiratory syndrome (SARS) has emerged as a highly contagious, sometimes fatal disease. To find disease-specific B cell epitopes, phage-displayed random peptide libraries were panned on serum immunoglobulin (Ig) G antibodies from patients with SARS. Forty-nine immunopositive phage clones that bound specifically to serum from patients with SARS were selected. These phageborne peptides had 4 consensus motifs, of which 2 corresponded to amino acid sequences reported for SARS-associated coronavirus (SARSCoV). Synthetic peptide binding and competitive-inhibition assays further confirmed that patients with SARS generated antibodies against SARS-CoV. Immunopositive phage clones and epitope-based peptide antigens demonstrated clinical diagnostic potential by reacting with serum from patients with SARS. Antibody-response kinetics were evaluated in 4 patients with SARS, and production of IgM, IgG, and IgA were documented as part of the immune response. In conclusion, B cell epitopes of SARS corresponded to novel coronavirus. Our epitope-based serologic test may be useful in laboratory detection of the virus and in further study of the pathogenesis of SARS.

negative: Acute Physiology and Chronic Health Evaluation II Score as a Predictor of Hospital Mortality in Patients of Coronavirus Disease 2019 OBJECTIVES: Coronavirus disease 2019 has emerged as a major global health threat with a great number of deaths in China. We aimed to assess the association between Acute Physiology and Chronic Health Evaluation II score and hospital mortality in patients with coronavirus disease 2019, and to compare the predictive ability of Acute Physiology and Chronic Health Evaluation II score, with Sequential Organ Failure Assessment score and Confusion, Urea, Respiratory rate, Blood pressure, Age 65 (CURB65) score. DESIGN: Retrospective observational cohort. SETTING: Tongji Hospital in Wuhan, China. SUBJECTS: Confirmed patients with coronavirus disease 2019 hospitalized in the ICU of Tongji hospital from January 10, 2020, to February 10, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 178 potentially eligible patients with symptoms of coronavirus disease 2019, 23 patients (12.92%) were diagnosed as suspected cases, and one patient (0.56%) suffered from cardiac arrest immediately after admission. Ultimately, 154 patients were enrolled in the analysis and 52 patients (33.77%) died. Mean Acute Physiology and Chronic Health Evaluation II score (23.23 ± 6.05) was much higher in deaths compared with the mean Acute Physiology and Chronic Health Evaluation II score of 10.87 ± 4.40 in survivors (p < 0.001). Acute Physiology and Chronic Health Evaluation II score was independently associated with hospital mortality (adjusted hazard ratio, 1.07; 95% CI, 1.01–1.13). In predicting hospital mortality, Acute Physiology and Chronic Health Evaluation II score demonstrated better discriminative ability (area under the curve, 0.966; 95% CI, 0.942–0.990) than Sequential Organ Failure Assessment score (area under the curve, 0.867; 95% CI, 0.808–0.926) and CURB65 score (area under the curve, 0.844; 95% CI, 0.784–0.905). Based on the cut-off value of 17, Acute Physiology and Chronic Health Evaluation II score could predict the death of patients with coronavirus disease 2019 with a sensitivity of 96.15% and a specificity of 86.27%. Kaplan-Meier analysis showed that the survivor probability of patients with coronavirus disease 2019 with Acute Physiology and Chronic Health Evaluation II score less than 17 was notably higher than that of patients with Acute Physiology and Chronic Health Evaluation II score greater than or equal to 17 (p < 0.001). CONCLUSIONS: Acute Physiology and Chronic Health Evaluation II score was an effective clinical tool to predict hospital mortality in patients with coronavirus disease 2019 compared with Sequential Organ Failure Assessment score and CURB65 score. Acute Physiology and Chronic Health Evaluation II score greater than or equal to 17 serves as an early warning indicator of death and may provide guidance to make further clinical decisions.

negative: Cumulative biological source index: Volumes 1–20

negative: Research Communications of the 25th ECVIM‐CA Congress

negative: HEART BRAKE-An unusual cardiac manifestation of Coronavirus disease 2019 (COVID-19) Abstract: A 49-year-old male presented with worsening high-grade fevers, dry cough and shortness of breath, tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and was noted to have bradycardia with intermittent high-degree AV block. However, cardiac biomarkers and echocardiography were normal, making this an unusual and interesting manifestation showing myocardial involvement of this novel coronavirus.

negative: Compounds with Therapeutic Potential against Novel Respiratory 2019 Coronavirus Currently, the expansion of the novel human respiratory coronavirus (known as SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2], COVID-2019 [coronavirus disease 2019], or 2019-nCoV [2019 novel coronavirus]) has stressed the need for therapeutic alternatives to alleviate and stop this new epidemic. The previous epidemics of infections by high-morbidity human coronaviruses, such as SARS-CoV in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, prompted the characterization of compounds that could be potentially active against the currently emerging novel coronavirus, SARS-CoV-2. The most promising compound is remdesivir (GS-5734), a nucleotide analog prodrug currently in clinical trials for treating Ebola virus infections. Remdesivir inhibited the replication of SARS-CoV and MERS-CoV in tissue cultures, and it displayed efficacy in nonhuman animal models. In addition, a combination of the human immunodeficiency virus type 1 (HIV-1) protease inhibitors lopinavir/ritonavir and interferon beta (LPV/RTV–IFN-β) was shown to be effective in patients infected with SARS-CoV. LPV/RTV–IFN-β also improved clinical parameters in marmosets and mice infected with MERS-CoV. Remarkably, the therapeutic efficacy of remdesivir appeared to be superior to that of LPV/RTV–IFN-β against MERS-CoV in a transgenic humanized mouse model. The relatively high mortality rates associated with these three novel human coronavirus infections, SARS-CoV, MERS-CoV, and SARS-CoV-2, have suggested that proinflammatory responses might play a role in the pathogenesis. It remains unknown whether the generated inflammatory state should be targeted. Therapeutics that target the coronavirus alone might not be able to reverse highly pathogenic infections. This minireview aims to provide a summary of therapeutic compounds that have shown potential in fighting SARS-CoV-2 infections.

negative: Mysterious Virus: A Review on Behavior and Treatment Approaches of the Novel Coronavirus, 2019-nCoV Abstract At the end of the year 2019, the novel coronavirus (2019-nCoV) was spreading in Wuhan, China, and the outbreak process has a high speed. It was recognized as a pandemic by the World Health Organization (WHO) on 11 March 2020. Coronaviruses are enveloped and single-stranded RNA that have several families including Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The pathogenesis mechanism and disease outcomes of SARS and MERS are now clear to some extent, but little information is available for 2019-nCoV. This newly identified corona virus infection represents flu-like symptoms, but usually the first symptoms are fever and dry cough. There has been no specific treatment against 2019-nCoV up to now, and physicians only apply supportive therapy. In the present article, we made an attempt to review the behavior of the virus around the world, epidemiology, a pathway for influx into the host cells, clinical presentation, as well as the treatments currently in use and future approaches; nitazoxanide may be our dream drug. We hope that this review has a positive impact on public knowledge for helping to deal with the 2019-nCoV and move one step forward toward its treatment in the near future.

negative: Gene expression profiling of whole blood in ipilimumab-treated patients for identification of potential biomarkers of immune-related gastrointestinal adverse events BACKGROUND: Treatment with ipilimumab, a fully human anti-CTLA-4 antibody approved for the treatment of advanced melanoma, is associated with some immune-related adverse events (irAEs) such as colitis (gastrointestinal irAE, or GI irAE) and skin rash, which are managed by treatment guidelines. Nevertheless, predictive biomarkers that can help identify patients more likely to develop these irAEs could enhance the management of these toxicities. METHODS: To identify candidate predictive biomarkers associated with GI irAEs, gene expression profiling was performed on whole blood samples from 162 advanced melanoma patients at baseline, 3 and 11 weeks after the start of ipilimumab treatment in two phase II clinical trials (CA184004 and CA184007). Overall, 49 patients developed Grade 2 or higher (grade 2+) GI irAEs during the course of treatment. A repeated measures analysis of variance (ANOVA) was used to evaluate the differences in mean expression levels between the GI irAE and No-GI irAE groups of patients at the three time points. RESULTS: In baseline samples, 27 probe sets showed differential mean expression (≥ 1.5 fold, P ≤ 0.05) between the GI irAE and No-GI irAE groups. Most of these probe sets belonged to three functional categories: immune system, cell cycle, and intracellular trafficking. Changes in gene expression over time were also characterized. In the GI irAE group, 58 and 247 probe sets had a ≥ 1.5 fold change in expression from baseline to 3 and 11 weeks after first ipilimumab dose, respectively. In particular, on-treatment expression increases of CD177 and CEACAM1, two neutrophil-activation markers, were closely associated with GI irAEs, suggesting a possible role of neutrophils in ipilimumab-associated GI irAEs. In addition, the expression of several immunoglobulin genes increased over time, with greater increases in patients with grade 2+ GI irAEs. CONCLUSIONS: Gene expression profiling of peripheral blood, sampled before or early in the course of treatment with ipilimumab, resulted in the identification of a set of potential biomarkers that were associated with occurrence of GI irAEs. However, because of the low sensitivity of these biomarkers, they cannot be used alone to predict which patients will develop GI irAEs. Further investigation of these biomarkers in a larger patient cohort is warranted.

negative: Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin Since the SARS outbreak 18 years ago, a large number of severe acute respiratory syndrome related coronaviruses (SARSr-CoV) have been discovered in their natural reservoir host, bats1-4. Previous studies indicated that some of those bat SARSr-CoVs have the potential to infect humans5-7. Here we report the identification and characterization of a novel coronavirus (nCoV-2019) which caused an epidemic of acute respiratory syndrome in humans, in Wuhan, China. The epidemic, started from December 12th, 2019, has caused 198 laboratory confirmed infections with three fatal cases by January 20th, 2020. Full-length genome sequences were obtained from five patients at the early stage of the outbreak. They are almost identical to each other and share 79.5% sequence identify to SARS-CoV. Furthermore, it was found that nCoV-2019 is 96% identical at the whole genome level to a bat coronavirus. The pairwise protein sequence analysis of seven conserved non-structural proteins show that this virus belongs to the species of SARSr-CoV. The nCoV-2019 virus was then isolated from the bronchoalveolar lavage fluid of a critically ill patient, which can be neutralized by sera from several patients. Importantly, we have confirmed that this novel CoV uses the same cell entry receptor, ACE2, as SARS-CoV.

negative: Abstract of 44th National Conference of Association of Clinical Biochemists of India (ACBICON 2017)

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

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

negative: Emerging 2019 Novel Coronavirus (2019-nCoV) Pneumonia BACKGROUND: The chest CT findings of patients with 2019 Novel Coronavirus (2019-nCoV) pneumonia have not previously been described in detail. PURPOSE: To investigate the clinical, laboratory, and imaging findings of emerging 2019-nCoV pneumonia in humans. MATERIALS AND METHODS: Fifty-one patients (25 men and 26 women; age range 16–76 years) with laboratory-confirmed 2019-nCoV infection by using real-time reverse transcription polymerase chain reaction underwent thin-section CT. The imaging findings, clinical data, and laboratory data were evaluated. RESULTS: Fifty of 51 patients (98%) had a history of contact with individuals from the endemic center in Wuhan, China. Fever (49 of 51, 96%) and cough (24 of 51, 47%) were the most common symptoms. Most patients had a normal white blood cell count (37 of 51, 73%), neutrophil count (44 of 51, 86%), and either normal (17 of 51, 35%) or reduced (33 of 51, 65%) lymphocyte count. CT images showed pure ground-glass opacity (GGO) in 39 of 51 (77%) patients and GGO with reticular and/or interlobular septal thickening in 38 of 51 (75%) patients. GGO with consolidation was present in 30 of 51 (59%) patients, and pure consolidation was present in 28 of 51 (55%) patients. Forty-four of 51 (86%) patients had bilateral lung involvement, while 41 of 51 (80%) involved the posterior part of the lungs and 44 of 51 (86%) were peripheral. There were more consolidated lung lesions in patients 5 days or more from disease onset to CT scan versus 4 days or fewer (431 of 712 lesions vs 129 of 612 lesions; P < .001). Patients older than 50 years had more consolidated lung lesions than did those aged 50 years or younger (212 of 470 vs 198 of 854; P < .001). Follow-up CT in 13 patients showed improvement in seven (54%) patients and progression in four (31%) patients. CONCLUSION: Patients with fever and/or cough and with conspicuous ground-glass opacity lesions in the peripheral and posterior lungs on CT images, combined with normal or decreased white blood cells and a history of epidemic exposure, are highly suspected of having 2019 Novel Coronavirus (2019-nCoV) pneumonia. © RSNA, 2020

negative: Distribution of the 2019-nCoV Epidemic and Correlation with Population Emigration from Wuhan, China BACKGROUNDS: The ongoing new coronavirus (2019-nCoV) pneumonia outbreak is spreading in China and has not reached its peak. Five millions of people had emigrated from Wuhan before the city lockdown, which potentially represent a source of virus spreaders. Case distribution and its correlation with population emigration from Wuhan in early epidemic are of great importance for early warning and prevention of future outbreak. METHODS: The officially reported cases of 2019-nCoV pneumonia were collected as of January 30, 2020. Time and location information of these cases were extracted analyzed with ArcGIS and WinBUGS. Population migration data of Wuhan City and Hubei province were extracted from Baidu Qianxi and analyzed for their correlation with case number. FINDINGS: The 2019-nCoV pneumonia cases were predominantly distributed in Hubei and other provinces of South China. Hot spot provinces included Sichuan and Yunnan provinces that are adjacent to Hubei. While Wuhan city has the highest number of cases, the time risk is relatively stable. Numbers of cases in some cities are relatively low, but the time risks are continuously rising. The case numbers of different provinces and cities of Hubei province were highly correlated with the emigrated populations from Wuhan. Lockdown of 19 cities of Hubei province, and implementation of nationwide control measures efficiently prevented the exponential growth of case number. INTERPRETATION: Population emigrated from Wuhan was the main infection source for other cities and provinces. Some cities with low case number but were in rapid increase. Due to the upcoming Spring Festival return transport wave, understanding of the trends of risks in different regions is of great significance for preparedness for both individuals and institutions.

negative: Future Veterinary Diagnostics Abstract The development of rapid, accurate, and sensitive diagnostic methods for detecting pathogens is the basis for treating, controlling, and eradicating infectious diseases of veterinary importance. Scientific and technological advancements have revolutionized the field of veterinary diagnostics. Genome sequencing has allowed efficient, sensitive, and specific diagnostic assays to be developed based on the detection of nucleic acids. The integration of advances in biochemistry, proteomics, engineering, and medicine offers enormous potential for the rapid and accurate diagnosis of viral, microbial, genetic, and metabolic disease. In the future, polymerase chain reaction assays, microarray testing, genomic analysis, and metabolic profiling will be accomplished in a rapid, portable, sensitive, and cost-efficient manner.

negative: What’s new about circulating biomarkers in pediatric acute lung disease

negative: Molecular pathology of emerging coronavirus infections Respiratory viruses can cause a wide spectrum of pulmonary diseases, ranging from mild, upper respiratory tract infections to severe and life-threatening lower respiratory tract infections, including the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Viral clearance and subsequent recovery from infection require activation of an effective host immune response; however, many immune effector cells may also cause injury to host tissues. Severe acute respiratory syndrome (SARS) coronavirus and Middle East respiratory syndrome (MERS) coronavirus cause severe infection of the lower respiratory tract, with 10% and 35% overall mortality rates, respectively; however, >50% mortality rates are seen in the aged and immunosuppressed populations. While these viruses are susceptible to interferon treatment in vitro, they both encode numerous genes that allow for successful evasion of the host immune system until after high virus titres have been achieved. In this review, we discuss the importance of the innate immune response and the development of lung pathology following human coronavirus infection.

negative: 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.

negative: Pathogenetic determinants in Kawasaki disease: the haematological point of view Kawasaki disease is a multisystemic vasculitis that can result in coronary artery lesions. It predominantly affects young children and is characterized by prolonged fever, diffuse mucosal inflammation, indurative oedema of the hands and feet, a polymorphous skin rash and non‐suppurative lymphadenopathy. Coronary artery involvement is the most important complication of Kawasaki disease and may cause significant coronary stenosis resulting in ischemic heart disease. The introduction of intravenous immunoglobulin decreases the incidence of coronary artery lesions to less than 5%. The etiopathogenesis of this disease remains unclear. Several lines of evidence suggest that an interplay between a microbial infection and a genetic predisposition could take place in the development of the disease. In this review, we summarize the state of the art of pathogenetic mechanisms of Kawasaki disease underscoring the relevance of haematological features as a novel field of investigation.

negative: En mann i 90-årene med feber og tørrhoste./ En mann i 90-årene med feber og tørrhoste./ A man in his nineties with fever and dry cough BACKGROUND: COVID-19 can cause a fatal outcome in elderly patients, as this case report illustrates. CASE PRESENTATION: An active male in his nineties with a high level of function, despite several severe chronic diseases, was admitted to Oslo University Hospital after two days of fatigue, fever, dyspnoea and dry cough. He scored qSOFA 1 of 3 points due to high respiratory rate, and SIRS 2 of 4 points due to high respiratory rate and fever of 39.4º C. PCR for influenza virus was negative and he received benzylpenicillin for pneumonia. The chest X-ray taken initially showed no lung affection. On day 5 after symptom debut he was tested for COVID-19 which was positive. He had not been travelling to high-risk areas or been exposed to any known confirmed COVID-19 patients. On the same day, a chest CT scan was performed that showed ground-glass opacities. In subsequent days the patient's health rapidly deteriorated. He developed irreversible respiratory failure with hypoxia without hypercapnia despite substantial oxygen support. Chest X-ray taken on disease day 7 showed progression of consolidations. The patient died 9 days after symptom debut. INTERPRETATION: This case illustrates a severe course of COVID-19 with fatal outcome. The patient was also one of the earliest admitted with COVID-19 in a Norwegian hospital and marked a new phase of the epidemic, as he had not been travelling to high-risk areas or been exposed to any confirmed COVID-19 patients.

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: Clinical outcomes of 402 patients with COVID-2019 from a single center in Wuhan, China The SARS-CoV-2 outbreak is causing widespread infections and significant mortality. Previous studies describing clinical characteristics of the disease contained small cohorts from individual centers or larger series consisting of mixed cases from different hospitals. We report analyses of mortality and disease severity among 402 patients from a single hospital. The cohort included 297 patients with confirmed and 105 with suspected diagnosis. The latter group met the criteria for clinical diagnosis but nucleic acid tests results were initially interpreted as suspicious. Data were compared between genders and among different age groups. The overall case fatality is 5.2%. However, patients 70 years of age or older suffered a significantly higher mortality (17.8%), associated with more patients having severe or critical illness (57.5%). Patients 50 years of age or older had a mortality of 8.0%, and those younger than 50 years, 1.2%. Male patients had a mortality of 7.6% versus 2.9% in females.

negative: Can procalcitonin help identify associated bacterial infection in patients with severe influenza pneumonia? A multicentre study PURPOSE: To determine whether procalcitonin (PCT) levels could help discriminate isolated viral from mixed (bacterial and viral) pneumonia in patients admitted to the intensive care unit (ICU) during the A/H1N1v2009 influenza pandemic. METHODS: A retrospective observational study was performed in 23 French ICUs during the 2009 H1N1 pandemic. Levels of PCT at admission were compared between patients with confirmed influenzae A pneumonia associated or not associated with a bacterial co-infection. RESULTS: Of 103 patients with confirmed A/H1N1 infection and not having received prior antibiotics, 48 (46.6%; 95% CI 37–56%) had a documented bacterial co-infection, mostly caused by Streptococcus pneumoniae (54%) or Staphylococcus aureus (31%). Fifty-two patients had PCT measured on admission, including 19 (37%) having bacterial co-infection. Median (range 25–75%) values of PCT were significantly higher in patients with bacterial co-infection: 29.5 (3.9–45.3) versus 0.5 (0.12–2) μg/l (P < 0.01). For a cut-off of 0.8 μg/l or more, the sensitivity and specificity of PCT for distinguishing isolated viral from mixed pneumonia were 91 and 68%, respectively. Alveolar condensation combined with a PCT level of 0.8 μg/l or more was strongly associated with bacterial co-infection (OR 12.9, 95% CI 3.2–51.5; P < 0.001). CONCLUSIONS: PCT may help discriminate viral from mixed pneumonia during the influenza season. Levels of PCT less than 0.8 μg/l combined with clinical judgment suggest that bacterial infection is unlikely.

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

negative: Utilize State Transition Matrix Model to Predict the Novel Corona Virus Infection Peak and Patient Distribution Background: Since December 2019, a pneumonia caused by the 2019 novel coronavirus (2019-nCoV) has broken out in Wuhan, Hubei province, China. The continuous rising of infected cases has imposed overwhelming pressure on public health decision and medical resource allocation in China. We managed to forecast the infection peak time in Hubei province and the severe and critical case distribution. Methods: We used data resource according to cases reported by the National Health Commission of the People's Republic of China (Jan 25, 2019, to Feb 28, 2020) as the training set to deduce the arrival of the peak infection time and the number of severe and critical cases in Wuhan on subsequent days. Medical observation, discharge, infected, non-Severe, infected and severe, cure and death data were collected and analyzed. Using this state transition matrix model, we will be able predict when the inflection peak time (the maximum open infection cases) in Hubei Province will occur. Also, we can use this model to predict the patient distribution (severe, non-severe) to better allocate medical resource. Under relative pessimistic scenario, the inflection peak time is April 6-April 14. The numbers of critically ill and critically ill patients will lie between 8300-9800 and 2200-2700, respectively. Results: In very optimistic scenarios (daily NCC decay rate of -10%), the peak time of open inflection cases will arrive around February 23-February 26. At the same time, there will be a peak in the numbers of severely ill and critically ill patients, between 6800-7200 and 1800-2000, respectively. In a relative optimistic scenario (daily NCC decay rate of -5%), the inflection case peak time will arrive around February 28-March 2. The numbers of critically ill and critically ill patients will lie between 7100-7800 and 1900-2200, respectively. In a relatively pessimistic scenario (daily NCC decay rate of -1%), the inflection peak time does not arrive around the end of March. Estimated time is April 6-April 14. The numbers of critically ill and critically ill patients will lie between 8300-9800 and 2200-2700, respectively. We are using the diagnosis rate, mortality rate, cure rate as the 2/8 data. There should be room for improvement, if these metrics continue to improve. In that case, the peak time will arrive earlier than our estimation. Also, the severe and critical case ratios are likely to decline as the virus becomes less toxic and medical conditions improve. If that happens, the peak numbers will be lower than predicted above. Conclusion: We can infer that we are still not close to the end of this outbreak and the number of critically ill patients is still climbing. Assisting critical care resources in Hubei province requires the government to consider further tilt, and it is vital to make reasonable management of doctors and medical assistance systems to curb the transmission trend.

negative: Predicting the severity of acute bronchiolitis in infants: Should we use a clinical score or a biomarker? Krebs von den Lungen 6 antigen (KL‐6) has been shown to be a useful biomarker of the severity of Respiratory syncytial virus bronchiolitis. To assess the correlation between the clinical severity of acute bronchiolitis, serum KL‐6, and the causative viruses, 222 infants with acute bronchiolitis presenting at the Pediatric Emergency Department of Estaing University Hospital, Clermont‐Ferrand, France, were prospectively enrolled from October 2011 to May 2012. Disease severity was assessed with a score calculated from oxygen saturation, respiratory rate, and respiratory effort. A nasopharyngeal aspirate was collected to screen for a panel of 20 respiratory viruses. Serum was assessed and compared with a control group of 38 bronchiolitis‐free infants. No significant difference in KL‐6 levels was found between the children with bronchiolitis (mean 231 IU/mL ± 106) and those without (230 IU/mL ± 102), or between children who were hospitalized or not, or between the types of virus. No correlation was found between serum KL‐6 levels and the disease severity score. The absence of Human Rhinovirus was a predictive factor for hospitalization (OR 3.4 [1.4–7.9]; P = 0.006). Older age and a higher oxygen saturation were protective factors (OR 0.65[0.55–0.77]; P < 0.0001 and OR 0.67 [0.54–0.85] P < 0.001, respectively). These results suggest that in infants presenting with bronchiolitis for the first time, clinical outcome depends more on the adaptive capacities of the host than on epithelial dysfunction intensity. Many of the features of bronchiolitis are affected by underlying disease and by treatment. J. Med. Virol. 86:1944–1952, 2014. © 2013 Wiley Periodicals, Inc.

negative: Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany

negative: Chapter 132 Acute disseminated encephalomyelitis Abstract The advent of magnetic resonance imaging (MRI) has contributed to increase the interest and awareness in childhood white matter disorders. Pediatric inflammatory demyelinating diseases of the central nervous system (CNS) are clinically heterogeneous with respect to their mode of presentation, clinical severity, rate of progression, and prognosis. Acute disseminated encephalomyelitis (ADEM) is an immune-mediated inflammatory disorder of the CNS, typically transitory and self-limiting. The highest incidence of ADEM is observed during childhood. It is characterized by an acute encephalopathy with polyfocal neurological deficits. In the absence of specific biological markers the diagnosis of ADEM is still based on clinical features and MRI evidence of widespread demyelination, after ruling out other possible explanations for an acute encephalopathy. Over the past decade, many retrospective patient studies have focused on clinical and neuroimaging features, in an attempt to define specific diagnostic criteria. The occurrence of relapses in children with ADEM poses diagnostic difficulties in its differentiation from multiple sclerosis (MS) and neuromyelitis optica (NMO). With the widespread use of high-dose steroids, the long-term prognosis of ADEM with regard to functional and cognitive recovery is favorable. This chapter summarizes the available literature on ADEM in children, including the proposed consensus definitions for its monophasic and relapsing variants.

negative: The third coronavirus epidemic in the third millennium: what’s next?

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

negative: Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China An in-depth annotation of the newly discovered coronavirus (2019-nCoV) genome has revealed differences between 2019-nCoV and severe acute respiratory syndrome (SARS) or SARS-like coronaviruses. A systematic comparison identified 380 amino acid substitutions between these coronaviruses, which may have caused functional and pathogenic divergence of 2019-nCoV.

negative: Long-term Psychological and Occupational Effects of Providing Hospital Healthcare during SARS Outbreak Healthcare workers (HCWs) found the 2003 outbreak of severe acute respiratory syndrome (SARS) to be stressful, but the long-term impact is not known. From 13 to 26 months after the SARS outbreak, 769 HCWs at 9 Toronto hospitals that treated SARS patients and 4 Hamilton hospitals that did not treat SARS patients completed a survey of several adverse outcomes. Toronto HCWs reported significantly higher levels of burnout (p = 0.019), psychological distress (p<0.001), and posttraumatic stress (p<0.001). Toronto workers were more likely to have reduced patient contact and work hours and to report behavioral consequences of stress. Variance in adverse outcomes was explained by a protective effect of the perceived adequacy of training and support and by a provocative effect of maladaptive coping style and other individual factors. The results reinforce the value of effective staff support and training in preparation for future outbreaks.

negative: IL-1β, IL-6, and RANTES as Biomarkers of Chikungunya Severity BACKGROUND: Little is known about the immunopathogenesis of Chikungunya virus. Circulating levels of immune mediators and growth factors were analyzed from patients infected during the first Singaporean Chikungunya fever outbreak in early 2008 to establish biomarkers associated with infection and/or disease severity. METHODS AND FINDINGS: Adult patients with laboratory-confirmed Chikungunya fever infection, who were referred to the Communicable Disease Centre/Tan Tock Seng Hospital during the period from January to February 2008, were included in this retrospective study. Plasma fractions were analyzed using a multiplex-microbead immunoassay. Among the patients, the most common clinical features were fever (100%), arthralgia (90%), rash (50%) and conjunctivitis (40%). Profiles of 30 cytokines, chemokines, and growth factors were able to discriminate the clinical forms of Chikungunya from healthy controls, with patients classified as non-severe and severe disease. Levels of 8 plasma cytokines and 4 growth factors were significantly elevated. Statistical analysis showed that an increase in IL-1β, IL-6 and a decrease in RANTES were associated with disease severity. CONCLUSIONS: This is the first comprehensive report on the production of cytokines, chemokines, and growth factors during acute Chikungunya virus infection. Using these biomarkers, we were able to distinguish between mild disease and more severe forms of Chikungunya fever, thus enabling the identification of patients with poor prognosis and monitoring of the disease.

negative: Overcoming Barriers: The Endothelium As a Linchpin of Coronavirus Disease 2019 Pathogenesis? OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a global pandemic involving >5 500 000 cases worldwide as of May 26, 2020. The culprit is the severe acute respiratory syndrome coronavirus-2, which invades cells by binding to angiotensin-converting enzyme 2. While the majority of patients mount an appropriate antiviral response and recover at home, others progress to respiratory distress requiring hospital admission for supplemental oxygen. In severe cases, deterioration to acute respiratory distress syndrome necessitating mechanical ventilation, development of severe thrombotic events, or cardiac injury and dysfunction occurs. In this review, we highlight what is known to date about coronavirus disease 2019 and cardiovascular risk, focusing in on the putative role of the endothelium in disease susceptibility and pathogenesis. Approach and Results: Cytokine-driven vascular leak in the lung alveolar-endothelial interface facilitates acute lung injury in the setting of viral infection. Given that the virus affects multiple organs, including the heart, it likely gains access into systemic circulation by infecting or passing from the respiratory epithelium to the endothelium for viral dissemination. Indeed, cardiovascular complications of coronavirus disease 2019 are highly prevalent and include acute cardiac injury, myocarditis, and a hypercoagulable state, all of which may be influenced by altered endothelial function. Notably, the disease course is worse in individuals with preexisting comorbidities that involve endothelial dysfunction and may be linked to elevated ACE2 (angiotensin-converting enzyme 2) expression, such as diabetes mellitus, hypertension, and cardiovascular disease. CONCLUSIONS: Rapidly emerging data on coronavirus disease 2019, together with results from studies on severe acute respiratory syndrome coronavirus-1, are providing insight into how endothelial dysfunction may contribute to the pandemic that is paralyzing the globe. This may, in turn, inform the design of biomarkers predictive of disease course, as well as therapeutics targeting pathogenic endothelial responses.

negative: Dilated cardiomyopathy Dilated cardiomyopathy (DCM) is a clinical diagnosis characterized by left ventricular or biventricular dilation and impaired contraction that is not explained by abnormal loading conditions (for example, hypertension and valvular heart disease) or coronary artery disease. Mutations in several genes can cause DCM, including genes encoding structural components of the sarcomere and desmosome. Nongenetic forms of DCM can result from different aetiologies, including inflammation of the myocardium due to an infection (mostly viral); exposure to drugs, toxins or allergens; and systemic endocrine or autoimmune diseases. The heterogeneous aetiology and clinical presentation of DCM make a correct and timely diagnosis challenging. Echocardiography and other imaging techniques are required to assess ventricular dysfunction and adverse myocardial remodelling, and immunological and histological analyses of an endomyocardial biopsy sample are indicated when inflammation or infection is suspected. As DCM eventually leads to impaired contractility, standard approaches to prevent or treat heart failure are the first-line treatment for patients with DCM. Cardiac resynchronization therapy and implantable cardioverter–defibrillators may be required to prevent life-threatening arrhythmias. In addition, identifying the probable cause of DCM helps tailor specific therapies to improve prognosis. An improved aetiology-driven personalized approach to clinical care will benefit patients with DCM, as will new diagnostic tools, such as serum biomarkers, that enable early diagnosis and treatment.

negative: Multiplex PCR and Microarray for Detection of Swine Respiratory Pathogens Porcine respiratory disease complex (PRDC) is one of the most important health concerns for pig producers and can involve multiple viral and bacterial pathogens. No simple, single‐reaction diagnostic test currently exists for the simultaneous detection of major pathogens commonly associated with PRDC. Furthermore, the detection of most of the bacterial pathogens implicated in PRDC currently requires time‐consuming culture‐based methods that can take several days to obtain results. In this study, a novel prototype automated microarray that integrates and automates all steps of post‐PCR microarray processing for the simultaneous detection and typing of eight bacteria and viruses commonly associated with PRDC is described along with associated multiplex reverse transcriptase PCR. The user‐friendly assay detected and differentiated between four viruses [porcine reproductive and respiratory syndrome virus (PRRSV), influenza A virus, porcine circovirus type 2, porcine respiratory corona virus], four bacteria (Mycoplasma hyopneumoniae, Pasteurella multocida, Salmonella enterica serovar Choleraesuis, Streptococcus suis), and further differentiated between type 1 and type 2 PRRSV as well as toxigenic and non‐toxigenic P. multocida. The assay accurately identified and typed a panel of 34 strains representing the eight targeted pathogens and was negative when tested with 34 relevant and/or closely related non‐target bacterial and viral species. All targets were also identified singly or in combination in a panel of clinical lung samples and/or experimentally inoculated biological material.

negative: The aftermath of coronavirus disease of 2019: devastation or a new dawn for nephrology?

negative: Pulmonary Pathology of Early-Phase 2019 Novel Coronavirus (COVID-19) Pneumonia in Two Patients With Lung Cancer Abstract There is currently a lack of pathologic data on the novel coronavirus (severe acute respiratory syndrome coronavirus 2) pneumonia, or coronavirus disease 2019 (COVID-19), from autopsy or biopsy. Two patients who recently underwent lung lobectomies for adenocarcinoma were retrospectively found to have had COVID-19 at the time of the operation. These two cases thus provide important first opportunities to study the pathology of COVID-19. Pathologic examinations revealed that apart from the tumors, the lungs of both patients exhibited edema, proteinaceous exudate, focal reactive hyperplasia of pneumocytes with patchy inflammatory cellular infiltration, and multinucleated giant cells. Hyaline membranes were not prominent. Because both patients did not exhibit symptoms of pneumonia at the time of operation, these changes likely represent an early phase of the lung pathology of COVID-19 pneumonia.

negative: Personalized medicine in severe influenza Existing therapies against infectious diseases may only be effective in limited subpopulations during specific phases of diseases, incorporating theranostics, and there is a clear need to individualize different therapeutic approaches depending on the host. Influenza A virus infection evolves into a severe respiratory failure in some young adult patients, related to an exaggerated inflammatory response. Mortality rates remain high despite antiviral treatment and aggressive respiratory support. The influenza A virus (IAV) infection will induce a proinflammatory innate immune response through recognition of viral RNA by Toll-like receptor (TLR) 7 and retinoic acid-inducible gene 1 (RIG-I) molecules by nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB route). Anti-inflammatory therapies focused on modulating this inflammatory response to “all patients” have not been satisfactory. Steroids should be avoided because they do not improve survival and promote superinfections. Since clinical judgment has often been proven inadequate, interest in the use of biomarkers to monitor host response and to assess severity and complications is growing. It is well known that, if used appropriately, these can be helpful tools to predict not only severity but also mortality. We need more biomarkers that predict host response: it is time to change lactate measurement to proteomics and transcriptomics. Theranostics describes an approach covering both diagnosis and coupled therapy. Death is usually a fatal complication of a dysregulated immune response more than the acute virulence of the infectious agent. Future research demonstrating the usefulness of adjunctive therapy in a subset of critically ill patients with IAV pneumonia is an unmet clinical need.

negative: COVID-19 Outbreak and Surgical Practice: Unexpected Fatality in Perioperative Period Little is known about surgical practice in the initial phase of coronavirus disease 2019 (COVID-19) global crisis. This is a retrospective case series of 4 surgical patients (cholecystectomy, hernia repair, gastric bypass, and hysterectomy) who developed perioperative complications in the first few weeks of COVID-19 outbreak in Tehran, Iran in the month of February 2020. COVID-19 can complicate the perioperative course with diagnostic challenge and a high potential fatality rate. In locations with widespread infections and limited resources, the risk of elective surgical procedures for index patient and community may outweigh the benefit.

negative: Laboratory Parameters in Detection of COVID-19 Patients with Positive RT-PCR; a Diagnostic Accuracy Study INTRODUCTION: The role of laboratory parameters in screening of COVID-19 cases has not been definitely established. This study aimed to evaluate the accuracy of laboratory parameters in predicting cases with positive RT-PCR for COVID-19. METHODS: This diagnostic accuracy study was conducted on suspected COVID-19 patients, who presented to Behpooyan Clinic Medical center in Tehran (Iran) from 22 February to 14 March, 2020. Patients were divided into two groups based on the results of real time reverse transcriptase‐polymerase chain reaction (RT-PCR) for COVID-19, and the accuracy of different laboratory parameters in predicting cases with positive RT-PCR was evaluated using area under the ROC curve (AUC). RESULTS: Two hundred cases with the mean age of 41.3± 14.6 (range: 19-78) years were studied (0.53% male). The result of RT-PCR for COVID-19 was positive in 70 (35%) cases. Patients with positive RT-PCR had significantly higher neutrophil (NEU) count (p = 0.0001), and C-reactive protein (CRP) (p = 0.04), lactate dehydrogenase (LDH) (p = 0.0001), aspartate aminotransferase (AST) (p = 0.001), alanine aminotransferase (ALT) (p = 0.0001), and Urea (p = 0.001) levels in serum. In addition, patients with positive RT-PCR had lower white blood cell (WBC) count (p = 0.0001) and serum albumin level (p = 0.0001) compared to others. ALT (AUC = 0.879), CRP (AUC = 0.870), NEU (AUC = 0.858), LDH (AUC = 0.835), and Urea (AUC = 0.835) had very good accuracy in predicting cases with positive RT-PCR for COVID-19, respectively. CONCLUSION: Our findings suggest that level of LDH, CRP, ALT and NEU can be used to predict the result of COVID-19 test. They can help in detection of COVID-19 patients.

negative: Acute Respiratory Distress Syndrome in Cancer Patients Acute respiratory distress syndrome (ARDS) is a heterogeneous form of acute, diffuse lung injury that is characterized by dysregulated inflammation, increased alveolar-capillary interface permeability, and non-cardiogenic pulmonary edema. In the general population, the incidence and mortality associated with ARDS over the last two decades have steadily declined in parallel with optimized approaches to pneumonia and other underlying causes of ARDS as well as increased utilization of multimodal treatment strategies that include lung-protective ventilation. In the cancer settings, significant declines in the incidence and mortality of ARDS over the past two decades have also been reported, although these rates remain significantly higher than those in the general population. Epidemiologic studies identify infection, including disseminated fungal pneumonias, as a major underlying cause of ARDS in the cancer setting. More than half of cancer patients who develop ARDS will not survive to hospital discharge. Those who do survive often face a protracted and often incomplete recovery, resulting in significant long-term physical, psychological, and cognitive sequelae. The residual organ dysfunction and poor functional status after ARDS may delay or preclude subsequent cancer treatments. As such, close collaboration between the critical care physicians and oncology team is essential in identifying and reversing the underlying causes and optimizing treatments for cancer patients with ARDS. This chapter reviews the diagnosis and common causes of ARDS in cancer and gives an update on the general management principles for cancer patients with ARDS in the ICU.

negative: COVID-19: An Early Review of Its Global Impact and Considerations for Parkinson’s Disease Patient Care While many infectious disorders are unknown to most neurologists, COVID-19 is very different. It has impacted neurologists and other health care workers, not only in our professional lives but also through the fear and panic within our own families, colleagues, patients and their families, and even in the wider public. COVID-19 affects all sorts of individuals, but the elderly with underlying chronic conditions are particularly at risk of severe disease, or even death. Parkinson’s disease (PD) shares a common profile as an age-dependent degenerative disorder, frequently associated with comorbidities, particularly cardiovascular diseases, so PD patients will almost certainly fall into the high-risk group. Therefore, the aim of this review is to explore the risk of COVID-19 in PD based on the susceptibility to severe disease, its impact on PD disease severity, potential long-term sequelae, and difficulties of PD management during this outbreak, where neurologists face various challenges on how we can maintain effective care for PD patients without exposing them, or ourselves, to the risk of infection. It is less than six months since the identification of the original COVID-19 case on New Year’s Eve 2019, so it is still too early to fully understand the natural history of COVID-19 and the evidence on COVID-19-related PD is scant. Though the possibilities presented are speculative, they are theory-based, and supported by prior evidence from other neurotrophic viruses closely related to SARS-CoV-2. Neurologists should be on high alert and vigilant for potential acute and chronic complications when encountering PD patients who are suspected of having COVID-19.

negative: Efficacy of glutathione therapy in relieving dyspnea associated with COVID-19 pneumonia: A report of 2 cases PURPOSE: Infection with COVID-19 potentially can result in severe outcomes and death from “cytokine storm syndrome”, resulting in novel coronavirus pneumonia (NCP) with severe dyspnea, acute respiratory distress syndrome (ARDS), fulminant myocarditis and multiorgan dysfunction with or without disseminated intravascular coagulation. No published treatment to date has been shown to adequately control the inflammation and respiratory symptoms associated with COVID-19, apart from oxygen therapy and assisted ventilation. We evaluated the effects of using high dose oral and/or IV glutathione in the treatment of 2 patients with dyspnea secondary to COVID-19 pneumonia. METHODS: Two patients living in New York City (NYC) with a history of Lyme and tick-borne co-infections experienced a cough and dyspnea and demonstrated radiological findings consistent with novel coronavirus pneumonia (NCP). A trial of 2 g of PO or IV glutathione was used in both patients and improved their dyspnea within 1 h of use. Repeated use of both 2000 mg of PO and IV glutathione was effective in further relieving respiratory symptoms. CONCLUSION: Oral and IV glutathione, glutathione precursors (N-acetyl-cysteine) and alpha lipoic acid may represent a novel treatment approach for blocking NF-κB and addressing “cytokine storm syndrome” and respiratory distress in patients with COVID-19 pneumonia.

