query: what are the mortality rates overall and in specific populations

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

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

positive: 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.

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

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

positive: Mortality rate and gender differences in COVID-19 patients dying in Italy: A comparison with other countries.

positive: Demographic science aids in understanding the spread and fatality rates of COVID-19 Governments around the world must rapidly mobilize and make difficult policy decisions to mitigate the coronavirus disease 2019 (COVID-19) pandemic. Because deaths have been concentrated at older ages, we highlight the important role of demography, particularly, how the age structure of a population may help explain differences in fatality rates across countries and how transmission unfolds. We examine the role of age structure in deaths thus far in Italy and South Korea and illustrate how the pandemic could unfold in populations with similar population sizes but different age structures, showing a dramatically higher burden of mortality in countries with older versus younger populations. This powerful interaction of demography and current age-specific mortality for COVID-19 suggests that social distancing and other policies to slow transmission should consider the age composition of local and national contexts as well as intergenerational interactions. We also call for countries to provide case and fatality data disaggregated by age and sex to improve real-time targeted forecasting of hospitalization and critical care needs.

positive: Rate of Intensive Care Unit admission and outcomes among patients with coronavirus: A systematic review and Meta-analysis. BACKGROUND The rate of ICU admission among patients with coronavirus varied from 3% to 100% and the mortality was as high as 86% of admitted patients. The objective of the systematic review was to investigate the rate of ICU admission, mortality, morbidity, and complications among patients with coronavirus. METHODS A comprehensive strategy was conducted in PubMed/Medline; Science direct and LILACS from December 2002 to May 2020 without language restriction. The Heterogeneity among the included studies was checked with forest plot, χ2 test, I2 test, and the p-values. All observational studies reporting rate of ICU admission, the prevalence of mortality and its determinants among ICU admitted patients with coronavirus were included and the rest were excluded. RESULT A total of 646 articles were identified from different databases and 50 articles were selected for evaluation. Thirty-seven Articles with 24983 participants were included. The rate of ICU admission was 32% (95% CI: 26 to 38, 37 studies and 32, 741 participants). The Meta-Analysis revealed that the pooled prevalence of mortality in patients with coronavirus disease in ICU was 39% (95% CI: 34 to 43, 37 studies and 24, 983 participants). CONCLUSION The Meta-Analysis revealed that approximately one-third of patients admitted to ICU with severe Coronavirus disease and more than thirty percent of patients admitted to ICU with a severe form of COVID-19 for better care died which warns the health care stakeholders to give attention to intensive care patients. REGISTRATION This Systematic review and Meta-Analysis was registered in Prospero international prospective register of systemic reviews (CRD42020177095) on April 9/2020.

positive: A County-Level Susceptibility Index and Coronavirus Disease 2019 Mortality in the United States: A Socioecological Study As of June 2020, the United States (US) has experienced the highest number of deaths related to coronavirus disease 2019 (Covid-19) in the world, but significant geographic heterogeneity exists at the county-level. Therefore, we sought to classify counties in the United States across multiple domains utilizing a socioecological framework and examine the association between these county-level groups and Covid-19 mortality. We harmonized and linked county-level sociodemographic, health, and environmental metrics associated with increased susceptibility for Covid-19 mortality. Latent class analysis defined a county-level susceptibility index (CSI) based on these metrics (n=2701 counties). Next, we used linear regression models to estimate the associations of the CSI and Covid-19 deaths per capita and initial mortality doubling time (as of 6/2/20), adjusted for days since first Covid-19 case. We identified 4 groups classified by the CSI with distinct sociodemographic, health, and environmental profiles and widespread geographic dispersion. Covid-19 deaths per capita were significantly higher in the group consisting of rural, vulnerable counties (55.8 [95% CI 50.3-61.2] deaths per 100,000) compared with the group with diverse, urban counties (32.2 [27.3-37.0]) at similar points in the outbreak (76 days since first case). Our findings can inform equitable resource allocation for Covid-19 to allow targeted public health preparedness and response in vulnerable counties.