negative: Cystatin D (CST5): An ultra-early inflammatory biomarker of traumatic brain injury Traumatic brain injury (TBI) is set to become the leading cause of neurological disability across all age groups. Currently, no reliable biomarkers exist to help diagnose the severity of TBI to identify patients who are at risk of developing secondary injuries. Thus, the discovery of reliable biomarkers for the management of TBI would improve clinical interventions. Inflammatory markers are particularly suited for biomarker discovery as TBI leads to very early alterations in inflammatory proteins. Using the Proseek Multiplex Inflammation assay, we measured in patients that had suffered mild TBI (n = 10) or severe TBI (n = 10) with extra-cranial injury or extracranial injury only (EC) (n = 10), 92 inflammation-associated proteins in serum obtained: <1 hr (within 1-hour), 4–12 hr and 48–72 hr post injury. Changes were compared to healthy volunteers (HV). Our results identified CST5, AXIN1 and TRAIL as novel early biomarkers of TBI. CST5 identified patients with severe TBI from all other cohorts and importantly was able to do so within the first hour of injury. AXIN1 and TRAIL were able to discriminate between TBI and HV at <1 hr. We conclude that CST5, AXIN1 and TRAIL are worthy of further study in the context of a pre-hospital or pitch-side test to detect brain injury.

negative: Acute Lung Injury Results from Innate Sensing of Viruses by an ER Stress Pathway Incursions of new pathogenic viruses into humans from animal reservoirs are occurring with alarming frequency. The molecular underpinnings of immune recognition, host responses, and pathogenesis in this setting are poorly understood. We studied pandemic influenza viruses to determine the mechanism by which increasing glycosylation during evolution of surface proteins facilitates diminished pathogenicity in adapted viruses. ER stress during infection with poorly glycosylated pandemic strains activated the unfolded protein response, leading to inflammation, acute lung injury, and mortality. Seasonal strains or viruses engineered to mimic adapted viruses displaying excess glycans on the hemagglutinin did not cause ER stress, allowing preservation of the lungs and survival. We propose that ER stress resulting from recognition of non-adapted viruses is utilized to discriminate “non-self” at the level of protein processing and to activate immune responses, with unintended consequences on pathogenesis. Understanding this mechanism should improve strategies for treating acute lung injury from zoonotic viral infections.

negative: Does the novel coronavirus 2019 like heart more than the other family members of coronaviruses? The disaster due to the novel coronavirus disease 2019 (COVID-19) around the world has made investigators enthusiastic about working on different aspects of COVID-19. However, although the pandemic of COVID-19 has not yet ended, it seems that COVID-19 compared to the other coronavirus infections (the Middle East Respiratory Syndrome [MERS] and Severe Acute Respiratory Syndrome [SARS]) is more likely to target the heart. Comparing the previous presentations of the coronavirus family and the recent cardiovascular manifestations of COVID-19 can also help in predicting possible future challenges and taking measures to tackle these issues.

negative: Predictions of 2019-nCoV Transmission Ending via Comprehensive Methods Since the SARS outbreak in 2003, a lot of predictive epidemiological models have been proposed. At the end of 2019, a novel coronavirus, termed as 2019-nCoV, has broken out and is propagating in China and the world. Here we propose a multi-model ordinary differential equation set neural network (MMODEs-NN) and model-free methods to predict the interprovincial transmissions in mainland China, especially those from Hubei Province. Compared with the previously proposed epidemiological models, the proposed network can simulate the transportations with the ODEs activation method, while the model-free methods based on the sigmoid function, Gaussian function, and Poisson distribution are linear and fast to generate reasonable predictions. According to the numerical experiments and the realities, the special policies for controlling the disease are successful in some provinces, and the transmission of the epidemic, whose outbreak time is close to the beginning of China Spring Festival travel rush, is more likely to decelerate before February 18 and to end before April 2020. The proposed mathematical and artificial intelligence methods can give consistent and reasonable predictions of the 2019-nCoV ending. We anticipate our work to be a starting point for comprehensive prediction researches of the 2019-nCoV.

negative: Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Coronavirus Diseases Since the outbreak of the novel coronavirus disease COVID-19, caused by the SARS-CoV-2 virus, this disease has spread rapidly around the globe. Considering the potential threat of a pandemic, scientists and physicians have been racing to understand this new virus and the pathophysiology of this disease to uncover possible treatment regimens and discover effective therapeutic agents and vaccines. To support the current research and development, CAS has produced a special report to provide an overview of published scientific information with an emphasis on patents in the CAS content collection. It highlights antiviral strategies involving small molecules and biologics targeting complex molecular interactions involved in coronavirus infection and replication. The drug-repurposing effort documented herein focuses primarily on agents known to be effective against other RNA viruses including SARS-CoV and MERS-CoV. The patent analysis of coronavirusrelated biologics includes therapeutic antibodies, cytokines, and nucleic acid-based therapies targeting virus gene expression as well as various types of vaccines. More than 500 patents disclose methodologies of these four biologics with the potential for treating and preventing coronavirus infections, which may be applicable to COVID-19. The information included in this report provides a strong intellectual groundwork for the ongoing development of therapeutic agents and vaccines.

negative: 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 the pathophysiology. Here we use state-of-the-art deep neural networks over an institution-wide machine intelligence platform for the augmented curation of 8.2 million clinical notes from 14,967 patients subjected to COVID-19 PCR diagnostic testing. By contrasting the Electronic Health Record (EHR)-derived clinical phenotypes of COVID-19-positive (COVIDpos, n=272) versus COVID-19-negative (COVIDneg, n=14,695) patients over each day of the week preceding the PCR testing date, we identify diarrhea (2.8-fold), change in appetite (2-fold), anosmia/dysgeusia (28.6-fold), and respiratory failure (2.1-fold) as significantly amplified in COVIDpos over COVIDneg patients. The specific combination of cough and diarrhea has a 4-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 training underlying neural networks, thus promising EHR-powered early diagnosis for a broad spectrum of diseases.

negative: ESICM 2013 - Abstracts of Oral Presentations and Poster Sessions

negative: Surveillance of acute respiratory infections in Mumbai during 2011-12. PURPOSE Acute respiratory infections (ARIs) are a leading cause of morbidity and mortality in individuals aged less than 5 years. ARI often leads to hospitalisation, and it has been indicated that causative viral and bacterial infections go undetermined and results in the occurrence of resistant strains. The objective of the study was to assess the prevalence of various viral and bacterial infections in patients with ARIs. MATERIALS AND METHODS Two hundred samples were collected from July 2011 to July 2012 with patients suffering from ARI. Viral and bacterial infections were determined by real time reverse transcriptase polymerase chain reaction. RESULTS Influenza-like illness (ILI) consisted of 109 patients and ARI consisted of 91 patients. Pandemic influenza A H1N1 was the major viral infection with 21 (19.2%) patients in ILI as compared with 16 (17.4%) patients in ARI. Respiratory syncytial virus (RSV) was found to be 1 (0.9%) in ILI and ARI. Viral co-infections were 16 (14.4%) in ILI and 4 (4.37%) in ARI where pandemic influenza A H1N1 and influenza type B were major contributors. In bacterial infections, Streptococcus pneumoniae with 11 (10.9%) cases were predominant in both the groups. Bacterial co-infection accounted for only 1 (1.09%) case in both the groups but the most significant finding was the viral-bacterial co-infection in which Haemophilus influenzae was the major co-infecting bacteria with the influenza viruses with 4 (4.36%) cases as compared with Streptotoccus pneumoniae. CONCLUSION This data indicate the need to undertake continued surveillance that will help to better define the circulation of respiratory viruses along with the bacterial infections.

negative: 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.

negative: Thrombocytopenia and coagulation disorders due to COVID 19 infection with concomitant cardiovascular diseases requiring anti-platelet and anticoagulant therapy, which strategy?

negative: Plasmon-Enhanced Fluorescence Biosensors: a Review Surfaces of metallic films and metallic nanoparticles can strongly confine electromagnetic field through its coupling to propagating or localized surface plasmons. This interaction is associated with large enhancement of the field intensity and local optical density of states which provides means to increase excitation rate, raise quantum yield, and control far field angular distribution of fluorescence light emitted by organic dyes and quantum dots. Such emitters are commonly used as labels in assays for detection of chemical and biological species. Their interaction with surface plasmons allows amplifying fluorescence signal (brightness) that accompanies molecular binding events by several orders of magnitude. In conjunction with interfacial architectures for the specific capture of target analyte on a metallic surface, plasmon-enhanced fluorescence (PEF) that is also referred to as metal-enhanced fluorescence (MEF) represents an attractive method for shortening detection times and increasing sensitivity of various fluorescence-based analytical technologies. This review provides an introduction to fundamentals of PEF, illustrates current developments in design of metallic nanostructures for efficient fluorescence signal amplification that utilizes propagating and localized surface plasmons, and summarizes current implementations to biosensors for detection of trace amounts of biomarkers, toxins, and pathogens that are relevant to medical diagnostics and food control.

negative: Looking beyond the coronavirus: lessons and principles.

negative: Tissue and cellular tropism of the coronavirus associated with severe acute respiratory syndrome: an in‐situ hybridization study of fatal cases Severe acute respiratory syndrome (SARS) is a new human infectious disease with significant morbidity and mortality. The disease has been shown to be associated with a new coronavirus (SARS‐CoV). The clinical and epidemiological aspects of SARS have been described. Moreover, the viral genome of SARS‐CoV has been fully sequenced. However, much of the biological behaviour of the virus is not known and data on the tissue and cellular tropism of SARS‐CoV are limited. In this study, six fatal cases of SARS were investigated for the tissue and cellular tropism of SARS‐CoV using an in‐situ hybridization (ISH) technique. Among all the tissues studied, positive signals were seen in pneumocytes in the lungs and surface enterocytes in the small bowel. Infected pneumocytes were further confirmed by immunofluorescence–fluorescence in‐situ hybridization (FISH) analysis. These results provide important information concerning the tissue tropism of SARS‐CoV, which is distinct from previously identified human coronaviruses, and suggest the possible involvement of novel receptors in this infection. Whereas the lung pathology was dominated by diffuse alveolar damage, the gut was relatively intact. These findings indicated that tissue responses to SARS‐CoV infection are distinct in different organs. Copyright © 2004 John Wiley & Sons, Ltd.

negative: Cost-Benefit of Stockpiling Drugs for Influenza Pandemic We analyzed strategies for the use of stockpiled antiviral drugs in the context of a future influenza pandemic and estimated cost-benefit ratios. Current stockpiling of oseltamivir appears to be cost-saving to the economy under several treatment strategies, including therapeutic treatment of patients and postexposure prophylactic treatment of patients' close contacts.

negative: 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.

negative: Global profiling of SARS-CoV-2 specific IgG/ IgM responses of convalescents using a proteome microarray COVID-19 is caused by SARS-CoV-2, and has become a global pandemic. There is no highly effective medicine or vaccine, most of the patients were recovered by their own immune response, especially the virus specific IgG and IgM responses. However, the IgG/ IgM responses is barely known. To enable the global understanding of SARS-CoV-2 specific IgG/ IgM responses, a SARS-CoV-2 proteome microarray with 18 out of the 28 predicted proteins was constructed. The microarray was applied to profile the IgG/ IgM responses with 29 convalescent sera. The results suggest that at the convalescent phase 100% of patients had IgG/ IgM responses to SARS-CoV-2, especially to protein N, S1 but not S2. S1 purified from mammalian cell demonstrated the highest performance to differentiate COVID-19 patients from controls. Besides protein N and S1, significant antibody responses to ORF9b and NSP5 were also identified. In-depth analysis showed that the level of S1 IgG positively correlate to age and the level of LDH (lactate dehydrogenase), especially for women, while the level of S1 IgG negatively correlate to Ly% (Lymphocyte percentage). This study presents the first whole picture of the SARS-CoV-2 specific IgG/ IgM responses, and provides insights to develop precise immuno-diagnostics, effective treatment and vaccine.

negative: Cross‐species transmission of the newly identified coronavirus 2019‐nCoV The current outbreak of viral pneumonia in the city of Wuhan, China, was caused by a novel coronavirus designated 2019‐nCoV by the World Health Organization, as determined by sequencing the viral RNA genome. Many initial patients were exposed to wildlife animals at the Huanan seafood wholesale market, where poultry, snake, bats, and other farm animals were also sold. To investigate possible virus reservoir, we have carried out comprehensive sequence analysis and comparison in conjunction with relative synonymous codon usage (RSCU) bias among different animal species based on the 2019‐nCoV sequence. Results obtained from our analyses suggest that the 2019‐nCoV may appear to be a recombinant virus between the bat coronavirus and an origin‐unknown coronavirus. The recombination may occurred within the viral spike glycoprotein, which recognizes a cell surface receptor. Additionally, our findings suggest that 2019‐nCoV has most similar genetic information with bat coronovirus and most similar codon usage bias with snake. Taken together, our results suggest that homologous recombination may occur and contribute to the 2019‐nCoV cross‐species transmission.

negative: A Unique Protease Cleavage Site Predicted in the Spike Protein of the Novel Pneumonia Coronavirus (2019-nCoV) Potentially Related to Viral Transmissibility

negative: CD4(+) T-cell counts and interleukin-8 and CCL-5 plasma concentrations discriminate disease severity in children with RSV infection BACKGROUND: Current tools to predict the severity of respiratory syncytial virus (RSV) infection might be improved by including immunological parameters. We hypothesized that a combination of inflammatory markers would differentiate between severe and mild disease in RSV-infected children. METHODS: Blood and nasopharyngeal samples from 52 RSV-infected children were collected during acute infection and after recovery. Retrospectively, patients were categorized into three groups based on disease severity: mild (no supportive treatment), moderate (supplemental oxygen and/or nasogastric feeding), and severe (mechanical ventilation). Clinical data, number of flow-defined leukocyte subsets, and cytokine concentrations were compared. RESULTS: Children with severe RSV infection were characterized by young age; lymphocytopenia; increased interleukin (IL)-8, granulocyte colony-stimulating factor (G-CSF), and IL-6 concentrations; and decreased chemokine (C-C motif) ligand (CCL-5) concentrations in plasma. The combination of plasma levels of IL-8 and CCL-5, and CD4(+) T-cell counts, with cutoff values of 67 pg/ml, 13 ng/ml, and 2.3 × 10(6)/ml, respectively, discriminated severe from mild RSV infection with 82% sensitivity and 96% specificity. CONCLUSION: This study demonstrates that the combination of CD4(+) T-cell counts and IL-8 and CCL-5 plasma concentrations correlates with disease severity in RSV-infected children. In addition to clinical features, these immunological markers may be used to assess severity of RSV infection and guide clinical management. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/pr.2012.163) contains supplementary material, which is available to authorized users.

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: [2019-nCoV: new challenges from coronavirus]. The outbreak of pneumonia caused by the novel coronavirus (2019-nCoV) in Wuhan, Hubei province of China, at the end of 2019 shaped tremendous challenges to China's public health and clinical treatment. The virus belongs to the β genus Coronavirus in the family Corornaviridae, and is closely related to SARS-CoV and MERS-CoV, causing severe symptoms of pneumonia. The virus is transmitted through droplets, close contact, and other means, and patients in the incubation period could potentially transmit the virus to other persons. According to current observations, 2019-nCoV is weaker than SARS in pathogenesis, but has stronger transmission competence; it's mechanism of cross-species spread might be related with angiotensin-converting enzyme Ⅱ (ACE2), which is consistent with the receptor SARS-CoV. After the outbreak of this disease, Chinese scientists invested a lot of energy to carry out research by developing rapid diagnostic reagents, identifying the characters of the pathogen, screening out clinical drugs that may inhibit the virus, and are rapidly developing vaccines. The emergence of 2019-nCoV reminds us once again of the importance of establishing a systematic coronavirus surveillance network. It also poses new challenges to prevention and control of the emerging epidemic and rapidly responses on scientific research.

negative: Diagnostic cerebrospinal fluid biomarkers for Parkinson's disease: A pathogenetically based approach Abstract The inaccuracy of the early diagnosis of Parkinson's disease (PD) has been a major incentive for studies aimed at the identification of biomarkers. Brain-derived cerebrospinal fluid (CSF) proteins are potential biomarkers considering the major role that proteins play in PD pathogenesis. In this review, we discuss the current hypotheses about the pathogenesis of PD and identify the most promising candidate biomarkers among the CSF proteins studied so far. The list of potential markers includes proteins involved in various pathogenetic processes, such as oxidative stress and protein aggregation. This list will undoubtedly grow in the near future by application of CSF proteomics and subsequent validation of identified proteins. Probably a single biomarker will not suffice to reach high sensitivity and specificity, because PD is pathogenetically heterogeneous and shares etiological factors with other neurodegenerative diseases. Furthermore, identified candidate biomarkers will have to be thoroughly validated before they can be implemented as diagnostic aids.

negative: Incorporating Human Movement Data to Improve Epidemiological Estimates for 2019-nCoV Estimating the key epidemiological features of the novel coronavirus (2019-nCoV) epidemic proves to be challenging, given incompleteness and delays in early data reporting, in particular, the severe under-reporting bias in the epicenter, Wuhan, Hubei Province, China. As a result, the current literature reports widely varying estimates. We developed an alternative geo-stratified debiasing estimation framework by incorporating human mobility with case reporting data in three stratified zones, i.e., Wuhan, Hubei Province excluding Wuhan, and mainland China excluding Hubei. We estimated the latent infection ratio to be around 0.12% (18,556 people) and the basic reproduction number to be 3.24 in Wuhan before the city's lockdown on January 23, 2020. The findings based on this debiasing framework have important implications to prioritization of control and prevention efforts.

negative: The Cytokine and Chemokine Profiles in Patients with Hand, Foot and Mouth Disease of Different Severities in Shanghai, China, 2010 BACKGROUND AND PURPOSE: Systemic upregulation of inflammatory cytokines is characteristic of critical severe hand, foot, and mouth disease (HFMD) with pulmonary edema. Thus, immunomodulatory medicines such as steroids, including methylprednisolone, have been proposed to treat patients with severe HFMD in China, because it is postulated that inflammatory cytokines play a role in the development of severe complications. This study is to further investigate the inflammatory response in the relatively mild HFMD patients, and whether steroid treatment has a beneficial effect on the suppression of inflammation in HFMD patients. METHOD: We measured the levels of 50 kinds of chemokines, cytokines, growth factors and soluble receptors in serum samples from control patients without HFMD and the HFMD patients with or without prior treatment of intravenous methylprednisolone. RESULTS: Our present study found that even relatively mild HFMD patients without central nervous system (CNS) complications had elevated serum levels of inflammatory cytokines, including interleukin (IL)-3, IL-6, IL-12p40, and tumor necrosis factor (TNF)-α, which suggested systemic inflammation. In contrast, these patients also have decreased levels of other serum biomarkers, including IL-1Ra, IL-8, IL-16, soluble ICAM-1, CXCL-1, and CCL27. The dysregulation of cytokine and chemokine expression may be involved in CNS complications and unbalanced circulating leukocytes in HFMD patients. Surprisingly, patients treated with methylprednisolone had no difference in the expression levels of HFMD-associated biomarkers instead had slightly increased levels of IL-17A, which was not associated with the occurrence of HFMD. CONCLUSION: Whether steroid treatment has any beneficial effect on the prognosis of HFMD patients requires to be further investigated.

negative: Genomic determinants of pathogenicity in SARS-CoV-2 and other human coronaviruses SARS-CoV-2 poses an immediate, major threat to public health across the globe. Here we report an in-depth molecular analysis to reconstruct the evolutionary origins of the enhanced pathogenicity of SARS-CoV-2 and other coronaviruses that are severe human pathogens. Using integrated comparative genomics and machine learning techniques, we identify key genomic features that differentiate SARS-CoV-2 and the viruses behind the two previous deadly coronavirus outbreaks, SARS-CoV and MERS-CoV, from less pathogenic coronaviruses. These features include enhancement of the nuclear localization signals in the nucleocapsid protein and distinct inserts in the spike glycoprotein that appear to be associated with high case fatality rate of these coronaviruses as well as the host switch from animals to humans. The identified features could be crucial elements of coronavirus pathogenicity and possible targets for diagnostics, prognostication and interventions.

negative: A Novel Coronavirus from Patients with Pneumonia in China, 2019 In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)

negative: Estimating the number of undetected COVID-19 cases exported internationally from all of China During the early phase of the COVID-19 pandemic, when SARS-CoV-2 was chiefly reported in the city of Wuhan, cases exported to other locations were largely predicted using flight travel data from Wuhan. However, given Wuhan’s connectivity to other cities in mainland China prior to the lockdown, there has likely been a substantial risk of exportation of cases from other Chinese cities. It is likely that many of these exportations remained undetected because early international case definitions for COVID-19 required a recent travel history from Wuhan. Here, we combine estimates of prevalence in 18 Chinese cities with estimates of flight volume, accounting for the effects of travel bans and the timing of Lunar New Year, to approximate the number of cases exported from cities outside of Wuhan from early December 2019 to late February 2020. We predict that for every one case from Wuhan exported internationally, there were approximately 2.9 cases from large Chinese cities exported internationally that likely remained undetected. Additionally, we predict the number of exported cases in six destinations for which predictions on exported cases have yet to be made, surveillance has likely been low, and where health care systems will likely face issues in managing current or potential outbreaks. We observe heterogeneities in exported case counts across these destinations. The predicted number of cases exported to Egypt and South Africa exceeds the predicted number of cases exported to Mauritania. These trends may anticipate differences in the timing and emergence of local transmission in these countries. Our findings highlight the importance of setting accurate travel history requirements for case definition guidelines in the initial phase of an epidemic, and actively updating these guidelines as the epidemic advances.

negative: COVID-19 Illness in Native and Immunosuppressed States: A Clinical-Therapeutic Staging Proposal

negative: Risk Factors and Etiologies of Pediatric Acute Respiratory Distress Syndrome The risk factors for acute respiratory distress syndrome (ARDS) have been a focus for clinicians and researchers from the original description in 1967 to the most recent Pediatric Acute Lung Injury Consensus Conference (PALICC). Indeed, there are many comorbidities and risk factors that predispose a patient to develop pediatric ARDS (PARDS) including, but not limited to, immunodeficiency, weight extremes, genetics, and environmental factors. These are particularly important to investigators because accurate prediction of which patients are at greatest risk of PARDS – both the development of PARDS and worse clinical outcomes after PARDS has been established – is key to identifying the next generation of diagnostic techniques and preventative strategies. In addition to those risk factors, there are specific disease processes that lead to the development of PARDS, often divided into direct or pulmonary insults and indirect or extrapulmonary insults. Finally, beyond the clinically visible risk factors, researchers are attempting to identify novel biomarkers to uncover hidden phenotypes of PARDS and enrich the prognostication and prediction of patient outcomes. This chapter delves into each of these concepts.

negative: Screening of FDA-approved drugs using a MERS-CoV clinical isolate from South Korea identifies potential therapeutic options for COVID-19 In 2015, the Middle East respiratory syndrome coronavirus (MERS-CoV) reached the Republic of Korea, resulting from nosocomial transmission, and was the largest epidemic outside of the Arabian Peninsula. To date, despite various strategies to identify CoV interventions, there are only limited therapeutic options available. To address these unmet medical needs, we used a South Korean MERS-CoV clinical isolate and screened 5,406 compounds, including US Food and Drug Administration (FDA)-approved drugs and bioactive molecules, confirmed 221 hits by dose-response curve analysis in the primary assay, and selected 54 hits with a therapeutic index (TI) greater than 6. Time-of-addition studies with 12 FDA-approved drugs demonstrated that eight and four therapeutics act on the early- and late stages of the viral life cycle, respectively. Among the early acting drugs, three therapeutics with a TI greater than 100 were cardiotonic agents. Together, our results identify potential therapeutic options for treatment of MERS-CoV infections and could provide a basis for a wider range of coronaviruses, including the currently emerging coronavirus disease 2019 (COVID-19) outbreak.

negative: Proteomic strategies for the discovery of novel diagnostic and therapeutic targets for infectious diseases Viruses have developed numerous and elegant strategies to manipulate the host cell machinery to establish a productive infectious cycle. The interaction of viral proteins with host proteins plays an important role in infection and pathogenesis, often bypassing traditional host defenses such as the interferon response and apoptosis. Host–viral protein interactions can be studied using a variety of proteomic approaches ranging from genetic and biochemical to large scale high throughput technologies. Protein interactions between host and viral proteins are greatly influenced by host signal transduction pathways. In this review, we will focus on comparing proteomic information obtained through differing technologies and how their integration can be used to determine the functional aspect of the host response to infection. We will briefly review and evaluate techniques employed to elucidate viral–host interactions with a primary focus on Protein Microarrays (PMA) and Mass Spectrometry (MS) as potential tools in the discovery of novel therapeutic targets. As many potential molecular markers and targets are proteins, proteomic profiling is expected to yield both clearer and more direct answers to functional and pharmacologic questions.

negative: CD9 Tetraspanin: A New Pathway for the Regulation of Inflammation? CD9 belongs to the tetraspanin superfamily. Depending on the cell type and associated molecules, CD9 has a wide variety of biological activities such as cell adhesion, motility, metastasis, growth, signal transduction, differentiation, and sperm–egg fusion. This review focuses on CD9 expression by hematopoietic cells and its role in modulating cellular processes involved in the regulation of inflammation. CD9 is functionally very important in many diseases and is involved either in the regulation or in the mediation of the disease. The role of CD9 in various diseases, such as viral and bacterial infections, cancer and chronic lung allograft dysfunction, is discussed. This review focuses also on its interest as a biomarker in diseases. Indeed CD9 is primarily known as a specific exosome marker however, its expression is now recognized as an anti-inflammatory marker of monocytes and macrophages. It was also described as a marker of murine IL-10-competent Breg cells and IL-10-secreting CD9(+) B cells were associated with better allograft outcome in lung transplant patients, and identified as a new predictive biomarker of long-term survival. In the field of cancer, CD9 was both identified as a favorable prognostic marker or as a predictor of metastatic potential depending on cancer types. Finally, this review discusses strategies to target CD9 as a therapeutic tool. Because CD9 can have opposite effects depending on the situation, the environment and the pathology, modulating CD9 expression or blocking its effects seem to be a new promising therapeutic strategy.

negative: Active surveillance for suspected COVID-19 cases in inpatients with information technology

negative: Immune-epidemiological parameters of the novel coronavirus – a perspective Introduction: At the end of 2019, Wuhan, a city in China with a population of about 11 million, witnessed the outbreak of unusual pneumonia. As of 29 March 2020, the disease has spread to more 199 countries and territories worldwide. The 2019 novel coronavirus, 2019-nCoV, is known as the probable causative agent of the illness. Areas covered: Here, the epidemiological dynamics of the coronavirus disease 2019 (COVID-19) that stand in close relation to distinct immunogenetic characters of the pathogen are discussed, to understand the ability and inability of the immune system in combatting COVID-19. Expert opinion: The elderly population is at increased risk of developing and dying from COVID-19. Comorbidity is present in more than 30% of cases with COVID-19. Except for less than 1% of the total, a chronic condition has been found in all cases that died from COVID-19. Men are more than 1.5 times more likely to die from COVID-19. Evidence links aging to cytokine dysregulation and T-cell repertoire reduction, male population to relatively reduced anti-viral immunity, and COVID-19-related comorbidities to hyper inflammation. The transmission of COVID-19 is influenced by the host-related factors that are known to be associated with immune dysregulation.

negative: Identification of Urinary CD44 and Prosaposin as Specific Biomarkers of Urinary Tract Infections in Children With Neurogenic Bladders PURPOSE: Distinguishing urinary tract infection (UTI) from urinary tract colonization (UTC) in children with neurogenic bladders who require clean intermittent catheterization (CIC) is challenging. Our objective was to identify urinary proteins to distinguish UTI from UTC in CIC-dependent children that have potential to serve as objective markers of UTI. EXPERIMENTAL DESIGN: A total of 10 CIC-dependent children were included in the mass spectrometry analysis (UTI = 5, UTC = 5). Quantitative profiling of urine proteins with isobaric protein labeling was performed using tandem mass spectrometry. Candidate markers were normalized using a collective mixture of proteins from all samples. Relative quantitative abundance of proteins across all samples were compared. Proteins with >50% change in the average abundance were identified as proteins of interest, which were then measured using enzyme-linked immunosorbent assay (ELISA) in an additional 40 samples (no growth = 10, UTC = 15, UTI = 15). RESULTS: Mass spectrometry revealed 8 differentially expressed proteins. Of these, apolipoprotein D, alpha-amylase 2B, non-secretory ribonuclease, CD44 antigen, and prosaposin were measurable by ELISA. Concentrations of both CD44 and prosaposin were significantly higher in UTI, with area under the curves (AUCs) of 0.72 and 0.78, respectively. CONCLUSION: Urinary CD44 and prosaposin are candidate markers that may assist with the diagnosis of UTI in CIC-dependent children.

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

negative: The 2019 coronavirus: Learning curves, lessons, and the weakest link In the space of just six weeks, a new coronavirus, from a family that historically was not viewed as a global health concern, has become daily headline news around the globe. The 21st century marked its arrival with the emergence of three previously unknown coronaviruses. SARS-CoV (severe acute respiratory syndrome coronavirus) was recognized in November 2002 [1, 2], MERS-CoV (Middle East respiratory syndrome coronavirus) in June 2012 [3, 4], and 2019-nCoV in December 2019 [5]. Previously, human coronaviruses, known since the 1960s, were viewed as being only marginally relevant to the clinic, except for infants, the elderly, and immunocompromised individuals [1, 6, 7].

negative: Norwegian Coronavirus Disease 2019 (NO COVID-19) Pragmatic Open label Study to assess early use of hydroxychloroquine sulphate in moderately severe hospitalised patients with coronavirus disease 2019: A structured summary of a study protocol for a randomised controlled trial OBJECTIVES: The hypothesis of the study is that treatment with hydroxychloroquine sulphate in hospitalised patients with coronavirus disease 2019 (Covid-19) is safe and will accelerate the virological clearance rate for patients with moderately severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) when compared to standard care. Furthermore, we hypothesize that early treatment with hydroxychloroquine sulphate is associated with more rapid resolve of clinical symptoms as assessed by the National Early Warning Score 2 (NEWS2), decreased admission rate to intensive care units and mortality, and improvement in protein biomarker profiles (C-reactive protein, markers of renal and hepatic injury, and established cardiac biomarkers like cardiac troponin and B-type natriuretic peptide). TRIAL DESIGN: The study is a two-arm, open label, pragmatic randomised controlled group sequential adaptive trial designed to assess the effect on viral loads and clinical outcome of hydroxychloroquine sulphate therapy in addition to standard care compared to standard care alone in patients with established Covid-19. By utilizing resources already paid for by the hospitals (physicians and nurses in daily clinical practice), this pragmatic trial can include a larger number of patients over a short period of time and at a lower cost than studies utilizing traditional randomized controlled trial designs with an external study organization. The pragmatic approach will enable swift initiation of randomisation and allocation to treatment. PARTICIPANTS: Patients will be recruited from all inpatients at Akershus University Hospital, Lørenskog, Norway. Electronic real-time surveillance of laboratory reports from the Department of Microbiology will be examined regularly for SARS-CoV-2 positive subjects. All of the following conditions must apply to the prospective patient at screening prior to inclusion: (1) Hospitalisation; (2) Adults 18 years or older; (3) Moderately severe Covid-19 disease (NEWS2 of 6 or less); (4) SARS-CoV-2 positive nasopharyngeal swab; (5) Expected time of hospitalisation > 48 hours; and (6) Signed informed consent must be obtained and documented according to Good Clinical Practice guidelines of the International Conference on Harmonization, and national/local regulations. Patients will be excluded from participation in the study if they meet any of the following criteria: (1) Requiring intensive care unit admission at screening; (2) History of psoriasis; (3) Known adverse reaction to hydroxychloroquine sulphate; (4) Pregnancy; or (5) Prolonged corrected QT interval (>450 ms). Clinical data, including standard hospital biochemistry, medical therapy, vital signs, NEWS2, and microbiology results (including blood culture results and reverse transcriptase polymerase chain reaction [RT-PCR] for other upper airway viruses), will be automatically extracted from the hospital electronic records and merged with the study specific database. INTERVENTION AND COMPARATOR: Included patients will be randomised in a 1:1 ratio to (1) standard care with the addition of 400 mg hydroxychloroquine sulphate (Plaquenil(TM)) twice daily for seven days or (2) standard care alone. MAIN OUTCOMES: The primary endpoint of the study is the rate of decline in SARS-CoV-2 viral load in oropharyngeal samples as assessed by RT-PCR in samples collected at baseline, 48 and 96 hours after randomization and administration of drug for the intervention arm. Secondary endpoints include change in NEWS2 at 96 hours after randomisation, admission to intensive care unit, mortality (in-hospital, and at 30 and 90 days), duration of hospital admission, clinical status on a 7-point ordinal scale 14 days after randomization ([1] Death [2] Hospitalised, on invasive mechanical ventilation or extracorporeal membrane oxygenation [3] Hospitalised, on non-invasive ventilation or high flow oxygen devices [4] Hospitalized, requiring supplemental oxygen [5] Hospitalised, not requiring supplemental oxygen [6] Not hospitalized, but unable to resume normal activities [7] Not hospitalised, with resumption of normal activities), and improvement in protein biomarker profiles (C-reactive protein, markers of renal and hepatic injury, and established cardiac biomarkers like cardiac troponin and B-type natriuretic peptide) at 96 hours after randomization. RANDOMISATION: Eligible patients will be allocated in a 1:1 ratio, using a computer randomisation procedure. The allocation sequence has been prepared by an independent statistician. BLINDING (MASKING): Open label randomised controlled pragmatic trial without blinding, no active or placebo control. The virologist assessing viral load in the oropharyngeal samples and the statistician responsible for analysis of the data will be blinded to the treatment allocation for the statistical analyses. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): This is a group sequential adaptive trial where analyses are planned after 51, 101, 151 and 202 completed patients, with a maximum sample size of 202 patients (101 patients allocated to intervention and standard care and 101 patients allocated to standard care alone). TRIAL STATUS: Protocol version 1.3 (March 26, 2020). Recruitment of first patient on March 26, 2020, and 51 patients were included as per April 28, 2020. Study recruitment is anticipated to be completed by July 2020. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT04316377. Trial registered March 20, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

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

negative: 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: Combination of four clinical indicators predicts the severe/critical symptom of patients infected COVID-19 BACKGROUND: Despite the death rate of COVID-19 is less than 3%, the fatality rate of severe/critical cases is high, according to World Health Organization (WHO). Thus, screening the severe/critical cases before symptom occurs effectively saves medical resources. METHODS AND MATERIALS: In this study, all 336 cases of patients infected COVID-19 in Shanghai to March 12(th), were retrospectively enrolled, and divided in to training and test datasets. In addition, 220 clinical and laboratory observations/records were also collected. Clinical indicators were associated with severe/critical symptoms were identified and a model for severe/critical symptom prediction was developed. RESULTS: Totally, 36 clinical indicators significantly associated with severe/critical symptom were identified. The clinical indicators are mainly thyroxine, immune related cells and products. Support Vector Machine (SVM) and optimized combination of age, GSH, CD3 ratio and total protein has a good performance in discriminating the mild and severe/critical cases. The area under receiving operating curve (AUROC) reached 0.9996 and 0.9757 in the training and testing dataset, respectively. When the using cut-off value as 0.0667, the recall rate was 93.33% and 100% in the training and testing datasets, separately. Cox multivariate regression and survival analyses revealed that the model significantly discriminated the severe/critical cases and used the information of the selected clinical indicators. CONCLUSION: The model was robust and effective in predicting the severe/critical COVID cases.

negative: SheddomeDB: the ectodomain shedding database for membrane-bound shed markers BACKGROUND: A number of membrane-anchored proteins are known to be released from cell surface via ectodomain shedding. The cleavage and release of membrane proteins has been shown to modulate various cellular processes and disease pathologies. Numerous studies revealed that cell membrane molecules of diverse functional groups are subjected to proteolytic cleavage, and the released soluble form of proteins may modulate various signaling processes. Therefore, in addition to the secreted protein markers that undergo secretion through the secretory pathway, the shed membrane proteins may comprise an additional resource of noninvasive and accessible biomarkers. In this context, identifying the membrane-bound proteins that will be shed has become important in the discovery of clinically noninvasive biomarkers. Nevertheless, a data repository for biological and clinical researchers to review the shedding information, which is experimentally validated, for membrane-bound protein shed markers is still lacking. RESULTS: In this study, the database SheddomeDB was developed to integrate publicly available data of the shed membrane proteins. A comprehensive literature survey was performed to collect the membrane proteins that were verified to be cleaved or released in the supernatant by immunological-based validation experiments. From 436 studies on shedding, 401 validated shed membrane proteins were included, among which 199 shed membrane proteins have not been annotated or validated yet by existing cleavage databases. SheddomeDB attempted to provide a comprehensive shedding report, including the regulation of shedding machinery and the related function or diseases involved in the shedding events. In addition, our published tool ShedP was embedded into SheddomeDB to support researchers for predicting the shedding event on unknown or unrecorded membrane proteins. CONCLUSIONS: To the best of our knowledge, SheddomeDB is the first database for the identification of experimentally validated shed membrane proteins and currently may provide the most number of membrane proteins for reviewing the shedding information. The database included membrane-bound shed markers associated with numerous cellular processes and diseases, and some of these markers are potential novel markers because they are not annotated or validated yet in other databases. SheddomeDB may provide a useful resource for discovering membrane-bound shed markers. The interactive web of SheddomeDB is publicly available at http://bal.ym.edu.tw/SheddomeDB/. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-017-1465-7) contains supplementary material, which is available to authorized users.

negative: Annotation of long non-coding RNAs expressed in Collaborative Cross founder mice in response to respiratory virus infection reveals a new class of interferon-stimulated transcripts The outcome of respiratory virus infection is determined by a complex interplay of viral and host factors. Some potentially important host factors for the antiviral response, whose functions remain largely unexplored, are long non-coding RNAs (lncRNAs). Here we systematically inferred the regulatory functions of host lncRNAs in response to influenza A virus and severe acute respiratory syndrome coronavirus (SARS-CoV) based on their similarity in expression with genes of known function. We performed total RNA-Seq on viral-infected lungs from eight mouse strains, yielding a large data set of transcriptional responses. Overall 5,329 lncRNAs were differentially expressed after infection. Most of the lncRNAs were co-expressed with coding genes in modules enriched in genes associated with lung homeostasis pathways or immune response processes. Each lncRNA was further individually annotated using a rank-based method, enabling us to associate 5,295 lncRNAs to at least one gene set and to predict their potential cis effects. We validated the lncRNAs predicted to be interferon-stimulated by profiling mouse responses after interferon-α treatment. Altogether, these results provide a broad categorization of potential lncRNA functions and identify subsets of lncRNAs with likely key roles in respiratory virus pathogenesis. These data are fully accessible through the MOuse NOn-Code Lung interactive database (MONOCLdb).

negative: Dublin Pathology 2015. 8th Joint Meeting of the British Division of the International Academy of Pathology and the Pathological Society of Great Britain & Ireland

negative: Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR BACKGROUND: The ongoing outbreak of the recently emerged novel coronavirus (2019-nCoV) poses a challenge for public health laboratories as virus isolates are unavailable while there is growing evidence that the outbreak is more widespread than initially thought, and international spread through travellers does already occur. AIM: We aimed to develop and deploy robust diagnostic methodology for use in public health laboratory settings without having virus material available. METHODS: Here we present a validated diagnostic workflow for 2019-nCoV, its design relying on close genetic relatedness of 2019-nCoV with SARS coronavirus, making use of synthetic nucleic acid technology. RESULTS: The workflow reliably detects 2019-nCoV, and further discriminates 2019-nCoV from SARS-CoV. Through coordination between academic and public laboratories, we confirmed assay exclusivity based on 297 original clinical specimens containing a full spectrum of human respiratory viruses. Control material is made available through European Virus Archive – Global (EVAg), a European Union infrastructure project. CONCLUSION: The present study demonstrates the enormous response capacity achieved through coordination of academic and public laboratories in national and European research networks.

negative: Superiority of Transcriptional Profiling Over Procalcitonin for Distinguishing Bacterial From Viral Lower Respiratory Tract Infections in Hospitalized Adults Background. Distinguishing between bacterial and viral lower respiratory tract infection (LRTI) remains challenging. Transcriptional profiling is a promising tool for improving diagnosis in LRTI. Methods. We performed whole blood transcriptional analysis in 118 patients (median age [interquartile range], 61 [50–76] years) hospitalized with LRTI and 40 age-matched healthy controls (median age, 60 [46–70] years). We applied class comparisons, modular analysis, and class prediction algorithms to identify and validate diagnostic biosignatures for bacterial and viral LRTI. Results. Patients were classified as having bacterial (n = 22), viral (n = 71), or bacterial-viral LRTI (n = 25) based on comprehensive microbiologic testing. Compared with healthy controls, statistical group comparisons (P < .01; multiple-test corrections) identified 3376 differentially expressed genes in patients with bacterial LRTI, 2391 in viral LRTI, and 2628 in bacterial-viral LRTI. Patients with bacterial LRTI showed significant overexpression of inflammation and neutrophil genes (bacterial > bacterial-viral > viral), and those with viral LRTI displayed significantly greater overexpression of interferon genes (viral > bacterial-viral > bacterial). The K–nearest neighbors algorithm identified 10 classifier genes that discriminated between bacterial and viral LRTI with a 95% sensitivity (95% confidence interval, 77%–100%) and 92% specificity (77%–98%), compared with a sensitivity of 38% (18%–62%) and a specificity of 91% (76%–98%) for procalcitonin. Conclusions. Transcriptional profiling is a helpful tool for diagnosis of LRTI.

negative: Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro

negative: Rapidly Fatal Infections Emergency physicians are trained to separate “sick” from “not sick” patients during their training. Nevertheless, every emergency physician will face situations in which early intervention is critical to their patient's outcome. Infectious diseases are responsible for many of these potentially poor outcomes. This article discusses early identification and treatment for several rapidly fatal infections, including two newly identified travel-related illnesses.

negative: RESEARCH COMMUNICATIONS OF THE 28th ECVIM‐CA CONGRESS

negative: COVID-19: Immunology and treatment options Abstract The novel coronavirus SARS-CoV2 causes COVID-19, a pandemic threatening millions. As protective immunity does not exist in humans and the virus is capable of escaping innate immune responses, it can proliferate, unhindered, in primarily infected tissues. Subsequent cell death results in the release of virus particles and intracellular components to the extracellular space, which result in immune cell recruitment, the generation of immune complexes and associated damage. Infection of monocytes/macrophages and/or recruitment of uninfected immune cells can result in massive inflammatory responses later in the disease. Uncontrolled production of pro-inflammatory mediators contributes to ARDS and cytokine storm syndrome. Antiviral agents and immune modulating treatments are currently being trialled. Understanding immune evasion strategies of SARS-CoV2 and the resulting delayed massive immune response will result in the identification of biomarkers that predict outcomes as well as phenotype and disease stage specific treatments that will likely include both antiviral and immune modulating agents.

negative: Chinese herbal medicine for coronavirus disease 2019: a systematic review and meta-analysis Currently, coronavirus disease 2019 (COVID-19), which can lead to severe respiratory failure and death, is now a global pandemic with no specific anti-viral drugs or vaccines. However, It is worth noting that traditional Chinese medicine (TCM), especially Chinese herbal medicine (CHM), has been widely applied in mainland China since outbreak, bringing new hope for the prevention and control of COVID-19. A comprehensive literature searching was conducted in 7 electronic databases from their inception up to June 21, 2020 to evaluate the efficacy and safety of CHM for COVID-19. Eighteen randomized controlled trials (RCTs) involving 2275 patients were enrolled. Most of CHMs were originated from classical Chinese herbal formulas. Liquoric Root (Gancao, Radix Glycyrrhizae), Baical Skullcap Root (Huangqin, Radix Scutellariae Baicalensis), Pinellia Rhizome (Banxia, Rhizoma Pinelliae Tematae), Forsythia Fruit (Lianqiao, Fructus Forsythiae Suspensae), and Bitter Apricot Seed (Kuxingren, Semen Armeniacae Amarum) were most frequently used Chinese herbs. The most commonly used dosage formulation was decoction. Our meta-analyses found that comparing CHM group and conventional western medicine group, CHM group has improvements in several clinical parameters including lung CT, clinical cure rate, ranging from mild to critical cases, length of hospital stay, total score of clinical symptoms, fever reduction time, symptom score of fever, number of cough reduction cases, symptom score of cough, number of fatigue reduction cases, symptom score of fatigue, disappearing time of fatigue, TCM syndrome, viral nucleic acid testing, and inflammatory biomarkers (C-reactive protein). Besides, no severe adverse effects was identified by CHM. CHM, especially classical Chinese herbal formulas, could be used as potential candidates for COVID-19 in this battle.

negative: 2019-nCoV epidemic: what about pregnancies?

negative: Artesunate: could be an alternative drug to chloroquine in COVID-19 treatment? SARS (Severe Acute Respiratory Syndrome Coronavirus)-CV-2 (2019-nCov), which showed up in China in December 2019 and spread all over the world, has becomed a serious health problem. An effective, safe and proven treatment has not yet been found. Chloroquine has been recommended by some authors to be used for the treatment of patients infected with this virus however chloroquine may have side effects and drug resistance problems. Artesunate is a semisynthetic derivative of artemisinin, an antimalarial drug. Artesunate was thought to be an effective treatment for covid-19 because of its anti-inflammatory activity, NF-κB (nuclear Factor kappa B)-coronavirus effect and chloroquine-like endocytosis inhibition mechanism.

negative: Clinical Characteristics of 2019 Novel Infected Coronavirus Pneumonia：A Systemic Review and Meta-analysis Background:A Novel pneumonia associated with the 2019 coronavirus infected pneumonia (NCIP) suddenly broke out in Wuhan, China in December 2019. 37287 confirmed cases and 813 death case in China (Until 8th/Feb/2019) have been reported in just fortnight. Although this risky pneumonia with high infection rates and high mortality rates need to be resolved immediately, major gaps in our knowledge of clinical characters of it were still not be established. The aim of this study is to summaries and analysis the clinical characteristics of 2019-nCoV pneumonia. Methods: Literature have been systematically performed a search on PubMed, Embase, Web of Science, GreyNet International, and The Cochrane Library from inception up to February 8, 2020. The Newcastle-Ottawa Scale was used to assess quality, and publication bias was analyzed by Egger test. In the single-arm meta-analysis, A fix-effects model was used to obtain a pooled incidence rate. We conducted subgroup analysis according to geographic region and research scale. Results: A total of nine studies including 356 patients were included in this study, the mean age was 52.4 years and 221 (62.1%) were male. The pooled incidences rate of symptoms as follows: pharyngalgia (12.2%, 95% CI: 0.087-0.167), diarrhea (9.2%, 95% CI: 0.062-0.133) and headache (8.9%, 95% CI: 0.063-0.125). Meanwhile, 5.7% (95% CI: 0.027-0.114) of patients were found without any symptoms although they were diagnosed by RT-PCR. In the terms of CT imaging examination, the most of patients showed bilateral mottling or ground-glass opacity, 8.6% (95% CI: 0.048-0.148) of patients with crazy-paving pattern, and 11.5% (95% CI: 0.064-0.197) of patients without obvious CT imaging presentations. The pooled incidence of mortality was 8.9% (95% CI: 0.062-0.126). Conclusions: To our knowledge, this is the first evidence-based medicine research to further elaborate the clinical characteristics of NCIP, which is beneficial to the next step of prevention and treatment.

negative: Characterization of the Lipidomic Profile of Human Coronavirus-Infected Cells: Implications for Lipid Metabolism Remodeling upon Coronavirus Replication Lipids play numerous indispensable cellular functions and are involved in multiple steps in the replication cycle of viruses. Infections by human-pathogenic coronaviruses result in diverse clinical outcomes, ranging from self-limiting flu-like symptoms to severe pneumonia with extrapulmonary manifestations. Understanding how cellular lipids may modulate the pathogenicity of human-pathogenic coronaviruses remains poor. To this end, we utilized the human coronavirus 229E (HCoV-229E) as a model coronavirus to comprehensively characterize the host cell lipid response upon coronavirus infection with an ultra-high performance liquid chromatography-mass spectrometry (UPLC–MS)-based lipidomics approach. Our results revealed that glycerophospholipids and fatty acids (FAs) were significantly elevated in the HCoV-229E-infected cells and the linoleic acid (LA) to arachidonic acid (AA) metabolism axis was markedly perturbed upon HCoV-229E infection. Interestingly, exogenous supplement of LA or AA in HCoV-229E-infected cells significantly suppressed HCoV-229E virus replication. Importantly, the inhibitory effect of LA and AA on virus replication was also conserved for the highly pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV). Taken together, our study demonstrated that host lipid metabolic remodeling was significantly associated with human-pathogenic coronavirus propagation. Our data further suggested that lipid metabolism regulation would be a common and druggable target for coronavirus infections.

negative: The Efficacy of Contact Tracing for the Containment of the 2019 Novel Coronavirus (COVID-19). Contact tracing is a central public health response to infectious disease outbreaks, especially in the early stages of an outbreak when specific treatments are limited. Importation of novel Coronavirus (COVID-19) from China and elsewhere into the United Kingdom highlights the need to understand the impact of contact tracing as a control measure. Using detailed survey information on social encounters coupled to predictive models, we investigate the likely efficacy of the current UK definition of a close contact (within 2 meters for 15 minutes or more) and the distribution of secondary cases that may go untraced. Taking recent estimates for COVID-19 transmission, we show that less than 1 in 5 cases will generate any subsequent untraced cases, although this comes at a high logistical burden with an average of 36.1 individuals (95th percentiles 0-182) traced per case. Changes to the definition of a close contact can reduce this burden, but with increased risk of untraced cases; we estimate that any definition where close contact requires more than 4 hours of contact is likely to lead to uncontrolled spread.

negative: Potential Mechanisms of Cardiac Injury and Common Pathways of Inflammation in Patients With COVID-19 Due to the lack of prospective, randomized, controlled clinical studies on inflammation and cardiovascular involvement, the exact mechanism of cardiac injury among patients with Coronavirus Disease 2019 (COVID-19) still remains uncertain. It was demonstrated that there is a high and significantly positive linear correlation between troponin T and plasma high-sensitivity C-reactive protein levels, biomarkers of cardiac injury and systemic inflammation, respectively. Cardiac injury and inflammation is a relatively common association among patients hospitalized with COVID-19, and it is related to higher risk of in-hospital mortality. In our literature search, we identified several potential mechanisms of myocardial tissue damage, namely, coronavirus-associated acute myocarditis, angiotensin-converting enzyme 2 receptor binding affinity to the virus Spike protein, increased cytokine secretion, and hypoxia-induced cardiac myocyte apoptosis. Elucidation of the disease pathogenesis and prospective histopathological studies are crucial for future proper treatment in case of renewed outbreaks. Of interest is that with hundred of thousands of bodies available for autopsy studies, no prospective investigation has been reported so far. Strong efforts and continued research of the cardiovascular complications and identification of risk factors for poor prognosis in COVID-19 are steadily needed. The high morbidity and mortality of COVID-19, its monumental economic burden and social impact, the despair of a new pandemic outbreak, and the thread of potential utilization of novel severe acute respiratory syndrome coronavirus 2 as biologic weapons make it a preponderant necessity to better comprehend the therapeutic management of this lethal disease. Emerging as an acute infectious disease, COVID-19 may become a chronic epidemic because of genetic recombination. Therefore, we should be ready for the reemergence of COVID-19 or other coronaviruses.

negative: Effect of TLR agonist on infections bronchitis virus replication and cytokine expression in embryonated chicken eggs Abstract Avian infectious bronchitis (IB) is an acute, highly infectious and contagious viral disease of chickens caused by avian infectious bronchitis virus (IBV) belonging to the genus Coronavirus and family Coronaviridae. It can affect all age groups of birds. The toll-like receptors (TLRs) are a major class of innate immune pattern recognition receptors that have a key role in immune response and defense against various infections.The TLRs are essential for initiation of innate immune responses and in the development of adaptive immune responses. An in ovo model was employed to study the antiviral activity of TLR ligands (Pam3CSK4, LPS and CpG ODN) on replication of IBV. It was hypothesized that optimum dose and specific timing of TLR ligands may reduce viral load of IBV in specific pathogen free (SPF) embryonated chicken eggs (ECEs). Further, the mechanism involved in the TLR-mediated antiviral response in chorioallantoic membrane (CAM) of ECEs was investigated. The ECEs of 9–11 days old were treated with different doses (high, intermediate and low) of TLR-2 (Pam3CSK4), TLR-4 (LPS) and TLR-21 (CpG ODN) ligands. In addition, to know the timing of TLR ligand treatment, six time intervals were analyzed viz. 36, 24 and 12 h prior to infection, time of infection (co-administration of TLR ligands and avian IBV) and 12 and 24 h post-IBV infection. For studying the relative expression of immuno-stimulatory genes (IFN-α, IFN-β, IFN-γ, IL-1β, iNOS and OAS) in CAM, TLR ligands were administered through intra-allantoicroute and CAM were collected at 4, 8 and 16 h post treatment. The results demonstrated that intermediate dose of all the three TLR ligands significantly reduced virus titers and used in the present study. However, the LPS reduced virus titer pre- and post-IBV infection but Pam3CSK4 and CpG ODN reduced only pre-IBV infection. Further analysis showed that TLR ligands induced IFN-γ, IL-1β and IFN stimulated genes viz. iNOS and OAS genes in CAM. The present study pointed towards the novel opportunities for rational design of LPS as immuno-stimulatory agent in chickens with reference to IBV. It may be speculated that in ovo administration of these TLR ligands may enhance resistance against viral infection in neonatal chicken and may contribute towards the development of more effective and safer vaccines including in ovo vaccines.

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: The Cellular and Physiological Basis for Lung Repair and Regeneration: Past, Present, and Future The respiratory system, which includes the trachea, airways, and distal alveoli, is a complex multi-cellular organ that intimately links with the cardiovascular system to accomplish gas exchange. In this review and as members of the NIH/NHLBI-supported Progenitor Cell Translational Consortium, we discuss key aspects of lung repair and regeneration. We focus on the cellular compositions within functional niches, cell-cell signaling in homeostatic health, the responses to injury, and new methods to study lung repair and regeneration. We also provide future directions for an improved understanding of the cell biology of the respiratory system, as well as new therapeutic avenues.

negative: Chapter 1 Introduction Abstract A biomarker may refer to a protein whose concentration refers to the severity or presence of some disease state. These biomarkers may be detectable and measurable by a variety of methods including physical examination, laboratory assays, and medical imaging. College Hill indicates that “Biomarkers are valued tools used across the biological spectrum from research to diagnostics, as indicators of normal or disease processes to assess pharmacological responses.” Biomarker (biological marker) is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic response to a therapeutic intervention. Biomarkers are proposed to measure the delivery of drugs to their intended targets, and to understand and predict pathophysiology, and how it is altered by therapy, through monitoring variables known to have chemical relevance. The intent is to use biomarkers for their predictive power to select compounds and design dosing regimens for meeting the pharmacokinetic criteria for a new drug.

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

negative: [Pharmacotherapeutic options for SARS-CoV-2 infection / COVID-19]. There is currently no proven effective therapy for COVID-19. Without wishing to be exhaustive, the drugs most studied in this regard are presented below. Each of the listed therapeutic options is considered experimental at this stage. However, given the severe public health implications of the epidemic and the potentially fatal outcome of COVID-19 patients treated in the intensive care unit, their use 'off-label' should be considered. Orv Hetil. 2020; 161 (17): 685-688.

negative: Research Communications of the 27(th) ECVIM‐CA Congress: Intercontinental, Saint Julian's, Malta, 14th to 16th September 2017

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: Revisión Narrativa Sobre La Respuesta Inmunitaria Frente A Coronavirus: Descripción General, Aplicabilidad Para Sars-Cov2 E Implicaciones Terapéuticas Abstract The new coronavirus (SARS-CoV2) that causes a severe acute respiratory syndrome emerged in Wuhan, China, in December 2019. It produces the aforementioned disease due to coronavirus 2019 (COVID-19), and has led to a declaration of a world public health emergency by the World Health Organisation. This new SARS-CoV2 virus could share characteristics and an immune response similar to those described for other coronavirus. Given its activity on the interferon pathway, and the manner in which it dysregulates innate immunity, the use of treatments directed at modulating or containing this could be of interest. A narrative review was made of the current evidence about immunity against coronavirus and it applicability to SARS-CoV2. The physiopathogenesis is also described, along with the underlying leucocyte activity, with the intention of clarifying the possible usefulness of inflammatory biomarkers and the development of personalised treatments.

negative: Procalcitonin and C-reactive protein perform better than the neutrophil/lymphocyte count ratio in evaluating hospital acquired pneumonia BACKGROUND: The relationship between biomarkers and hospital-acquired pneumonia (HAP) is understudied, especially in severe cases admitted to the intensive care unit (ICU). Compared with community-acquired pneumonia (CAP), HAP might have different traits regarding biomarkers due to the previous history in hospitals. METHODS: A total of 593 adult patients were enrolled in this retrospective cohort study to determine the neutrophil/lymphocyte count ratio (NLCR), procalcitonin (PCT), C-reactive protein (CRP) and serum lactate level upon admission to the ICU. According to diagnosis, patients were divided into two groups: non-infection and HAP. Discriminant analysis was performed based on better outcomes of diagnostic performance and severity evaluation. The diagnostic performance of each individual biomarker was assessed by constructing receiver operating characteristic (ROC) curves and calculating the area under each ROC curve (AUROC). Multivariable analysis was also applied to determine the most appropriate prognostic factors. RESULTS: NLCR, PCT and CRP were markedly different between the non-infection and HAP groups. NLCR had a worse ability to discriminate severe infection (AUROC 0.626; 95% CI 0.581–0.671) than conventional markers such as CRP (0.685, 95% CI 0.641–0.730) and PCT (0.661, 95% CI 0.615–0.707). In addition, the AUROC of composite biomarkers, especially the combination of NLCR, CRP and WBC, was significantly greater than that of any single biomarker. CONCLUSIONS: NLCR was not comparable to conventional single biomarkers, such as CRP and PCT, for diagnosing or evaluating the severity of HAP. Composite biomarkers that have good accessibility, especially the combination of NLCR, CRP and WBC, could help with early diagnosis and severity evaluation.

negative: The discovery and identification of a candidate proteomic biomarker of active tuberculosis BACKGROUND: Noninvasive and convenient biomarkers for early diagnosis of tuberculosis (TB) remain an urgent need. The aim of this study was to discover and identify potential biomarkers specific for TB. METHODS: The surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF MS) combined with weak cation exchange (WCX) magnetic beads was used to screen serum samples from 180 cases of TB and 211 control subjects. A classification model was established by Biomarker Pattern Software (BPS). Candidate protein biomarkers were purified by reverse phase-high performance liquid chromatography (RP-HPLC), identified by MALDI-TOF MS, LC-MS/MS and validated using enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 35 discriminating m/z peaks were detected that were related to TB (P < 0.01). The model of biomarkers based on the four biomarkers (2554.6, 4824.4, 5325.7, and 8606.8 Da) was established which could distinguish TB from controls with the sensitivity of 83.3% and the specificity of 84.2%. The candidate biomarker with m/z of 2554.6 Da was found to be up-regulated in TB patients, and was identified as a fragment of fibrinogen, alpha polypeptide isoform alpha-E preproprotein. Analysis in 22 patients with TB showed increased fibrinogen degradation product (FDP) (5,005 ± 1,297 vs. 4,010 ± 1,181 ng/mL, P < 0.05) and in 142 patients showed elevated plasma fibrinogen levels. CONCLUSIONS: A diagnostic model for TB with high sensitivity and specificity was developed using mass spectrometry combined with magnetic beads. Fibrinogen was identified as a potential biomarker for TB and showed diagnostic values in clinical application.

negative: Chapter 20 The potential of exosomes as theragnostics in various clinical situations Abstract Exosomes are membrane-bound cargo measuring 30–140nm comprised of a lipid bilayer containing various proteins, RNAs, DNAs, and bioactive lipids that can be transferred between cells. They have been shown to be produced and released by many different types of healthy and diseased cells. Exosomes are secreted by all types of cells in culture, and are also found in various body fluids including blood, saliva, urine, and breast milk. Exosomes are essential for healthy physiological as well as pathological processes. In addition to their normal function, exosomes are involved in the development and progression of various diseases, potentiating cellular stress and damage. Pathogens take advantage of exosome release from infected host cells by manipulating host-derived exosomes to evade the immune system responses. Exosomes are involved in other pathological conditions such as neurodegenerative diseases, liver diseases, heart failure, cancer, diabetes, kidney diseases, osteoporosis and atherosclerotic cardiovascular disease. Hence, we can exploit exosomes as biomarkers and vaccines and modify them rationally for therapeutic interventions including tissue engineering. Further studies on exosomes will explore their potential and provide new methodology for effective clinical diagnostics and therapeutic strategies: such uses can be called exosome theragnostics. This chapter reviews the potential theragnostic (diagnostic and therapeutic) application of exosomes in major organ systems in clinical fields.

negative: The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells The emergence of a novel, highly pathogenic coronavirus, 2019-nCoV, in China, and its rapid national and international spread pose a global health emergency. Coronaviruses use their spike proteins to select and enter target cells and insights into nCoV-2019 spike (S)-driven entry might facilitate assessment of pandemic potential and reveal therapeutic targets. Here, we demonstrate that 2019-nCoV-S uses the SARS-coronavirus receptor, ACE2, for entry and the cellular protease TMPRSS2 for 2019-nCoV-S priming. A TMPRSS2 inhibitor blocked entry and might constitute a treatment option. Finally, we show that the serum form a convalescent SARS patient neutralized 2019-nCoV-S-driven entry. Our results reveal important commonalities between 2019-nCoV and SARS-coronavirus infection, which might translate into similar transmissibility and disease pathogenesis. Moreover, they identify a target for antiviral intervention. One sentence summary The novel 2019 coronavirus and the SARS-coronavirus share central biological properties which can guide risk assessment and intervention.

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: Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses The new coronavirus (2019-nCoV) outbreak from December 2019 in Wuhan, Hubei, China, has been declared a global public health emergency. Angiotensin I converting enzyme 2 (ACE2), is the host receptor by 2019-nCov to infect human cells. Although ACE2 is reported to be expressed in lung, liver, stomach, ileum, kidney and colon, its expressing levels are rather low, especially in the lung. 2019-nCoV may use co-receptors/auxiliary proteins as ACE2 partner to facilitate the virus entry. To identify the potential candidates, we explored the single cell gene expression atlas including 119 cell types of 13 human tissues and analyzed the single cell co-expression spectrum of 51 reported RNA virus receptors and 400 other membrane proteins. Consistent with other recent reports, we confirmed that ACE2 was mainly expressed in lung AT2, liver cholangiocyte, colon colonocytes, esophagus keratinocytes, ileum ECs, rectum ECs, stomach epithelial cells, and kidney proximal tubules. Intriguingly, we found that the candidate co-receptors, manifesting the most similar expression patterns with ACE2 across 13 human tissues, are all peptidases, including ANPEP, DPP4 and ENPEP. Among them, ANPEP and DPP4 are the known receptors for human CoVs, suggesting ENPEP as another potential receptor for human CoVs. We also conducted “CellPhoneDB” analysis to understand the cell crosstalk between CoV-targets and their surrounding cells across different tissues. We found that macrophages frequently communicate with the CoVs targets through chemokine and phagocytosis signaling, highlighting the importance of tissue macrophages in immune defense and immune pathogenesis.

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: Two resource distribution strategies for dynamic mitigation of influenza pandemics As recently pointed out by the Institute of Medicine, the existing pandemic containment and mitigation models lack the dynamic decision support capabilities. We present two simulation-based optimization models for developing dynamic predictive resource distribution strategies for cross-regional pandemic outbreaks. In both models, the underlying simulation mimics the disease and population dynamics of the affected regions. The quantity-based optimization model generates a progressive allocation of limited quantities of mitigation resources, including vaccines, antiviral, administration capacities, and social distancing enforcement resources. The budget-based optimization model strives instead allocating a total resource budget. Both models seek to minimize the impact of ongoing outbreaks and the expected impact of potential outbreaks. The models incorporate measures of morbidity, mortality, and social distancing, translated into the societal and economic costs of lost productivity and medical expenses. The models were calibrated using historic pandemic data and implemented on a sample outbreak in Florida, with over four million inhabitants. The quantity-based model was found to be inferior to the budget-based model, which was advantageous in its ability to balance the varying relative cost and effectiveness of individual resources. The models are intended to assist public health policy makers in developing effective distribution policies for mitigation of influenza pandemics.

negative: Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease caused by a novel coronavirus, but its immunopathological mechanisms have not yet been fully elucidated. We investigated changes in plasma T helper (Th) cell cytokines, inflammatory cytokines and chemokines in 20 patients diagnosed with SARS. Cytokine profile of SARS patients showed marked elevation of Th1 cytokine interferon (IFN)-γ, inflammatory cytokines interleukin (IL)-1, IL-6 and IL-12 for at least 2 weeks after disease onset, but there was no significant elevation of inflammatory cytokine tumour necrosis factor (TNF)-α, anti-inflammatory cytokine IL-10, Th1 cytokine IL-2 and Th2 cytokine IL-4. The chemokine profile demonstrated significant elevation of neutrophil chemokine IL-8, monocyte chemoattractant protein-1 (MCP-1), and Th1 chemokine IFN-γ-inducible protein-10 (IP-10). Corticosteroid reduced significantly IL-8, MCP-1 and IP-10 concentrations from 5 to 8 days after treatment (all P < 0·001). Together, the elevation of Th1 cytokine IFN-γ, inflammatory cytokines IL-1, IL-6 and IL-12 and chemokines IL-8, MCP-1 and IP-10 confirmed the activation of Th1 cell-mediated immunity and hyperinnate inflammatory response in SARS through the accumulation of monocytes/macrophages and neutrophils.

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: The differential diagnosis of pulmonary infiltrates in cancer patients during the outbreak of the 2019 novel coronavirus disease/ 中华肿瘤杂志 Objective@#To investigate the principles of differential diagnosis of pulmonary infiltrates in cancer patients during the outbreak of novel coronavirus (2019-nCoV) by analyzing one case of lymphoma who presented pulmonary ground-glass opacities (GGO) after courses of chemotherapy.@*Methods@#Baseline demographics and clinicopathological data of eligible patients were retrieved from medical records. Information of clinical manifestations, history of epidemiology, lab tests and chest CT scan images of visiting patients from February 13 to February 28 were collected. Literatures about pulmonary infiltrates in cancer patients were searched from databases including PUBMED, EMBASE and CNKI.@*Results@#Among the 139 cancer patients underwent chest CT scans before chemotherapy, pulmonary infiltrates were identified in eight patients (5.8%), five of whom were characterized as GGOs in lungs. 2019-nCoV nuclear acid testing was performed in three patients and the results were negative. One case was a 66-year-old man diagnosed as non-Hodgkin lymphoma and underwent CHOP chemotherapy regimen. His chest CT scan image displayed multiple GGOs in lungs and the complete blood count showed decreased lymphocytes. This patient denied any contact with confirmed/suspected cases of 2019-nCoV infection and without fever and other respiratory symptoms. Considering the negative result of nuclear acid testing, this patient was presumptively diagnosed as viral pneumonia and an experiential anti-infection treatment had been prescribed for him.@*Conclusions@#The 2019 novel coronavirus disease (COVID-19) complicates the clinical scenario of pulmonary infiltrates in cancer patients. The epidemic history, clinical manifestation, CT scan image and lab test should be combined consideration. The 2019-nCoV nuclear acid testing might be applicated in more selected patients. Active anti-infection treatment and surveillance of patient condition should be initiated if infectious disease is considered.

negative: ACE2 Expression in Kidney and Testis May Cause Kidney and Testis Damage After 2019-nCoV Infection In December 2019 and January 2020, novel coronavirus (2019-nCoV) - infected pneumonia (NCIP) occurred in Wuhan, and has already posed a serious threat to public health. ACE2 (Angiotensin Converting Enzyme 2) has been shown to be one of the major receptors that mediate the entry of 2019-nCoV into human cells, which also happens in severe acute respiratory syndrome coronavirus (SARS). Several researches have indicated that some patients have abnormal renal function or even kidney damage in addition to injury in respiratory system, and the related mechanism is unknown. This arouses our interest in whether coronavirus infection will affect the urinary and male reproductive systems. Here in this study, we used the online datasets to analyze ACE2 expression in different human organs. The results indicate that ACE2 highly expresses in renal tubular cells, Leydig cells and cells in seminiferous ducts in testis. Therefore, virus might directly bind to such ACE2 positive cells and damage the kidney and testicular tissue of patients. Our results indicate that renal function evaluation and special care should be performed in 2019-nCoV patients during clinical work, because of the kidney damage caused by virus and antiviral drugs with certain renal toxicity. In addition, due to the potential pathogenicity of the virus to testicular tissues, clinicians should pay attention to the risk of testicular lesions in patients during hospitalization and later clinical follow-up, especially the assessment and appropriate intervention in young patients' fertility.

negative: Seroepidemiology of group I human coronaviruses in children BACKGROUND: Recently, several new human coronaviruses have been identified. OBJECTIVES: To define the seroepidemiology of group I human coronaviruses STUDY DESIGN: A recombinant protein enzyme linked immunosorbent assay (ELISA) based on portions of the nucleocapsid protein of group I human coronaviruses was developed and was used to screen serum from 243 children and young adults. RESULTS: For HCoV-229E, the percentages of seropositive individuals were 57.1% for infants < 2 months old; 38.9% for infants 2–3 months old; 4.7% for infants 4–5 months old; 42.9–50.0% for infants 6–12 months old; and 34.8–62.5% for individuals 1–20 years old. For HCoV-NL63, the percentages of seropositive individuals were 45.2% for infants < 2 months old; 11.1% for infants 2–3 months old; 4.7% for infants 4–5 months old; 28.6–40.0% for infants 6–12 months old; and 25.0–70.3% for individuals 1–20 years old. CONCLUSIONS: Infection with these viruses is common in childhood though the prevalence of these viruses may vary from year to year.

negative: Forecasting of COVID-19 Cases and Deaths Using ARIMA Models After the outbreak of severe acute respiratory syndrome (SARS-2002/2003) and middle east respiratory syndrome (MERS-2012/2014) in the world, new public health crisis, called new coronavirus disease (COVID-19), started in China in December 2019 and has spread all over countries. COVID-19 coronavirus has been global threat of the disease and infected humans rapidly. Control of the pandemi is urgently essential, and science community have continued to research treatment agents. Support therapy and intensive care units in hospitals are also efective to overcome of COVID-19. Statistic forecasting models could aid to healthcare system in preventation of COVID-19. This study aimed to compose of forecasting model that could be practical to predict the spread of COVID-19 in Italy, Spain and Turkey. For this purpose, we performed Auto Regressive Integrated Moving Average (ARIMA) model on the European Centre for Disease Prevention and Control COVID-19 data to predict the number of cases and deaths in COVID-19. According to the our results, while number of cases in Italy and Spain is expected to decrease as of July, in Turkey is expected to decline as of September. The number of deaths in Italy and Spain is expected to be the lowest in July. In Turkey, this number is expected to reach the highest in July. In addition, it is thought that if studies in which the sensitivity and validity of this method are tested with more cases, they will contribute to researchers working in this field. KEYWORDS: COVID-19, pandemi, ARIMA, time series analysis

negative: StralSV: assessment of sequence variability within similar 3D structures and application to polio RNA-dependent RNA polymerase BACKGROUND: Most of the currently used methods for protein function prediction rely on sequence-based comparisons between a query protein and those for which a functional annotation is provided. A serious limitation of sequence similarity-based approaches for identifying residue conservation among proteins is the low confidence in assigning residue-residue correspondences among proteins when the level of sequence identity between the compared proteins is poor. Multiple sequence alignment methods are more satisfactory--still, they cannot provide reliable results at low levels of sequence identity. Our goal in the current work was to develop an algorithm that could help overcome these difficulties by facilitating the identification of structurally (and possibly functionally) relevant residue-residue correspondences between compared protein structures. RESULTS: Here we present StralSV (structure-alignment sequence variability), a new algorithm for detecting closely related structure fragments and quantifying residue frequency from tight local structure alignments. We apply StralSV in a study of the RNA-dependent RNA polymerase of poliovirus, and we demonstrate that the algorithm can be used to determine regions of the protein that are relatively unique, or that share structural similarity with proteins that would be considered distantly related. By quantifying residue frequencies among many residue-residue pairs extracted from local structural alignments, one can infer potential structural or functional importance of specific residues that are determined to be highly conserved or that deviate from a consensus. We further demonstrate that considerable detailed structural and phylogenetic information can be derived from StralSV analyses. CONCLUSIONS: StralSV is a new structure-based algorithm for identifying and aligning structure fragments that have similarity to a reference protein. StralSV analysis can be used to quantify residue-residue correspondences and identify residues that may be of particular structural or functional importance, as well as unusual or unexpected residues at a given sequence position. StralSV is provided as a web service at http://proteinmodel.org/AS2TS/STRALSV/.

negative: Novel coronavirus: From discovery to clinical diagnostics Abstract A novel coronavirus designated as 2019-nCoV first appeared in Wuhan, China in late December 2019. Dozens of people died in China, and thousands of people infected as 2019-nCoV continues to spread around the world. We have described the discovery, emergence, genomic characteristics, and clinical diagnostics of 2019-nCoV.

negative: [Diagnosis and clinical management of 2019 novel coronavirus infection: an operational recommendation of Peking Union Medical College Hospital (V2.0)]. Since December 2019, China has been experiencing an outbreak of new infectious disease caused by 2019 novel coronavirus (2019-nCoV). The clinical features include fever, coughing, shortness of breath, and inflammatory pulmonary infiltration revealed by X ray. China rapidly identified 2019-nCoV-related pneumonia a statutory infectious disease. To standardize the diagnosis and treatment of this new infectious disease, operational guidelines for the diagnosis and management of 2019-nCoV infection is accomplished by Peking Union Medical College Hospital.

negative: Surgical Management of Patients With COVID-19 Infection. Recommendations of the Spanish Association of Surgeons Abstract Due to the current pandemic of respiratory disease known as coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus, many patients with confirmed or suspected COVID-19 infection will require elective surgery, surgery that cannot be postponed, or emergency surgical treatment. In these situations, special measures need to be adopted in order to minimize the possibility of transmission between patients, exposure of healthcare personnel and the development of postoperative complications. This document explains the main principles to consider when managing confirmed or suspected COVID-19 patients during evaluation as well as when surgical treatment is required.

negative: Global research trends of World Health Organization’s top eight emerging pathogens BACKGROUND: On December 8(th), 2015, World Health Organization published a priority list of eight pathogens expected to cause severe outbreaks in the near future. To better understand global research trends and characteristics of publications on these emerging pathogens, we carried out this bibliometric study hoping to contribute to global awareness and preparedness toward this topic. METHOD: Scopus database was searched for the following pathogens/infectious diseases: Ebola, Marburg, Lassa, Rift valley, Crimean-Congo, Nipah, Middle Eastern Respiratory Syndrome (MERS), and Severe Respiratory Acute Syndrome (SARS). Retrieved articles were analyzed to obtain standard bibliometric indicators. RESULTS: A total of 8619 journal articles were retrieved. Authors from 154 different countries contributed to publishing these articles. Two peaks of publications, an early one for SARS and a late one for Ebola, were observed. Retrieved articles received a total of 221,606 citations with a mean ± standard deviation of 25.7 ± 65.4 citations per article and an h-index of 173. International collaboration was as high as 86.9%. The Centers for Disease Control and Prevention had the highest share (344; 5.0%) followed by the University of Hong Kong with 305 (4.5%). The top leading journal was Journal of Virology with 572 (6.6%) articles while Feldmann, Heinz R. was the most productive researcher with 197 (2.3%) articles. China ranked first on SARS, Turkey ranked first on Crimean-Congo fever, while the United States of America ranked first on the remaining six diseases. Of retrieved articles, 472 (5.5%) were on vaccine – related research with Ebola vaccine being most studied. CONCLUSION: Number of publications on studied pathogens showed sudden dramatic rise in the past two decades representing severe global outbreaks. Contribution of a large number of different countries and the relatively high h-index are indicative of how international collaboration can create common health agenda among distant different countries.

negative: 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: Myocardial injury and COVID-19: Possible mechanisms 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: Prevention and treatment of COVID‐19 disease by controlled modulation of innate immunity The recent outbreak of coronavirus disease 2019 (COVID‐19), triggered by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) poses an enormous threat to global public health and economies. Human coronaviruses normally cause no or mild respiratory disease but in the past two decades, potentially fatal coronavirus infections have emerged, causing respiratory tract illnesses such as pneumonia and bronchitis. These include severe acute respiratory syndrome coronavirus (SARS‐CoV), followed by the Middle East respiratory syndrome coronavirus (MERS‐CoV), and recently the SARS‐CoV‐2 coronavirus outbreak which emerged in Wuhan, China, in December 2019. Currently, most COVID‐19 patients receive traditional supportive care including breathing assistance. To halt the ongoing spread of the pandemic SARS‐CoV‐2 coronavirus and rescue individual patients, established drugs and new therapies are under evaluation. Since it will be some time until a safe and effective vaccine will be available, the immediate priority is to harness innate immunity to accelerate early antiviral immune responses. Secondly since excessive inflammation is a major cause of pathology, targeted anti‐inflammatory responses are being evaluated to reduce inflammation‐induced damage to the respiratory tract and cytokine storms. Here, we highlight prominent immunotherapies at various stages of development which aim for augmented anti‐coronavirus immunity and reduction of pathological inflammation. This article is protected by copyright. All rights reserved

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: Does infection of 2019 novel coronavirus cause acute and/or chronic sialadenitis? Abstract 2019 novel coronavirus (2019-nCoV) is widespread in China and other countries. The target of 2019-nCoV and severe acute respiratory syndrome coronavirus (SARS-CoV) is angiotensin-converting enzyme 2 (ACE2) positive cells. ACE2 is present in the salivary gland duct epithelium, and thus it could be the target of 2019-nCoV and SARS-CoV. SARS-CoV-related animal model experiments show that it can infect the epithelial cells on the salivary gland duct in Chinese rhesus macaques by targeting ACE2. Clinical studies confirmed that 2019-nCoV and SARS-CoV could be detected in saliva of human patients. We hypothesize that the infection of 2019-nCoV and SARS-CoV will lead to inflammatory pathological lesions in patients’ target organs, and possibly inflammatory lesions in salivary glands. 2019-nCoV may cause acute sialoadenitis in the acute phase of infection. After the acute phase, chronic sialoadenitis may be caused by fibrosis repairment. Although there was no direct evidence to prove this, the available indirect evidence indicates a high probability of our hypothesis.

negative: The epidemiological and clinical features of COVID-19 and lessons from this global infectious public health event Abstract Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and represents a potentially fatal disease of great global public health importance. As of March 26, 2020, the outbreak of COVID-19 has resulted in 462,801 confirmed cases and 20,839 deaths globally, which is more than those caused by SARS and Middle East respiratory syndrome (MERS) in 2003 and 2013, respectively. The epidemic has posed considerable challenges worldwide. Under a strict mechanism of massive prevention and control, China has seen a rapid decrease in new cases of coronavirus; however, the global situation remains serious. Additionally, the origin of COVID-19 has not been determined and no specific antiviral treatment or vaccine is currently available. Based on the published data, this review systematically discusses the etiology, epidemiology, clinical characteristics, and current intervention measures related to COVID-19 in the hope that it may provide a reference for future studies and aid in the prevention and control of the COVID-19 epidemic.

negative: 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: Future Perspectives of Wastewater-Based Epidemiology: Monitoring Infectious Disease Spread and Resistance to the Community Level Abstract Infectious diseases are acknowledged as one of the most critical threats to global public health today. Climate change, unprecedented population growth with accelerated rates of antimicrobial resistance, have resulted in both the emergence of novel pathogenic organisms and the re-emergence of infections that were once controlled. The consequences have led to an increased vulnerability to infectious diseases globally. The ability to rapidly monitor the spread of diseases is key for prevention, intervention and control, however several limitations exist for current surveillance systems and the capacity to cope with the rapid population growth and environmental changes. Wastewater-Based Epidemiology (WBE) is a new epidemiology tool that has potential to act as a complementary approach for current infectious disease surveillance systems and an early warning system for disease outbreaks. WBE postulates that through the analysis of population pooled wastewater, infectious disease and resistance spread, the emergence of new disease outbreak to the community level can be monitored comprehensively and in real-time. This manuscript provides critical overview of current infectious disease surveillance status, as well as it introduces WBE and its recent advancements. It also provides recommendations for further development required for WBE application as an effective tool for infectious disease surveillance.

negative: Multiplex nested RT-PCR for the detection of porcine enteric viruses Abstract Porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), and porcine group A rotavirus (PRV-A) are major viruses causing enteric diseases of piglets. A multiplex nested reverse transcription polymerase chain reaction (multiplex nested RT-PCR) was developed for the detection of these viruses in field samples from piglets with diarrhea. A mixture of (1) three external pairs of primers, yielding in the amplification step two different amplicons with sizes of 950bp and 317bp and (2) three pairs of internal primers in a second round of PCR (nested PCR), yielding two different amplicons with sizes of 792bp and 208bp for TGEV and porcine PRV-A, respectively. The genome of PEDV was not detected after the amplification step but it was detected in the second round of PCR, yielding amplicon with size of 291bp. Multiplex nested RT-PCR can detect TGEV, PRV-A, and PEDV up to concentration 102 TCID50/mL, 101 TCID50/mL, and 27.2μg/μl of RNA, respectively. A total of 175 field samples were collected from swine with diarrhea from January 2005 until July 2007. The samples were tested for the presence of three viruses by a multiplex nested RT-PCR. Dual infections with PEDV and PRV-A were identified in seven specimens (4%) (n =6). Twenty-one (25%) infections were caused by PEDV and thirty-four infections (41%) were caused by PRV-A. The genome of TGEV was not detected in any of these field samples, however TGEV was detected in piglets infected experimentally. The multiplex nested RT-PCR is rapid, sensitive, and a cost-effective detection method for the detection of porcine enteric viruses.

negative: Severe acute respiratory syndrome-related coronavirus: The species and its viruses – a statement of the Coronavirus Study Group The present outbreak of lower respiratory tract infections, including respiratory distress syndrome, is the third spillover, in only two decades, of an animal coronavirus to humans resulting in a major epidemic. Here, the Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses, which is responsible for developing the official classification of viruses and taxa naming (taxonomy) of the Coronaviridae family, assessed the novelty of the human pathogen tentatively named 2019-nCoV. Based on phylogeny, taxonomy and established practice, the CSG formally recognizes this virus as a sister to severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus and designates it as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To facilitate communication, the CSG further proposes to use the following naming convention for individual isolates: SARS-CoV-2/Isolate/Host/Date/Location. The spectrum of clinical manifestations associated with SARS-CoV-2 infections in humans remains to be determined. The independent zoonotic transmission of SARS-CoV and SARS-CoV-2 highlights the need for studying the entire (virus) species to complement research focused on individual pathogenic viruses of immediate significance. This research will improve our understanding of virus-host interactions in an ever-changing environment and enhance our preparedness for future outbreaks.

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: Sample preparation for serum/plasma profiling and biomarker identification by mass spectrometry Abstract In this article, we present an overview of the different strategies for sample preparation for identification by mass spectrometry (MS) of biomarkers from serum and/or plasma. We consider the effects of the variables involved in sample collection, handling and storage, and describe different approaches for removal of high abundance proteins and serum/plasma fractionation. We review the advantages and disadvantages of such techniques as centrifugal ultrafiltration, different formats for solid phase extraction, organic solvent extraction, gel and capillary electrophoresis, and liquid chromatography. We also discuss a variety of current proteomic methods and their main applications for biomarker-related studies.

negative: [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.