positive: Cancer is associated with the severity and mortality of patients with COVID-19: a systematic review and meta-analysis Background: Cancer patients are considered a highly vulnerable population in the COVID-19 epidemic, but the relationship between cancer and the severity and mortality of patients with COVID-19 remains unclear. This study aimed to explore the prevalence of cancer in patients with COVID-19 and to examine whether cancer patients with COVID-19 may be at an increased risk of severe illness and mortality. Methods: A comprehensive electronic search in seven databases was performed, to identified studies reporting the prevalence of cancer in COVID-19 patients, or providing data of cancer between patients with severe or non-severe illness or between non-survivors and survivors. Meta-analyses were performed to estimate the pooled prevalence and odds risk (OR) using the inverse variance method with the random-effects model. Results: Thirty-four studies with 8080 patients were included. The pooled prevalence of cancer in patients with COVID-19 was 2.0% (95% CI: 2.0% to 3.0%). The prevalence in Italy (5.0%), France (6.0%), and Korea (4.0%) were higher than that in China (2.0%). Cancer was associated with a 2.84-fold significantly increased risk of severe illness (OR = 2.84, 95%CI: 1.75 to 4.62, P < 0.001) and a 2.60-fold increased risk of death (OR = 2.60, 95%CI: 1.28 to 5.26, P = 0.008) in patients with COVID-19. Sensitivity analyses showed that the results were stable after excluding studies with a sample size of less than 100. Conclusions: Cancer patients have an increased risk of COVID-19 and cancer was associated with a significantly increased risk of severity and mortality of patients with COVID-19.

positive: Estimating Lower Bounds for COVID-19 Mortality from Northern Italian Towns For COVID-19 the Infection Fatality Rate or IFR - a crucial variable in epidemiological modeling - is difficult to estimate because many cases are asymptomatic and the overall infection rate is generally not known. Circumstances in the Italian provinces of Milano, Bergamo, Brescia, and Lodi allow estimation of lower bounds for age- and sex-specific all-cause excess mortality (a proxy for IFR) since anecdotal reports indicate some towns were close to fully infected. Using data from ISTAT on mortality from January 1 through April 15 for 2020 and the three preceding years, I estimate excess mortality by sex and age categories (0-14, 15-54, 55-64, 65-74, and 75+ years) while controlling for town-specific mortality that proxies for town-specific infection rate. The 99th percentile from the tail of the town distribution gives a lower-bound estimate for COVID-19 mortality. The overall population-weighted mortality at the 99th percentile is 1.09 percent (95% CI 1.06-1.14). The age- and sex-specific rates vary considerably: for men age 65-74 the estimate is 2.10 percent (95% CI 1.94-2.28) which is 3.5-times higher than men 55-64 and 2.7-times higher than women 65-74.

positive: Identification of Vulnerable Populations and Areas at Higher Risk of COVID-19 Related Mortality in the U.S. Background The role of health-related disparities including sociodemographic, environmental, and critical care capacity in the COVID-19 pandemic are poorly understood. In the present study, we characterized vulnerable populations located in areas at higher risk of COVID-19 related mortality and low critical healthcare capacity in the U.S. Methods Using Bayesian multilevel analysis and small area disease risk mapping, we assessed the spatial variation of COVID-19 related mortality risk for the U.S. in relation with healthcare disparities including race, ethnicity, poverty, air quality, and critical healthcare capacity. Results Overall, highly populated, regional air hub areas, and minorities had an increased risk of COVID-19 related mortality. We found that with an increase of only 1 ug/m3 in long term PM2.5 exposure, the COVID-19 mortality rate increased by 13%. Counties with major air hubs had 18% increase in COVID-19 related death compared to counties with no airport connectivity. Sixty-eight percent of the counties with high COVID-19 related mortality risk were also counties with lower critical care capacity than national average. These counties were primary located at the North- and South-Eastern regions of the country. Conclusion The existing disparity in health and environmental risk factors that exacerbate the COVID-19 related mortality, along with the regional healthcare capacity, determine the vulnerability of populations to COVID-19 related mortality. The results from this study can be used to guide the development of strategies for the identification and targeting preventive strategies in vulnerable populations with a higher proportion of minority groups living in areas with poor air quality and low healthcare capacity.

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

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

positive: Association of country-wide coronavirus mortality with demographics, testing, lockdowns, and public wearing of masks. Background. Wide variation between countries has been noted in per-capita mortality from the disease (COVID-19) caused by the SARS-CoV-2 virus. Determinants of this variation are not fully understood. Methods. Potential predictors of country-wide per-capita coronavirus-related mortality were studied, including age, sex ratio, temperature, urbanization, viral testing, smoking, duration of infection, lockdowns, and public mask-wearing norms and policies. Multivariable linear regression analysis was performed. Results. In univariate (but not multivariable) analyses, prevalence of smoking, per-capita gross domestic product, and colder average country temperature were positively associated with coronavirus-related mortality. In a multivariable analysis of 183 countries, urbanization, the duration of the infection in the country, and percent of the population at least 60 years of age were all positively associated with per-capita mortality, while duration of mask-wearing by the public was negatively associated with mortality (all p<0.001). In countries with cultural norms or government policies supporting public mask-wearing, per-capita coronavirus mortality increased on average by just 5.4% each week, as compared with 48% each week in remaining countries. In the multivariable analysis, lockdowns tended to be associated with less mortality (p=0.31), and per-capita testing with higher reported mortality (p=0.26), though neither association was statistically significant. Conclusions. Societal norms and government policies supporting the wearing of masks by the public are independently associated with less mortality from COVID-19.

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

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

positive: A statistical forecast of LOW mortality and morbidity due to COVID-19, in ARGENTINA and other Southern Hemisphere countries. A set of open source programs in Python is devised to fit a parametric integrated Gaussian equation to cumulative deaths due to COVID-19 in Southern Hemisphere countries. The programs were successfully tested using data from advanced outbreak trajectories (Italy and Spain). The procedure was applied to data reported by Argentina. The projected total death toll will be 182 (277-182) with a peak of deaths (6(+/-2)) the 14 of April. The outbreak begins the 9th of March and end completely the 20th of May. However, already on 1st of May, 2 s (95.45%) of the deaths have occurred. The death toll arises from a number of infected individuals between 36412 and 2275. Then, they were to use to process data from several Southern Hemisphere countries: Argentina, Brazil, Mexico, Peru, Colombia, Ecuador, Cuba, Chile, Panama, Australia, Bolivia, Honduras, New Zealand, Paraguay, Guatemala, Venezuela, Uruguay, El Salvador, Jamaica, Haiti, Costa Rica and Nicaragua. The trend is to show low number of total deaths compared with other disease outbreaks. A total projected number of deaths between 15148 and 9939 deaths for a total population of ca. 664 M inhabitants. The projected death toll is much lower (5-10 times) than those forecasted by the Imperial College Group (ICG) even considering the best scenario of total suppression of virus transmission. Using actual mortality rates it is possible to back calculate which number of infected individuals would produce such mortality. The calculated number of infected individuals (worst case scenario) is below 2.5 million. This is significantly lower than that calculated by ICG (> 45 millions). In most countries the outbreak will end in May or early June. The dynamics of the outbreaks seems to do not saturate the health services (hospital beds) but only Peru, Ecuador and Panama should have not enough ICU beds for grave COVID-19 patients