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

negative: 2019 novel coronavirus (2019-nCoV) and 2019-nCoV pneumonia/ 中华微生物学和免疫学杂志 In the middle of December in 2019, a pneumonia outbreak caused by a new coronavirus, 2019 novel coronavirus (2019-nCoV), emerged in the populations in Wuhan city of China. The epidemic spreads rapidly and has been disseminated throughout the country and to 13 other counties in Asia, Europe, Oceania and North America. To accurately and deeply understand the biological characteristics, epidemiological features and pathogenicity of 2019-nCoV and related immunological characteristics, microbiological examinations and public protection measure, this study reviewed 2019-nCoV and 2019-nCoV pneumonia based on the newest relevant literatures and the newest version of National Diagnosis and Treatment Scheme of 2019-nCoV pneumonia.

negative: Sequence-Based Human Leukocyte Antigen—B Typing of Patients Infected with Ebola Virus in Uganda in 2000: Identification of Alleles Associated with Fatal and Nonfatal Disease Outcomes The Sudan species of Ebola virus (SEBOV) causes severe, often fatal infection in ∼50% of infected humans. We sought to determine whether the human leukocyte antigen—B (HLA-B) locus has a role in the outcome of SEBOV disease by typing 77 cases from an outbreak in northern Uganda in 2000–2001. Sequence-based HLA-B typing was performed using leukocytes isolated from 77 patients. Statistical analysis and a predictive discriminant analysis (PDA) were applied to typing data. Epitope prediction software was also applied to SEBOV sequences. Statistically significant associations were found between certain sets of alleles and either fatal or nonfatal disease outcomes. Alleles B*67 and B*15 were associated with fatal outcomes, whereas B*07 and B*14 were associated with nonfatal outcomes. The PDA-derived functions that were produced were 81.8% accurate in classifying patients into their correct outcome group. Several epitopes predicted to bind strongly to HLA-B*07 molecules were identified in the viral polymerase, nucleoprotein, and VP35 protein. HLA-B alleles associated with either fatal or nonfatal outcomes of SEBOV disease were identified and can be used in a predictive model. Studies of HLA-B—restricted epitopes could contribute to characterization of protective host responses and to vaccine development.

negative: In silico identification of vaccine targets for 2019-nCoV Background: The newly identified coronavirus known as 2019-nCoV has posed a serious global health threat. According to the latest report (18-February-2020), it has infected more than 72,000 people globally and led to deaths of more than 1,016 people in China. Methods: The 2019 novel coronavirus proteome was aligned to a curated database of viral immunogenic peptides. The immunogenicity of detected peptides and their binding potential to HLA alleles was predicted by immunogenicity predictive models and NetMHCpan 4.0. Results: We report in silico identification of a comprehensive list of immunogenic peptides that can be used as potential targets for 2019 novel coronavirus (2019-nCoV) vaccine development. First, we found 28 nCoV peptides identical to Severe acute respiratory syndrome-related coronavirus (SARS CoV) that have previously been characterized immunogenic by T cell assays. Second, we identified 48 nCoV peptides having a high degree of similarity with immunogenic peptides deposited in The Immune Epitope Database (IEDB). Lastly, we conducted a de novo search of 2019-nCoV 9-mer peptides that i) bind to common HLA alleles in Chinese and European population and ii) have T Cell Receptor (TCR) recognition potential by positional weight matrices and a recently developed immunogenicity algorithm, iPred, and identified in total 63 peptides with a high immunogenicity potential. Conclusions: Given the limited time and resources to develop vaccine and treatments for 2019-nCoV, our work provides a shortlist of candidates for experimental validation and thus can accelerate development pipeline.

negative: Cardiac Involvement in COVID-19—Assessment with Echocardiography and Cardiac Magnetic Resonance Imaging The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), started at the beginning of December 2019, in Wuhan, Hubei, China. Since then, the disease has been spreading quickly all over the world with dramatic consequences for global health. That is the reason why it was declared pandemic since March 11th, 2020. The clinical presentation of SARS-CoV-2 is quite variable. Respiratory symptoms dominate its clinical manifestations, but based on current observations, it can significantly affect the heart as well, thus leading to myocardial injury. Imaging plays a key role in the cardiovascular management of these patients, with the aim of improving their outcomes. This review article provides an overview as to strengths and weaknesses of cardiac magnetic resonance compared with echocardiography in the difficult management of these patients.

negative: Coronavirus, humanpathogenes Humanes Coronavirus, Gruppe 1 Coronavirus

negative: Return of the Coronavirus: 2019-nCoV The emergence of a novel coronavirus (2019-nCoV) has awakened the echoes of SARS-CoV from nearly two decades ago. Yet, with technological advances and important lessons gained from previous outbreaks, perhaps the world is better equipped to deal with the most recent emergent group 2B coronavirus.

negative: Interactome Mapping: Using Protein Microarray Technology to Reconstruct Diverse Protein Networks A major focus of systems biology is to characterize interactions between cellular components, in order to develop an accurate picture of the intricate networks within biological systems. Over the past decade, protein microarrays have greatly contributed to advances in proteomics and are becoming an important platform for systems biology. Protein microarrays are highly flexible, ranging from large-scale proteome microarrays to smaller customizable microarrays, making the technology amenable for detection of a broad spectrum of biochemical properties of proteins. In this article, we will focus on the numerous studies that have utilized protein microarrays to reconstruct biological networks including protein–DNA interactions, posttranslational protein modifications (PTMs), lectin–glycan recognition, pathogen–host interactions and hierarchical signaling cascades. The diversity in applications allows for integration of interaction data from numerous molecular classes and cellular states, providing insight into the structure of complex biological systems. We will also discuss emerging applications and future directions of protein microarray technology in the global frontier.

negative: Host and infectivity prediction of Wuhan 2019 novel coronavirus using deep learning algorithm The recent outbreak of pneumonia in Wuhan, China caused by the 2019 Novel Coronavirus (2019-nCoV) emphasizes the importance of detecting novel viruses and predicting their risks of infecting people. In this report, we introduced the VHP (Virus Host Prediction) to predict the potential hosts of viruses using deep learning algorithm. Our prediction suggests that 2019-nCoV has close infectivity with other human coronaviruses, especially the severe acute respiratory syndrome coronavirus (SARS-CoV), Bat SARS-like Coronaviruses and the Middle East respiratory syndrome coronavirus (MERS-CoV). Based on our prediction, compared to the Coronaviruses infecting other vertebrates, bat coronaviruses are assigned with more similar infectivity patterns with 2019-nCoVs. Furthermore, by comparing the infectivity patterns of all viruses hosted on vertebrates, we found mink viruses show a closer infectivity pattern to 2019-nCov. These consequences of infectivity pattern analysis illustrate that bat and mink may be two candidate reservoirs of 2019-nCov.These results warn us to beware of 2019-nCoV and guide us to further explore the properties and reservoir of it. It is of great value to identify whether a newly discovered virus has the risk of infecting human. Guo et al. proposed a virus host prediction method based on deep learning to detect what kind of host a virus can infect with DNA sequence as input. Applied to the Wuhan 2019 Novel Coronavirus, our prediction demonstrated that several vertebrate-infectious coronaviruses have strong potential to infect human. This method will be helpful in future viral analysis and early prevention and control of viral pathogens.

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: Sepsis: Clinical Approach, Evidence-Based at the Bedside Sepsis is a common disease in intensive care medicine representing almost one third of patient admissions. Its incidence has substantially increased over the past decades and overall mortality has declined during this period of time. It was reported that sepsis incidence increased from 82.7 to 240.4 per 100,000 population between 1979–2000. At the same time, sepsis global mortality decreased from 27.8 to 17.9% [1–3]. However, the absolute number of deaths significantly increased from 21.9 to 43.9 per 100,000 population. Male gender, some chronic diseases like diabetes, immunosuppressive states, human immunodeficiency virus infections, and malignancies are factors that increase the risk for sepsis. Some particular conditions like progressive number of organ dysfunctions, in-hospital-acquired infections and increasing age are associated with higher risk of death [1,4]. On the other hand, septic shock mortality only diminished from 61.6 to 53.1% [5]. This slight decline in mortality observed during recent decades could be attributable to improvements in supportive care and/or avoidance of iatrogenic complications. For example, the instrumentation of early goal resuscitation protocols not aiming at supranormal targets for cardiac output and oxygen delivery, and the use of lung protective strategies could explain at least in part this favorable change. Other strategies directed to treat the pathophysiological mechanisms involved in the septic process like recombinant human-activated protein-C (rhAPC), have also contributed to improve survival. However, mortality remains unacceptably high and further improvement in sepsis management is needed.

negative: [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.

negative: Effect of selected gastrointestinal parasites and viral agents on fecal S100A12 concentrations in puppies as a potential comparative model BACKGROUND: Previous data suggest that fecal S100A12 has clinical utility as a biomarker of chronic gastrointestinal inflammation (idiopathic inflammatory bowel disease) in both people and dogs, but the effect of gastrointestinal pathogens on fecal S100A12 concentrations is largely unknown. The role of S100A12 in parasite and viral infections is also difficult to study in traditional animal models due to the lack of S100A12 expression in rodents. Thus, the aim of this study was to evaluate fecal S100A12 concentrations in a cohort of puppies with intestinal parasites (Cystoisospora spp., Toxocara canis, Giardia sp.) and viral agents that are frequently encountered and known to cause gastrointestinal signs in dogs (coronavirus, parvovirus) as a comparative model. METHODS: Spot fecal samples were collected from 307 puppies [median age (range): 7 (4−13) weeks; 29 different breeds] in French breeding kennels, and fecal scores (semiquantitative system; scores 1−13) were assigned. Fecal samples were tested for Cystoisospora spp. (C. canis and C. ohioensis), Toxocara canis, Giardia sp., as well as canine coronavirus (CCV) and parvovirus (CPV). S100A12 concentrations were measured in all fecal samples using an in-house radioimmunoassay. Statistical analyses were performed using non-parametric 2-group or multiple-group comparisons, non-parametric correlation analysis, association testing between nominal variables, and construction of a multivariate mixed model. RESULTS: Fecal S100A12 concentrations ranged from < 24−14,363 ng/g. Univariate analysis only showed increased fecal S100A12 concentrations in dogs shedding Cystoisospora spp. (P = 0.0384) and in dogs infected with parvovirus (P = 0.0277), whereas dogs infected with coronavirus had decreased fecal S100A12 concentrations (P = 0.0345). However, shedding of any single enteropathogen did not affect fecal S100A12 concentrations in multivariate analysis (all P > 0.05) in this study. Only fecal score and breed size had an effect on fecal S100A12 concentrations in multivariate analysis (P < 0.0001). CONCLUSIONS: An infection with any single enteropathogen tested in this study is unlikely to alter fecal S100A12 concentrations, and these preliminary data are important for further studies evaluating fecal S100A12 concentrations in dogs or when using fecal S100A12 concentrations as a biomarker in patients with chronic idiopathic gastrointestinal inflammation.

negative: A Case of Coronavirus Disease 2019 With Concomitant Acute Cerebral Infarction and Deep Vein Thrombosis We report a case of a 75-year-old woman diagnosed with severe coronavirus disease 2019 (COVID-19) complicated by acute cerebral infarction. The patient was admitted to our hospital on 5 February 2020 with severe COVID-19. On 20 February 2020, she was diagnosed with concomitant acute cerebral infarction via head computed tomography (CT) and deep vein thrombosis in both lower limbs. After symptomatic and supportive treatments, the patient was discharged on 13 March 2020. She will comply with quarantine for another 2 weeks and receive rehabilitation training from a specialist doctor. Cerebral infarction should be considered and promptly managed in patients with COVID-19.

negative: Detection and Monitoring of SARS Coronavirus in the Plasma and Peripheral Blood Lymphocytes of Patients with Severe Acute Respiratory Syndrome

negative: Inhibition of novel β coronavirus replication by a combination of interferon-α2b and ribavirin The identification of a novel β coronavirus, nCoV, as the causative agent of severe respiratory illness in humans originating in Saudi Arabia, Qatar and Jordan has raised concerns about the possibility of a coronavirus pandemic similar to that of SARS-CoV. As a definitive treatment regimen has never been thoroughly evaluated for coronavirus infections, there is an urgent need to rapidly identify potential therapeutics to address future cases of nCoV. To determine an intervention strategy, the effect of interferon-α2b and ribavirin on nCoV isolate hCoV-EMC/2012 replication in Vero and LLC-MK2 cells was evaluated. hCoV-EMC/2012 was sensitive to both interferon-α2b and ribavirin alone in Vero and LLC-MK2 cells, but only at relatively high concentrations; however, when combined, lower concentrations of interferon-α2b and ribavirin achieved comparable endpoints. Thus, a combination of interferon-α2b and ribavirin, which are already commonly used in the clinic, may be useful for patient management in the event of future nCoV infections.

negative: Detection of the nucleocapsid protein of severe acute respiratory syndrome coronavirus in serum: Comparison with results of other viral markers Abstract A capture enzyme-enhanced chemiluminescence immunoassay (ECLIA) based on three specific monoclonal antibodies to detect the nucleocapsid (N) protein of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in the serial serum samples from SARS patients was developed. The anti-SARS-CoV IgG and the viral RNA were also detected in the sera by ELISA and RT-PCR, respectively. During the first 10 days after onset, anti-SARS-CoV IgG, SARS-CoV RNA and the N protein were detected in 21.4, 42.9, and 90% of the patients’ sera, respectively. The detection rate of the N protein during days 11–15 of the disease was still significantly higher than those of anti-SARS-CoV IgG and SARS-CoV RNA. The data demonstrated that detection of the N protein with the capture ECLIA appears to be more useful than detection of other viral makers for rapid diagnosis of SARS in patients.

negative: Prognostic Hemostasis Biomarkers in Acute Ischemic Stroke. Objectives- The prediction of patients at risk for poor clinical outcome after acute ischemic stroke remains challenging. An imbalance of coagulation factors may play an important role in progression and prognosis of these patients. In this systematic review, we assessed the current literature on hemostasis biomarkers and the association with poor clinical outcome in acute ischemic stroke. Approach and Results- A systematic search of Embase, Medline, Cochrane Library, Web of Science, and Google Scholar was performed on studies reporting on hemostasis biomarkers and clinical outcome after acute ischemic stroke. Studies were considered eligible if blood samples were collected within 72 hours after symptom onset. Additionally, clinical outcome should be assessed using a disability score (Barthel Index or modified Rankin scale). Methodological quality of included studies was assessed with an adapted version of the Quality Assessment of Diagnostic Accuracy Studies questionnaire. A total of 80 articles were read full text, and 41 studies were considered eligible for inclusion, reporting on 37 different hemostasis biomarkers. No single biomarker appeared to be effective in predicting poor clinical outcome in acute ischemic stroke patients. Conclusions- Based on current literature, no clear recommendations can be provided on which hemostasis biomarkers are a predictor of clinical outcome after acute ischemic stroke. However, some biomarkers show promising results and need to be further investigated and validated in large populations with clear defined study designs.

negative: An updated estimation of the risk of transmission of the novel coronavirus (2019-nCov) The basic reproduction number of an infectious agent is the average number of infections one case can generate over the course of the infectious period, in a naïve, uninfected population. It is well-known that the estimation of this number may vary due to several methodological issues, including different assumptions and choice of parameters, utilized models, used datasets and estimation period. With the spreading of the novel coronavirus (2019-nCoV) infection, the reproduction number has been found to vary, reflecting the dynamics of transmission of the coronavirus outbreak as well as the case reporting rate. Due to significant variations in the control strategies, which have been changing over time, and thanks to the introduction of detection technologies that have been rapidly improved, enabling to shorten the time from infection/symptoms onset to diagnosis, leading to faster confirmation of the new coronavirus cases, our previous estimations on the transmission risk of the 2019-nCoV need to be revised. By using time-dependent contact and diagnose rates, we refit our previously proposed dynamics transmission model to the data available until January 29th(,) 2020 and re-estimated the effective daily reproduction ratio that better quantifies the evolution of the interventions. We estimated when the effective daily reproduction ratio has fallen below 1 and when the epidemics will peak. Our updated findings suggest that the best measure is persistent and strict self-isolation. The epidemics will continue to grow, and can peak soon with the peak time depending highly on the public health interventions practically implemented.

negative: A novel coronavirus outbreak of global health concern

negative: Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province BACKGROUND: A novel coronavirus (2019-nCoV) causing an outbreak of pneumonia in Wuhan, Hubei province of China was isolated in January 2020. This study aims to investigate its epidemiologic history, and analyze the clinical characteristics, treatment regimens, and prognosis of patients infected with 2019-nCoV during this outbreak. METHODS: Clinical data from 137 2019-nCoV-infected patients admitted to the respiratory departments of the respiratory departments of nine tertiary hospitals in Hubei province from December 30, 2019 to January 24, 2020 were retrospectively collected, including general status, clinical manifestations, laboratory test results, imaging characteristics, and treatment regimens. RESULTS: None of the 137 patients (61 males, 76 females, aged 20–83 years, median age 57 years) had a definite history of exposure to Huanan Seafood Wholesale Market. Major initial symptoms included fever (112/137, 81.8%), coughing (66/137, 48.2%), and muscle pain or fatigue (44/137, 32.1%), with other, less typical initial symptoms observed at low frequency, including heart palpitations, diarrhea, and headache. Nearly 80% of the patients had normal or decreased white blood cell counts, and 72.3% (99/137) had lymphocytopenia. Lung involvement was present in all cases, with most chest computed tomography scans showing lesions in multiple lung lobes, some of which were dense; ground-glass opacity co-existed with consolidation shadows or cord-like shadows. Given the lack of effective drugs, treatment focused on symptomatic and respiratory support. Immunoglobulin G was delivered to some critically ill patients according to their conditions. Systemic corticosteroid treatment did not show significant benefits. Notably, early respiratory support facilitated disease recovery and improved prognosis. The risk of death was primarily associated with age, underlying chronic diseases, and median interval from the appearance of initial symptoms to dyspnea. CONCLUSIONS: The majority of patients with 2019-nCoV pneumonia present with fever as the first symptom, and most of them still showed typical manifestations of viral pneumonia on chest imaging. Middle-aged and elderly patients with underlying comorbidities are susceptible to respiratory failure and may have a poorer prognosis.

negative: Comparative analyses of SAR-CoV2 genomes from different geographical locations and other coronavirus family genomes reveals unique features potentially consequential to host-virus interaction and pathogenesis The ongoing pandemic of the coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). We have performed an integrated sequence-based analysis of SARS-CoV2 genomes from different geographical locations in order to identify its unique features absent in SARS-CoV and other related coronavirus family genomes, conferring unique infection, facilitation of transmission, virulence and immunogenic features to the virus. The phylogeny of the genomes yields some interesting results. Systematic gene level mutational analysis of the genomes has enabled us to identify several unique features of the SARS-CoV2 genome, which includes a unique mutation in the spike surface glycoprotein (A930V (24351C>T)) in the Indian SARS-CoV2, absent in other strains studied here. We have also predicted the impact of the mutations in the spike glycoprotein function and stability, using computational approach. To gain further insights into host responses to viral infection, we predict that antiviral host-miRNAs may be controlling the viral pathogenesis. Our analysis reveals nine host miRNAs which can potentially target SARS-CoV2 genes. Interestingly, the nine miRNAs do not have targets in SARS and MERS genomes. Also, hsa-miR-27b is the only unique miRNA which has a target gene in the Indian SARS-CoV2 genome. We also predicted immune epitopes in the genomes

negative: Prediction of fatal adverse prognosis in patients with fever-related diseases based on machine learning: A retrospective study BACKGROUND: Fever is the most common chief complaint of emergency patients. Early identification of patients at an increasing risk of death may avert adverse outcomes. The aim of this study was to establish an early prediction model of fatal adverse prognosis of fever patients by extracting key indicators using big data technology. METHODS: A retrospective study of patients’ data was conducted using the Emergency Rescue Database of Chinese People's Liberation Army General Hospital. Patients were divided into the fatal adverse prognosis group and the good prognosis group. The commonly used clinical indicators were compared. Recursive feature elimination (RFE) method was used to determine the optimal number of the included variables. In the training model, logistic regression, random forest, adaboost and bagging were selected. We also collected the emergency room data from December 2018 to December 2019 with the same inclusion and exclusion criterion. The performance of the model was evaluated by accuracy, F1-score, precision, sensitivity and the areas under receiver operator characteristic curves (ROC-AUC). RESULTS: The accuracy of logistic regression, decision tree, adaboost and bagging was 0.951, 0.928, 0.924, and 0.924, F1-scores were 0.938, 0.933, 0.930, and 0.930, the precision was 0.943, 0.938, 0.937, and 0.937, ROC-AUC were 0.808, 0.738, 0.736, and 0.885, respectively. ROC-AUC of ten-fold cross-validation in logistic and bagging models were 0.80 and 0.87, respectively. The top six coefficients and odds ratio (OR) values of the variables in the Logistic regression were cardiac troponin T (CTnT) (coefficient=0.346, OR = 1.413), temperature (T) (coefficient=0.235, OR = 1.265), respiratory rate (RR) (coefficient= –0.206,OR = 0.814), serum kalium (K) (coefficient=0.137, OR = 1.146), pulse oxygen saturation (SPO(2)) (coefficient= –0.101, OR = 0.904), and albumin (ALB) (coefficient= –0.043, OR = 0.958). The weights of the top six variables in the bagging model were: CTnT, RR, lactate dehydrogenase, serum amylase, heartrate, and systolic blood pressure. CONCLUSIONS: The main clinical indicators of concern included CTnT, RR, SPO(2), T, ALB and K. The bagging model and logistic regression model had better diagnostic performance comprehesively. Those may be conducive to the early identification of critical patients with fever by physicians.

negative: Cross-reactivity of antibody against SARS-coronavirus nucleocapsid protein with IL-11 Abstract Infection of SARS-associated coronavirus (SARS-CoV) induced a strong anti-nucleocapsid (anti-N) antibody response. However, the pathophysiological significance of the anti-N antibodies in SARS pathogenesis is largely unknown. To profile the anti-N antibodies, a phage-displayed scFv library was prepared from mice immunized with heat-inactivated SARS-CoV-infected Vero E6 cell lysate. Specific anti-N scFvs were isolated by panning against a recombinant nucleocapsid protein and reactivity was confirmed with phage-ELISA. Sequence analysis indicated that two of the isolated anti-N scFv clones were identical and displayed a high homology with an scFv specific for interleukin 11 (IL-11), an anti-inflammatory cytokine derived from bone marrow stroma cells. In a neutralization assay, IL-11-induced STAT 3 phosphorylation in rat intestinal epithelial IEC-18 cells was completely suppressed by the anti-N scFv clone L9N01.

negative: Influenza D Virus Infection in Dromedary Camels, Ethiopia Influenza D virus has been found to cause respiratory diseases in livestock. We surveyed healthy dromedary camels in Ethiopia and found a high seroprevalence for this virus, in contrast to animals co-existing with the camels. Our observation implies that dromedary camels may play an important role in the circulation of influenza D virus.

negative: Corona Epidemic in Indian context: Predictive Mathematical Modelling The novel Coronavirus pathogen Covid-19 is a cause of concern across the world as the human-to-human infection caused by it is spreading at a fast pace. The virus that first manifested in Wuhan, China has travelled across continents. The increase in number of deaths in Italy, Iran, USA, and other countries has alarmed both the developed and developing countries. Scientists are working hard to develop a vaccine against the virus, but until now no breakthrough has been achieved. India, the second most populated country in the world, is working hard in all dimensions to stop the spread of community infection. Health care facilities are being updated; medical and paramedical staffs are getting trained, and many agencies are raising awareness on the issues related to this virus and its transmission. The administration is leaving no stone unturned to prepare the country to mitigate the adverse effects. However, as the number of infected patients, and those getting cured is changing differently in different states everyday it is difficult to predict the spread of the virus and its fate in Indian context. Different states have adopted measures to stop the community spread. Considering the vast size of the country, the population size and other socio-economic conditions of the states, a single uniform policy may not work to contain the disease. In this paper, we discuss a predictive mathematical model that can give us some idea of the fate of the virus, an indicative data and future projections to understand the further course this pandemic can take. The data can be used by the health care agencies, the Government Organizations and the Planning Commission to make suitable arrangements to fight the pandemic. Though the model is preliminary, it can be used at regional level to manage the health care system in the present scenario. The recommendations can be made, and advisories prepared based on the predictive results that can be implemented at regional levels.

negative: Biomarkers of Infectious Diseases Infection is defined as a pathologic process caused by the invasion of normally sterile tissue or fluid or body cavity by pathogenic or potentially pathogenic microorganisms. Sepsis is defined as the presence of organ dysfunction occurring as the result of a dysregulated host response to an infection.

negative: Defense Agents in Milk: A. Defense Agents in Human Milk

negative: Ebola Viral Disease in West Africa: A Threat to Global Health, Economy and Political Stability The West African sub-continent is currently experiencing its first, and ironically, the largest and longest Ebola viral diseases (EVD) outbreak ever documented in modern medical history. The current outbreak is significant in several ways, including longevity, magnitude of morbidity and mortality, occurrence outside the traditional niches, rapid spread and potential of becoming a global health tragedy. The authors provided explicit insights into the current and historical background, drivers of the epidemic, societal impacts, status of vaccines and drugs development and proffered recommendations to halt and prevent future occurrences. The authors reviewed mainly five databases and a hand search of key relevant literature. We reviewed 51 articles that were relevant up until the 18(th) of August 2014. The authors supplemented the search with reference list of relevant articles and grey literature as well as relevant Internet websites. Article searches were limited to those published either in English or French. There are strong indications that the EVD may have been triggered by increased human activities and encroachment into the forest ecosystem spurred by increasing population and poverty-driven forest-dependent local economy. Containment efforts are being hampered by weak and fragile health systems, including public health surveillance and weak governance, certain socio-anthropological factors, fast travels (improved transport systems) and globalization. The societal impacts of the EBV outbreak are grave, including economic shutdown, weakening of socio-political systems, psychological distress, and unprecedented consumption of scarce health resources. The research and development (R&D) pipeline for product against EBV seems grossly insufficient. The outbreak of Ebola and the seeming difficulty to contain the epidemic is simply a reflection of the weak health system, poor surveillance and emergency preparedness/response, poverty and disconnect between the government and the people in many West African countries. Although interventions by the United Nations and other international development agencies could ultimately halt the epidemic, local communities must be engaged to build trust and create demand for the public health interventions being implemented in the Ebola-ravaged populations. In the intermediate and long term, post-Ebola rehabilitation should focus on strengthening of health systems, improving awareness about zoonosis and health behaviors, alleviating poverty and mitigating the impact of triggering factors. Finally, national governments and international development partners should mobilize huge resources and investments to spur or facilitate R&D of disease control tools for emerging and pernicious infectious diseases (not limited to EVD).

negative: 2019-nCoV epidemic: address mental health care to empower society

negative: 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.

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

negative: Urine Peptidomic and Targeted Plasma Protein Analyses in the Diagnosis and Monitoring of Systemic Juvenile Idiopathic Arthritis PURPOSE: Systemic juvenile idiopathic arthritis is a chronic pediatric disease. The initial clinical presentation can mimic other pediatric inflammatory conditions, which often leads to significant delays in diagnosis and appropriate therapy. SJIA biomarker development is an unmet diagnostic/prognostic need to prevent disease complications. EXPERIMENTAL DESIGN: We profiled the urine peptidome to analyze a set of 102 urine samples, from patients with SJIA, Kawasaki disease (KD), febrile illnesses (FI), and healthy controls. A set of 91 plasma samples, from SJIA flare and quiescent patients, were profiled using a customized antibody array against 43 proteins known to be involved in inflammatory and protein catabolic processes. RESULTS: We identified a 17-urine-peptide biomarker panel that could effectively discriminate SJIA patients at active, quiescent, and remission disease states, and patients with active SJIA from confounding conditions including KD and FI. Targeted sequencing of these peptides revealed that they fall into several tight clusters from seven different proteins, suggesting disease-specific proteolytic activities. The antibody array plasma profiling identified an SJIA plasma flare signature consisting of tissue inhibitor of metalloproteinase-1 (TIMP1), interleukin (IL)-18, regulated upon activation, normal T cell expressed and secreted (RANTES), P-Selectin, MMP9, and L-Selectin. CONCLUSIONS AND CLINICAL RELEVANCE: The urine peptidomic and plasma protein analyses have the potential to improve SJIA care and suggest that SJIA urine peptide biomarkers may be an outcome of inflammation-driven effects on catabolic pathways operating at multiple sites. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12014-010-9058-8) contains supplementary material, which is available to authorized users.

negative: Functional assessment of cell entry and receptor usage for lineage B β-coronaviruses, including 2019-nCoV Over the past 20 years, several coronaviruses have crossed the species barrier into humans, causing outbreaks of severe, and often fatal, respiratory illness. Since SARS- CoV was first identified in animal markets, global viromics projects have discovered thousands of coronavirus sequences in diverse animals and geographic regions. Unfortunately, there are few tools available to functionally test these novel viruses for their ability to infect humans, which has severely hampered efforts to predict the next zoonotic viral outbreak. Here we developed an approach to rapidly screen lineage B betacoronaviruses, such as SARS-CoV and the recent 2019-nCoV, for receptor usage and their ability to infect cell types from different species. We show that host protease processing during viral entry is a significant barrier for several lineage B viruses and that bypassing this barrier allows several lineage B viruses to enter human cells through an unknown receptor. We also demonstrate how different lineage B viruses can recombine to gain entry into human cells and confirm that human ACE2 is the receptor for the recently emerging 2019-nCoV.

negative: Antiviral Response in the Nasopharynx Identifies Patients With Respiratory Virus Infection BACKGROUND: Despite the high burden of respiratory infection and the importance of early and accurate diagnosis, there is no simple diagnostic test to rule in viral infection as a cause of respiratory symptoms. METHODS: We performed RNA sequencing on human nasal epithelial cells following stimulation of the intracellular viral recognition receptor RIG-I. Next, we evaluated whether measuring identified host mRNAs and proteins from patient nasopharyngeal swabs could predict the presence of a respiratory virus in the sample. RESULTS: Our first study showed that a signature of 3 mRNAs, CXCL10, IFIT2, and OASL, predicted respiratory virus detection with an accuracy of 97% (95% confidence interval [CI], 0.9–1.0), and identified proteins correlating with virus detection. In a second study, elevated CXCL11 or CXCL10 protein levels identified samples containing respiratory viruses, including viruses not on the initial test panel. Overall area under the curve (AUC) values were: CXCL11 AUC = 0.901 (95% CI, 0.86–0.94); CXCL10 AUC = 0.85 (95% CI, 0.80–0.91). CONCLUSIONS: Host antiviral mRNAs and single host proteins detectable using nasopharyngeal swabs accurately predict the presence of viral infection. This approach holds promise for developing rapid, cost-effective tests to improve management of patients with respiratory illnesses.

negative: Interleukin-35 on B cell and T cell induction and regulation Interleukin (IL)-35 is a relatively newly discovered member of IL-12 cytokine family that is unique in that it is a dimer formed by two subunits. The review documents the structure, secretion and signal transduction of IL-35, the regulation effect of IL-35 on B cells and T cells as well as the adoptive transfer of IL-35+ regulatory B cells (Breg), therapeutic prospects of recombinant IL-35 (rIL-35) and IL-35 regulation role in various diseases. B-cell regulation expands the regulatory range of IL-35 and alters the view that IL-10 is the chief immune mechanism for Breg cells which secrete IL-35. IL-35 induces Breg cells, which then can induce Treg cells. IL-35 also plays an immunomodulatory role in the human body.

negative: Current Trends in Diagnostics of Viral Infections of Unknown Etiology Viruses are evolving at an alarming rate, spreading and inconspicuously adapting to cutting-edge therapies. Therefore, the search for rapid, informative and reliable diagnostic methods is becoming urgent as ever. Conventional clinical tests (PCR, serology, etc.) are being continually optimized, yet provide very limited data. Could high throughput sequencing (HTS) become the future gold standard in molecular diagnostics of viral infections? Compared to conventional clinical tests, HTS is universal and more precise at profiling pathogens. Nevertheless, it has not yet been widely accepted as a diagnostic tool, owing primarily to its high cost and the complexity of sample preparation and data analysis. Those obstacles must be tackled to integrate HTS into daily clinical practice. For this, three objectives are to be achieved: (1) designing and assessing universal protocols for library preparation, (2) assembling purpose-specific pipelines, and (3) building computational infrastructure to suit the needs and financial abilities of modern healthcare centers. Data harvested with HTS could not only augment diagnostics and help to choose the correct therapy, but also facilitate research in epidemiology, genetics and virology. This information, in turn, could significantly aid clinicians in battling viral infections.

negative: A family cluster of three confirmed cases infected with avian influenza A (H7N9) virus in Zhejiang Province of China BACKGROUND: A total of 453 laboratory-confirmed cases infected with avian influenza A (H7N9) virus (including 175 deaths) have been reported till October 2,2014, of which 30.68% (139/453) of the cases were identified from Zhejiang Province. We describe the largest reported cluster of virologically confirmed H7N9 cases, comprised by a fatal Index case and two mild secondary cases. METHODS: A retrospective investigation was conducted in January of 2014. Three confirmed cases, their close contacts, and relevant environments samples were tested by real-time reverse transcriptase-polymerase chain reaction (RT-PCR), viral culture, and sequencing. Serum samples were tested by haemagglutination inhibition (HI) assay. RESULTS: The Index case, a 49-year-old farmer with type II diabetes, who lived with his daughter (Case 2, aged 24) and wife (Case 3, aged 43) and his son-in-law (H7N9 negative). The Index case and Case 3 worked daily in a live bird market. Onset of illness in Index case occurred in January 13, 2014 and subsequently, he died of multi-organ failure on January 20. Case 2 presented with mild symptoms on January 20 following frequent unprotected bed-side care of the Index case between January 14 to 19, and exposed to live bird market on January 17. Case 3 became unwell on January 23 after providing bedside care to the Index case on January 17 to 18, and following the contact with Case 2 during January 21 to 22 at the funeral of the Index case. The two secondary cases were discharged on February 2 and 5 separately after early treatment with antiviral medication. Four virus strains were isolated and genome analyses showed 99.6 ~100% genetic homology, with two amino mutations (V192I in NS and V280A in NP). 42% (11/26) of environmental samples collected in January were H7N9 positive. Twenty-five close contacts remained well and were negative for H7N9 infection by RT-PCR and HI assay. CONCLUSIONS: In the present study, the Index case was infected from a live bird market while the two secondary cases were infected by the Index case during unprotected exposure. This family cluster is, therefore, compatible with non-sustained person-to-person transmission of avian influenza A/H7N9. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0698-6) contains supplementary material, which is available to authorized users.

negative: A Review of Cardiac Complications in Coronavirus Disease 2019 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has shown an association with acute myocardial injury, cardiomyopathy, and myocarditis. Individuals with myocardial involvement in association with the coronavirus disease 2019 (COVID-19) may be at increased risk of developing severe illness. Cardiomyopathies are a heterogeneous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction that usually exhibit inappropriate ventricular hypertrophy or dilation and are due to a variety of causes that frequently are genetic. It has been primarily divided into three subsets: genetic, mixed, and acquired cardiomyopathy. We anticipate that, because of the high inflammatory response, other cardiovascular complications may also occur in COVID-19 patients with severe symptoms. This review explores new information as it pertains to COVID-19 and cardiac complications.

negative: Diagnosis and Assessment of Microbial Infections with Host and Microbial microRNA Profiles Biomarkers are continuously being sought in the field of diagnostic microbiology for the laboratory diagnosis and assessment of microbial infections. A set of clinical and laboratory criteria necessary for an ideal diagnostic marker of infection have previously been proposed by Ng and his colleagues [1]. According these criteria, an ideal biomarker should possess at a minimum the following characteristics: (a) biochemically, a biomarker should be stable and remain significantly deregulated in the body fluid compartment for at least 12–24 h even after commencement of appropriate treatment that may allow an adequate time window for specimen collection or storage without significant decomposition of the active compound until laboratory processing; (b) its concentration should be determined quantitatively and the method of measurement should be automatic, rapid, easy, and inexpensive; (c) the collection of a specimen should be minimally invasive and require a small volume (e.g., <0.5 mL blood). Numerous biomarkers have been found and tested in clinical practice. Currently, microRNA (miRNA) molecules are without a doubt the biomarkers with the greatest potential capacities in the diagnostic microbiology field.

negative: Obesity as a predictor for a poor prognosis of COVID-19: A systematic review BACKGROUND AND AIMS: COVID-19 is an emerging pandemic due to droplet infection of 2019-novel coronavirus (2019-nCoV). Due to its rapid transmission and high case-fatality rate, recognition of its risk and prognostic factor is important. Obesity has been associated with impaired immune system, increasing the susceptibility for 2019-nCoV infection. We aimed to study the impact of obesity to the prognosis and disease severity of COVID-19. METHODS: A systematic search and handsearching was conducted in four databases: Cochrane, MEDLINE, EMBASE, and PubMed. The identified articles were screened using the chosen eligibility criteria. We obtained three retrospective cohort studies (Wu J et al., Lighter J et al., and Simonnet A et al.) to be critically appraised using Newcastle Ottawa Scale. RESULTS: The findings of all included studies were consistent in stating the contribution of obesity as a risk factor to increase the requirement for advanced medical care. Study with the highest quality, Simonnet A et al., reported an increase need of invasive mechanical ventilation in COVID-19 patients with body mass index higher than 35 kg/m(2), OR: 7.36 (1.63–33.14; p = 0.021). This is associated with a higher mortality rate in obese population infected with COVID-19. CONCLUSION: Obesity is an independent risk and prognostic factor for the disease severity and the requirement of advanced medical care in COVID-19. This systematic review highlights a particularly vulnerable group – obese, and emphasises on the importance of treatment aggression and disease prevention in this population group.

negative: Background K(2P) Channels KCNK3/9/15 Limit the Budding of Cell Membrane-derived Vesicles The main function of background two-pore potassium (K(2P)) channels KCNK3/9/15 is to stabilize the cell membrane potential. We previously observed that membrane potential depolarization enhances the release of HIV-1 viruses. Because membrane polarization affects the biomembrane directly, here we examined the effects of KCNK3/9/15 on the budding of nonviral vesicles. We found that depolarization by knocking down endogenous KCNK3/9/15 promoted secretion of cell-derived vesicles. We further used Vpu (an antagonist of KCNK3) as a model for the in vivo study of depolarization-stimulated secretion. Vpu is a HIV-1-encoded, ion channel-like protein (viroporin) capable of enhancing virus release and depolarizing the cell membrane potential. We found that Vpu could also promote nonviral vesicle release, perhaps through a similar mechanism that Vpu utilizes to promote viral particle release. Notably, T cells expressing Vpu alone became pathologically low in intracellular K(+) and insensitive to extracellular K(+) or membrane potential stimulation. In contrast, heterologous expression of KCNK3 in T cells stabilized the cell potentials by maintaining intracellular K(+). We thus concluded that KCNK3/9/15 expression limits membrane depolarization and depolarization-induced secretion at least in part by maintaining intracellular K(+).

negative: 2019 novel coronavirus of pneumonia in Wuhan, China: emerging attack and management strategies An ongoing outbreak of 2019-nCoV pneumonia was first identified in Wuhan, Hubei province, China at the end of 2019. With the spread of the new coronavirus accelerating, person-to-person transmission in family homes or hospitals, and intercity spread of 2019-nCoV occurred. At least 40,261 cases confirmed, 23,589 cases suspected, 909 cases death and 3444 cases cured in China and worldwide 24 countries confirmed 383 cases being diagnosed, 1 case death in February 10th, 2020. At present, the mortality of 2019-nCoV in China is 2.3%, compared with 9.6% of SARS and 34.4% of MERS reported by WHO. It seems the new virus is not as fatal as many people thought. Chinese authorities improved surveillance network, made the laboratory be able to recognize the outbreak within a few weeks and announced the virus genome that provide efficient epidemiological control. More comprehensive information is required to understand 2019-nCoV feature, the epidemiology of origin and spreading, and the clinical phenomina. According to the current status, blocking transmission, isolation, protection, and alternative medication are the urgent management strategies against 2019-nCoV.

negative: A Database Solution for Laboratory Information Management In our laboratory, we have developed a database system, which we believe is of immediate interest to the general scientific community. The database represents a computer‐based replacement for the laboratory notebooks used in the majority of research laboratories worldwide. In addition, the database provides an effective tool for organizing and managing laboratory information at all levels, spanning from managing and revising standard operating procedures and producing documentation of research activities to keeping track of data and conclusions. Using the commercially available database toolkit software filemaker pro, we have developed a relational database solution for management of laboratory information. The system consists of a hierarchy of five interrelated databases, each pertaining to a separate type of information, namely, overall project information, information relating to individual experiment setups, documentation of daily research activity, generated data and descriptions of standard operating procedures. Like other databases, each individual database consists of a number of records, each comprised of a set of fields in which information is entered. In each record, a certain field is reserved to specify the relation of the record to a record in another database at a higher level. Thus, the database is essentially five databases linked by a hierarchy of one‐to‐many relations, organizing information in a folder‐like structure. Importantly, the database system allows multiple users to access and edit records simultaneously, and the data entered in one database immediately becomes accessible through the other databases. The limitations of laboratory notebooks are apparent when looking for information, which is dispersed throughout one or more notebooks, or possibly on loose sheets of paper or printouts ‘somewhere’. The often complicated process of gathering laboratory data or results when writing grant applications or research papers is made considerably easier with the database system. Thus, the database solution presented should be broadly attractive to researchers, irrespective of their scientific discipline.

negative: Advances in MALDI Mass Spectrometry in Clinical Diagnostic Applications The concept of matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) was first reported in 1985. Since then, MALDI MS technologies have been evolving, and successfully used in genome, proteome, metabolome, and clinical diagnostic research. These technologies are high-throughput and sensitive. Emerging evidence has shown that they are not only useful in qualitative and quantitative analyses of proteins, but also of other types of biomolecules, such as DNA, glycans, and metabolites. Recently, parallel fragmentation monitoring (PFM), which is a method comparable to selected reaction monitoring, has been reported. This highlights the potentials of MALDI-TOF/TOF tandem MS in quantification of metabolites. Here we critically review the applications of the major MALDI MS technologies, including MALDI-TOF MS, MALDI-TOF/TOF MS, SALDI-TOF MS, MALDI-QqQ MS, and SELDI-TOF MS, to the discovery and quantification of disease biomarkers in biological specimens, especially those in plasma/serum specimens. Using SELDI-TOF MS as an example, the presence of systemic bias in biomarker discovery studies employing MALDI-TOF MS and its possible solutions are also discussed in this chapter. The concepts of MALDI, SALDI, SELDI, and PFM are complementary to each other. Theoretically, all these technologies can be combined, leading to the next generation of the MALDI MS technologies. Real applications of MALDI MS technologies in clinical diagnostics should be forthcoming.

negative: Outcome reporting from protocols of clinical trials of Coronavirus Disease 2019 (COVID-19): a review Objectives: To examine heterogeneity of outcomes in protocols of clinical trials of Coronavirus Disease 2019 (COVID-19) and to identify outcomes for prioritization in developing a core outcome set (COS) in this field. Design: This study is a review. Data sources: Databases of ICMJE-accepted clinical trial registry platform were searched on February 14, 2020. Eligibility Criteria: Randomized controlled trials (RCTs) and non-RCTs of COVID-19 were considered.Conditions of patients include common type, severe type or critical type. Interventions include traditional Chinese medicine (TCM) and Western medicine. We excluded trials that for discharged patients, psychological intervention and complications of COVID-19. Data extraction and synthesis: The general information and outcomes, outcome measurement instruments and measurement times were extracted. The results were analysed by descriptive analysis. Results: 19 registry platforms were searched. A total of 97 protocols were included from 160 protocols. For protocols of TCM clinical trials, 76 outcomes from 16 outcome domains were reported, and almost half (34/76, 44.74%) of outcomes were reported only once; the most frequently reported outcome was time of SARS-CoV-2 RNA turns to negative. 27 (27/76, 35.53%) outcomes were provided one or more outcome measurement instruments. 10 outcomes were provided one or more measurement time frame. For protocols of western medicine clinical trials, 126 outcomes from 17 outcome domains were reported; almost half (62/126, 49.21%) of outcomes were reported only once; the most frequently reported outcome was proportion of patients with negative SARS-CoV-2. 27 outcomes were provided one or more outcome measurement instruments. 40 (40/126, 31.75%) outcomes were provided one or more measurement time frame. Conclusion: Outcome reporting in protocols of clinical trials of COVID-19 is inconsistent. Thus, developing a core outcome set is necessary. Keywords: Outcomes; clinical trials, COVID-19; review.

negative: In silico approach to screen compounds active against parasitic nematodes of major socio-economic importance BACKGROUND: Infections due to parasitic nematodes are common causes of morbidity and fatality around the world especially in developing nations. At present however, there are only three major classes of drugs for treating human nematode infections. Additionally the scientific knowledge on the mechanism of action and the reason for the resistance to these drugs is poorly understood. Commercial incentives to design drugs that are endemic to developing countries are limited therefore, virtual screening in academic settings can play a vital role is discovering novel drugs useful against neglected diseases. In this study we propose to build robust machine learning model to classify and screen compounds active against parasitic nematodes. RESULTS: A set of compounds active against parasitic nematodes were collated from various literature sources including PubChem while the inactive set was derived from DrugBank database. The support vector machine (SVM) algorithm was used for model development, and stratified ten-fold cross validation was used to evaluate the performance of each classifier. The best results were obtained using the radial basis function kernel. The SVM method achieved an accuracy of 81.79% on an independent test set. Using the model developed above, we were able to indentify novel compounds with potential anthelmintic activity. CONCLUSION: In this study, we successfully present the SVM approach for predicting compounds active against parasitic nematodes which suggests the effectiveness of computational approaches for antiparasitic drug discovery. Although, the accuracy obtained is lower than the previously reported in a similar study but we believe that our model is more robust because we intentionally employed stringent criteria to select inactive dataset thus making it difficult for the model to classify compounds. The method presents an alternative approach to the existing traditional methods and may be useful for predicting hitherto novel anthelmintic compounds.

negative: Abstract of 29th Regional Congress of the ISBT

negative: 2019-Novel Coronavirus-Related Acute Cardiac Injury Cannot Be Ignored PURPOSE OF THE REVIEW: Coronavirus disease 2019 (COVID-19), a new infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has reached a pandemic status. Although SARSCoV-2 causes primarily respiratory problems, concurrent cardiac injury cannot be ignored since it may be an independent predictor for adverse outcomes. To resolve these issues, we aim to summarize the prevalence and its underlying mechanisms of acute cardiac injury in the setting of SARS-CoV-2 infection. RECENT FINDINGS: The main clinical manifestation of SARS-CoV-2 infection is pneumonia, cardiovascular complications have also been identified in the earliest reported cases from Wuhan, the epicenter of the outbreak. Given the SARS-CoV-2 likely uses the angiotensin-converting enzyme-2 (ACE2) receptors as its host receptor, ACE2-related signaling pathways may play a key role in mediating myocardial injury. SUMMARY: SARS-CoV-2 infection related acute cardiac injury cannot be ignored, and its underlying mechanisms remain speculated. We would suggest that health professionals investigate cardiac function as part of the routine care.

negative: Pathophysiological Characteristics and Therapeutic Approaches for Pulmonary Injury and Cardiovascular Complications of Coronavirus Disease 2019 Abstract The pandemic of coronavirus disease 2019 (COVID-19) has emerged as a major health crisis, with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) having infected over a million people around the world within a few months of its identification as a human pathogen. Initially, SARS-CoV-2 infects cells in the respiratory system and causes inflammation and cell death. Subsequently, the virus spreads out and damages other vital organs and tissues, triggering a complicated spectrum of pathophysiological changes and symptoms, including cardiovascular complications. Acting as the receptor for SARS-CoV entering mammalian cells, angiotensin converting enzyme-2 (ACE2) plays a pivotal role in the regulation of cardiovascular cell function. Diverse clinical manifestations and laboratory abnormalities occur in patients with cardiovascular injury in COVID-19, characterizing the development of this complication, as well as providing clues to diagnosis and treatment. This review provides a summary of the rapidly appearing laboratory and clinical evidence for the pathophysiology and therapeutic approaches to COVID-19 pulmonary and cardiovascular complications.