positive: Risk Factors for Mortality and Respiratory Support in Elderly Patients Hospitalized with COVID-19 in Korea BACKGROUND: The mortality risk of coronavirus disease 2019 (COVID-19) is higher in patients with older age, and many elderly patients are reported to require advanced respiratory support. METHODS: We reviewed medical records of 98 patients aged ≥ 65 years who were hospitalized with COVID-19 during a regional outbreak in Daegu/Gyeongsangbuk-do province of Korea. The outcome measures were in-hospital mortality and the treatment with mechanical ventilation (MV) or high-flow nasal cannula (HFNC). RESULTS: The median age of the patients was 72 years; 55.1% were female. Most (74.5%) had at least one underlying condition. Overall case fatality rate (CFR) was 20.4%, and median time to death after admission was 8 days. The CFR was 6.1% among patients aged 65–69 years, 22.7% among those aged 70–79 years, and 38.1% among those aged ≥ 80 years. The CFR among patients who required MV was 43.8%, and the proportion of patients received MV/HFNC was 28.6%. Nosocomial acquisition, diabetes, chronic lung diseases, and chronic neurologic diseases were significant risk factors for both death and MV/HFNC. Hypotension, hypoxia, and altered mental status on admission were also associated with poor outcome. CRP > 8.0 mg/dL was strongly associated with MV/HFNC (odds ratio, 26.31; 95% confidence interval, 7.78–88.92; P < 0.001), and showed better diagnostic characteristics compared to commonly used clinical scores. CONCLUSION: Patients aged ≥ 80 years had a high risk of requiring MV/HFNC, and mortality among those severe patients was very high. Severe initial presentation and laboratory abnormalities, especially high CRP, were identified as risk factors for mortality and severe hospital course.

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

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

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

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

positive: COVID-19 in Dialysis Patients: Adding a Few More Pieces to the Puzzle Abstract The clinical presentation and mortality rate in maintenance hemodialysis (MHD) patients with COVID-19 are not well established. Recent data from Italy and Spain suggest that these patients present with wide range of symptoms, with a significant portion being asymptomatic. There is prolonged positivity of pharyngeal swabs in MHD patients. The mortality rates are very high, reaching almost 30%. These data highlight the importance of diligent oversight and care of MHD patients during COVID-19 pandemic.

positive: Factors Associated With Surgical Mortality and Complications Among Patients With and Without Coronavirus Disease 2019 (COVID-19) in Italy. Importance There are limited data on mortality and complications rates in patients with coronavirus disease 2019 (COVID-19) who undergo surgery. Objective To evaluate early surgical outcomes of patients with COVID-19 in different subspecialties. Design, Setting, and Participants This matched cohort study conducted in the general, vascular and thoracic surgery, orthopedic, and neurosurgery units of Spedali Civili Hospital (Brescia, Italy) included patients who underwent surgical treatment from February 23 to April 1, 2020, and had positive test results for COVID-19 either before or within 1 week after surgery. Gynecological and minor surgical procedures were excluded. Patients with COVID-19 were matched with patients without COVID-19 with a 1:2 ratio for sex, age group, American Society of Anesthesiologists score, and comorbidities recorded in the surgical risk calculator of the American College of Surgeons National Surgical Quality Improvement Program. Patients older than 65 years were also matched for the Clinical Frailty Scale score. Exposures Patients with positive results for COVID-19 and undergoing surgery vs matched surgical patients without infection. Screening for COVID-19 was performed with reverse transcriptase-polymerase chain reaction assay in nasopharyngeal swabs, chest radiography, and/or computed tomography. Diagnosis of COVID-19 was based on positivity of at least 1 of these investigations. Main Outcomes and Measures The primary end point was early surgical mortality and complications in patients with COVID-19; secondary end points were the modeling of complications to determine the importance of COVID-19 compared with other surgical risk factors. Results Of 41 patients (of 333 who underwent operation during the same period) who underwent mainly urgent surgery, 33 (80.5%) had positive results for COVID-19 preoperatively and 8 (19.5%) had positive results within 5 days from surgery. Of the 123 patients of the combined cohorts (78 women [63.4%]; mean [SD] age, 76.6 [14.4] years), 30-day mortality was significantly higher for those with COVID-19 compared with control patients without COVID-19 (odds ratio [OR], 9.5; 95% CI, 1.77-96.53). Complications were also significantly higher (OR, 4.98; 95% CI, 1.81-16.07); pulmonary complications were the most common (OR, 35.62; 95% CI, 9.34-205.55), but thrombotic complications were also significantly associated with COVID-19 (OR, 13.2; 95% CI, 1.48-∞). Different models (cumulative link model and classification tree) identified COVID-19 as the main variable associated with complications. Conclusions and Relevance In this matched cohort study, surgical mortality and complications were higher in patients with COVID-19 compared with patients without COVID-19. These data suggest that, whenever possible, surgery should be postponed in patients with COVID-19.