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

negative: Broad-spectrum coronavirus antiviral drug discovery Introduction: The highly pathogenic coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are lethal zoonotic viruses that have emerged into human populations these past 15 years. These coronaviruses are associated with novel respiratory syndromes that spread from person-to-person via close contact, resulting in high morbidity and mortality caused by the progression to Acute Respiratory Distress Syndrome (ARDS). Areas covered: The risks of re-emergence of SARS-CoV from bat reservoir hosts, the persistence of MERS-CoV circulation, and the potential for future emergence of novel coronaviruses indicate antiviral drug discovery will require activity against multiple coronaviruses. In this review, approaches that antagonize viral nonstructural proteins, neutralize structural proteins, or modulate essential host elements of viral infection with varying levels of efficacy in models of highly pathogenic coronavirus disease are discussed. Expert opinion: Treatment of SARS and MERS in outbreak settings has focused on therapeutics with general antiviral activity and good safety profiles rather than efficacy data provided by cellular, rodent, or nonhuman primate models of highly pathogenic coronavirus infection. Based on lessons learned from SARS and MERS outbreaks, lack of drugs capable of pan-coronavirus antiviral activity increases the vulnerability of public health systems to a highly pathogenic coronavirus pandemic.

negative: Longitudinal profile of immunoglobulin G (IgG), IgM, and IgA antibodies against the severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein in patients with pneumonia due to the SARS coronavirus. By using a recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) nucleocapsid protein-based enzyme-linked immunosorbent assay (ELISA) and serum specimens serially collected (from day 0 to day 240 after symptom onset) from patients with pneumonia due to SARS-CoV, we analyzed the longitudinal profiles of immunoglobulin G (IgG), IgM, and IgA antibodies against the SARS-CoV nucleocapsid protein in patients with pneumonia due to SARS-CoV. For IgG, the median optical density at 450 nm (OD450) turned positive at day 17 and a biphasic response was observed. At day 240, all patients were still positive for anti-nucleocapsid protein IgG antibody. For IgM, the median OD450 turned positive at day 20.5, peaked at about day 80, and fell to below the baseline level at about day 180. At day 240, 36% of the patients were still positive for anti-nucleocapsid protein IgM antibody. For IgA, the median OD450 turned positive at day 17, peaked at about day 50, and fell to below the baseline level at about day 180. At day 240, 36% of the patients were still positive for anti-nucleocapsid protein IgA antibody. The time of seroconversion detected by the recombinant SARS-CoV nucleocapsid protein-based ELISA and that detected by indirect immunofluorescence assay were similar. The median times of seroconversion for IgG, IgM, and IgA detected by the indirect immunofluorescence assay were 17 days (17 days by ELISA), 16.5 days (20.5 days by ELISA), and 17.5 days (17 days by ELISA), respectively, after disease onset. One, four, and one of the six patients who died did not produce any IgG, IgM, and IgA antibodies against the nucleocapsid protein of SARS-CoV, respectively, although these antibodies were detected in all six patients by the indirect immunofluorescence assay. Further studies should be performed to see whether SARS-CoV nucleocapsid protein antibody positivity has any prognostic significance.

negative: Biomarker discovery in infectious diseases using SELDI. Surface enhanced laser desorption ionization-time of flight is a mass spectrometric-based method that requires a minimal amount of sample for analysis and can be used for high-throughput screening. It has been used to discover serum or tissue protein signatures and biomarkers for infectious diseases in the fields of virology (hepatitis B and C viruses, severe acute respiratory syndrome, HIV-1, human T-cell leukemia virus-1 and BK virus), parasitology (trypanosomiasis) and bacteriology (intra-amniotic inflammation, tuberculosis and bacterial endocarditis). The protein signatures, or biomarkers, can be used to diagnose infection, predict disease states and to inform on disease processes. Careful attention to experimental design, sample handling and storage, and the use of appropriate internal controls is crucial to success.

negative: The lockdown of Hubei Province causing different transmission dynamics of the novel coronavirus (2019-nCoV) in Wuhan and Beijing Background: After the outbreak of novel coronavirus (2019-nCoV) starting in late 2019, a number of researchers have reported the predicted the virus transmission dynamics. However, under the strict control policy the novel coronavirus does not spread naturally outside Hubei Province, and none of the prediction closes to the real situation. Methods and findings: We used the traditional SEIR model, fully estimated the effect of control measures, to predict the virus transmission in Wuhan, the capital city of Hubei Province, and Beijing. We forecast that the outbreak of 2019-nCoV would reach its peak around March 6±10 in Wuhan and March 20±16 in Beijing, respectively. The infectious population in Beijing would be much less (only 0.3%) than those in Wuhan at the peak of this transmission wave. The number of confirmed cases in cities inside Hubei Province grow exponentially, whereas those in cities outside the province increase linearly. Conclusions: The unprecedented province lockdown substantially suspends the national and global outbreak of 2019-nCoV.

negative: Genomic variance of the 2019-nCoV coronavirus There is rising global concern for the recently emerged novel Coronavirus (2019-nCov). Full genomic sequences have been released by the worldwide scientific community in the last few weeks in order to understand the evolutionary origin and molecular characteristics of this virus. Taking advantage of all the genomic information currently available, we constructed a phylogenetic tree including also representatives of other coronaviridae, such as Bat coronavirus (BCoV) and SARS. We confirm high sequence similarity (>99%) between all sequenced 2019-nCoVs genomes available, with the closest BCoV sequence sharing 96.2% sequence identity, confirming the notion of a zoonotic origin of 2019-nCoV. Despite the low heterogeneity of the 2019-nCoV genomes, we could identify at least two hyper-variable genomic hotspots, one of which is responsible for a Serine/Leucine variation in the viral ORF8-encoded protein. Finally, we perform a full proteomic comparison with other coronaviridae, identifying key aminoacidic differences to be considered for antiviral strategies deriving from previous anti-coronavirus approaches.

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: 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: Recognizing Right Ventricular Dysfunction in COVID-19 Related Respiratory Illness COVID-19, coronavirus, Right ventricular failure, Heart failure, Acute cor pulmonale, Shock, ARDS

negative: Noninvasive ventilation in acute respiratory failure due to H1N1 influenza: A word of caution

negative: Comparison of immunoglobulin G responses to the spike and nucleocapsid proteins of severe acute respiratory syndrome (SARS) coronavirus in patients with SARS. Both the nucleocapsid (N) and the spike (S) proteins of severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) are able to induce strong humoral responses in humans following an infection. To compare the immunoglobulin G (IgG) responses to the S and N proteins of SARS-CoV in SARS patients during the manifestation/convalescent period with those during the postinfection period, serum samples were collected from hospitalized SARS patients within 6 weeks after the onset of illness (set 1; 57 sequential samples from 19 patients) or 2 to 3 months after their recovery (set 2; 33 postinfection samples from 33 subjects). Serum samples from 100 healthy blood donors (set 3), collected in 2002, were also included. The specific IgG response to whole virus, the fragment from positions 450 to 650 of the S protein (S450-650), and the full-length N protein of SARS-CoV were measured by enzyme-linked immunosorbent assays (ELISAs). Western blot assays were carried out to confirm the ELISA results. Fifty-one of the serum samples in set 1 (89%) bound to the N protein, a proportion similar to that which recognized whole virus (79%) and the S-protein fragment (77%). All 33 serum samples from set 2 were strongly positive for N-protein-specific IgG, while 27 (82%) were positive for anti-S450-650 IgG. Two of the serum samples from set 3 were strongly positive for anti-N-protein IgG but not anti-S450-650 IgG. Similar levels of IgG responses to the S and N proteins were observed in SARS patients during the manifestation and convalescent stages. In the postinfection period, however, a number of patients had much lower serum IgG levels against S450-650 than against the N protein.

negative: Clinical characteristics and factors predicting respiratory failure in adenovirus pneumonia BACKGROUND AND OBJECTIVE: Limited data exist regarding factors predicting respiratory failure (RF) in non‐immunocompromised patients with adenovirus (AdV) pneumonia. METHODS: We described characteristics of AdV pneumonia (n = 91) versus non‐AdV pneumonia (n = 55) and compared clinico‐laboratory and radiological characteristics in patient groups categorized by RF. RESULTS: All 91 AdV pneumonia patients presented with acute respiratory symptoms and radiological infiltrations and had significantly lower levels of white blood cell counts and platelet counts compared with non‐AdV pneumonia. Of them, 67 patients had mild pneumonia without RF (non‐RF), 14 patients had no RF at admission but progressed to RF during hospitalization (progressed to RF) and 10 patients had RF at admission (initial RF). Initial monocyte percentage and absolute monocyte counts in RF patient groups (progressed to RF and initial RF) were significantly lower than those of non‐RF patients (both P < 0.001), and the differences among progressed to RF and initial RF patients were not significant. Chest computed tomography findings such as dominant pattern or distribution, clinical symptoms, and bacterial or viral co‐infections other than AdV were not discriminable between patients who had RF and those who did not. On univariate analysis, initial monocytopenia, multilobar infiltrations and pleural effusion were associated with RF. However, on multivariable analysis, only initial monocytopenia remained significant (P = 0.004) for predicting RF. CONCLUSION: Our data suggest that initial monocytopenia may help to predict RF during the course of AdV pneumonia in non‐immunocompromised patients.

negative: Identification of Coronavirus Isolated from a Patient in Korea with COVID-19 OBJECTIVES: Following reports of patients with unexplained pneumonia at the end of December 2019 in Wuhan, China, the causative agent was identified as coronavirus (SARS-CoV-2), and the 2019 novel coronavirus disease was named COVID-19 by the World Health Organization. Putative patients with COVID-19 have been identified in South Korea, and attempts have been made to isolate the pathogen from these patients. METHODS: Upper and lower respiratory tract secretion samples from putative patients with COVID-19 were inoculated onto cells to isolate the virus. Full genome sequencing and electron microscopy were used to identify the virus. RESULTS: The virus replicated in Vero cells and cytopathic effects were observed. Full genome sequencing showed that the virus genome exhibited sequence homology of more than 99.9% with SARS-CoV-2 which was isolated from patients from other countries, for instance China. Sequence homology of SARS-CoV-2 with SARS-CoV, and MERS-CoV was 77.5% and 50%, respectively. Coronavirus-specific morphology was observed by electron microscopy in virus-infected Vero cells. CONCLUSION: SARS-CoV-2 was isolated from putative patients with unexplained pneumonia and intermittent coughing and fever. The isolated virus was named BetaCoV/Korea/KCDC03/2020.

negative: Strategies for the prevention and management of coronavirus disease 2019 Early protection, early identification, early diagnosis, and early isolation are crucial to combat with Covid-19 outbreaks

negative: A host-protein signature is superior to other biomarkers for differentiating between bacterial and viral disease in patients with respiratory infection and fever without source: a prospective observational study Bacterial and viral infections often present with similar symptoms. Etiologic misdiagnosis can alter the trajectory of patient care, including antibiotic overuse. A host-protein signature comprising tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein-10 (IP-10), and C-reactive protein (CRP) was validated recently for differentiating bacterial from viral disease. However, a focused head-to-head comparison of its diagnostic performance against other biomarker candidates for this indication was lacking in patients with respiratory infection and fever without source. We compared the signature to other biomarkers and prediction rules using specimens collected prospectively at two secondary medical centers from children and adults. Inclusion criteria included fever > 37.5 °C, symptom duration ≤ 12 days, and presentation with respiratory infection or fever without source. Comparator method was based on expert panel adjudication. Signature and biomarker cutoffs and prediction rules were predefined. Of 493 potentially eligible patients, 314 were assigned unanimous expert panel diagnosis and also had sufficient specimen volume. The resulting cohort comprised 175 (56%) viral and 139 (44%) bacterial infections. Signature sensitivity 93.5% (95% CI 89.1–97.9%), specificity 94.3% (95% CI 90.7–98.0%), or both were significantly higher (all p values < 0.01) than for CRP, procalcitonin, interleukin-6, human neutrophil lipocalin, white blood cell count, absolute neutrophil count, and prediction rules. Signature identified as viral 50/57 viral patients prescribed antibiotics, suggesting potential to reduce antibiotic overuse by 88%. The host-protein signature demonstrated superior diagnostic performance in differentiating viral from bacterial respiratory infections and fever without source. Future utility studies are warranted to validate potential to reduce antibiotic overuse. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10096-018-3261-3) contains supplementary material, which is available to authorized users.

negative: A precision medicine approach to managing 2019 novel coronavirus pneumonia In December 2019, several patients with pneumonia of an unknown cause were detected in Wuhan, China. On 7 January 2020, the causal organism was identified as a new coronavirus, later named as the 2019 novel coronavirus (2019-nCoV). Genome sequencing found the genetic sequence of 2019-nCoV homologous to that of severe acute respiratory syndrome-associated coronavirus. As of 29 January 2020, the virus had been diagnosed in more than 7000 patients in China and 77 patients in other countries. It is reported that both symptomatic and asymptomatic patients with 2019-nCoV can play a role in disease transmission via airborne and contact. This finding has caused a great concern about the prevention of illness spread. The clinical features of the infection are not specific and are often indistinguishable from those of other respiratory infections, making it difficult to diagnose. Given that the virus has a strong ability to spread between individuals, it is of top priority to identify potential or suspected patients as soon as possible—or the virus may cause a serious pandemic. Therefore, a precision medicine approach to managing this disease is urgently needed for detecting and controlling the spread of the virus. In this article, we present such an approach to managing 2019-nCoV-related pneumonia based on the unique traits of the virus recently revealed and on our experience with coronaviruses at West China Hospital in Chengdu, China.

negative: Toward a consensus view in the management of acute facial injuries during the Covid-19 pandemic In unprecedented times OMFS surgeons are faced with dilemmas over treatment priority, safety of staff, safety of patients and the most appropriate use of available resource. Efforts should be made to provide best evidence based care, this will mean revisiting old techniques, and risk stratifying patients on a case by case basis. Recent experience from colleagues internationally has shown that even the wealthiest health care infrastructure is at best fragile. We hope this paper will add to the debate and hopefully provide a framework to decision making in OMFS trauma care during this difficult time.

negative: Signals of T(h)2 immune response from COVID-19 patients requiring intensive care

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: Biomarkers of sepsis: time for a reappraisal INTRODUCTION: Sepsis biomarkers can have important diagnostic, therapeutic, and prognostic functions. In a previous review, we identified 3370 references reporting on 178 different biomarkers related to sepsis. In the present review, we evaluate the progress in the research of sepsis biomarkers. METHODS: Using the same methodology as in our previous review, we searched the PubMed database from 2009 until September 2019 using the terms “Biomarker” AND “Sepsis.” There were no restrictions by age or language, and all studies, clinical and experimental, were included. RESULTS: We retrieved a total of 5367 new references since our previous review. We identified 258 biomarkers, 80 of which were new compared to our previous list. The majority of biomarkers have been evaluated in fewer than 5 studies, with 81 (31%) being assessed in just a single study. Apart from studies of C-reactive protein (CRP) or procalcitonin (PCT), only 26 biomarkers have been assessed in clinical studies with more than 300 participants. Forty biomarkers have been compared to PCT and/or CRP for their diagnostic value; 9 were shown to have a better diagnostic value for sepsis than either or both of these biomarkers. Forty-four biomarkers have been evaluated for a role in answering a specific clinical question rather than for their general diagnostic or prognostic properties in sepsis. CONCLUSIONS: The number of biomarkers being identified is still increasing although at a slower rate than in the past. Most of the biomarkers have not been well-studied; in particular, the clinical role of these biomarkers needs to be better evaluated.

negative: Searching immunodominant epitopes prior to epidemic: HLA class II-restricted SARS-CoV spike protein epitopes in unexposed individuals Identification of dominant T cell epitopes within newly emerging and re-emerging infectious organisms is valuable in understanding pathogenic immune responses and potential vaccine designs. However, difficulties in obtaining samples from patients or convalescent subjects have hampered research in this direction. We demonstrated a strategy, tetramer-guided epitope mapping, that specific CD4+ T cell epitopes can be identified by using PBMC from subjects that have not been exposed to the infectious organism. Sixteen HLA-DR0401- and 14 HLA-DR0701-restricted epitopes within spike protein of severe acute respiratory syndrome-coronavirus (SARS-CoV) were identified. Among these, spike protein residues 159–171, 166–178, 449–461 and 1083–1097 were identified to contain naturally processed immunodominant epitopes based on strong in vitro T cell responses of PBMC (as assayed by tetramer staining) to intact spike protein stimulation. These immunodominant epitopes were confirmed in vivo in HLA-DR0401 transgenic mice by immunizing with spike protein. Furthermore, the epitope-specific T cells from naive donors secreted IFN-γ and IL-13 upon re-stimulation with corresponding tetramers. Our study demonstrates a strategy to determine potential immunodominant epitopes for emerging infectious pathogens prior to their epidemic circulation.

negative: The Serum Profile of Hypercytokinemia Factors Identified in H7N9-Infected Patients can Predict Fatal Outcomes The novel avian origin influenza A (H7N9) virus has caused severe diseases in humans in eastern China since the spring of 2013. Fatal outcomes of H7N9 infections are often attributed to the severe pneumonia and acute respiratory distress syndrome (ARDS). There is urgent need to discover biomarkers predicting the progression of disease and fatal outcome of potentially lethal flu infections, based on sound statistical analysis. We discovered that 34 of the 48 cytokines and chemokines examined in this study were significantly elevated in the plasma samples from patients infected with H7N9. We report for the first time that the levels of MIF, SCF, MCP-1, HGF, and SCGF-β are highly positively linked to disease severity and the profile of mediators MIF, SCF, MCP-1, HGF, SCGF-β, IP-10, IL-18, and IFN-γ is an independent outcome predictor.

negative: Ultra-high-throughput clinical proteomics reveals classifiers of COVID-19 infection Summary The COVID-19 pandemic is an unprecedented global challenge and point-of-care diagnostic classifiers are urgently required. Here, we present a platform for ultra-high throughput serum and plasma proteomics that builds on ISO13485 standardisation and high-flow liquid chromatography to facilitate implementation in clinical laboratories. Our low-cost workflow quantifies 180 proteomes per day per mass spectrometer, enables high precision quantification, and reduces batch effects for large-scale and longitudinal studies. We use our platform on samples collected from a cohort of early hospitalized cases of the SARS-CoV-2 pandemic and identify 27 potential biomarkers that are differentially expressed depending on the WHO severity grade of COVID-19. They include complement factors, the coagulation system, inflammation modulators, and pro-inflammatory upstream and downstream of interleukin 6. All protocols and software for implementing our approach are freely available. In total, our platform supports the development of routine proteomic assays to aid clinical decision making and generate hypotheses about potential COVID-19 therapeutic targets.

negative: The Association Between Serum Uric Acid Level and Prognosis in Critically Ill Patients, Uric Acid as a Prognosis Predictor. BACKGROUND Uric acid is synthesized from xanthine via xanthine oxidase as an end-product of purine metabolism. Uric acid is a major non-enzymatic antioxidant in the blood, and it exerts a protective action on vitamin C. There are a limited number of ICU studies related to uric acid, which is a valuable prognostic biomarker. This study aimed to evaluate the utility of uric acid as a biomarker in predicting the outcomes of critically ill patients. METHODS This prospective, multi-centered cohort study included 128 patients from two different intensive care units who met the study inclusion criteria between May 2017 and October 2017. Study inclusion criteria were first admission to the ICU, age > 18 years, and ICU stay > 24 hours. In each patient, baseline serum uric acid levels were measured after acute interventions, prior to the initiation of the treatment process. RESULTS When comparing the last uric acid levels of patients, the median last uric acid levels in the non-survival and survival groups were significantly different (p = 0.001). A last uric acid level > 4.5 mg/dL was associated with a 2.638 times higher risk (relative risk) for mortality. According to ROC analysis, a cutoff value of 1.5 for the ratio between the last two uric acid levels had a sensitivity of 0.21 and a specificity of 0.96 for predicting mortality. A 1.5-fold increase in the uric acid level yielded a positive predictive value of 92.6% and a negative predictive value of 65.2% for predicting mortality. The median uric level in the patient subset with ARDS, was significantly higher than those without ARDS (p = 0.001). CONCLUSIONS Results of this study indicate that a time-dependent increase in uric acid levels can be used as an important biomarker for predicting mortality in critically ill patients; further, uric acid levels should possibly be included in the current mortality risk scoring systems. In addition, elevation of uric acid, a simple, inexpensive, and readily available biomarker, may provide guidance in the diagnostic stage and in predicting clinical outcomes of patients with sepsis or ARDS.

negative: Rapidly decreased HBV RNA predicts responses of pegylated interferons in HBeAg-positive patients: a longitudinal cohort study BACKGROUND: As an important anti-HBV drug, pegylated interferon α (PegIFNα) offers promising clinical efficacy, but biomarkers that accurately forecast treatment responses are yet to be elucidated. Here, we evaluated whether HBV RNA could act as an early monitor of pegylated interferon responses. METHODS: We analyzed a phase 3, multicenter, randomized cohort of 727 HBeAg-positive non-cirrhotic patients receiving a 48-week treatment of PegIFNα-2a or PegIFNα-2b and a 24-week treatment-free follow-up. Serum levels of HBV RNA, HBV DNA, HBeAg, and HBsAg were measured at weeks 0, 12, 24, 48, and 72. RESULTS: HBeAg seroconversion and HBsAg loss at week 72 were observed in 217 (29.8%) and 21 (2.9%) patients, respectively. During the 48-week treatment, HBV RNA decreased more rapidly than HBV DNA and HBsAg, but HBV RNA and HBeAg shared similar dynamics with positive correlations. Multivariate regression analyses consistently revealed the significance of HBV RNA at weeks 0, 12, 24, and 48 to monitor HBeAg seroconversion but not HBsAg loss. Although baseline HBV RNA only showed a modest AUC performance, HBV RNA with a significant increase of AUC at week 12 outperformed other HBV biomarkers to forecast HBeAg seroconversion (p value < 0.05). HBV RNA ≤ 1000 copies/mL was an optimized cutoff at week 12 that offered better prediction than other HBV biomarkers. This optimized cutoff plus patient age, HBV genotype B, and HBeAg offered a strong estimation of HBeAg seroconversion (accuracy 95.2%, true negative rate 99.8%). CONCLUSION: HBV RNA at week 12 is an effective monitor of HBeAg seroconversion in HBeAg-positive patients treated with pegylated interferons. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12072-020-10015-3) contains supplementary material, which is available to authorized users.

negative: Interplay of host regulatory network on SARS-CoV-2 binding and replication machinery We dissect the mechanism of SARS-CoV-2 in human lung host from the initial phase of receptor binding to viral replication machinery. We constructed two independent lung protein interactome to reveal the signaling process on receptor activation and host protein hijacking machinery in the pathogenesis of virus. Further, we test the functional role of the hubs derived from both interactome. Most hubs proteins were differentially regulated on SARS-CoV-2 infection. Also, the proteins of viral replication hubs were related with cardiovascular disease, diabetes and hypertension confirming the vulnerability and severity of infection in the risk individual. Additionally, the hub proteins were closely linked with other viral infection, including MERS and HCoVs which suggest similar infection pattern in SARS-CoV-2. We identified five interconnecting cascades between hubs of both networks that show the preparation of optimal environment in the host for viral replication process upon receptor attachment. Interestingly, we propose that seven potential miRNAs, targeting the intermediate phase that connects receptor and viral replication process a better choice as a drug for SARS-CoV-2.

negative: PROGNOSTIC FACTORS FOR CLINICAL COURSE OF PATIENTS WITH COVID-19: PROTOCOL FOR A RAPID LIVING SYSTEMATIC REVIEW CONTEXT AND OBJECTIVE: Determining prognostic factors in a context of health crises such as the COVID-19 scenario may provide the best possible care for patients and optimize the management and the resource utilization of the health system. Thus, we aim to systematically review the prognostic factors for different outcomes of patients with COVID-19. DESIGN AND SETTING: Protocol for a rapid living systematic review methodology following the recommendations proposed by the Cochrane Handbook. METHODS: We will include prospective and retrospective longitudinal cohorts. In view of the limited amount of information, we will also include case-control studies. We will search PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), LILACS, Scopus and SciELO to identify published, ongoing, and unpublished studies. No language restrictions will be applied. We will perform the critical appraisal of included studies with the Quality in Prognosis Studies (QUIPS) tool and the certainty of evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE).

negative: Evidence Based Management Guideline for the COVID-19 Pandemic - Review article ABSTRACT COVID-19 has now been declared a pandemic. To date, COVID-19 has affected over 944,181 people worldwide, resulting in over 47,312 reported deaths. Numerous preventative strategies and non-pharmaceutical interventions have been employed to mitigate the spread of disease including careful infection control, the isolation of patients, and social distancing. Management is predominantly focused on the provision of supportive care, with oxygen therapy representing the major treatment intervention. Medical therapy involving corticosteroids and antivirals have also been encouraged as part of critical management schemes. However, there is at present no specific antiviral recommended for the treatment of COVID-19, and no vaccine is currently available. Despite the strategic implementation of these measures, the number of new reported cases continues to rise at a profoundly alarming rate. As new findings emerge, there is an urgent need for up-to-date management guidelines. In response to this call, we review what is currently known regarding the management of COVID-19, and offer an evidence-based review of current practice.

negative: Viral agents in marmoset colitis: Dr. Robert Russell, University of Washington, Seattle, and Dr. David Brian, University of Tennessee, Knoxville

negative: Lessons from the USA Delayed Response to the COVID-19 Pandemic.

negative: 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).

negative: COVID-19 and Kidney Disease: Molecular Determinants and Clinical Implications in Renal Cancer CONTEXT: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic that erupted in December 2019 has affected more than a million people from over 200 countries, claiming over 70 000 lives (by April 7, 2020). As the viral infection is driven by increased angiotensin-converting enzyme-2 (ACE2) expression, with the kidney exhibiting the highest expression, it is crucial to gain insights into the mechanisms underlying renal cell carcinoma (RCC) and coronavirus disease 2019 (COVID-19). OBJECTIVE: This study considers up-to-date information on the biological determinants shared by COVID-19 and renal disease, and aims to provide evidence-based recommendations for the clinical management of RCC patients with COVID-19. EVIDENCE ACQUISITION: A literature search was performed using all sources (MEDLINE, EMBASE, ScienceDirect, Cochrane Libraries, and Web of Science). As of March 31, 2020, the Center for Disease Control reported that of the adults hospitalized for COVID-19 with underlying conditions in the USA, 74.8% had chronic renal disease. EVIDENCE SYNTHESIS: Evidence is discussed from epidemiological studies on SARS-CoV-2 pandemic and molecular studies on the role of kidney in facilitating routes for SARS-CoV-2 entry, leading to increased virulence of SARS-CoV-2 and clinical manifestation of symptoms in RCC. CONCLUSIONS: This analysis will advance our understanding of (1) the molecular signatures shared by RCC and COVID-19 and (2) the clinical implications of overlapping signaling pathways in the therapeutic management of RCC and COVID-19 patients. PATIENT SUMMARY: Amid the coronavirus disease 2019 (COVID-19) pandemic, patients diagnosed with renal cell carcinoma and infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may receive complimentary treatment modalities to enhance therapeutic response.

negative: Proteomic analysis reveals platelet factor 4 and beta‐thromboglobulin as prognostic markers in severe acute respiratory syndrome Previously, we reported that proteomic fingerprints were present in sera of patients with severe acute respiratory syndrome (SARS), and could separate patients into subgroups with different prognoses. In the present study, we examined the prognostic values of the SARS‐associated proteomic features by biostatistical analysis, and deciphered the identities of those with prognostic values. Data of 20 SARS‐associated serum proteomic features and ten serological variables from 38 SARS adult patients before treatment were subjected to multivariate logistic regression. Proteomic features of m/z 6634, m/z 7769, m/z 8635, and m/z 8865 were identified as independent prognostic markers. After purification by cation‐exchange chromatography and gel electrophoresis, proteomic features of m/z 7769 and m/z 8865 were found to be platelet factor 4 (PF4) and beta‐thromboglobulin (beta‐TG) by tandem mass spectrometry, respectively. The associations of decreased serum PF4 and increased serum beta‐TG levels with poor prognosis were confirmed by Western blot. Previous studies suggest that PF4 and beta‐TG are involved in the pathogenesis of acute respiratory distress syndrome (ARDS) in a negative and positive way, respectively. Our results suggest that PF4 and beta‐TG may also play similar roles in the development of ARDS in SARS patients.

negative: Corticosteroids for critically ill COVID-19 patients with cytokine release syndrome: a limited case series

negative: Systematic review and meta-analysis of predictive symptoms and comorbidities for severe COVID-19 infection Background/introduction COVID−19, a novel coronavirus outbreak starting in China, is now a rapidly developing public health emergency of international concern. The clinical spectrum of COVID−19 disease is varied, and identifying factors associated with severe disease has been described as an urgent research priority. It has been noted that elderly patients with pre-existing comorbidities are more vulnerable to more severe disease. However, the specific symptoms and comorbidities that most strongly predict disease severity are unclear. We performed a systematic review and meta-analysis to identify the symptoms and comorbidities predictive of COVID−19 severity. Method This study was prospectively registered on PROSPERO. A literature search was performed in three databases (MEDLINE, EMBASE and Global Health) for studies indexed up to 5th March 2020. Two reviewers independently screened the literature and both also completed data extraction. Quality appraisal of studies was performed using the STROBE checklist. Random effects meta-analysis was performed for selected symptoms and comorbidities to identify those most associated with severe COVID−19 infection or ICU admission. Results Of the 2259 studies identified, 42 were selected after title and abstract analysis, and 7 studies (including 1813 COVID−19 patients) were chosen for inclusion. The ICU group were older (62.4 years) compared to the non-ICU group (46 years), with a significantly higher proportion of males (67.2% vs. 57.1%, p=0.04). Dyspnoea was the only significant symptom predictive for both severe disease (pOR 3.70, 95% CI 1.83 − 7.46) and ICU admission (pOR 6.55, 95% CI 4.28 − 10.0). Notwithstanding the low prevalence of COPD in severe disease and ICU-admitted groups (4.5% and 9.7%, respectively), COPD was the most strongly predictive comorbidity for both severe disease (pOR 6.42, 95% CI 2.44 − 16.9) and ICU admission (pOR 17.8, 95% CI 6.56 − 48.2). Cardiovascular disease and hypertension were also strongly predictive for both severe disease and ICU admission. Those with CVD and hypertension were 4.4 (95% CI 2.64 − 7.47) and 3.7 (95% CI 2.22 − 5.99) times more likely to have an ICU admission respectively, compared to patients without the comorbidity. Conclusions Dyspnoea was the only symptom strongly predictive for both severe disease and ICU admission, and could be useful in guiding clinical management decisions early in the course of illness. When looking at ICU-admitted patients, who represent the more severe end of the spectrum of clinical severity, COPD patients are particularly vulnerable, and those with cardiovascular disease and hypertension are also at a high-risk of severe illness. To aid clinical assessment, risk stratification, efficient resource allocation, and targeted public health interventions, future research must aim to further define those at high-risk of severe illness with COVID−19.

negative: The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes Since December 2019, a newly identified coronavirus (2019 novel coronavirus, 2019-nCov) is causing outbreak of pneumonia in one of largest cities, Wuhan, in Hubei province of China and has draw significant public health attention. The same as severe acute respiratory syndrome coronavirus (SARS-CoV), 2019-nCov enters into host cells via cell receptor angiotensin converting enzyme II (ACE2). In order to dissect the ACE2-expressing cell composition and proportion and explore a potential route of the 2019-nCov infection in digestive system infection, 4 datasets with single-cell transcriptomes of lung, esophagus, gastric, ileum and colon were analyzed. The data showed that ACE2 was not only highly expressed in the lung AT2 cells, esophagus upper and stratified epithelial cells but also in absorptive enterocytes from ileum and colon. These results indicated along with respiratory systems, digestive system is a potential routes for 2019-nCov infection. In conclusion, this study has provided the bioinformatics evidence of the potential route for infection of 2019-nCov in digestive system along with respiratory tract and may have significant impact for our healthy policy setting regards to prevention of 2019-nCoV infection.

negative: 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.

negative: Coronavirus Epidemic and Extracorporeal Therapies in Intensive Care: si vis pacem para bellum

negative: Overlapping CD8+ and CD4+ T-cell epitopes identification for the progression of epitope-based peptide vaccine from nucleocapsid and glycoprotein of emerging Rift Valley fever virus using immunoinformatics approach Abstract Rift Valley fever virus (RVFV) is an emergent arthropod-borne zoonotic infectious viral pathogen which causes fatal diseases in the humans and ruminants. Currently, no effective and licensed vaccine is available for the prevention of RVFV infection in endemic as well as in non-endemic regions. So, an immunoinformatics-driven genome-wide screening approach was performed for the identification of overlapping CD8+ and CD4+ T-cell epitopes and also linear B-cell epitopes from the conserved sequences of the nucleocapsid (N) and glycoprotein (G) of RVFV. We identified overlapping 99.39% conserved 1 CD8+ T-cell epitope (MMHPSFAGM) from N protein and 100% conserved 7 epitopes (AVFALAPVV, LAVFALAPV, FALAPVVFA, VFALAPVVF, IAMTVLPAL, FFDWFSGLM, and FLLIYLGRT) from G protein and also identified IL-4 and IFN-γ induced (99.39% conserved) 1 N protein CD4+ T-cell epitope (HMMHPSFAGMVDPSL) and 100% conserved 5 G protein CD4+ T-cell epitopes (LPALAVFALAPVVFA, PALAVFALAPVVFAE, GIAMTVLPALAVFAL, GSWNFFDWFSGLMSW, and FFLLIYLGRTGLSKM). The overlapping CD8+ and CD4+ T-cell epitopes were bound with most conserved HLA-C*12:03 and HLA-DRB1*01:01, respectively with the high binding affinity (kcal/mol). The combined population coverage analysis revealed that the allele frequencies of these epitopes are high in endemic and non-endemic regions. Besides, we found 100% conserved and non-allergenic 2 decamer B-cell epitopes, GVCEVGVQAL and RVFNCIDWVH of G protein had the sequence similarity with the nonamer CD8+ T-cell epitopes, VCEVGVQAL and RVFNCIDWV, respectively. Consequently, these epitopes may be used for the development of epitope-based peptide vaccine against emerging RVFV. However, in vivo and in vitro experiments are required for their efficient use as a vaccine.

negative: Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations Summary As coronavirus disease 2019 (COVID-19) spreads across the world, the intensive care unit (ICU) community must prepare for the challenges associated with this pandemic. Streamlining of workflows for rapid diagnosis and isolation, clinical management, and infection prevention will matter not only to patients with COVID-19, but also to health-care workers and other patients who are at risk from nosocomial transmission. Management of acute respiratory failure and haemodynamics is key. ICU practitioners, hospital administrators, governments, and policy makers must prepare for a substantial increase in critical care bed capacity, with a focus not just on infrastructure and supplies, but also on staff management. Critical care triage to allow the rationing of scarce ICU resources might be needed. Researchers must address unanswered questions, including the role of repurposed and experimental therapies. Collaboration at the local, regional, national, and international level offers the best chance of survival for the critically ill.

negative: Focus on Receptors for Coronaviruses with Special Reference to Angiotensin-converting Enzyme 2 as a Potential Drug Target - A Perspective. Coronaviruses (CoVs) possess an enveloped, single, positive-stranded RNA genome which encodes for four membrane proteins, namely spike (S), envelope (E), membrane (M) and nucleocapsid (N) proteins 3-5 [1]. With regard to pathogenicity, S proteins are essential for viral entry into host cells [2, 3]. SARS-CoV binds to the angiotensin-converting enzyme (ACE)2 which is present on nonimmune cells, such as respiratory and intestinal epithelial cells, endothelial cells, kidney cells (renal tubules) and cerebral neurons and immune cells, such as alveolar monocytes/macrophages [4-6]. Of note, CD209L or liver/lymph node special intercellular adhesion molecule-3-grabbing non-integrin (SIGN) and dendritic cell (DC)-SIGN are alternative receptors for SARS-CoV but with lower affinity [7]. In the case of MERS-CoV, S proteins bind to the host cell receptor dipeptidyl peptidase 4 (DPP4 or CD26) which is broadly expressed on intestinal, alveolar, renal, hepatic and prostate cells as well as on activated leukocytes [8]. Then, viruses replicate in target cells with release of mature virions, which, in turn, invade new target cells [9]. Evidence has been provided that SARSCoV proteins are cleaved into two subunits, S1 and S2, respectively, and the amino acids 318-510 of the S1 represent the receptor-binding domain (RBD) which binds to ACE2 [10, 11]. Quite importantly, in the context of RBD there is the receptor-binding motif (RBM) (amino acids 424- 494), which accounts for complete binding to ACE2 [11]. Moreover, by means of two residues at positions 479 and 487 RBD allows virus progression and tropism [10, 11]. In the case of MERSCoV, its RBM binds to DPP4 with residues 484-567, thus, suggesting that its RBD differs from that of SARS-CoV [12, 13]. In a very recent paper, Wan and associates [14] have investigated the receptor recognition by COVID-19 (a new term to indicate the 2019-nCoV in Wuhan) on the bases of structural studies. In this respect, the sequence of COVID-19 RBM is similar to that of SARSCoV, thus, implicating that ACE2 may represent the binding receptors for COVID-19. Furthermore, gln493 residue of COVID-19 RBM seems to allow interaction with human ACE2, thus, suggesting the ability of this virus to infect human cells. According, to Wan and associates structural analysis [14], COVID-19 binds to human ACE2 with a lesser efficiency than human SARS-CoV (2002) but with higher affinity than human SARS-CoV (2003). Furthermore, same authors predicted that a single mutation at the 501 position may enhance the COVID-19 RBD binding capacity to human ACE2 and this evolution should be monitored in infected patients [14]. These predictive findings by Wan and associates [14] are confirmed by two contemporary studies by Letko and Muster [15] and Peng and associates [16]. In particular, the report by Peng and associates [16], points out the possible origin of COVID-19 from bats [16]. From a pathogenic point of view, evidence has been provided that binding of S2 to ACE2 receptor leads to its down-regulation with subsequent lung damage in the course of SARS-CoV infection [17]. Down-regulation of ACE2 causes excessive production of angiotensin (ANG) II by the related enzyme ACE with stimulation of ANG type 1a receptor (AT1R) and enhanced lung vascular permeability [18]. In particular, same authors have reported that recombinant ACE2 could attenuate severe acute lung injury in mice [18]. Moreover, Battle and associates [19] also proposed to use already available recombinant ACE2 for intercepting COVID-19 and attenuating infection. In the previous paragraphs, the presence of ACE2 on immune cells has been pointed out and, by analogy to epithelial cells, this receptor may also be down-regulated following viral entry. Therefore, in CoV-infected animal models and in infected humans further investigations are required to clarify a possible reduced expression of ACE2 on immune cells. In fact, in the course of SARS-CoV infection, a number of immune disorders have been detected. Three reports have demonstrated the ability of CoV to inhibit interferon (IFN)- production in the course of SARS acting as IFN antagonist [20-22]. In senescent Balb/c mice, depletion of T lymphocytes is associated to more severe interstitial pneumonitis and delayed clearance of SARS-CoV, thus, suggesting a protective role played by these cells [23]. In this connection, both SARS-CoV and MERS-CoV have been shown to induce T cell apoptosis, thus, aggravating the clinical course of disease [24, 25]. Quite interestingly, memory CD8+ T cells specific for SARS-CoV M and N proteins have been detected up to 11 years post-infection [26]. As far as humoral immune responsiveness is concerned, evidence has been provided that S1 subunit from MERS-CoV is highly immunogenic in mice [27]. Moreover, monoclonal antibodies have been shown to be highly neutralizing against MERS-CoV replication and endowed with post exposure effectiveness in susceptible mice [28, 29]. Human neutralizing antibodies have also been isolated from a recovered patient, thus, suggesting the role of humoral immunity in the control of the persistence of CoV in the host [30]. In particular, IgG response occurs early in infection and its prolonged production may serve for virus clearance during recovery also in view of the absence of viremia in convalescent sera from SARS patients [31]. According to current literature, severity of COVID-19 infection correlates with lymphopenia and patients who died from COVID-19 had lower lymphocyte counts when compared to survivors [32, 33]. These data suggest that lymphocyte-mediated anti-viral activity is poorly effective against COVID-19. Despite lymphopenia, evidence for an exaggerate release of proinflammatory cytokines [interleukin (IL)-1 and IL-6] has been reported in the course acute respiratory syndrome in COVID19 infected patients, thus, aggravating the clinical course of disease [34]. As recently reported, during COVID-19 pandemic in both Italy and China higher frequency of fatalities have been observed in the frail elderly population with previous comorbidities [35]. It is well known that decline of immunity occurs in ageing and, therefore, COVID-19 may gain easier access to the respiratory tract in frail elderly patients [36]. There is evidence that ACE2 protects from severe acute lung failure and operates as a negative regulator of the renin-angiotensin system (RAS) [18, 37]. It is well known that ANG II via activation of the AT1R promotes detrimental effects on the host, such as, vasoconstriction, reactive oxygen species generation, inflammation and matrix remodelling [38]. ACE2 counterbalances the noxious effects exhibited by ANG II and AT1R via activation of AT2R which arrests cell growth, inflammation and fibrosis [39]. In this framework, Gurwitz [40] proposed to use AT1R blockers, such as losartan, as a potential treatment of COVID-19 infection. In fact, losartan as well as olmesartan, used for treating hypertension in patients, were able to increase ACE2 expression after 28 days treatment of rats with myocardial infarction [41]. Then, Gurwitz suggests to evaluate severity of symptoms in COVID-19 infected patients under previous chronic treatment with AT1R blockers in comparison to COVID-19 infected patients who did not take AT1R blockers [40]. Quite interestingly, 75% of aged COVID-19 infected patients admitted to Italian hospitals had hypertension [unpublished data]. However, the putative effects of ACE-2 down-regulation on the cardiovascular system in the course of COVID-19 pandemic need more intensive studies. Taken together, these evidences suggest that CoV-induced down-regulation of ACE2 activates RAS with collateral damage to organs, such as lungs, in the course of SARS-related pneumonia. Then, putative therapeutic measures aimed at increasing ACE2 levels on respiratory epithelial cells should be taken into serious consideration. Quite interestingly, over the past few years, three key papers have demonstrated the ability of a polyphenol, resveratrol (RES), to experimentally deactivate the RAS system in maternal and post-weaning high fat diet, arterial ageing and high fat diet, respectively [42-44]. In all these experimental models, RES led to an increase of ACE2 with reduction of organ damage, such as liver steatosis and aorta media thickness and decrease of adipose tissue mass, respectively. As far as the mechanism of action of RES is concerned, this polyphenol is able to activate sirtuin (Sirt)1 [45-47]. In turn, Sirt1 down-regulates AT1R expression via ACE2 up-regulation [43, 48]. Of importance, Lin and associates [48] have demonstrated the ability of RES to in vitro inhibit MERS-CoV infection of Vero E6 cells, thus, prolonging cell survival in virtue of an anti-apoptotic mechanism. These findings suggest a direct antiviral effect exerted by RES. It would be very interestingly to evaluate the direct effects of RES on COVID-19, in vitro. The data above discussed strongly suggest, that RES, as an activators of ACE2, should be investigated in animal models of CoV-induced severe pneumonia, also taking into account the antioxidant, anti-inflammatory and immunomodulating effects exerted by polyphenols [49]. Then, successful animal studies may pave the way for RES-based human trials in COVID-infected patients. Note added in proof During the reviewing process of this perspective other related papers have been published. Hanff and associates [50] have discussed the possible association between COVID-19-associated cardiovascular mortality and dysregulation of the Renin Angiotensin System (RAS). From a pharmacologic point of view, RAS inhibition leads to upregulation of ACE2, thus, attenuating acute respiratory syndrome and myocarditis in COVID-19-infected patients. Conversely, increase in ACE2 expression may facilitate the access into the host of COVID-19, thus, aggravating the clinical picture. Such a dilemma would be solved by clinical trials based on RAS blo

negative: Chapter 7 Scientific Advances in the Diagnosis of Emerging and Reemerging Viral Human Pathogens Abstract Despite scientific advances, the diagnosis of infectious diseases is primarily possible through vaccination and later by antibiotics. Emerging and reemerging pathologies are still considered to be dangerous to humanity because of the unique nature of these diseases: it is the encounter between two living organisms that have coexisted for millions of years within the people on the same planet without being previously recognized. These infectious agents, such as bacteria, viruses, fungi, or parasites, pose no threat to humans. In fact, only a few hundred are able to inflict damage to the human host. In addition, the spectrum of human disease caused by a particular pathogen varies considerably depending on the factors related to the ecological agent, the host, and the infectious agents. Several emerging or reemerging infectious agents are organisms that could be used in biological control. The differentiation of a natural epidemic from a bioterrorian event is based on several epidemiological indices as well as on the molecular characterization of the pathogen(s) involved. The role of pathologists is indeed very important. It is in this context that this chapter aims to discuss the various scientific advances, particularly molecular, in terms of diagnosis of these diseases; the new discoveries in the role of nanotechnologies and nanobiosensors; and also the implication of biomarkers, especially microRNAs (miRNAs), since it was reported that a single miRNA has the ultimate capacity to target multiple genes simultaneously. In a viral infection context, miRNAs have been connected with the interplay between host and pathogen and occupy a major role in the host–parasite interaction and pathogenesis. It is in this context that various molecular and nanomethods for the detection of emerging viruses and experimental validation of miRNAs during quelling viruses target transcripts will be discussed in this chapter.

negative: COVID-19 and Nigeria: Putting the realities in context Abstract Background The Coronavirus Disease 2019 (COVID-19) which was previously known as 2019-novel Coronavirus (2019-nCoV) was first reported in Wuhan,China in December, 2019. As at today the disease has evolved into a serious global emergency leading to its declaration as a pandemic recently. Body On the African continent, Nigeria is just experiencing the direct effects of this pandemic having recorded her index case in February, 2020 with an increasing number of cases by the day and current case fatality ratio of 0.03 as at 13 April, 2020. Although the recorded cases may albeit seem low, it has been forecasted that Africa will have a fair share of the worst effects of this disease by the end of the pandemic. Generally, African countries have fragile health systems and this remains a source of concern especially in the event of increased outbreaks. Nigeria's current national health systems cannot effectively respond to the growing needs of already infected patients requiring admission into Intensive care units (ICUs) for Acute Respiratory Diseases (ARDs) and SARS COV-2 pnuemonia. This has grim implications for Nigeria especially as increased cases that may require critical care looms. The provision of quarantine or isolation facilities can also be a challenge in Africa and availability of rapid diagnostic kits for fast and reliable testing and diagnosis of the disease. Conclusion There is an urgent need to put in perspective the realities peculiar to Nigeria, and explore available collective measures and interventions to address the Coronavirus pandemic.

negative: Monoclonal antibodies for the S2 subunit of spike of SARS-CoV cross-react with the newly-emerged SARS-CoV-2 The emergence of a novel coronavirus, SARS-CoV-2, at the end of 2019 has resulted in widespread human infections across the globe. While genetically distinct from SARS-CoV, the etiological agent that caused an outbreak of severe acute respiratory syndrome (SARS) in 2003, both coronaviruses exhibit receptor binding domain (RBD) conservation and utilize the same host cell receptor, angiotensin-converting enzyme 2 (ACE2), for virus entry. Therefore, it will be important to test the cross-reactivity of antibodies that have been previously generated against the surface spike (S) glycoprotein of SARS-CoV in order to aid research on the newly emerged SARS-CoV-2. Here, we show that an immunogenic domain in the S2 subunit of SARS-CoV S is highly conserved in multiple strains of SARS-CoV-2. Consistently, four murine monoclonal antibodies (mAbs) raised against this immunogenic SARS-CoV fragment were able to recognise the S protein of SARS-CoV-2 expressed in a mammalian cell line. Importantly, one of them (mAb 1A9) was demonstrated to detect S in SARS-CoV-2-infected cells. To our knowledge, this is the first study showing that mAbs targeting the S2 domain of SARS-CoV can cross-react with SARS-CoV-2 and this observation is consistent with the high sequence conservation in the S2 subunit. These cross-reactive mAbs may serve as tools useful for SARS-CoV-2 research as well as for the development of diagnostic assays for its associated coronavirus disease COVID-19.

negative: 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.

negative: Can Search Query Forecast successfully in China's 2019-nCov pneumonia? Recently the novel coronavirus (2019-nCov) pneumonia outbreak in China then the world, and the Number of infections and death continues to increases. Search Query performs well in forecasting the epidemics. It is still a question whether search engine data can forecast the drift and the inflexion in 2019-nCov pneumonia. Based on the Baidu Search Index, we propose three prediction models: composite Index, composite Index with filtering and suspected NCP(Novel Coronavirus Pneumonia). The result demonstrates that the predictive model of composite index with filtering performs the best while the model of suspected NCP has the highest forecast error. We further predict the out-of-the-set NCP confirmed cases and monitor that the next peak of new diagnoses will occur on February 16th and 17th.

negative: Biomarkers of Pulmonary Diseases Lungs and airways are affected by several pathologies, the most important of which are inflammation, infection and cancer. Some of the biomarkers of these pathologies are similar to those found in involvement of other organs. This chapter will briefly discuss general issues of biomarkers of pulmonary disorders listed in Table 16.1. Biomarkers of lung cancer are described in Chapter 13.

negative: Severe Community-Acquired Pneumonia Severe community-acquired pneumonia necessitating intensive care unit admission is associated with high morbidity, mortality, and health-care cost. This review article serves to summarize the epidemiology, diagnosis, treatment, and prognosis of this common life-threatening condition. Current practice guidelines as well as the role of several scoring systems (such as the PSI, CURB-65, and IDSA/ATS criteria) used to predict CAP severity, prognosis, and site of care are reviewed. In addition, common complications and prevention strategies are discussed.

negative: Why is it difficult to accurately predict the COVID-19 epidemic? Since the COVID-19 outbreak in Wuhan City in December of 2019, numerous model predictions on the COVID-19 epidemics in Wuhan and other parts of China have been reported. These model predictions have shown a wide range of variations. In our study, we demonstrate that nonidentifiability in model calibrations using the confirmed-case data is the main reason for such wide variations. Using the Akaike Information Criterion (AIC) for model selection, we show that an SIR model performs much better than an SEIR model in representing the information contained in the confirmed-case data. This indicates that predictions using more complex models may not be more reliable compared to using a simpler model. We present our model predictions for the COVID-19 epidemic in Wuhan after the lockdown and quarantine of the city on January 23, 2020. We also report our results of modeling the impacts of the strict quarantine measures undertaken in the city after February 7 on the time course of the epidemic, and modeling the potential of a second outbreak after the return-to-work in the city.

negative: Effectiveness of glucocorticoid therapy in patients with severe coronavirus disease 2019: protocol of a randomized controlled trial BACKGROUND: At the end of 2019, a novel coronavirus outbreak emerged in Wuhan, China, and its causative organism has been subsequently designated the 2019 novel coronavirus (2019-nCoV). The effectiveness of adjunctive glucocorticoid therapy in the management of 2019-nCoV-infected patients with severe lower respiratory tract infections is not clear, and warrants further investigation. METHODS: The present study will be conducted as an open-labeled, randomized, controlled trial. We will enrol 48 subjects from Chongqing Public Health Medical Center. Each eligible subject will be assigned to an intervention group (methylprednisolone via intravenous injection at a dose of 1–2 mg/kg/day for 3 days) or a control group (no glucocorticoid use) randomly, at a 1:1 ratio. Subjects in both groups will be invited for 28 days of follow-up which will be scheduled at four consecutive visit points. We will use the clinical improvement rate as our primary endpoint. Secondary endpoints include the timing of clinical improvement after intervention, duration of mechanical ventilation, duration of hospitalization, overall incidence of adverse events, as well as rate of adverse events at each visit, and mortality at 2 and 4 weeks. DISCUSSION: The present coronavirus outbreak is the third serious global coronavirus outbreak in the past two decades. Oral and parenteral glucocorticoids have been used in the management of severe respiratory symptoms in coronavirus-infected patients in the past. However, there remains no definitive evidence in the literature for or against the utilization of systemic glucocorticoids in seriously ill patients with coronavirus-related severe respiratory disease, or indeed in other types of severe respiratory disease. In this study, we hope to discover evidence either supporting or opposing the systemic therapeutic administration of glucocorticoids in patients with severe coronavirus disease 2019. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2000029386, http://www.chictr.org.cn/showproj.aspx?proj=48777.

negative: Two consecutive myocardial tissue insults for inpatients with COVID-19

negative: Impact of isolation on hospitalised patients who are infectious: systematic review with meta-analysis OBJECTIVE: To systematically review the literature exploring the impact of isolation on hospitalised patients who are infectious: psychological and non-psychological outcomes. DESIGN: Systematic review with meta-analysis. DATA SOURCES: Embase, Medline and PsycINFO were searched from inception until December 2018. Reference lists and Google Scholar were also handsearched. RESULTS: Twenty-six papers published from database inception to December 2018 were reviewed. A wide range of psychological and non-psychological outcomes were reported. There was a marked trend for isolated patients to exhibit higher levels of depression, the pooled standardised mean difference being 1.28 (95% CI 0.47 to 2.09) and anxiety 1.45 (95% CI 0.56 to 2.34), although both had high levels of heterogeneity, and worse outcomes for a range of care-related factors but with significant variation. CONCLUSION: The review indicates that isolation to contain the risk of infection has negative consequences for segregated patients. Although strength of the evidence is weak, comprising primarily single-centre convenience samples, consistency of the effects may strengthen this conclusion. More research needs to be undertaken to examine this relationship and develop and test interventions to reduce the negative effects of isolation.

negative: Clinical course of severe and critical COVID-19 in hospitalized pregnancies: a US cohort study Abstract Background The COVID-19 pandemic has had an impact on healthcare systems around the world with 3.0 million infected and 208,000 resultant mortalities as of this writing. Information regarding infection in pregnancy is still limited. Objectives To describe the clinical course of severe and critical infection in hospitalized pregnant women with positive laboratory testing for SARS-CoV2. Study Design This is a cohort study of pregnant women with severe or critical COVID-19 infection hospitalized at 12 US institutions between March 5, 2020 and April 20, 2020. Severe infection was defined according to published criteria by patient reported dyspnea, respiratory rate > 30 per minute, blood oxygen saturation ≤ 93% on room air, partial pressure of arterial oxygen to fraction of inspired oxygen <300 and/or lung infiltrates >50% within 24 to 48 hours on chest imaging. Critical disease was defined by respiratory failure, septic shock, and/or multiple organ dysfunction or failure. Women were excluded if they had presumed COVID-19 infection but laboratory testing was negative. The primary outcome was median duration from hospital admission to discharge. Secondary outcomes included need for supplemental oxygen, intubation, cardiomyopathy, cardiac arrest, death, and timing of delivery. The clinical courses are described by the median disease day on which these outcomes occurred after the onset of symptoms. Treatment and neonatal outcomes are also reported. Results Of 64 pregnant women hospitalized with COVID-19, 44 (69%) had severe and 20 (31%) critical disease. The following pre-existing comorbidities were observed: 25% had a pulmonary condition, 17% had cardiac disease and the mean BMI was 34 kg/m2. Gestational age at symptom onset was at a mean 29 ±6 weeks and at hospital admission a mean of 30 ±6 weeks, on a median day of disease 7 since first symptoms. Eighty-one percent of women were treated with hydroxychloroquine; 9% of women with severe disease and 65% of women with critical disease received remdesivir. All women with critical disease received either prophylactic or therapeutic anticoagulation during their admission. The median duration of hospital stay was 6 days (6 days for severe, 10.5 days for critical, p=0.01). For those who required it, intubation usually occurred around day 9, and peak respiratory support for women with severe disease occurred on day 8. In women with critical disease, prone positioning was performed in 20% of cases, the rate of ARDS was 70%, and re-intubation was necessary in 20%. There was one case of maternal cardiac arrest, but no cases of cardiomyopathy and no maternal deaths. Thirty-two (50%) women in this cohort delivered during their COVID-19 hospitalization (34% of severe and 85% of critical women). Eighty-eight percent (15/17) of pregnant women with critical COVID-19 who delivered during their disease course were delivered preterm, 94% of them via cesarean; in all, 75% (15/20) of critically ill women delivered preterm. There were no stillbirths or neonatal deaths, or cases of vertical transmission. Conclusion In hospitalized pregnant women with severe or critical COVID-19 infection, admission typically occurred about 7 days after symptom onset, and the duration of hospitalization was 6 days (6 severe versus 12 critical). Critically ill women had a high rate of ARDS, and there was one case of cardiac arrest, but there were no cases of cardiomyopathy, or maternal mortality. Hospitalization for severe or critical COVID-19 infection resulted in delivery during the course of infection in 50% of this cohort, usually in the third trimester. There were no perinatal deaths in this cohort.

negative: MicroRNA Biomarkers for Infectious Diseases: From Basic Research to Biosensing In the pursuit of improved diagnostic tests for infectious diseases, several classes of molecules have been scrutinized as prospective biomarkers. Small (18–22 nucleotide), non-coding RNA transcripts called microRNAs (miRNAs) have emerged as promising candidates with extensive diagnostic potential, due to their role in numerous diseases, previously established methods for quantitation and their stability within biofluids. Despite efforts to identify, characterize and apply miRNA signatures as diagnostic markers in a range of non-infectious diseases, their application in infectious disease has advanced relatively slowly. Here, we outline the benefits that miRNA biomarkers offer to the diagnosis, management, and treatment of infectious diseases. Investigation of these novel biomarkers could advance the use of personalized medicine in infectious disease treatment, which raises important considerations for validating their use as diagnostic or prognostic markers. Finally, we discuss new and emerging miRNA detection platforms, with a focus on rapid, point-of-care testing, to evaluate the benefits and obstacles of miRNA biomarkers for infectious disease.

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

negative: Rethinking COVID-19 in children: Lessons learned from pediatric viral and inflammatory cardiovascular diseases

negative: A network-based method with privacy-preserving for identifying influential providers in large healthcare service systems Abstract In data science, networks provide a useful abstraction of the structure of many complex systems, ranging from social systems and computer networks to biological networks and physical systems. Healthcare service systems are one of the main social systems that can also be understood using network-based approaches, for example, to identify and evaluate influential providers. In this paper, we propose a network-based method with privacy-preserving for identifying influential providers in large healthcare service systems. First, the provider-interacting network is constructed by employing publicly available information on locations and types of healthcare services of providers. Second, the ranking of nodes in the generated provider-interacting network is conducted in parallel on the basis of four nodal influence metrics. Third, the impact of the top-ranked influential nodes in the provider-interacting network is evaluated using three indicators. Compared with other research work based on patient-sharing networks, in this paper, the provider-interacting network of healthcare service providers can be roughly created according to the locations and the publicly available types of healthcare services, without the need for personally private electronic medical claims, thus protecting the privacy of patients. The proposed method is demonstrated by employing Physician and Other Supplier Data CY 2017, and can be applied to other similar datasets to help make decisions for the optimization of healthcare resources in the response to public health emergencies.

negative: Asymptomatic novel coronavirus pneumonia patient outside Wuhan: The value of CT images in the course of the disease Abstract The purpose of this case report is to describe the imaging and associated clinical features of an asymptomatic novel coronavirus pneumonia (COVID-19) patient outside Wuhan, China. The principle findings are that in this patient with laboratory-confirmed COVID-19, CT findings preceded symptoms and included bilateral pleural effusions, previously not reported in association with COVID-19. The role of this case report is promotion of potential recognition amongst radiologists of this new disease, which has been declared a global health emergency by the World Health Organization (WHO).

negative: Medical imaging informatics research and development trends—an editorial

negative: Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection It has been known that, the novel Coronavirus, 2019-nCoV, which is considered similar to SARS-CoV and originated from Wuhan (China), invades human cells via the receptor angiotensin converting enzyme II (ACE2). Moreover, lung cells that have ACE2 expression may be the main target cells during 2019-nCoV infection. However, some patients also exhibit non-respiratory symptoms, such as kidney failure, implying that 2019-nCoV could also invade other organs. To construct a risk map of different human organs, we analyzed the single-cell RNA sequencing (scRNA-seq) datasets derived from major human physiological systems, including the respiratory, cardiovascular, digestive, and urinary systems. Through scRNA-seq data analyses, we identified the organs at risk, such as lung, heart, esophagus, kidney, bladder, and ileum, and located specific cell types (i.e., type II alveolar cells (AT2), myocardial cells, proximal tubule cells of the kidney, ileum and esophagus epithelial cells, and bladder urothelial cells), which are vulnerable to 2019-nCoV infection. Based on the findings, we constructed a risk map indicating the vulnerability of different organs to 2019-nCoV infection. This study may provide potential clues for further investigation of the pathogenesis and route of 2019-nCoV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s11684-020-0754-0 and is accessible for authorized users.

negative: The potential role of TNFα in 2019 novel coronavirus pneumonia The outbreak of 2019 novel coronavirus has spread rapidly in multiple countries. We report the first case of 2019-nCoV infection in a patient with Ankylosing Spondylitisthe (AS), who was a biological agent (anti-TNFα) user in Wenzhou, China, and describe the clinical course and management of the case.

negative: Middle East respiratory syndrome coronavirus: a comprehensive review The Middle East respiratory syndrome coronavirus was first identified in 2012 and has since then remained uncontrolled. Cases have been mostly reported in the Middle East, however travel-associated cases and outbreaks have also occurred. Nosocomial and zoonotic transmission of the virus appear to be the most important routes. The infection is severe and highly fatal thus necessitating rapid and efficacious interventions. Here, we performed a comprehensive review of published literature and summarized the epidemiology of the virus. In addition, we summarized the virological aspects of the infection and reviewed the animal models used as well as vaccination and antiviral tested against it.

negative: Can SARS-CoV-2-infected women breastfeed after viral clearance? The recently emerged novel coronavirus pneumonia, named the coronavirus disease 2019 (COVID-19), shares several clinical characteristics with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and spread rapidly throughout China in December of 2019 (Huang et al., 2020). The pathogen 2019 novel coronavirus (2019-nCoV) is now named SARS coronavirus 2 (SARS-CoV-2) and is highly infectious. As of Apr. 9, 2020, over 80 000 confirmed cases had been reported, with an estimated mortality rate of 4.0% (Chinese Center for Disease Control and Prevention, 2020). Person-to-person transmission and familial clustering have been reported (Chan et al., 2020; Nishiura et al., 2020; Phan et al., 2020). However, there is no evidence of fetal intrauterine infection in pregnant women who have been infected with SARS-CoV-2 in their third trimester (Chen et al., 2020). It is unclear whether breastfeeding transmits the virus from previously infected and recovered mothers to their babies. Here we report the clinical course of a pregnant woman with COVID-19. In order to determine whether SARS-CoV-2 can be transmitted to newborns through breastfeeding, we measured viral RNA in the patient's breastmilk samples at different time points after delivery.

negative: Discrimination of Kawasaki disease with concomitant adenoviral detection differentiating from isolated adenoviral infection PURPOSE: Human adenovirus infection mimics Kawasaki disease (KD) but can be detected in KD patients. The aim of this study was to determine the clinical differences between KD with adenovirus infection and only adenoviral infection and to identify biomarkers for prediction of adenovirus-positive KD from isolated adenoviral infection. METHODS: A total of 147 patients with isolated adenovirus were identified by quantitative polymerase chain reaction. In addition, 11 patients having KD with adenovirus, who were treated with intravenous immunoglobulin therapy during the acute phase of KD were also evaluated. RESULTS: Compared with the adenoviral infection group, the KD with adenovirus group was significantly associated with frequent lip and tongue changes, skin rash and changes in the extremities. In the laboratory parameters, higher C-reactive protein (CRP) level and presence of hypoalbuminemia and sterile pyuria were significantly associated with the KD group. In the multivariate analysis, lip and tongue changes (odds ratio [OR], 1.416; 95% confidence interval [CI], 1.151–1.741; P=0.001), high CRP level (OR, 1.039; 95% CI 1.743–1.454; P= 0.021) and sterile pyuria (OR 1.052; 95% CI 0.861–1.286; P=0.041) were the significant predictive factors of KD. In addition, the cutoff CRP level related to KD with adenoviral detection was 56 mg/L, with a sensitivity of 81.8% and a specificity of 75.9%. CONCLUSION: Lip and tongue changes, higher serum CRP level and sterile pyuria were significantly correlated with adenovirus-positive KD.

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: Tear biomarkers for keratoconus Keratoconus is a progressive corneal thinning, ectatic condition, which affects vision. Recent advances in corneal topography measurements has helped advance proper diagnosis of this condition and increased research and clinical interests in the disease etiopathogenesis. Considerable progress has been achieved in understanding the progression of the disease and tear fluid has played a major role in the progress. This review discusses the importance of tear fluid as a source of biomarker for keratoconus and how advances in technology have helped map the complexity of tears and thereby molecular readouts of the disease. Expanding knowledge of the tear proteome, lipidome and metabolome opened up new avenues to study keratoconus and to identify probable prognostic or diagnostic biomarkers for the disease. A multidimensional approach of analyzing tear fluid of patients layering on proteomics, lipidomics and metabolomics is necessary in effectively decoding keratoconus and thereby identifying targets for its treatment.

negative: Biomarkers of sepsis: clinically useful? PURPOSE OF REVIEW The purpose of this review is to indicate recent developments in biomarkers of sepsis and to evaluate their impact on clinical use. According to the 'surviving sepsis campaign,' diagnosis of sepsis and infection is urgent; early and specific treatment is most effective to reduce complications and to decrease mortality. RECENT FINDINGS A variety of biomarkers of sepsis is presently available. The diagnostic spectrum of the various markers, however, is different. Some primarily indicate severity of inflammation (e.g. interleukin-6), others respond to infection, but do not indicate the host response well (endotoxin, lipoprotein binding protein, triggering receptor on myeloid cells). There are new markers with limited clinical experience, for example triggering receptor on myeloid cells or mid-pro atrial natriuretic peptide (Seristra, Brahms AG, Hennigsdorf, Germany). Procalcitonin is a well-established biomarker of sepsis that fulfills several criteria of clinical needs: it responds both to infection and severity of inflammation and thus has an impact on therapy. Recent studies indicate that antibiotic treatment can also be guided by procalcitonin. Further indications, including diagnosis of invasive bacterial infections and diagnosis of sepsis in neonates and children have been reported recently. SUMMARY Recent data and cumulative analyses indicate that biomarkers of sepsis improve diagnosis of sepsis. However, only a few markers have impact on therapy and fulfill the clinical requirements. Procalcitonin is a well-established marker, indicating infection, sepsis, and progression to the more severe stages of the disease. Today, this biomarker should be in the diagnostic portfolio of an intensive care unit or emergency ward.

negative: First infection by all four non-severe acute respiratory syndrome human coronaviruses takes place during childhood BACKGROUND: Non-severe acute respiratory syndrome (non-SARS)-related human coronaviruses (HCoVs), including HCoV-229E, -HKU1, -NL63, and -OC43, have been detected in respiratory tract samples from children and adults. However, the natural prevalence of antibodies against these viruses in serum among population is unknown. METHODS: To measure antibodies to the spike (S) protein of the four common non-SARS HCoVs, recombinant S proteins of the four HCoVs were expressed and characterised in 293 T cell. An S-protein-based indirect immunofluorescence assay (IFA) was then developed to detect anti-S IgG and IgM for the four individual HCoVs and applied to serum samples from a general asymptomatic population (218 children and 576 adults) in Beijing. RESULTS: Of 794 blood samples tested, only 29 (3.65%) were negative for anti-S IgG. The seropositivity of the four anti-S IgG antibodies was >70% within the general population. The majority of seroconversions to four-HCoV positivity first occurred in children. Both S-IgG and S-IgM antibodies were detectable among children and increased with age, reaching a plateau at 6 years of age. However, no anti-S IgM was detected in healthy adults. CONCLUSION: Large proportions of children and adults in Beijing have evidence of anti-S IgG against four the HCoVs, and first infections by all four non-SARS HCoVs takes place during childhood.

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: Sex Differences in Severity and Mortality Among Patients With COVID-19: Evidence from Pooled Literature Analysis and Insights from Integrated Bioinformatic Analysis Objective: To conduct a meta-analysis of current studies that examined sex differences in severity and mortality in patients with COVID-19, and identify potential mechanisms underpinning these differences. Methods: We performed a systematic review to collate data from observational studies examining associations of sex differences with clinical outcomes of COVID-19. PubMed, Web of Science and four preprint servers were searched for relevant studies. Data were extracted and analyzed using meta-analysis where possible, with summary data presented otherwise. Publicly available bulk RNA sequencing (RNA-seq), single-cell RNA sequencing (scRNA-seq), and chromatin immunoprecipitation sequencing (ChIP-seq) data were analyzed to explore the potential mechanisms underlying the observed association. Results: 39 studies met inclusion criteria, representing 77932 patients, of which 41510 (53.3%) were males. Men were at a markedly increased risk of developing severe cases compared with women. Furthermore, the pooled odds ratio (OR) of mortality for male group compared with the female group indicated significant higher mortality rate for male. Data from scRNA-seq suggest that men have a higher amount of ACE2-expressing pulmonary alveolar type II cells than women. Sex-based immunological differences exist. The expression of androgen receptor (AR) is positively correlated with ACE2, and there is evidence that AR may directly regulate the expression of ACE2. Conclusions: This meta-analysis detected an increased severity and mortality rate in the male populations with COVID-19, which might be attributable to the sex-based differences in cellular compositions and immunological microenvironments of the lung. The host cell receptor ACE2 is likely regulated by AR signaling pathway, which is identified as a potential target for prevention and treatment of SARS-Cov-2 infections in men.

negative: Microbiologic Diagnostic Workup of Acute Respiratory Failure with Pulmonary Infiltrates after Allogeneic Hematopoietic Stem Cell Transplantation: Findings in the Era of Molecular- and Biomarker-Based Assays Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) recipients frequently develop acute respiratory failure (ARF) with pulmonary infiltrates. Molecular- and biomarker-based assays enhance pathogen detection, but data on their yield in this population are scarce. This was a retrospective single-center study of 156 consecutive HSCT recipients admitted to the intensive care unit (ICU) between May 2013 and July 2017. Findings from a microbiologic diagnostic workup using currently available methods on bronchoalveolar lavage (BAL) and blood samples from 66 patients (age, 58 years [range, 45 to 64]; HSCT to ICU, 176 days [range, 85 to 407]) with ARF and pulmonary infiltrates were analyzed. In 47 patients (71%) a causative pathogen was identified (fungal, n = 28; viral, n = 26; bacterial, n = 18). Polymicrobial findings involving several pathogen groups occurred in 20 patients (30%). Culture (12/16, 75%), galactomannan (13/15, 87%), and Aspergillus-PCR (8/9, 89%) from BAL but not serum galactomannan (6/14, 43%) helped to diagnose invasive aspergillosis (n = 16, 24%). Aspergillus-PCR detected azole resistance in 2 cases. Mucorales was found in 7 patients (11%; BAL culture, n = 6; Mucorales-PCR, n = 1). Patients with identified pathogens had higher Simplified Acute Physiology Score II scores (P = .049) and inferior ICU survival (6% versus 37%, P < .01), which largely related to the presence of an invasive fungal infection. Eight patients (12%) had 1 or more viruses with uncertain lung pathogenicity as the sole microbiologic finding. A diagnostic microbiologic workup incorporating molecular- and biomarker-based assays identified pathogens in most HSCT recipients with ARF and pulmonary infiltrates admitted to the ICU. Implications of polymicrobial infection and pathogen patterns in these patients warrant further investigation.

negative: Rhinovirus, Coronavirus, Enterovirus, and Bocavirus After Hematopoietic Cell Transplantation or Solid Organ Transplantation Respiratory viral infections represent a significant cause of morbidity and mortality in immunocompromised hosts. Newer molecular detection assays have allowed for the characterization of several respiratory viruses not previously recognized as having significant clinical impact in the immunocompromised population. Human rhinoviruses are the most common respiratory viruses detected in the upper respiratory tract of hematopoietic cell transplant and lung transplant recipients, and evidence on the impact on clinical outcomes is mounting. Other respiratory viruses including enteroviruses (EVs), coronaviruses (CoVs), and bocavirus may also contribute to pulmonary disease; however, data is limited in the immunocompromised population. Further studies are needed to define the epidemiology, risk factors, and clinical outcomes of these infections; this data will help inform decisions regarding development of antiviral therapy and infection prevention strategies.

negative: Detection and characterization of microRNA expression profiling and its target genes in response to canine parvovirus in Crandell Reese Feline Kidney cells BACKGROUND: MicroRNAs (miRNAs) play an essential role in gene regulators in many biological and molecular phenomena. Unraveling the involvement of miRNA as a key cellular factor during in vitro canine parvovirus (CPV) infection may facilitate the discovery of potential intervention candidates. However, the examination of miRNA expression profiles in CPV in tissue culture systems has not been fully elucidated. METHOD: In the present study, we utilized high-throughput small RNA-seq (sRNA-seq) technology to investigate the altered miRNA profiling in miRNA libraries from uninfected (Control) and CPV-2c infected Crandell Reese Feline Kidney cells. RESULTS: We identified five of known miRNAs (miR-222-5p, miR-365-2-5p, miR-1247-3p, miR-322-5p and miR-361-3p) and three novel miRNAs (Novel 137, Novel 141 and Novel 102) by sRNA-seq with differentially expressed genes in the miRNA repertoire of CPV-infected cells over control. We further predicted the potential target genes of the aforementioned miRNAs using sequence homology algorithms. Notably, the targets of miR-1247-3p exhibited a potential function associated with cellular defense and humoral response to CPV. To extend the probing scheme for gene targets of miR-1247-3p, we explored and performed Gene Ontology (GO) enrichment analysis of its target genes. We discovered 229 putative targets from a total of 38 enriched GO terms. The top over-represented GO enrichment in biological process were lymphocyte activation and differentiation, marginal zone B cell differentiation, negative regulation of cytokine production, negative regulation of programed cell death, and negative regulation of signaling. We next constructed a GO biological process network composed of 28 target genes of miR-1247-3p, of which, some genes, namely BCL6, DLL1, GATA3, IL6, LEF1, LFNG and WNT1 were among the genes with obviously intersected in multiple GO terms. CONCLUSION: The miRNA-1247-3p and its cognate target genes suggested their great potential as novel therapeutic targets or diagnostic biomarkers of CPV or other related viruses.