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

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

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

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

positive: Estimating the infection and case fatality ratio for coronavirus disease (COVID-19) using age-adjusted data from the outbreak on the Diamond Princess cruise ship, February 2020 Adjusting for delay from confirmation to death, we estimated case and infection fatality ratios (CFR, IFR) for coronavirus disease (COVID-19) on the Diamond Princess ship as 2.6% (95% confidence interval (CI): 0.89-6.7) and 1.3% (95% CI: 0.38-3.6), respectively. Comparing deaths on board with expected deaths based on naive CFR estimates from China, we estimated CFR and IFR in China to be 1.2% (95% CI: 0.3-2.7) and 0.6% (95% CI: 0.2-1.3), respectively.

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

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

positive: Case fatality risk of the first pandemic wave of novel coronavirus disease 2019 (COVID-19) in China OBJECTIVE: To assess the case fatality risk (CFR) of COVID-19 in mainland China, stratified by region and clinical category, and estimate key time-to-event intervals. METHODS: We collected individual information and aggregated data on COVID-19 cases from publicly available official sources from December 29, 2019 to April 17, 2020. We accounted for right-censoring to estimate the CFR and explored the risk factors for mortality. We fitted Weibull, gamma, and lognormal distributions to time-to-event data using maximum-likelihood estimation. RESULTS: We analyzed 82,719 laboratory-confirmed cases reported in mainland China, including 4,632 deaths, and 77,029 discharges. The estimated CFR was 5.65% (95%CI: 5.50%-5.81%) nationally, with highest estimate in Wuhan (7.71%), and lowest in provinces outside Hubei (0.86%). The fatality risk among critical patients was 3.6 times that of all patients, and 0.8-10.3 fold higher than that of mild-to-severe patients. Older age (OR 1.14 per year; 95%CI: 1.11-1.16), and being male (OR 1.83; 95%CI: 1.10-3.04) were risk factors for mortality. The time from symptom onset to first healthcare consultation, time from symptom onset to laboratory confirmation, and time from symptom onset to hospitalization were consistently longer for deceased patients than for those who recovered. CONCLUSIONS: Our CFR estimates based on laboratory-confirmed cases ascertained in mainland China suggest that COVID-19 is more severe than the 2009 H1N1 influenza pandemic in hospitalized patients, particularly in Wuhan. Our study provides a comprehensive picture of the severity of the first wave of the pandemic in China. Our estimates can help inform models and the global response to COVID-19.

positive: Differential COVID-19-attributable mortality and BCG vaccine use in countries While mortality attributable to COVID-19 has devastated global health systems and economies, striking regional differences have been observed. The Bacille Calmette Guerin (BCG) vaccine has previously been shown to have non-specific protective effects on infections, as well as long-term efficacy against tuberculosis. Using publicly available data we built a simple log-linear regression model to assess the association of BCG use and COVID-19-attributable mortality per 1 million population after adjusting for confounders including country economic status (GDP per capita), and proportion of elderly among the population. The timing of country entry into the pandemic epidemiological trajectory was aligned by plotting time since the 100th reported case. Countries with economies classified as lower-middle-income, upper-middle-income and high-income countries (LMIC, UMIC, HIC) had median crude COVID-19 log-mortality of 0.4 (Interquartile Range (IQR) 0.1, 0.4), 0.7 (IQR 0.2, 2.2) and 5.5 (IQR 1.6, 13.9), respectively. COVID-19-attributable mortality among BCG-using countries was 5.8 times lower [95% CI 1.8-19.0] than in non BCG-using countries. Notwithstanding limitations due to testing constraints in LMICs, case ascertainment bias and a plausible rise of cases as countries progress along the epidemiological trajectory, these analyses provide intriguing observations that urgently warrant mobilization of resources for prospective randomized interventional studies and institution of systematic disease surveillance, particularly in LMICs.

positive: 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.