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

negative: Potential benefits of precise corticosteroids therapy for severe 2019-nCoV pneumonia Salvage corticosteroids treatment for critical patients with 2019-nCoV? Corticosteroids are widely used to prevent lung injury caused by severe community-acquired pneumonia (sCAP) due to their excellent pharmacological effects on the suppression of exuberant and dysfunctional systematic inflammation5. Some scholars may not support the corticosteroids treatment for novel coronavirus pneumonia (NCP), because observational studies and systematic reviews have indicated inconclusive clinical evidence on the effect of corticosteroids therapy for viral pneumonias (such as SARS, MERS and H1N1). Additionally, pulse-dose therapy or long-term administration to high dose of corticosteroids in early stage were reported to be possibly harmful6,7,8. However, these conclusions obscured the clinical benefits of corticosteroids on some subgroups of patients, particularly those with severe symptoms, as the clinical effects might be related to the indication (severities of illness), the timing of intervention, the dose and duration of corticosteroids therapy9.

negative: The distinctive gastric fluid proteome in gastric cancer reveals a multi-biomarker diagnostic profile BACKGROUND: Overall gastric cancer survival remains poor mainly because there are no reliable methods for identifying highly curable early stage disease. Multi-protein profiling of gastric fluids, obtained from the anatomic site of pathology, could reveal diagnostic proteomic fingerprints. METHODS: Protein profiles were generated from gastric fluid samples of 19 gastric cancer and 36 benign gastritides patients undergoing elective, clinically-indicated gastroscopy using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry on multiple ProteinChip arrays. Proteomic features were compared by significance analysis of microarray algorithm and two-way hierarchical clustering. A second blinded sample set (24 gastric cancers and 29 clinically benign gastritides) was used for validation. RESULTS: By significance analysyis of microarray, 60 proteomic features were up-regulated and 46 were down-regulated in gastric cancer samples (p < 0.01). Multimarker clustering showed two distinctive proteomic profiles independent of age and ethnicity. Eighteen of 19 cancer samples clustered together (sensitivity 95%) while 27/36 of non-cancer samples clustered in a second group. Nine non-cancer samples that clustered with cancer samples included 5 pre-malignant lesions (1 adenomatous polyp and 4 intestinal metaplasia). Validation using a second sample set showed the sensitivity and specificity to be 88% and 93%, respectively. Positive predictive value of the combined data was 0.80. Selected peptide sequencing identified pepsinogen C and pepsin A activation peptide as significantly down-regulated and alpha-defensin as significantly up-regulated. CONCLUSION: This simple and reproducible multimarker proteomic assay could supplement clinical gastroscopic evaluation of symptomatic patients to enhance diagnostic accuracy for gastric cancer and pre-malignant lesions.

negative: A spatial model of CoVID-19 transmission in England and Wales: early spread and peak timing Background: An outbreak of a novel coronavirus, named CoVID-19, was first reported in China on 31 December 2019. As of 9 February 2020, cases have been reported in 25 countries, including probable cases of human-to-human transmission in England. Methods: We adapted an existing national-scale metapopulation model to capture the spread of CoVID-19 in England and Wales. We used 2011 census data to capture population sizes and population movement, together with parameter estimates from the current outbreak in China. Results: We predict that a CoVID-19 outbreak will peak 126 to 147 days (~4 months) after the start of person-to-person transmission in England and Wales in the absence of controls, assuming biological parameters remain unchanged. Therefore, if person-to-person transmission persists from February, we predict the epidemic peak would occur in June. The starting location has minimal impact on peak timing, and model stochasticity varies peak timing by 10 days. Incorporating realistic parameter uncertainty leads to estimates of peak time ranging from 78 days to 241 days after person-to-person transmission has been established. Seasonal changes in transmission rate substantially impact the timing and size of the epidemic peak, as well as the total attack rate. Discussion: We provide initial estimates of the potential course of CoVID-19 in England and Wales in the absence of control measures. These results can be refined with improved estimates of epidemiological parameters, and permit investigation of control measures and cost effectiveness analyses. Seasonal changes in transmission rate could shift the timing of the peak into winter months, which will have important implications for healthcare capacity planning.

negative: COVID-19 and acute myocardial injury: the heart of the matter or an innocent bystander?

negative: CD8+ T cell cross-reactivity against SARS-CoV-2 conferred by other coronavirus strains and influenza virus While individuals infected with coronavirus disease 2019 (COVID-19) manifested a broad range in susceptibility and severity to the disease, the pre-existing immune memory of related pathogens can influence the disease outcome. Here, we investigated the potential extent of T cell cross-reactivity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be conferred by other coronaviruses and influenza virus, and generated a map of public and private predicted CD8+ T cell epitopes between coronaviruses. Moreover, to assess the potential risk of self-reactivity and/or diminished T cell response for peptides identical or highly similar to the host, we identified predicted epitopes with high sequence similarity with human proteome. Lastly, we compared predicted epitopes from coronaviruses with epitopes from influenza virus deposited in IEDB to support vaccine development against different virus strains. We believe the comprehensive in silico profile of private and public predicted epitopes across coronaviruses and influenza viruses will facilitate design of vaccines capable of protecting against various viral infections.

negative: Investigation of serum protein profiles in scrapie infected sheep by means of SELDI-TOF-MS and multivariate data analysis BACKGROUND: Classical scrapie in sheep is a fatal neurodegenerative disease associated with the conversion PrP(C) to PrP(Sc). Much is known about genetic susceptibility, uptake and dissemination of PrP(Sc) in the body, but many aspects of prion diseases are still unknown. Different proteomic techniques have been used during the last decade to investigate differences in protein profiles between affected animals and healthy controls. We have investigated the protein profiles in serum of sheep with scrapie and healthy controls by SELDI-TOF-MS and LC-MS/MS. Latent Variable methods such as Principal Component Analysis, Partial Least Squares-Discriminant Analysis and Target Projection methods were used to describe the MS data. RESULTS: The serum proteomic profiles showed variable differences between the groups both throughout the incubation period and at the clinical end stage of scrapie. At the end stage, the target projection model separated the two groups with a sensitivity of 97.8%, and serum amyloid A was identified as one of the protein peaks that differed significantly between the groups. CONCLUSIONS: At the clinical end stage of classical scrapie, ten SELDI peaks significantly discriminated the scrapie group from the healthy controls. During the non-clinical incubation period, individual SELDI peaks were differently expressed between the groups at different time points. Investigations of differences in -omic profiles can contribute to new insights into the underlying disease processes and pathways, and advance our understanding of prion diseases, but comparison and validation across laboratories is difficult and challenging.

negative: Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and Outcome of COVID-19 : A Systematic Review and Meta-analysis Importace: There is conflicting evidence about the role of angiotensin converting enzymes inhibitors (ACEIs) and angiotensin receptors blockers (ARBs) in the pathogenesis and outcome of patients infected with acute severe respiratory syndrome coronavirus 2 (SASR-CoV-2) virus and growing public concern. Methods: We systematically reviewed the literature and performed a meta-analysis using inverse variance random effect models including all studies that evaluate the role of ACEIs/ARBs and reported adjusted odds ratio. Results: Nine studies met our eligibility criteria that enrolled a population of 58615 patients infected with SASR-CoV-2. Prior use of ACEIs/ARBs were associated with significant reduction of inpatient mortality among infected patients with SASR-CoV-2, adjusted odds ratio from 4 studies 0.33, 95% confidence interval ( 0.22,0.49) with zero in between studies heterogeneity and with significant reduction of critical or fatal outcome , pooled adjusted odds ratio from 5 studies 0.32,95% confidence interval ( 0.22,0.46) with no in between studies heterogeneity. Conclusion: Our findings suggest that prior use ACEIs /ARBs is associated with a decreased risk of death or critical outcome among SASR-CoV-2 infected patients.This findings is limited by the observational nature of included studies.However, it provides a reassurance to the public not to stop prescribed ACEIs /ARBs due to fear of severe COVID-19. It also calls upon investigators and ethics committee to reconsider the ongoing randomized trials of discontinuation of these drugs.

negative: Measures for diagnosing and treating infections by a novel coronavirus responsible for a pneumonia outbreak originating in Wuhan, China Abstract On 10 January 2020, a new coronavirus causing a pneumonia outbreak in Wuhan City in central China was denoted as 2019-nCoV by the World Health Organization (WHO). As of 24 January 2020, there were 887 confirmed cases of 2019-nCoV infection, including 26 deaths, reported in China and other countries. Therefore, combating this new virus and stopping the epidemic is a matter of urgency. Here, we focus on advances in research and development of fast diagnosis methods, as well as potential prophylactics and therapeutics to prevent or treat 2019-nCoV infection.

negative: Viral infection in acute exacerbation of idiopathic pulmonary fibrosis. RATIONALE Idiopathic pulmonary fibrosis is a progressive, uniformly fatal interstitial lung disease. An acute exacerbation of idiopathic pulmonary fibrosis is an episode of acute respiratory worsening without an identifiable etiology. Occult viral infection has been proposed as a possible cause of acute exacerbation. OBJECTIVES To use unbiased genomics-based discovery methods to define the role of viruses in acute exacerbation of idiopathic pulmonary fibrosis. METHODS Bronchoalveolar lavage and serum from patients with acute exacerbation of idiopathic pulmonary fibrosis, stable disease, and acute lung injury were tested for viral nucleic acid using multiplex polymerase chain reaction, pan-viral microarray, and high-throughput cDNA sequencing. MEASUREMENTS AND MAIN RESULTS Four of forty-three patients with acute exacerbation of idiopathic pulmonary fibrosis had evidence of common respiratory viral infection (parainfluenza [n = 1], rhinovirus [n = 2], coronavirus [n = 1]); no viruses were detected in the bronchoalveolar lavage from stable patients. Pan-viral microarrays revealed additional evidence of viral infection (herpes simplex virus [n = 1], Epstein-Barr virus [n = 2], and torque teno virus [TTV] [n = 12]) in patients with acute exacerbation. TTV infection was significantly more common in patients with acute exacerbation than stable controls (P = 0.0003), but present in a similar percentage of acute lung injury controls. Deep sequencing of a subset of acute exacerbation cases confirmed the presence of TTV but did not identify additional viruses. CONCLUSIONS Viral infection was not detected in most cases of acute exacerbation of idiopathic pulmonary fibrosis. TTV was present in a significant minority of cases, and cases of acute lung injury; the clinical significance of this finding remains to be determined.

negative: Clinical features and outcomes of 197 adult discharged patients with COVID-19 in Yichang, Hubei Purpose To investigate the epidemiology and clinical features of discharged adult patients with COVID-19 in Yichang. Method The retrospective study recruited 197 cases of COVID-19 discharged from Yichang Central People's Hospital and Yichang Third People's Hospital from Jan 17 to Feb 26, 2020. All cases were confirmed by real-time RT-PCR or chest computer tomography (CT).The survivors were followed up until March 4,2020. Clinical data, including demographic characteristic, presentation, exposure history, laboratory examination, radiology and prognosis were enrolled and analyzed by SPSS 19.0 software. Results There were 197 adult discharged patients with COVID-19 in this study. Statistical analysis indicated that the average age was 55.94 years, and female patients were 50.3%. Those patients mainly resided in urban with exposure history in 2 weeks. Fever, cough and weakness were the common symptoms. Leucocytes were mainly normal or decreased in 185 patents, both lymphocytes and eosinophils reduced, the ratios were 56.9% and 50.3%, respectively. On the contrary, lactate dehydrogenases raised in 65 patients. C-reactive protein elevated in the most of patients. The sensitivity of RT-PCR was 63.5%. Chest CT indicated that bilateral patchy shadows were the most common imaging manifestations.169 patients recovered and transferred to a designated hospital for observation, and the others turned worst and died of acute respiratory failure. Conclusion COIVD-19 infection have become a life-threaten public health problem, the sensitivity of RT-PCR was limited. Chest CT scan was recommended for the suspected patients. Moreover, lymphocytopenia and eosinophils declining without leukocytes increasing may be considered as a useful evidence for the diagnosis.

negative: The immune vulnerability landscape of the 2019 Novel Coronavirus, SARS-CoV-2 The outbreak of the 2019 Novel Coronavirus (SARS-CoV-2) rapidly spread from Wuhan, China to more than 150 countries, areas or territories, causing staggering number of infections and deaths. A systematic profiling of the immune vulnerability landscape of SARS-CoV-2, which can bring critical insights into the immune clearance mechanism, peptide vaccine development, and antiviral antibody development, is lacking. In this study, we investigated the potential of the SARS-CoV-2 viral proteins to induce class I and II MHC presentation and to form linear antibody epitopes. We created an online database to broadly share the predictions as a resource for the research community. Using this resource, we showed that genetic variations in SARS- CoV-2, though still few for the moment, already follow the pattern of mutations in related coronaviruses, and could alter the immune vulnerability landscape of this virus. Importantly, we discovered evidence that SARS-CoV-2, along with related coronaviruses, used mutations to evade attack from the human immune system. Overall, we present an immunological resource for SARS-CoV-2 that could promote both therapeutic development and mechanistic research.

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: [Options for controlling new Corona virus infection - 2019-nCoV]. According to the Situation Report 65 of the World Health Organization of March 25, 2020, the COVID-19 incidence rate indicates 413 467 confirmed cases and 18 433 deaths. Genetic diversification of the Corona virus has resulted in strains that cause severe respiratory tract infections in humans via drip and animal mediation. S-proteins covering its surface, which bind to the cell receptor - angiotensin converting enzyme 2 (ACE-2) and transmembrane serine protease (TMPRSS2) are important in shaping virus activity. The course of infection varies from mild to severe. The ability to control infection is limited because there are no drugs that fully inhibit 2019-nCoV. Interferon-alpha (5 million U twice daily by inhalation), lopinavir/ritonavir (400/100 mg twice daily orally), as well as chloroquine (500 mg twice daily orally for 10 days) and azithromycin (500 mg twice per day) cause a milder course of the disease and reduce the duration of treatment. The administration of glucocorticosteroids and research drugs (tocilizumab) is acceptable for massive infiltrative lesions in the pulmonary parenchyma causing severe lung injury (ALI) and acute respiratory distress syndrome (ARDS). In the system operation it is necessary to create the socalled a safety matrix that would take into account the existing threat on the one hand and all available services and resources on the other. Precise analysis and separation of individual tasks can enable the creation of a real crisis management plan.

negative: Viral and bacterial co-infection in severe pneumonia triggers innate immune responses and specifically enhances IP-10: a translational study Mixed viral and bacterial infections are widely described in community-acquired pneumonia; however, the clinical implications of co-infection on the associated immunopathology remain poorly studied. In this study, microRNA, mRNA and cytokine/chemokine secretion profiling were investigated for human monocyte-derived macrophages infected in-vitro with Influenza virus A/H1N1 and/or Streptococcus pneumoniae. We observed that the in-vitro co-infection synergistically increased interferon-γ-induced protein-10 (CXCL10, IP-10) expression compared to the singly-infected cells conditions. We demonstrated that endogenous miRNA-200a-3p, whose expression was synergistically induced following co-infection, indirectly regulates CXCL10 expression by targeting suppressor of cytokine signaling-6 (SOCS-6), a well-known regulator of the JAK-STAT signaling pathway. Additionally, in a subsequent clinical pilot study, immunomodulators levels were evaluated in samples from 74 children (≤5 years-old) hospitalized with viral and/or bacterial community-acquired pneumonia. Clinically, among the 74 cases of pneumonia, patients with identified mixed-detection had significantly higher (3.6-fold) serum IP-10 levels than those with a single detection (P = 0.03), and were significantly associated with severe pneumonia (P < 0.01). This study demonstrates that viral and bacterial co-infection modulates the JAK-STAT signaling pathway and leads to exacerbated IP-10 expression, which could play a major role in the pathogenesis of pneumonia.

negative: A Simple Scoring Method for Predicting the Low Risk of Persistent Acute Kidney Injury in Critically Ill Adult Patients The renal angina index has been proposed to identify patients at high risk of persistent AKI, based on slight changes in serum creatinine and patient conditions. However, a concise scoring method has only been proposed for pediatric patients, and not for adult patients yet. Here, we developed and validated a concise scoring method using data on patients admitted to ICUs in 21 Japanese hospitals from 2012 to 2014. We randomly assigned to either discovery or validation cohorts, identified the factors significantly associated with persistent AKI using a multivariable logistic regression model in the discovery cohort to establish a scoring system, and assessed the validity of the scoring in the validation cohort using receiver operating characteristic analysis and the calibration slope. Among 8,320 patients admitted to the ICUs, persistent AKI was present in 1,064 (12.8%) patients. In the discovery cohort (n = 4,151), ‘hyperbilirubinemia’, ‘sepsis’ and ‘ventilator and/or vasoactive’ with small changes in serum creatinine were selected to establish the scoring. In the validation cohort (n = 4,169), the predicting model based on this scoring had a c-statistic of 0.79 (95%CI, 0.77–0.81) and was well calibrated. In conclusion, we established a concise scoring method to identify potential patients with persistent AKI, which performed well in the validation cohort.

negative: Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection A newly identified coronavirus, 2019-nCoV, has been posing significant threats to public health since December 2019. ACE2, the host cell receptor for severe acute respiratory syndrome coronavirus (SARS), has recently been demonstrated in mediating 2019-nCoV infection. Interestingly, besides the respiratory system, substantial proportion of SARS and 2019-nCoV patients showed signs of various degrees of liver damage, the mechanism and implication of which have not yet been determined. Here, we performed an unbiased evaluation of cell type specific expression of ACE2 in healthy liver tissues using single cell RNA-seq data of two independent cohorts, and identified specific expression in cholangiocytes. The results indicated that virus might directly bind to ACE2 positive cholangiocytes but not necessarily hepatocytes. This finding suggested the liver abnormalities of SARS and 2019-nCoV patients may not be due to hepatocyte damage, but cholangiocyte dysfunction and other causes such as drug induced and systemic inflammatory response induced liver injury. Our findings indicate that special care of liver dysfunction should be installed in treating 2019-nCoV patients during the hospitalization and shortly after cure.

negative: Th2 predominance and CD8+ memory T cell depletion in patients with severe acute respiratory syndrome Abstract The immune spectrum of severe acute respiratory syndrome (SARS) is poorly understood. To define the dynamics of the immune spectrum in SARS, serum levels of cytokines, chemokines, immunoglobulins, complement and specific antibodies against SARS-associated coronavirus (SARS-CoV) were assayed by enzyme-linked immunosorbent assay (ELISA), and phenotypes of peripheral lymphocytes were analyzed by flow cytometry in 95 SARS-infected patients. Results showed that interleukin (IL)-10 and transforming growth factor β (TGF-β) were continuously up-regulated during the entirety of SARS. Regulated on activation normally T cell-expressed and secreted (RANTES) levels were decreased, while monocyte chemoattractant protein-1 (MCP-1) was elevated in acute patients. Immunoglobulins and complement were elevated during the first month of SARS. Both serum-positive rates and titers of specific IgM and IgG antibodies responding to SARS-CoV peaked at days 41–60 from the onset of SARS. CD4+ and CD8+ T lymphocytes decreased significantly in acute-phase. CD3+CD8+CD45RO+ T lymphocytes were decreased by 36.78% in the convalescent patients. Conclusion: SARS-CoV seemed to elicit effective humoral immunity but inhibited cellular immunity, especially CD8+ memory T lymphocytes over time. Prolonged overproduction of IL-10 and TGF-β may play an important role in the disease.

negative: 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.

negative: Modeling the effect of COVID-19 disease on the cardiac function: a computational study Background The effect of COVID-19 on the cardiac function and on the vascular system increases the morbidity and mortality of infected subjects with cardiovascular diseases. Objectives To provide preliminary results on cardiac global outcomes (such as cardiac output, ventricular pressures) obtained by means of computational models in plausible scenarios characterized by COVID-19. Methods We considered a lumped parameters computational model of the cardiovascular system, which models, from the mechanical point of view, the systemic and pulmonary circulations, the four cardiac valves and the four heart chambers, through mathematical equations of the underlying physical processes. To study the effect of COVID-19, we varied the heart rate, the contractility and the pulmonary resistances in suitable ranges. Results Our computations on individuals with both otherwise normal and impaired cardiac functions revealed that COVID-19 worsen cardiac function, as shown by a decrease of some cardiac biomarkers values such as cardiac output and ejection fraction. In the case of existing impaired cardiac function, the presence of COVID-19 lead to values outside the normal ranges. Conclusions Computational models revealed to be an effective tool to study the effect of COVID-19 on the cardiovascular system. Such effect could be significant for patients with impaired cardiac function. This is especially useful to perform a sensitivity analysis of the hemodynamics for different conditions. CONDENSED ABSTRACT Emerging studies address how COVID-19 infection might impact the cardiovascular system. This relates particularly to the development of myocardial injury, acute coronary syndrome, myocarditis, arrhythmia, and heart failure. Prospective treatment approach is advised for these patients. By the assessment of conventional important biomarkers obtained with new sources as a 0-dimentional computational model, we propose a new study protocol as an effective method to evaluate short-term prognosis. The clinical protocol proposed will help to rapidly identify which patients require intensive monitoring, diagnostic strategy and most adequate therapy.

negative: Updated understanding of the outbreak of 2019 novel coronavirus (2019‐nCoV) in Wuhan, China To help health workers and the public recognize and deal with the 2019 novel coronavirus (2019‐nCoV) quickly, effectively, and calmly with an updated understanding. A comprehensive search from Chinese and worldwide official websites and announcements was performed between 1 December 2019 and 9:30 am 26 January 2020 (Beijing time). A latest summary of 2019‐nCoV and the current outbreak was drawn. Up to 24 pm, 25 January 2020, a total of 1975 cases of 2019‐nCoV infection were confirmed in mainland China with a total of 56 deaths having occurred. The latest mortality was approximately 2.84% with a total of 2684 cases still suspected. The China National Health Commission reported the details of the first 17 deaths up to 24 pm, 22 January 2020. The deaths included 13 males and 4 females. The median age of the people who died was 75 (range 48‐89) years. Fever (64.7%) and cough (52.9%) were the most common first symptoms among those who died. The median number of days from the occurence of the first symptom to death was 14.0 (range 6‐41) days, and it tended to be shorter among people aged 70 years or more (11.5 [range 6‐19] days) than those aged less than 70 years (20 [range 10‐41] days; P = .033). The 2019‐nCoV infection is spreading and its incidence is increasing nationwide. The first deaths occurred mostly in elderly people, among whom the disease might progress faster. The public should still be cautious in dealing with the virus and pay more attention to protecting the elderly people from the virus.

negative: Clinical Perspective on 2019 Novel Coronavirus Pneumonia: A Systematic Review of Published Case Reports The ongoing pandemic of 2019 novel coronavirus (2019-nCoV), which originated from Wuhan, China, has led to 68,279 deaths due to 2019-nCoV pneumonia as of May 5, 2020. We conducted a systematic review and included 16 case reports to summarize the transmission and pathology of 2019-nCoV, and clinical presentation, laboratory and imaging findings, and treatment in 2019-nCoV pneumonia. The disease is mild in most people; in some, it may progress to severe pneumonia with acute respiratory distress syndrome (ARDS). Patients with mild illness usually recover at home, with supportive care and isolation in accordance with guidelines. Patients who have moderate to severe pneumonia are usually monitored in the hospital. Although there is no definitive treatment for 2019-nCoV pneumonia so far, some antiviral drugs have shown promising results. The use of lopinavir/ritonavir and remdesivir was associated with significant clinical improvement in severe pneumonia. Nonetheless, we need more randomized clinical trials (RCTs) and treatment guidelines for developing effective management of the 2019-nCoV and improve patient outcomes by reducing mortality in high-risk patients. We also need more clinical trials and management guidelines for the effective management of 2019-nCoV pneumonia.

negative: Genetic Profiles in Pharmacogenes Indicate Personalized Drug Therapy for COVID-19 Background: The coronavirus disease 2019 (COVID-19) has become a global pandemic currently. Many drugs showed potential for COVID-19 therapy. However, genetic factors which can lead to different drug efficiency and toxicity among populations are still undisclosed in COVID-19 therapy. Methods: We selected 67 potential drugs for COVID-19 therapy (DCTs) from clinical guideline and clinical trials databases. 313 pharmaco-genes related to these therapeutic drugs were included. Variation information in 125,748 exomes were collected for racial differences analyses. The expression level of pharmaco-genes in single cell resolution was evaluated from single-cell RNA sequencing (scRNA-seq) data of 17 healthy adults. Results: Pharmacogenes, including CYP3A4, ABCB1, SLCO1B1, ALB, CYP3A5, were involved in the process of more than multi DCTs. 224 potential drug-drug interactions (DDI) of DCTs were predicted, while 112 of them have been reported. Racial discrepancy of common nonsynonymous mutations was found in pharmacogenes including: VDR, ITPA, G6PD, CYP3A4 and ABCB1 which related to DCTs including ribavirin, -interferon, chloroquine and lopinavir. Moreover, ACE2, the target of 2019-nCoV, was only found in parts of lung cells, which makes drugs like chloroquine that prevent virus binding to ACE2 more specific than other targeted drugs such as camostat mesylate. Conclusions: At least 17 drugs for COVID-19 therapy with predictable pharmacogenes should be carefully utilized in risk races which are consisted of more risk allele carriers. At least 29 drugs with potential of DDIs are reported to be affected by other DDIs, they should be replaced by similar drugs without interaction if it is possible. Drugs which specifically targeted to infected cells with ACE2 such as chloroquine are preferred in COVID-19 therapy.

negative: A Novel Coronavirus (COVID-19) Outbreak A Call for Action

negative: Impact of immune enhancement on Covid-19 polyclonal hyperimmune globulin therapy and vaccine development Abstract The pandemic spread of a novel coronavirus – SARS coronavirus-2 (SARS-CoV-2) as a cause of acute respiratory illness, named Covid-19, is placing the healthcare systems of many countries under unprecedented stress. Global economies are also spiraling towards a recession in fear of this new life-threatening disease. Vaccines that prevent SARS-CoV-2 infection and therapeutics that reduces the risk of severe Covid-19 are thus urgently needed. A rapid method to derive antiviral treatment for Covid-19 is the use of convalescent plasma derived hyperimmune globulin. However, both hyperimmune globulin and vaccine development face a common hurdle – the risk of antibody-mediated disease enhancement. The goal of this review is to examine the body of evidence supporting the hypothesis of immune enhancement that could be pertinent to Covid-19. We also discuss how this risk could be mitigated so that both hyperimmune globulin and vaccines could be rapidly translated to overcome the current global health crisis.

negative: [Recommendation for the diagnosis and treatment of novel coronavirus infection in children in Hubei (Trial version 1)]. Since December 2019, a cluster of patients have been diagnosed to be infected with 2019 novel coronavirus (2019-nCoV) in Wuhan, China. The epidemic has been spreading to other areas of the country and abroad. A few cases have progressed rapidly to acute respiratory distress syndrome and/or multiple organ function failure. The epidemiological survey has indicated that the general population is susceptible to 2019-nCoV. A total of 14 children (6 months to 14 years of age, including 5 cases in Wuhan) have been confirmed to be infected with 2019-nCoV in China so far. In order to further standardize and enhance the clinical management of 2019-nCoV infection in children, reduce the incidence, and decrease the number of severe cases, we have formulated this diagnosis and treatment recommendation according to the recent information at home and abroad.

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: Review and Prospect of Pathological Features of Corona Virus Disease Abstract: Since 2003, coronavirus has caused multiple major public health events that resulted in global epidemics, such as severe acute respiratory syndrome ï¼SARSï¼, Middle East respiratory syndrome ï¼MERSï¼ and corona virus disease 2019 ï¼COVID-19ï¼. Especially since COVID-19 outbroke in Wuhan, Hubei, in December 2019, coronavirus has had a significant impact on people's health and lives. But so far, the pathological diagnosis of COVID-19 has been relatively deficientï¼ it is still confined to the pathological findings of punctured organs, and the majority of medical workers have poor awareness of its pathological characteristics. The COVID-19, as same as SARS and MERS, is caused by coronaviruses and can cause viral pneumonia. They have certain similarities. This article comprehensively reviews the pathological features observed in the autopsies of the aforementioned three diseases, in order to provide reference to the analysis of pathological changes of COVID-19.

negative: Biomarkers of lung‐related diseases: Current knowledge by proteomic approaches The lung epithelial surface is one of the vital barriers or sensors in the body responding to the external atmosphere and thereby always subjecting to direct toxicological exposure, stress, stimulus, or infection. Due to its relatively higher sensitivity in response to toxicants, the use of lung epithelial cell culture and lung tissue from animal models or patients has facilitated our learning to lung physiopathology and toxicopharmacology. The recent advancement of proteomics has made it possible to investigate the cellular response at a global level. In this review, the potential applications of proteomic approach in studying lung‐related diseases and biomarker discovery will be discussed. J. Cell. Physiol. 221: 535–543, 2009. © 2009 Wiley‐Liss, Inc.

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

negative: A review of equine sepsis Sepsis is defined as an exaggerated, systemic inflammatory response to infection and is a common condition in horses. Systemic inflammatory response syndrome (SIRS) associated with bacterial infection is a hallmark of sepsis. Sepsis in neonatal foals is a common sequela of failure of passive transfer and, in addition to development of SIRS, may be characterised by bacteraemia, pneumonia, enterocolitis, omphalophlebitis, meningoencephalitis or arthritis. Sepsis in mature horses is most commonly observed secondary to gastrointestinal lesions that result in disrupted mucosa and bacterial translocation into circulation (endotoxaemia). Pleuropneumonia and metritis may also cause sepsis in mature horses. Diagnosis of sepsis is based on SIRS criteria as well as suspected or confirmed infection. Due to the relatively low sensitivity of microbial culture and the subjectivity of sepsis scoring, many sepsis biomarkers are being studied for their usefulness in diagnosis and prognostication of sepsis in horses. Treatment of sepsis requires an intensive care approach that includes antimicrobial drug administration, fluid resuscitation and pressure support, and treatment for inflammation, endotoxaemia and coagulopathy. Early recognition of sepsis and prompt antimicrobial drug treatment are critical for a successful outcome. Multiple organ dysfunction syndrome may occur in severe cases of sepsis, with common manifestations including laminitis and coagulopathies. Although prognosis for septic mature horses depends highly on the primary disease process, the overall survival rate in septic neonatal foals ranges from 26 to 86%, with most studies indicating a survival rate of 45–60%.

negative: Factors associated with clinical outcome in 25 patients with avian influenza A (H7N9) infection in Guangzhou, China BACKGROUND: Guangzhou reported its first laboratory-confirmed case of influenza A (H7N9) on January 10, 2014. A total of 25 cases were reported from the first wave of the epidemic until April 8, 2014. The fatality rate was much higher than in previous reports. The objective of the current work was to describe the clinical and epidemiological characteristics of A (H7N9) patients in Guangzhou and explore possible reasons for the high fatality rate. METHODS: Clinical and epidemiological information regarding A (H7N9) cases in Guangzhou was collected through review of medical records and field research. Data regarding clinical and laboratory features, treatment, and outcomes were extracted. RESULTS: Of the 25 patients, 84 % (21/25) had one or more underlying diseases. Fifteen patients (60.0 %) developed moderate to severe acute respiratory distress syndrome (ARDS), and 14 (56 %) died of the ARDS or multiorgan failure. Patients with longer delay between onset of illness and initiation of oseltamivir treatment were more likely to develop ARDS. Elevated C-creative protein, aspartate aminotransferase, creatine kinase, and lymphocytopenia predicted a higher risk of developing ARDS. CONCLUSIONS: The presence of underlying diseases and clinical complications predicted poor clinical outcome. Early oseltamivir treatment was associated with a reduced risk of developing ARDS.

negative: Of chloroquine and COVID-19 Abstract Recent publications have brought attention to the possible benefit of chloroquine, a broadly used antimalarial drug, in the treatment of patients infected by the novel emerged coronavirus (SARS-CoV-2). The scientific community should consider this information in light of previous experiments with chloroquine in the field of antiviral research.

negative: IFNΛ3/4 locus polymorphisms and IFNΛ3 circulating levels are associated with COPD severity and outcomes BACKGROUND: Interferon lambdas (IFNLs) have important anti-viral/bacterial and immunomodulatory functions in the respiratory tract. How do IFNLs impact COPD and its exacerbations? METHODS: Five hundred twenty eight patients were recruited in a prospective observational multicentre cohort (PROMISE) study. The genetic polymorphisms (rs8099917 and rs12979860) within the IFNL3/4 gene region and circulating levels of IFNL3 in COPD patients were determined and associated with disease activity and outcome during a median follow-up of 24 months. RESULTS: The GG genotype significantly influenced severe exacerbation rate (42 vs. 23%; p = 0.032) and time to severe exacerbation (HR = 2.260; p = 0.012). Compared to the TT or TG genotypes, the GG genotype was associated with severe dyspnoea (modified medical research council score ≥ median 3; 22 vs 42%, p = 0.030). The CC genotype of the rs12979860 SNP was associated with a poorer prognosis (body mass index, airflow obstruction, dyspnea and exercise capacity index ≥ median 4; 46 vs. 36% TC vs. 20.5% TT; p = 0.031). Patients with stable COPD and at exacerbation had significantly lower circulating IFNL3 compared to healthy controls (p < 0.001 and p < 0.001, respectively). Circulating IFNL3 correlated to post-bronchodilator FEV(1)%predicted and the tissue maturation biomarker Pro-collagen 3. CONCLUSION: IFNL3/4 polymorphisms and circulating IFNL3 may be associated with disease activity and outcomes in COPD. TRIAL REGISTRATION: Clinical Trial registration http://www.isrctn.com/ identifier ISRCTN99586989 on 16 April 2008.

negative: What Have We Learned About Middle East Respiratory Syndrome Coronavirus Emergence in Humans? A Systematic Literature Review Background: Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in humans in 2012. A systematic literature review was conducted to synthesize current knowledge and identify critical knowledge gaps. Materials and Methods: We conducted a systematic review on MERS-CoV using PRISMA guidelines. We identified 407 relevant, peer-reviewed publications and selected 208 of these based on their contributions to four key areas: virology; clinical characteristics, outcomes, therapeutic and preventive options; epidemiology and transmission; and animal interface and the search for natural hosts of MERS-CoV. Results: Dipeptidyl peptidase 4 (DPP4/CD26) was identified as the human receptor for MERS-CoV, and a variety of molecular and serological assays developed. Dromedary camels remain the only documented zoonotic source of human infection, but MERS-like CoVs have been detected in bat species globally, as well as in dromedary camels throughout the Middle East and Africa. However, despite evidence of camel-to-human MERS-CoV transmission and cases apparently related to camel contact, the source of many primary cases remains unknown. There have been sustained health care-associated human outbreaks in Saudi Arabia and South Korea, the latter originating from one traveler returning from the Middle East. Transmission mechanisms are poorly understood; for health care, this may include environmental contamination. Various potential therapeutics have been identified, but not yet evaluated in human clinical trials. At least one candidate vaccine has progressed to Phase I trials. Conclusions: There has been substantial MERS-CoV research since 2012, but significant knowledge gaps persist, especially in epidemiology and natural history of the infection. There have been few rigorous studies of baseline prevalence, transmission, and spectrum of disease. Terms such as “camel exposure” and the epidemiological relationships of cases should be clearly defined and standardized. We strongly recommend a shared and accessible registry or database. Coronaviruses will likely continue to emerge, arguing for a unified “One Health” approach.

negative: Human monoclonal IgG selection of Plasmodium falciparum for the expression of placental malaria-specific variant surface antigens Pregnancy-associatedPlasmodium falciparum malaria (PAM) is a major cause of morbidity and mortality in African women and their offspring. PAM is characterized by accumulation of infected erythrocytes (IEs) that adhere to chondroitin sulphate A (CSA) in the placental intervillous space. We show here that human monoclonal IgG antibodies with specificity for variant surface antigens (VSA) specifically expressed by CSA-adhering IEs (VSA(PAM)) can be used in vitro to select parasites from nonpregnant donors to express VSA(PAM) and that this selection for VSA(PAM) expression results in preferential transcription of var2csa. The results corroborate current efforts to develop PAM-specific vaccines based on VAR2CSA.

negative: A distinct name is needed for the new coronavirus

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: Acute phase response in bovine coronavirus positive post-weaned calves with diarrhea Bovine coronavirus (BCoV) is associated with severe diarrhea in calves, winter dysentery in adult cattle, and respiratory diseases in cattle of all ages. This study aimed to investigate the relationship between white blood cell counts and haptoglobin (Hp) and serum amyloid A (SAA) levels in post-weaned calves with diarrhea caused by BCoV and those that recovered from diarrhea. Blood and fecal samples were collected twice from the same animals; 17 post-weaned calves with diarrhea (first) and 15 post-weaned calves that recovered from diarrhea (second). Real-time polymerase chain reaction revealed that all 17 fecal samples from post-weaned calves with diarrhea and one out of 15 from diarrhea-recovered calves were positive for BCoV and negative for Cryptosporidium spp., Escherichia coli K99, Salmonella spp., bovine rotavirus, and bovine viral diarrhea virus. No Eimeria oocysts were detected using the flotation method. In comparison with post-weaned calves with diarrhea, in diarrhea-recovered calves, the lymphocyte count was significantly higher (P = 0.018), and the monocyte count was significantly lower (P = 0.001); however, the number of monocytes was still high. Post-weaned calves with diarrhea had a significantly higher Hp concentration (P < 0.001) compared with diarrhea-recovered calves. The results indicated that increased Hp concentration and monocytosis but not SAA may be associated with diarrhea caused by BCoV. The present study suggests that the monitoring of Hp concentration and monocyte count is useful in the diagnosis of post-weaned calves with diarrhea caused by BCoV in this field.

negative: Characterization and application of monoclonal antibodies against N protein of SARS-coronavirus Abstract Severe acute respiratory syndrome-coronavirus (SARS-CoV) causes an infectious disease through respiratory route. Diagnosing the disease effectively and accurately at early stage is essential for preventing the disease transmission and performing antiviral treatment. In this study, we raised monoclonal antibodies (mAbs) against the nucleocapsid (N) protein of SARS-CoV and mapped epitopes by using different truncated N protein fragments. The mapping of those epitopes was valuable for constructing pair-Abs used in serological diagnosis. The results showed that all of the six raised mAbs were divided into two groups recognizing the region of amino acids 249–317 (A group) or 317–395 (B group). This region spanning amino acids 249–395 contains predominant B cell epitopes located at the C-terminus of N protein. One pair-Abs, consisting of N protein-specific rabbit polyclonal antibody and SARS-CoV N protein-specific mAb, was selected to construct a sandwich ELISA-kit. The kit was able to specifically detect SARS-CoV N proteins in serum samples.

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: Targeting Neprilysin (NEP) pathways: A potential new hope to defeat COVID-19 ghost COVID-19 is an ongoing viral pandemic disease that is caused by SARS-CoV2, inducing severe pneumonia in humans. However, several classes of repurposed drugs have been recommended, no specific vaccines or effective therapeutic interventions for COVID-19 are developed till now. Viral dependence on ACE-2, as entry receptors, drove the researchers into RAS impact on COVID-19 pathogenesis. Several evidences have pointed at Neprilysin (NEP) as one of pulmonary RAS components. Considering the protective effect of NEP against pulmonary inflammatory reactions and fibrosis, it is suggested to direct the future efforts towards its potential role in COVID-19 pathophysiology. Thus, the review aimed to shed light on the potential beneficial effects of NEP pathways as a novel target for COVID-19 therapy by summarizing its possible molecular mechanisms. Additional experimental and clinical studies explaining more the relationships between NEP and COVID-19 will greatly benefit in designing the future treatment approaches.

negative: SARS CTL Vaccine Candidates — HLA Supertype, Genome‐Wide Scanning and Biochemical Validation An effective SARS vaccine is likely to include components that can induce specific cytotoxic T‐cell (CTL) responses. The specificities of such responses are governed by HLA‐restricted presentation of SARS‐derived peptide epitopes. Exact knowledge of how the immune system handles protein antigens would allow for the identification of such linear sequences directly from genomic/proteomic sequence information. The latter was recently established when a causative coronavirus (SARS CoV) was isolated and full‐length sequenced. Here, we have combined advanced bioinformatics and high‐throughput immunology to perform an HLA supertype, genome‐wide scan for SARS‐specific cytotoxic T cell epitopes. The scan includes all nine human HLA supertypes in total covering >99% of all major human populations. For each HLA supertype, we have selected the 15 top candidates for test in biochemical‐binding assays. At this time (approximately 6 months after the genome was established), we have tested the majority of the HLA supertypes and identified almost 100 potential vaccine candidates. These should be further validated in SARS survivors and used for vaccine formulation. We suggest that immunobioinformatics may become a fast and valuable tool in rational vaccine design.

negative: [The differential diagnosis of pulmonary infiltrates in cancer patients during the outbreak of the 2019 novel coronavirus disease]. Objective: To investigate the principles of differential diagnosis of pulmonary infiltrates in cancer patients during the outbreak of novel coronavirus (2019-nCoV) by analyzing one case of lymphoma who presented pulmonary ground-glass opacities (GGO) after courses of chemotherapy. Methods: Baseline demographics and clinicopathological data of eligible patients were retrieved from medical records. Information of clinical manifestations, history of epidemiology, lab tests and chest CT scan images of visiting patients from February 13 to February 28 were collected. Literatures about pulmonary infiltrates in cancer patients were searched from databases including PUBMED, EMBASE and CNKI. Results: Among the 139 cancer patients underwent chest CT scans before chemotherapy, pulmonary infiltrates were identified in eight patients (5.8%), five of whom were characterized as GGOs in lungs. 2019-nCoV nuclear acid testing was performed in three patients and the results were negative. One case was a 66-year-old man diagnosed as non-Hodgkin lymphoma and underwent CHOP chemotherapy regimen. His chest CT scan image displayed multiple GGOs in lungs and the complete blood count showed decreased lymphocytes. This patient denied any contact with confirmed/suspected cases of 2019-nCoV infection and without fever and other respiratory symptoms. Considering the negative result of nuclear acid testing, this patient was presumptively diagnosed as viral pneumonia and an experiential anti-infection treatment had been prescribed for him. Conclusions: The 2019 novel coronavirus disease (COVID-19) complicates the clinical scenario of pulmonary infiltrates in cancer patients. The epidemic history, clinical manifestation, CT scan image and lab test should be combined consideration. The 2019-nCoV nuclear acid testing might be applicated in more selected patients. Active anti-infection treatment and surveillance of patient condition should be initiated if infectious disease is considered.