positive: A deeper look at COVID-19 CFR: health care impact and roots of discrepancy Intensive care capacity and proper testing play a paramount role in the COVID-19 Case Fatality Rate (CFR). Nevertheless, the real impact of such important measures has not been appreciated due to the lack of proper metrics. In this work, we have proposed a method for estimating a lower bound for the number of positive cases by using the reported data on the oldest age group and the regions' population distributions. The proposed estimation method improved the expected similarity between the age-distribution of positive cases and regions' population. Further, we have provided a quantitative measure for the impact of intensive care on the critical cases by comparing the CFR among those who did and did not receive intensive care. Our findings showed that the chance of living among non-ICU receivers is less than half of ICU receivers (~24% vs ~60%).

positive: Why case fatality ratios can be misleading: individual- and population-based mortality estimates and factors influencing them Different ways of calculating mortality ratios during epidemics have yielded very different results, particularly during the current COVID-19 pandemic. We formulate both a survival probability model and an associated infection duration-dependent SIR model to define individual- and population-based estimates of dynamic mortality ratios. The key parameters that affect the dynamics of the different mortality estimates are the incubation period and the time individuals were infected before confirmation of infection. We stress that none of these ratios are accurately represented by the often misinterpreted case fatality ratio (CFR), the number of deaths to date divided by the total number of confirmed infected cases to date. Using data on the recent SARS-CoV-2 outbreaks, we estimate and compare the different dynamic mortality ratios and highlight their differences. Informed by our modeling, we propose more systematic methods to determine mortality ratios during epidemic outbreaks and discuss sensitivity to confounding effects and uncertainties in the data.

positive: Heterogeneity in risk, testing and outcome of COVID-19 across outbreak settings in the Greater Toronto Area, Canada: an observational study Background: We compared the risk of, testing for, and death following COVID-19 infection across three settings (long-term care homes (LTCH), shelters, the rest of the population) in the Greater Toronto Area (GTA), Canada. Methods: We sourced person-level data from COVID-19 surveillance and reporting systems in Ontario, and examined settings with population-specific denominators (LTCH residents, shelters, and the rest of the population). We calculated cumulatively, the diagnosed cases per capita, proportion tested for COVID-19, daily and cumulative positivity, and case fatality proportion. We estimated the age- and sex-adjusted relative rate ratios for test positivity and case fatality using quasi-Poisson regression. Results: Between 01/23/2020-05/25/2020, we observed a shift in the proportion of cases: from travel-related and into LTCH and shelters. Cumulatively, compared to the rest of the population, the number of diagnosed cases per 100,000 was 59-fold and 18-fold higher among LTCH and shelter residents, respectively. By 05/25/2020, 77.2% of LTCH residents compared to 2.4% of the rest of the population had been tested. After adjusting for age and sex, LTCH residents were 2.5 times (95% confidence interval (CI): 2.3-2.8) more likely to test positive. Case fatality was 26.3% (915/3485), 0.7% (3/402), and 3.6% (506/14133) among LTCH residents, shelter population, and others in the GTA, respectively. After adjusting for age and sex, case fatality was 1.4-fold (95%CI: 1.1-1.9) higher among LTCH residents than the rest of the population. Interpretation: Heterogeneity across micro-epidemics among specific populations in specific settings may reflect underlying heterogeneity in transmission risks, necessitating setting-specific COVID-19 prevention and mitigation strategies.

positive: Excess Mortality Estimation During the COVID-19 Pandemic: Preliminary Data from Portugal. INTRODUCTION Portugal is experiencing the effects of the COVID-19 pandemic since March 2020. All-causes mortality in Portugal increased during March and April 2020 compared to previous years, but this increase is not explained by COVID-19 reported deaths. The aim of this study was to analyze and consider other criteria for estimating excessive all-cause mortality during the early COVID-19 pandemic period. MATERIAL AND METHODS Public data was used to estimate excess mortality by age and region between March 1 and April 22, proposing baselines adjusted for the lockdown period. RESULTS Despite the inherent uncertainty, it is safe to assume an observed excess mortality of 2400 to 4000 deaths. Excess mortality was associated with older age groups (over age 65). DISCUSSION The data suggests a ternary explanation for early excess mortality: COVID-19, non-identified COVID-19 and decrease in access to healthcare. The estimates have implications in terms of communication of non-pharmaceutical actions, for research, and to healthcare professionals. CONCLUSION The excess mortality occurred between March 1 and April 22 was 3 to 5 fold higher than what can be explained by the official COVID-19 deaths.

positive: Estimating clinical severity of COVID-19 from the transmission dynamics in Wuhan, China As of 29 February 2020 there were 79,394 confirmed cases and 2,838 deaths from COVID-19 in mainland China. Of these, 48,557 cases and 2,169 deaths occurred in the epicenter, Wuhan. A key public health priority during the emergence of a novel pathogen is estimating clinical severity, which requires properly adjusting for the case ascertainment rate and the delay between symptoms onset and death. Using public and published information, we estimate that the overall symptomatic case fatality risk (the probability of dying after developing symptoms) of COVID-19 in Wuhan was 1.4% (0.9–2.1%), which is substantially lower than both the corresponding crude or naïve confirmed case fatality risk (2,169/48,557 = 4.5%) and the approximator(1) of deaths/deaths + recoveries (2,169/2,169 + 17,572 = 11%) as of 29 February 2020. Compared to those aged 30–59 years, those aged below 30 and above 59 years were 0.6 (0.3–1.1) and 5.1 (4.2–6.1) times more likely to die after developing symptoms. The risk of symptomatic infection increased with age (for example, at ~4% per year among adults aged 30–60 years).

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

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

positive: SARS‐CoV‐2 viral spike G614 mutation exhibits higher case fatality rate AIM: The COVID pandemic is caused by infection with the SARS‐CoV‐2 virus. The major mutation detected to date in the SARS‐CoV‐2 viral envelope spike protein, which is responsible for virus attachment to the host and is also the main target for host antibodies, is a mutation of an aspartate (D) at position 614 found frequently in Chinese strains to a glycine (G). We sought to infer health impact of this mutation. RESULT: Increased case fatality rate correlated strongly with the proportion of viruses bearing G614 on a country by country basis. The amino acid at position 614 occurs at an internal protein interface of the viral spike, and the presence of G at this position was calculated to destabilize a specific conformation of the viral spike, within which the key host receptor binding site is more accessible. CONCLUSION: These results imply that G614 is a more pathogenic strain of SARS‐CoV‐2, which may influence vaccine design. The prevalence of this form of the virus should also be included in epidemiologic models predicting the COVID‐19 health burden and fatality over time in specific regions. Physicians should be aware of this characteristic of the virus to anticipate the clinical course of infection.

positive: On Identifying and Mitigating Bias in the Estimation of the COVID-19 Case Fatality Rate The relative case fatality rates (CFRs) between groups and countries are key measures of relative risk that guide policy decisions regarding scarce medical resource allocation during the ongoing COVID-19 pandemic. In the middle of an active outbreak when surveillance data is the primary source of information, estimating these quantities involves compensating for competing biases in time series of deaths, cases, and recoveries. These include time- and severity- dependent reporting of cases as well as time lags in observed patient outcomes. In the context of COVID-19 CFR estimation, we survey such biases and their potential significance. Further, we analyze theoretically the effect of certain biases, like preferential reporting of fatal cases, on naive estimators of CFR. We provide a partially corrected estimator of these naive estimates that accounts for time lag and imperfect reporting of deaths and recoveries. We show that collection of randomized data by testing the contacts of infectious individuals regardless of the presence of symptoms would mitigate bias by limiting the covariance between diagnosis and death. Our analysis is supplemented by theoretical and numerical results and a simple and fast open-source codebase at https://github.com/aangelopoulos/cfr-covid-19 .