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

negative: CT quantification of pneumonia lesions in early days predicts progression to severe illness in a cohort of COVID-19 patients Rationale: Some patients with coronavirus disease 2019 (COVID-19) rapidly develop respiratory failure or even die, underscoring the need for early identification of patients at elevated risk of severe illness. This study aims to quantify pneumonia lesions by computed tomography (CT) in the early days to predict progression to severe illness in a cohort of COVID-19 patients. Methods: This retrospective cohort study included confirmed COVID-19 patients. Three quantitative CT features of pneumonia lesions were automatically calculated using artificial intelligence algorithms, representing the percentages of ground-glass opacity volume (PGV), semi-consolidation volume (PSV), and consolidation volume (PCV) in both lungs. CT features, acute physiology and chronic health evaluation II (APACHE-II) score, neutrophil-to-lymphocyte ratio (NLR), and d-dimer, on day 0 (hospital admission) and day 4, were collected to predict the occurrence of severe illness within a 28-day follow-up using both logistic regression and Cox proportional hazard models. Results: We included 134 patients, of whom 19 (14.2%) developed any severe illness. CT features on day 0 and day 4, as well as their changes from day 0 to day 4, showed predictive capability. Changes in CT features from day 0 to day 4 performed the best in the prediction (area under the receiver operating characteristic curve = 0.93, 95% confidence interval [CI] 0.87~0.99; C-index=0.88, 95% CI 0.81~0.95). The hazard ratios of PGV and PCV were 1.39 (95% CI 1.05~1.84, P=0.023) and 1.67 (95% CI 1.17~2.38, P=0.005), respectively. CT features, adjusted for age and gender, on day 4 and in terms of changes from day 0 to day 4 outperformed APACHE-II, NLR, and d-dimer. Conclusions: CT quantification of pneumonia lesions can early and non-invasively predict the progression to severe illness, providing a promising prognostic indicator for clinical management of COVID-19.

negative: Advances in mass spectrometry for the identification of pathogens Mass spectrometry (MS) has become an important technique to identify microbial biomarkers. The rapid and accurate MS identification of microorganisms without any extensive pretreatment of samples is now possible. This review summarizes MS methods that are currently utilized in microbial analyses. Affinity methods are effective to clean, enrich, and investigate microorganisms from complex matrices. Functionalized magnetic nanoparticles might concentrate traces of target microorganisms from sample solutions. Therefore, nanoparticle‐based techniques have a favorable detection limit. MS coupled with various chromatographic techniques, such as liquid chromatography and capillary electrophoresis, reduces the complexity of microbial biomarkers and yields reliable results. The direct analysis of whole pathogenic microbial cells with matrix‐assisted laser desorption/ionization MS without sample separation reveals specific biomarkers for taxonomy, and has the advantages of simplicity, rapidity, and high‐throughput measurements. The MS detection of polymerase chain reaction (PCR)‐amplified microbial nucleic acids provides an alternative to biomarker analysis. This review will conclude with some current applications of MS in the identification of pathogens. © 2010 Wiley Periodicals, Inc., Mass Spec Rev 30:1203–1224, 2011

negative: [Perinatal and neonatal management plan for prevention and control of 2019 novel coronavirus infection (1st Edition)]. Since December 2019, the novel coronavirus (2019-nCoV) infection has been prevalent in China. Due to immaturity of immune function and the possibility of mother-fetal vertical transmission, neonates are particularly susceptible to 2019-nCoV. The perinatal-neonatal departments should cooperate closely and take integrated approaches, and the neonatal intensive care unit should prepare the emergency plan for 2019-nCoV infection as far as possible, so as to ensure the optimal management and treatment of potential victims. According to the latest 2019-nCoV national management plan and the actual situation, the Working Group for the Prevention and Control of Neonatal 2019-nCoV Infection in the Perinatal Period of the Editorial Committee of Chinese Journal of Contemporary Pediatrics puts forward recommendations for the prevention and control of 2019-nCoV infection in neonates.

negative: Cytokeratin 8/18 overexpression and complex formation as an indicator of GST-P positive foci transformation into hepatocellular carcinomas Abstract Screening of the proteome of microdissected glutathione S-transferase placental form (GST-P) positive foci and normal-appearing liver on anionic (Q10), and cationic (CM10) surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) ProteinChip arrays demonstrated significant overexpression of cytokeratin 8 (CK8; m/z 54,020), cytokeratin 18 (CK18; m/z 47,760), microsomal cytochrome 5A (m/z 15,224) and histone type 2 H2aa3 (m/z 15,964) in the livers of rats initiated with diethylnitrosamine (DEN) followed by 10 weeks on phenobarbital (PB) at a dose of 500 ppm. Furthermore, formation of CK8 and CK18 complexes due to CK8 phosphorylation at Ser73 and Ser431 was found to be strongly associated with promotion of hepatocarcinogenesis by PB and the development of hepatocellular carcinomas. The data were confirmed by immunohistochemistry and real-time Q-PCR and profound overexpression of CK8 and CK18 (CK8/18) proteins and mRNAs were detected in several large size GST-P positive foci and liver tumors. A strong correlation between CK8/18 positive foci development and multiplicity of hepatocellular carcinomas was further observed. Moreover, elevation of CK8/18 was strongly associated with induction of cell proliferation in GST-P positive foci and tumors. In conclusion, our data imply that CK8/18 overexpression, those two cytokeratins complex formation associated with histone type 2 H2aa3 up-regulation and intermediate filament reorganization may drive neoplastic transformation of GST-P positive foci during rat hepatocarcinogenesis leading to the formation of hepatocellular carcinomas.

negative: Human Coronaviruses: A Review of Virus–Host Interactions Human coronaviruses (HCoVs) are known respiratory pathogens associated with a range of respiratory outcomes. In the past 14 years, the onset of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have thrust HCoVs into spotlight of the research community due to their high pathogenicity in humans. The study of HCoV-host interactions has contributed extensively to our understanding of HCoV pathogenesis. In this review, we discuss some of the recent findings of host cell factors that might be exploited by HCoVs to facilitate their own replication cycle. We also discuss various cellular processes, such as apoptosis, innate immunity, ER stress response, mitogen-activated protein kinase (MAPK) pathway and nuclear factor kappa B (NF-κB) pathway that may be modulated by HCoVs.

negative: Serum IFN-γ–induced protein 10 (IP-10) as a biomarker for severity of acute respiratory infection in healthy adults BACKGROUND: The inflammatory chemokine, interferon-gamma inducible protein of 10 kDa (IP-10), is a biomarker associated with several conditions. OBJECTIVES: This study investigated serum concentrations of IP-10 in healthy individuals who developed acute respiratory infection (ARI). The hypothesis is that serum IP-10 concentrations correlate with ARI severity and detection of viral pathogens. STUDY DESIGN: Data come from a randomized controlled trial measuring the effects of mindfulness meditation or exercise on ARI (Clinical Trials ID: NCT01654289). Healthy adults ages 30–69 were followed for a single season for ARI incidence and severity. This trial is ongoing, and the investigators are still blinded. When a participant reported ARI symptoms, nasal swab and lavage for PCR-based viral identification and blood samples were collected within the first 72 hours of ARI symptoms. Serum IP-10 concentrations were measured by ELISA (R&D Systems, Inc. Quantikine ELISA, Minneapolis, MN). ARI severity was measured using the validated Wisconsin Upper Respiratory Symptom Survey (WURSS-24) until the ARI episode resolved. RESULTS: Serum IP-10 concentrations from 225 ARI episodes correlated with ARI global severity (rho 0.28 [95% CI: 0.15–0.39]; p<0.001). IP-10 concentrations were higher with an ARI in which a viral pathogen was detected compared to no viral pathogen detected (median 366 pg/ml [IQR: 227–486] vs 163 pg/ml [IQR: 127–295], p<0.0001). Influenza infections had higher IP-10 concentrations than coronavirus, enterovirus or rhinovirus, and paramyxovirus. CONCLUSION: Serum IP-10 concentration correlates with ARI global severity. Also, IP-10 concentration measured early in the course of the ARI correlates with the daily severity, duration, and illness symptoms.

negative: Identification of serum proteomic biomarkers for early porcine reproductive and respiratory syndrome (PRRS) infection BACKGROUND: Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant swine diseases worldwide. Despite its relevance, serum biomarkers associated with early-onset viral infection, when clinical signs are not detectable and the disease is characterized by a weak anti-viral response and persistent infection, have not yet been identified. Surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF MS) is a reproducible, accurate, and simple method for the identification of biomarker proteins related to disease in serum. This work describes the SELDI-TOF MS analyses of sera of 60 PRRSV-positive and 60 PRRSV-negative, as measured by PCR, asymptomatic Large White piglets at weaning. Sera with comparable and low content of hemoglobin (< 4.52 μg/mL) were fractionated in 6 different fractions by anion-exchange chromatography and protein profiles in the mass range 1–200 kDa were obtained with the CM10, IMAC30, and H50 surfaces. RESULTS: A total of 200 significant peaks (p < 0.05) were identified in the initial discovery phase of the study and 47 of them were confirmed in the validation phase. The majority of peaks (42) were up-regulated in PRRSV-positive piglets, while 5 were down-regulated. A panel of 14 discriminatory peaks identified in fraction 1 (pH = 9), on the surface CM10, and acquired at low focus mass provided a serum protein profile diagnostic pattern that enabled to discriminate between PRRSV-positive and -negative piglets with a sensitivity and specificity of 77% and 73%, respectively. CONCLUSIONS: SELDI-TOF MS profiling of sera from PRRSV-positive and PRRSV-negative asymptomatic piglets provided a proteomic signature with large scale diagnostic potential for early identification of PRRSV infection in weaning piglets. Furthermore, SELDI-TOF protein markers represent a refined phenotype of PRRSV infection that might be useful for whole genome association studies.

negative: Coronavirus derived expression systems Abstract Both helper dependent expression systems, based on two components, and single genomes constructed by targeted recombination, or by using infectious cDNA clones, have been developed. The sequences that regulate transcription have been characterized mainly using helper dependent expression systems and it will now be possible to validate them using single genomes. The genome of coronaviruses has been engineered by modification of the infectious cDNA leading to an efficient (>20 μg ml−1) and stable (>20 passages) expression of the foreign gene. The possibility of engineering the tissue and species tropism to target expression to different organs and animal species, including humans, increases the potential of coronaviruses as vectors. Thus, coronaviruses are promising virus vectors for vaccine development and, possibly, for gene therapy.

negative: Other Community Respiratory Viruses Polymerase chain reaction–based diagnosis has become the standard for viral pneumonia and other respiratory tract infections. Expansion of respiratory viral panels (RVPs) outside of influenza and, possibly, respiratory syncytial virus has led to the ability to diagnose viral infections for which no approved specific antiviral treatment exists. Careful clinical evaluation of the patient with a positive RVP is, therefore, critical given the limited repertoire of treatments. Generic treatments with intravenous immunoglobulin, ribavirin, and interferons may benefit select severe viral pneumonia patients, whereas cidofovir has activity for severe adenoviral pneumonia.

negative: A Biomarker-Based Approach to Infectious Disease in the Pediatric Emergency Department In modern pediatric emergency medicine, biomarker-based assays that enable quick bedside diagnostics and subsequent disease management can be valuable. There is a growing need for novel, disease-specific biomarkers that can improve the outcome of pediatric infectious diseases commonly encountered in the emergency department (ED). Viral respiratory infections, central nervous system infections, sepsis, and septic shock are acute disease states frequently encountered in the ED. In this review, we describe a host of novel biomarkers, including a diverse set of cytokines, chemokines, and nitric oxide–based metabolites. Based on disease pathophysiology, a rationale is provided for a molecular- or biomarker-based approach in the ED. Throughout this review, emphasis is placed on diagnostic rapidity because this relates directly to timeliness and quality of care in a busy ED. Once the biomarkers become more clinically available, in a rapid ED setting as bedside point-of-care assays, quality of care will be enhanced, not only by means of diagnostics but also in prognosticating severity of illness.

negative: Cardiovascular disease as a biomarker for an increased risk of COVID-19 infection and related poor prognosis

negative: Emerging Influenza and Psychosis: An Important Story in Psychological Medicine

negative: Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus-related coronavirus model BACKGROUND: Medicines for the treatment of 2019-novel coronavirus (2019-nCoV) infections are urgently needed. However, drug screening using live 2019-nCoV requires high-level biosafety facilities, which imposes an obstacle for those institutions without such facilities or 2019-nCoV. This study aims to repurpose the clinically approved drugs for the treatment of coronavirus disease 2019 (COVID-19) in a 2019-nCoV-related coronavirus model. METHODS: A 2019-nCoV-related pangolin coronavirus GX_P2V/pangolin/2017/Guangxi was described. Whether GX_P2V uses angiotensin-converting enzyme 2 (ACE2) as the cell receptor was investigated by using small interfering RNA (siRNA) -mediated silencing of ACE2. The pangolin coronavirus model was used to identify drug candidates for treating 2019-nCoV infection. Two libraries of 2406 clinically approved drugs were screened for their ability to inhibit cytopathic effects on Vero E6 cells by GX_P2V infection. The anti-viral activities and anti-viral mechanisms of potential drugs were further investigated. Viral yields of RNAs and infectious particles were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and plaque assay, respectively. RESULTS: The spike protein of coronavirus GX_P2V shares 92.2% amino acid identity with that of 2019-nCoV isolate Wuhan-hu-1, and uses ACE2 as the receptor for infection just like 2019-nCoV. Three drugs, including cepharanthine (CEP), selamectin, and mefloquine hydrochloride, exhibited complete inhibition of cytopathic effects in cell culture at 10 μmol/L. CEP demonstrated the most potent inhibition of GX_P2V infection, with a concentration for 50% of maximal effect [EC(50)] of 0.98 μmol/L. The viral RNA yield in cells treated with 10 μmol/L CEP was 15,393-fold lower than in cells without CEP treatment ([6.48 ± 0.02] × 10(−4)vs. 1.00 ± 0.12, t = 150.38, P < 0.001) at 72 h post-infection (p.i.). Plaque assays found no production of live viruses in media containing 10 μmol/L CEP at 48 h p.i. Furthermore, we found CEP had potent anti-viral activities against both viral entry (0.46 ± 0.12, vs.1.00 ± 0.37 t = 2.42, P < 0.05) and viral replication ([6.18 ± 0.95] × 10(−4)vs. 1.00 ± 0.43, t = 3.98, P < 0.05). CONCLUSIONS: Our pangolin coronavirus GX_P2V is a workable model for 2019-nCoV research. CEP, selamectin, and mefloquine hydrochloride are potential drugs for treating 2019-nCoV infection. Our results strongly suggest that CEP is a wide-spectrum inhibitor of pan-betacoronavirus, and further study of CEP for treatment of 2019-nCoV infection is warranted.

negative: Serum Surfactant Protein D (SP-D) is a Prognostic Marker of Poor Outcome in Patients with A/H1N1 Virus Infection INTRODUCTION: Surfactant protein D (SP-D) plays an important role in the innate responses against pathogens and its production is altered in lung disorders. METHODS: We studied the circulating levels of SP-D in 37 patients with acute respiratory distress syndrome due to the A/H1N1 virus infection and in 40 healthy controls. Cox logistic regression models were constructed to explore the association of SP-D levels and risk of death. RESULTS: Mortality rate after a 28-day was 32.42 %. Significant higher levels of SP-D were detected in A/H1N1 patients with fatal outcome (p < 0.05). After adjusting for confounding variables, levels of SP-D ≥250 ng/mL were associated with increased the risk of death (HR = 8.27, 95 % CI 1.1–64.1, p = 0.043). CONCLUSIONS: Our results revealed that higher circulating levels of SP-D are associated with higher mortality risk in critically ill A/H1N1 patients. SP-D might be a predictive factor of poor outcomes in viral pneumonia.

negative: Interleukin-6 Is a Potential Biomarker for Severe Pandemic H1N1 Influenza A Infection Pandemic H1N1 influenza A (H1N1pdm) is currently a dominant circulating influenza strain worldwide. Severe cases of H1N1pdm infection are characterized by prolonged activation of the immune response, yet the specific role of inflammatory mediators in disease is poorly understood. The inflammatory cytokine IL-6 has been implicated in both seasonal and severe pandemic H1N1 influenza A (H1N1pdm) infection. Here, we investigated the role of IL-6 in severe H1N1pdm infection. We found IL-6 to be an important feature of the host response in both humans and mice infected with H1N1pdm. Elevated levels of IL-6 were associated with severe disease in patients hospitalized with H1N1pdm infection. Notably, serum IL-6 levels associated strongly with the requirement of critical care admission and were predictive of fatal outcome. In C57BL/6J, BALB/cJ, and B6129SF2/J mice, infection with A/Mexico/4108/2009 (H1N1pdm) consistently triggered severe disease and increased IL-6 levels in both lung and serum. Furthermore, in our lethal C57BL/6J mouse model of H1N1pdm infection, global gene expression analysis indicated a pronounced IL-6 associated inflammatory response. Subsequently, we examined disease and outcome in IL-6 deficient mice infected with H1N1pdm. No significant differences in survival, weight loss, viral load, or pathology were observed between IL-6 deficient and wild-type mice following infection. Taken together, our findings suggest IL-6 may be a potential disease severity biomarker, but may not be a suitable therapeutic target in cases of severe H1N1pdm infection due to our mouse data.

negative: Immune responses induced by DNA vaccines bearing Spike gene of PEDV combined with porcine IL-18 Abstract Porcine epidemic diarrhea virus (PEDV) is the causative agent of porcine epidemic diarrhea, a highly contagious enteric disease of swine. The Spike (S) protein is one of the main structural proteins of PEDV capable of inducing neutralizing antibodies in vivo. Herein, we generated three distinct DNA constructs in the eukaryotic expression plasmid pVAX1; one encoding the S protein [pVAX1-(PEDV-S)], the second encoding the N-terminal fragment (S1) [pVAX1-(PEDV-S1)] containing potent antigenic sites, and the third expressing the porcine interleukin-18 (pIL-18) [pVAX1-(IL-18)]. Immunofluorescence assays in BHK-21 cells demonstrated successful protein expression from all 3 constructs. Kunming mice were injected separately with each of these constructs or with a pVAX1-(PEDV-S1)/pVAX1-(IL-18) combination, an attenuated PEDV vaccine, or vector only control. Animals were examined for T lymphocyte proliferation, anti-PEDV antibodies, IFN-γ and IL-4 protein levels, and cytotoxic T cell function in mouse peripheral blood and spleen. In all cases, results showed that pVAX1-(PEDV-S) and the combination of pVAX1-(PEDV-S1) with pVAX1-(IL-18) induced the strongest responses; however, pIL-18 had no adjuvant effects when given in combination with pVAX1-(PEDV-S1).

negative: Structural genomics and interactomics of 2019 Wuhan novel coronavirus, 2019-nCoV, indicate evolutionary conserved functional regions of viral proteins During its first month, the recently emerged 2019 Wuhan novel coronavirus (2019-nCoV) has already infected many thousands of people in mainland China and worldwide and took hundreds of lives. However, the swiftly spreading virus also caused an unprecedentedly rapid response from the research community facing the unknown health challenge of potentially enormous proportions. Unfortunately, the experimental research to understand the molecular mechanisms behind the viral infection and to design a vaccine or antivirals is costly and takes months to develop. To expedite the advancement of our knowledge we leverage the data about the related coronaviruses that is readily available in public databases, and integrate these data into a single computational pipeline. As a result, we provide a comprehensive structural genomics and interactomics road-maps of 2019-nCoV and use these information to infer the possible functional differences and similarities with the related SARS coronavirus. All data are made publicly available to the research community at http://korkinlab.org/wuhan

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: Risk map of the novel coronavirus (2019-nCoV) in China: proportionate control is needed Background China is running a national level antivirus campaign against the novel coronavirus (2019-nCoV). Strict control measures are being enforced in either the populated areas and remote regions. While the virus is closed to be under control, tremendous economic loss has been caused. Methods and findings We assessed the pandemic risk of 2019-nCoV for all cities/regions in China using the random forest algorithm, taking into account the effect of five factors: the accumulative and increased numbers of confirmed cases, total population, population density, and GDP. We defined four levels of the risk, corresponding to the four response levels to public health emergencies in China. The classification system has good consistency among cities in China, as the error rate of the confusion matrix is 1.58%. Conclusions The pandemic risk of 2019-nCoV is dramatically different among the 442 cities/regions. We recommend to adopt proportionate control policy according to the risk level to reduce unnecessary economic loss.

negative: A model for 2019-nCoV infection with treatment The current emergence of coronavirus (2019-nCoV or COVID-19) puts the world in threat. 2019-nCoV remains the outbreak of SARS-CoV 2002-2003. The structural research on the receptor recognition by SARS-CoV has identified the key interactions between SARS-CoV spike protein and its host receptor, also known as angiotensin converting enzyme 2 (ACE2). It controls both the cross-species and human-to-human transmissions of SARS-CoV. In this article, we have considered the infection dynamics of SARS-CoV-2 infection in the acute stage. Our aim is to propose and analyse a mathematical model for investigating the effect of CTL responses over the viral mutation to control the viral infection when a post-infection vaccine is administered at regular intervals. Dynamics of the system with and without impulses have been analysed using qualitative theory. Main findings are supported through numerical simulations.

negative: Initial Cluster of Novel Coronavirus (2019-nCoV) Infections in Wuhan, China Is Consistent with Substantial Human-to-Human Transmission Reanalysis of the epidemic curve from the initial cluster of cases with novel coronavirus (2019-nCoV) in December 2019 indicates substantial human-to-human transmission. It is possible that the common exposure history at a seafood market in Wuhan originated from the human-to-human transmission events within the market, and the early, strong emphasis that market exposure indicated animal-to-human transmission was potentially the result of observer bias. To support the hypothesis of zoonotic origin of 2019-nCoV stemming from the Huanan seafood market, the index case should have had exposure history related to the market and the virus should have been identified from animals sold at the market. As these requirements remain unmet, zoonotic spillover at the market must not be overemphasized.

negative: Associations between immune-suppressive and stimulating drugs and novel COVID-19—a systematic review of current evidence BACKGROUND: Cancer and transplant patients with COVID-19 have a higher risk of developing severe and even fatal respiratory diseases, especially as they may be treated with immune-suppressive or immune-stimulating drugs. This review focuses on the effects of these drugs on host immunity against COVID-19. METHODS: Using Ovid MEDLINE, we reviewed current evidence for immune-suppressing or -stimulating drugs: cytotoxic chemotherapy, low-dose steroids, tumour necrosis factorα (TNFα) blockers, interlukin-6 (IL-6) blockade, Janus kinase (JAK) inhibitors, IL-1 blockade, mycophenolate, tacrolimus, anti-CD20 and CTLA4-Ig. RESULTS: 89 studies were included. Cytotoxic chemotherapy has been shown to be a specific inhibitor for severe acute respiratory syndrome coronavirus in in vitro studies, but no specific studies exist as of yet for COVID-19. No conclusive evidence for or against the use of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of COVID-19 patients is available, nor is there evidence indicating that TNFα blockade is harmful to patients in the context of COVID-19. COVID-19 has been observed to induce a pro-inflammatory cytokine generation and secretion of cytokines, such as IL-6, but there is no evidence of the beneficial impact of IL-6 inhibitors on the modulation of COVID-19. Although there are potential targets in the JAK-STAT pathway that can be manipulated in treatment for coronaviruses and it is evident that IL-1 is elevated in patients with a coronavirus, there is currently no evidence for a role of these drugs in treatment of COVID-19. CONCLUSION: The COVID-19 pandemic has led to challenging decision-making about treatment of critically unwell patients. Low-dose prednisolone and tacrolimus may have beneficial impacts on COVID-19. The mycophenolate mofetil picture is less clear, with conflicting data from pre-clinical studies. There is no definitive evidence that specific cytotoxic drugs, low-dose methotrexate for auto-immune disease, NSAIDs, JAK kinase inhibitors or anti-TNFα agents are contraindicated. There is clear evidence that IL-6 peak levels are associated with severity of pulmonary complications.

negative: The use of proteomics in the discovery of serum biomarkers from patients with severe acute respiratory syndrome Severe acute respiratory syndrome (SARS) is a new infectious disease with a global impact. Understanding its pathogenesis and developing specific diagnostic methods for its early diagnosis are crucial for the effective management and control of this disease. By using proteomic technology, truncated forms of α(1)‐antitrypsin (TF‐α(1)‐AT) were found to increase significantly and consistently in sera of SARS patients compared to control subjects. The result showed a sensitivity of 100% for SARS patients and a specificity of 92.8% for controls. Furthermore, the levels of these proteins significantly correlated with certain clinico‐pathological parameters. The dramatic increase in TF‐α(1)‐AT may be the result of degradation of α(1)‐AT. As α(1)‐AT plays an important role in the protection of lung function, its degradation may be an important factor in the pathogenesis of SARS. These findings indicate that increased TF‐α(1)‐AT may be therapeutically relevant, and may also be a useful biological marker for the diagnosis of SARS.

negative: Myocarditis in the era of SARS-CoV-2: one piece of a complex puzzle?

negative: Genomic variance of the 2019‐nCoV coronavirus There is a rising global concern for the recently emerged novel coronavirus (2019‐nCoV). Full genomic sequences have been released by the worldwide scientific community in the last few weeks to understand the evolutionary origin and molecular characteristics of this virus. Taking advantage of all the genomic information currently available, we constructed a phylogenetic tree including also representatives of other coronaviridae, such as Bat coronavirus (BCoV) and severe acute respiratory syndrome. We confirm high sequence similarity (>99%) between all sequenced 2019‐nCoVs genomes available, with the closest BCoV sequence sharing 96.2% sequence identity, confirming the notion of a zoonotic origin of 2019‐nCoV. Despite the low heterogeneity of the 2019‐nCoV genomes, we could identify at least two hypervariable genomic hotspots, one of which is responsible for a Serine/Leucine variation in the viral ORF8‐encoded protein. Finally, we perform a full proteomic comparison with other coronaviridae, identifying key aminoacidic differences to be considered for antiviral strategies deriving from previous anti‐coronavirus approaches.

negative: Serial measurements in COVID-19-induced acute respiratory disease to unravel heterogeneity of the disease course: design of the Maastricht Intensive Care COVID cohort; MaastrICCht Background: The course of the disease in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in mechanically ventilated patients is unknown. To unravel the clinical heterogeneity of the SARS-CoV-2 infection in these patients, we designed the prospective observational Maastricht Intensive Care COVID cohort; MaastrICCht. We incorporated serial measurements that harbour aetiological, diagnostic and predictive information. The study aims to investigate the heterogeneity of the natural course of critically ill patients with SARS-CoV-2 infection. Study population: Mechanically ventilated patients admitted to the Intensive Care with SARS-CoV-2 infection. Main message: We will collect clinical variables, vital parameters, laboratory variables, mechanical ventilator settings, chest electrical impedance tomography, electrocardiograms, echocardiography as well as other imaging modalities to assess heterogeneity of the natural course of SARS-CoV-2 infection in critically ill patients. The MaastrICCht cohort is, also designed to foster various other studies and registries and intends to create an open-source database for investigators. Therefore, a major part of the data collection is aligned with an existing national Intensive Care data registry and two international COVID-19 data collection initiatives. Additionally, we create a flexible design, so that additional measures can be added during the ongoing study based on new knowledge obtained from the rapidly growing body of evidence. Conclusion: The spread of the COVID-19 pandemic requires the swift implementation of observational research to unravel heterogeneity of the natural course of the disease of SARS-CoV-2 infection in mechanically ventilated patients. Our design is expected to enhance aetiological, diagnostic and prognostic understanding of the disease. This paper describes the design of the MaastrICCht cohort.

negative: A Novel Coronavirus Outbreak from Wuhan City in China, Rapid Need for Emergency Departments Preparedness and Response; a Letter to Editor

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: A Precision Medicine Approach to SARS-CoV-2 Pandemic Management Purpose of review: Precision medicine (PM) represents a new paradigm in disease diagnosis, prevention, and treatment. To apply PM premises in an emerging coronavirus pandemic acquires potentially greater relevance in order to allow the selection of specific preventive measures as well as biomarkers that will be useful in disease management. Recent findings: The identification of the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as the responsible for the coronavirus disease 2019 (COVID-19) pandemic had led to a plethora of strategies to contain viral dissemination, affecting life styles and personal behaviors. Viral genomic sequencing has shown that SARS-CoV-2 spike protein utilizes angiotensin-converting enzyme 2 (ACE2) found on ciliated epithelial cells of the human lungs as its specific receptor. Neutralizing antibodies to the receptor-binding domain of the spike protein were detected in patients recovered from COVID-19; however, both T cells and NK cells were reduced in severe cases. Excessive and uncontrolled releases of pro-inflammatory cytokines such as IL-1B, IL-1RA, IL-7, IL-8, IL-9, IL-10, fibroblast growth factor (FGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor (TNFα) were increased in severe patients. These cytokines might be useful biomarkers of disease worsening and potential targets for new biological therapies currently under investigation. Summary: Present knowledge and recent developments in PM approach to COVID-19 disease prevention, evaluation, and management are pointed out. Better understanding of pathogenic pathways together with an accurate phenotype classification of patients presented with SARS-CoV-2 infection and symptoms might contribute to a more accurate definition of biomarkers and other diagnostic tools, which may lead to more precise mitigation strategies, personalized pharmacologic options, as well as new biological therapy developments.

negative: Artificial Intelligence (AI) applications for COVID-19 pandemic Abstract Background and aims Healthcare delivery requires the support of new technologies like Artificial Intelligence (AI), Internet of Things (IoT), Big Data and Machine Learning to fight and look ahead against the new diseases. We aim to review the role of AI as a decisive technology to analyze, prepare us for prevention and fight with COVID-19 (Coronavirus) and other pandemics. Methods The rapid review of the literature is done on the database of Pubmed, Scopus and Google Scholar using the keyword of COVID-19 or Coronavirus and Artificial Intelligence or AI. Collected the latest information regarding AI for COVID-19, then analyzed the same to identify its possible application for this disease. Results We have identified seven significant applications of AI for COVID-19 pandemic. This technology plays an important role to detect the cluster of cases and to predict where this virus will affect in future by collecting and analyzing all previous data. Conclusions Healthcare organizations are in an urgent need for decision-making technologies to handle this virus and help them in getting proper suggestions in real-time to avoid its spread. AI works in a proficient way to mimic like human intelligence. It may also play a vital role in understanding and suggesting the development of a vaccine for COVID-19. This result-driven technology is used for proper screening, analyzing, prediction and tracking of current patients and likely future patients. The significant applications are applied to tracks data of confirmed, recovered and death cases.

negative: Long-lived memory T lymphocyte responses against SARS coronavirus nucleocapsid protein in SARS-recovered patients Abstract The nucleocapsid (N) protein is a structural component of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) and can induce antibody responses in SARS patients during infection. However, it is not known whether SARS-CoV N protein can induce a long persistence of memory T-cell response in human. In this study, we found that peripheral blood mononuclear cells (PBMCs) from fully recovered SARS individuals rapidly produced IFN-γ and IL-2 following stimulation with a pool of overlapping peptides that cover the entire N protein sequence. The N-specific IFN-γ+CD4+ T cells were mainly composed of CD45RA−CCR7+CD62L− cells, whereas IFN-γ+CD8+ memory T cells were mostly contained within CD45RA+CCR7−CD62L− cell population. Epitope mapping study indicated that a cluster of overlapping peptides located in the C-terminal region (amino acids [aa] 331 to 362) of N protein contained at least two different T-cell epitopes. The results indicated that human memory T-cell responses specific for SARS-CoV N protein could persist for 2 years in the absence of antigen, which would be a valuable for the design of effective vaccines against SARS-CoV and for basic studies of human T-cell memory.

negative: Molecular Diagnostics in Sepsis: From Bedside to Bench Background Based on recent in vitro data, we tested the hypothesis that microarray expression profiles can be used to diagnose sepsis, distinguishing in vivo between sterile and infectious causes of systemic inflammation. Study design Exploratory studies were conducted using spleens from septic patients and from mice with abdominal sepsis. Seven patients with sepsis after injury were identified retrospectively and compared with six injured patients. C57BL/6 male mice were subjected to cecal ligation and puncture, or to IP lipopolysaccharide. Control mice had sham laparotomy or injection of IP saline, respectively. A sepsis classification model was created and tested on blood samples from septic mice. Results Accuracy of sepsis prediction was obtained using cross-validation of gene expression data from 12 human spleen samples and from 16 mouse spleen samples. For blood studies, classifiers were constructed using data from a training data set of 26 microarrays. The error rate of the classifiers was estimated on seven de-identified microarrays, and then on a subsequent cross-validation for all 33 blood microarrays. Estimates of classification accuracy of sepsis in human spleen were 67.1%; in mouse spleen, 96%; and in mouse blood, 94.4% (all estimates were based on nested cross-validation). Lists of genes with substantial changes in expression between study and control groups were used to identify nine mouse common inflammatory response genes, six of which were mapped into a single pathway using contemporary pathway analysis tools. Conclusions Sepsis induces changes in mouse leukocyte gene expression that can be used to diagnose sepsis apart from systemic inflammation.

negative: Outbreak investigation in cargo ship in times of COVID-19 crisis, Port of Santos, Brazil In February 2020, a Chinese cargo ship docked at the Port of Santos with reports of crew members with a feverish and respiratory condition. A team was gathered to verify the existence of suspected cases of COVID-19 inside the vessel and define its clearance. All 25 crew members were interviewed, and no suspected cases were found. The vessel was then cleared for port activities. The investigation resulted from the implementation of the contingency plan to face a public health emergency of international importance and several surveillance entities cooperated.

negative: Novel coronavirus 2019-nCoV: prevalence, biological and clinical characteristics comparison with SARS-CoV and MERS-CoV. OBJECTIVE Human infections with zoonotic coronavirus contain emerging and reemerging pathogenic characteristics which have raised great public health concern. This study aimed at investigating the global prevalence, biological and clinical characteristics of novel coronavirus, Wuhan China (2019-nCoV), Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection outbreaks. MATERIALS AND METHODS The data on the global outbreak of "2019-nCoV, SARS-CoV, and MERS-CoV" were obtained from World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), concerned ministries and research institutes. We also recorded the information from research documents published in global scientific journals indexed in ISI Web of Science and research centers on the prevalence, biological and clinical characteristics of 2019-nCoV, SARS-CoV, and MERS-CoV. RESULTS Worldwide, SARS-CoV involved 32 countries, with 8422 confirmed cases and 916 (10.87%) casualties from November 2002 to August 2003. MERS-CoV spread over 27 states, causing 2496 cases and 868 (34.77%) fatalities during the period April 2012 to December 2019. However, the novel coronavirus 2019-nCoV spread swiftly the global borders of 27 countries. It infected 34799 people and resulted in 724 (2.08%) casualties during the period December 29, 2019 to February 7, 2020. The fatality rate of coronavirus MERS-CoV was (34.77%) higher than SARS-CoV (10.87%) and 2019-nCoV (2.08%); however, the 2019-nCoV transmitted rapidly in comparison to SARS-CoV and MERS-CoV. CONCLUSIONS The novel coronavirus 2019-nCoV has diverse epidemiological and biological characteristics, making it more contagious than SARS-CoV and MERS-CoV. It has affected more people in a short time period compared to SARS-CoV and MERS-CoV, although the fatality rate of MERS-CoV was higher than SARS-CoV and 2019-nCoV. The major clinical manifestations in coronavirus infections 2019-nCoV, MERS-CoV, and SARS CoV are fever, chills, cough, shortness of breath, generalized myalgia, malaise, drowsy, diarrhea, confusion, dyspnea, and pneumonia. Global health authorities should take immediate measures to prevent the outbreaks of such emerging and reemerging pathogens across the globe to minimize the disease burden locally and globally.

negative: Combination of clinical symptoms and blood biomarkers can improve discrimination between bacterial or viral community-acquired pneumonia in children BACKGROUND: Differentiating bacterial from viral pneumonia is important for guiding targeted management and judicious use of antibiotics. We assessed if clinical characteristics and blood inflammatory biomarkers could be used to distinguish bacterial from viral pneumonia. METHODS: Western Australian children (≤17 years) hospitalized with radiologically-confirmed community-acquired pneumonia were recruited and clinical symptoms and management data were collected. C-reactive protein (CRP), white cell counts (WCC) and absolute neutrophil counts (ANC) were measured as part of routine care. Clinical characteristics and biomarker levels were compared between cases with definite bacterial pneumonia (clinical empyema and/or bacteria detected in blood or pleural fluid), presumed viral pneumonia (presence of ≥1 virus in nasopharyngeal swab without criteria for definite bacterial pneumonia), and other pneumonia cases (pneumonia in the absence of criteria for either definite bacterial or presumed viral pneumonia). The area-under-curve (AUC) of the receiver operating characteristic (ROC) curve for varying biomarker levels were used to characterise their utility for discriminating definite bacterial from presumed viral pneumonia. For biomarkers with AUC > 0.8 (fair discriminator), Youden index was measured to determine the optimal cut-off threshold, and sensitivity, specificity, predictive values (positive and negative) were calculated. We investigated whether better discrimination could be achieved by combining biomarker values with the presence/absence of symptoms. RESULTS: From May 2015 to October 2017, 230 pneumonia cases were enrolled: 30 with definite bacterial pneumonia, 118 with presumed viral pneumonia and 82 other pneumonia cases. Differences in clinical signs and symptoms across the groups were noted; more definite bacterial pneumonia cases required intravenous fluid and oxygen supplementation than presumed viral or other pneumonia cases. CRP, WCC and ANC were substantially higher in definite bacterial cases. For a CRP threshold of 72 mg/L, the AUC of ROC was 0.82 for discriminating definite bacterial pneumonia from presumed viral pneumonia. Combining the CRP with either the presence of fever (≥38(ο)C) or the absence of rhinorrhea improved the discrimination. CONCLUSIONS: Combining elevated CRP with the presence or absence of clinical signs/ symptoms differentiates definite bacterial from presumed viral pneumonia better than CRP alone. Further studies are required to explore combination of biomarkers and symptoms for use as definitive diagnostic tool. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12890-019-0835-5) contains supplementary material, which is available to authorized users.

negative: Improved survival rates in patients with H1N1 acute respiratory failure in Korea between 2009 and 2016 There was a pandemic of influenza A (H1N1) in 2009; in Korea, there was also an H1N1 epidemic in 2016. We aim to investigate whether survival had improved in the setting of recent advances in intensive care unit (ICU) management. We conducted a retrospective analysis of acute respiratory failure patients with H1N1 influenza pneumonia in 2016 and 2009 respectively at two tertiary referral hospitals in Korea. A total of 28 patients were treated in 2016, and 34 in 2009. There was no significant difference in SOFA scores on ICU admission day. In-hospital mortality was significantly lower in patients of 2016 compared to those of 2009 (18% vs. 44% P = 0.028). By multivariable analyses, the treatment year 2016 was associated with a greater likelihood of survival. Compared to the patients treated in 2009, those treated in 2016 were one seventh as likely to die after adjusting for other clinical variables (hazard ratio for mortality, 0.15; 95% confidence interval. 0.03–0.63, P = 0.010). Improved survival in patients who underwent extracorporeal membrane oxygenation treatment (in-hospital mortality, 17% vs. 60%, P = 0.242) and decreased tidal volumes during mechanical ventilation (median 5.4 mL/kg vs. median 9.2 mL/kg, P = 0.018) were observed in 2016 compared to 2009. Treatment outcomes for patients with H1N1 acute respiratory failure improved from 2009 to 2016 in two tertiary referral centers in South Korea.

negative: Reflections on the evolution of cardiac biomarkers.

negative: Cancer Biomarker Discovery: The Entropic Hallmark BACKGROUND: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. METHODOLOGY/PRINCIPAL FINDINGS: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. CONCLUSIONS/SIGNIFICANCE: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-througput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases.

negative: Autoimmune Cholangitis in the SJL/J Mouse is Antigen Non-specific Primary biliary cirrhosis (PBC) is an autoimmune disease characterized by intrahepatic bile duct destruction and the production of anti-mitochondrial antibodies (AMA). The absence of an animal model has been a striking impedance in defining the molecular basis of disease. Previous work has suggested that SJL/J mice immunize with the pyruvate dehydrogenase complex (PDC-E2), the major mitochondrial autoantigen of PBC, leads to the development of lymphoid cell infiltration in portal tracts and a model system coined autoimmune cholangitis. We hypothesized that this pathology would be augmented if immunization occurred in the presence of IFN-γ injections. Accordingly, SJL/J mice were immunized with PDC-E2 and, for purpose of control, α-casein. Subgroups of mice were also treated with exogenous IFN-γ. As expected, mice immunized with PDC-E2, with or without IFN-γ, developed high titer AMAs. In contrast, mice immunized with α-casein, develop antinuclear antibodies. More importantly, the livers from mice immunized with PDC-E2 and/or those immunized with α-casein all displayed lymphoid cell infiltration to the portal tracts, irrespective of bile duct size. Indeed, there was no significant difference between the experimental and the control groups by histologic analysis. Thus, autoimmune cholangitis in these mice is antigen non-specific.

negative: Current Insight into the Novel Coronavirus Disease 2019 (COVID-19) SARS-CoV-2 is a novel strain of coronavirus that has not been previously identified in humans. It has been declared a pandemic and has infected at least 1,844,683 individuals and caused 117,021 deaths as of 14th April 2020. Transmission among humans occurs via close contact with an infected individual that produces respiratory droplets. Patients have been shown to undergo acute respiratory distress syndrome, which is defined as cytokine storm. The diagnosis relies on detection of nucleic acid, IgG/IgM antibodies, and a chest radiograph of the suspected individuals. The genome of SARS-CoV-2 is similar to other coronaviruses that comprise of ten open reading frames (ORFs). SARS-CoV-2 spike protein exhibits higher affinity to ACE2 receptor as compared with SARS-CoV. Repurposing drugs like favipiravir, remdesivir, chloroquine, and TMPRSS2 protease inhibitors have been shown to be effective for the treatment of COVID-19. Personal protective measures should be followed to prevent SARS-CoV-2 infection. In addition, a clinical trial of SARS-CoV-2 vaccine, mRNA-1273, has been started. This chapter provides a glimpse of advancements made in the area of SARS-CoV-2 infection by proving recent clinical and research trials in the field.

negative: Rapid resolution of cytokine release syndrome and favorable clinical course of severe COVID-19 in a kidney transplant recipient treated with tocilizumab

negative: Associations of osteopontin and NT-proBNP with circulating miRNA levels in acute coronary syndrome The genomic regulatory networks underlying the pathogenesis of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) are incompletely understood. As intermediate traits, protein biomarkers report on underlying disease severity and prognosis in NSTE-ACS. We hypothesized that integration of dense microRNA (miRNA) profiling with biomarker measurements would highlight potential regulatory pathways that underlie the relationships between prognostic biomarkers, miRNAs, and cardiovascular phenotypes. We performed miRNA sequencing using whole blood from 186 patients from the TRILOGY-ACS trial. Seven circulating prognostic biomarkers were measured: NH(2)-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein, osteopontin (OPN), myeloperoxidase, growth differentiation factor 15, monocyte chemoattractant protein, and neopterin. We tested miRNAs for association with each biomarker with generalized linear models and controlled the false discovery rate at 0.05. Ten miRNAs, including known cardiac-related miRNAs 25-3p and 423-3p, were associated with NT-proBNP levels (min. P = 7.5 × 10(−4)) and 48 miRNAs, including cardiac-related miRNAs 378a-3p, 20b-5p and 320a, -b, and -d, were associated with OPN levels (min. P = 1.6 × 10(−6)). NT-proBNP and OPN were also associated with time to cardiovascular death, myocardial infarction (MI), or stroke in the sample. By integrating large-scale miRNA profiling with circulating biomarkers as intermediate traits, we identified associations of known cardiac-related and novel miRNAs with two prognostic biomarkers and identified potential genomic networks regulating these biomarkers. These results, highlighting plausible biological pathways connecting miRNAs with biomarkers and outcomes, may inform future studies seeking to delineate genomic pathways underlying NSTE-ACS outcomes.

negative: The diagnostic value of joint detection of serum IgMand IgG antibodies to 2019-nCoV in 2019-nCoV infection/ 中华检验医学杂志 Objective@#To investigate the diagnostic value of immunoglobulin M (IgM) and immunoglobulin G(IgG) antibodies to 2019 Novel Coronavirus (2019-nCoV) in 2019-nCoV infection.@*Method@#This is a retrospective study. Serum samples were collected from 284 patients including outpatients and inpatients in the Renmin Hospital of Wuhan University from January 20, 2020 to February 17, 2020. Among them 205 cases were 2019-nCoV infected patients, including 186 cases confirmed with nucleic acid test and 19 cases diagnosed by clinical symptoms and CT characteristics according to "the New Coronavirus Pneumonia Control Protocol (5th edition)" . A total of 79 subjects with other diseases but negative to 2019-nCoV infection were recruited as control group. Serum IgM and IgG antibodies to 2019-nCoV were measured with fully automated immunoassay technology for all subjects. Statistical significance between 2019-nCoV antibodies test and 2019-nCoV nucleic acid test was determined using the χ2 tests.@*Result@#The sensitivity of serum IgM and IgG antibodies to 2019-nCoV were 70.24%(144/205) and 96.10%(197/205) respectively and the specificity were 96.20%(76/79) and 92.41%(73/79) respectively. The positive and negative predictive values of 2019-nCoV antibodies were 95.63%(197/206) and 91.03% (71/78) respectively, and the positive and negative predictive values of 2019-nCoV nucleic acid test were 100%(186/186) and 80.61%(79/98) respectively. The total coincidence rate of diagnosing 2019-nCoV infection between antibody tests and nucleic acid test for 2019-nCoV were 88.03%(250/284).@*Conclusion@#Joint detection of serum IgM and IgG antibodies to 2019-nCoV is an effective screening and diagnostic indicators for 2019-nCoV infection, and an effective complement to the false negative results to nucleic acid test.