positive: The confounded crude case-fatality rates for COVID-19 hide more than they reveal - a comparison of age-specific and age-adjusted rates between six countries Background The reported crude case-fatality rates (CFRs) vary widely between countries. The serious limitations of using crude rates for comparisons are sometimes overlooked. In this paper we examined to what extent the age distribution of the cases is responsible for the differences in CFRs between countries. Methods Data on COVID-19 were extracted from the reports of individual countries. Overall and age-specific CFRs were available for six countries. The CFRs by country were adjusted for age using the direct method, using the combined age-specific number of cases of all six countries as the standard population. Findings The age distribution of the cases varied widely between countries. The crude CFRs varied between 1.6% and 11%. The differences in the age-specific CFRs were much smaller and the age-adjusted rates were much closer than the crude rates. The ratio of the crude CFR for the country with the highest to that with the lowest, was reduced substantially from 7.4 to 2.3 for the age-adjusted rates. Conclusions The age structure of the cases dramatically impacts on the differences in the crude CFRs between countries. Adjusting for age substantially reduces this variation. Other factors such as the differences in the definition of the denominators, the definition of a case and the standard of healthcare are likely to account for much of the residual variation. It is misleading to compare the crude COVID-19 CFRs between countries and should be avoided. Comparisons should be based on age-specific and age-adjusted rates. Key words: COVID-19, case-fatality rates, age-specific rates, age-adjusted rates, confounding

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

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

positive: SARS-CoV-2 in Italy: Population Density correlates with Morbidity and Mortality Since the beginning of the SARS-CoV-2/COVID-19 epidemic in China, elderly and multimorbid subjects showed a higher mortality rate. However, other factors could influence the mortality and the spread of contagion such as the population density. An archival research based on the Italian data stratified by region was performed in order to quantify the association between the population density, ageing index, number of positive cases, number of deaths, case-fatality rate, and medical equipment (gloves, masks, and ventilators). Results showed a significant positive linear relationship between the population density and cases, deaths, and case-fatality rate. No correlation with the ageing index was shown. Furthermore, we found a significant positive correlation between the number of medical supplies and population density, cases, and deaths. However, the medical supplies did not show any correlation with the case-fatality rate. Taken together, these findings suggest that the population density and the lack of medical equipment are key factors explaining morbidity and mortality of COVID-19 in Italy.

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

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

positive: Rate of Intensive Care Unit admission and outcomes among patients with coronavirus: A systematic review and Meta-analysis BACKGROUND: The rate of ICU admission among patients with coronavirus varied from 3% to 100% and the mortality was as high as 86% of admitted patients. The objective of the systematic review was to investigate the rate of ICU admission, mortality, morbidity, and complications among patients with coronavirus. METHODS: A comprehensive strategy was conducted in PubMed/Medline; Science direct and LILACS from December 2002 to May 2020 without language restriction. The Heterogeneity among the included studies was checked with forest plot, χ2 test, I2 test, and the p-values. All observational studies reporting rate of ICU admission, the prevalence of mortality and its determinants among ICU admitted patients with coronavirus were included and the rest were excluded. RESULT: A total of 646 articles were identified from different databases and 50 articles were selected for evaluation. Thirty-seven Articles with 24983 participants were included. The rate of ICU admission was 32% (95% CI: 26 to 38, 37 studies and 32, 741 participants). The Meta-Analysis revealed that the pooled prevalence of mortality in patients with coronavirus disease in ICU was 39% (95% CI: 34 to 43, 37 studies and 24, 983 participants). CONCLUSION: The Meta-Analysis revealed that approximately one-third of patients admitted to ICU with severe Coronavirus disease and more than thirty percent of patients admitted to ICU with a severe form of COVID-19 for better care died which warns the health care stakeholders to give attention to intensive care patients. REGISTRATION: This Systematic review and Meta-Analysis was registered in Prospero international prospective register of systemic reviews (CRD42020177095) on April 9/2020.

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

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

positive: Identification of Immune complement function as a determinant of adverse SARS-CoV-2 infection outcome Understanding the pathophysiology of SARS-CoV-2 infection is critical for therapeutics and public health intervention strategies. Viral-host interactions can guide discovery of regulators of disease outcomes, and protein structure function analysis points to several immune pathways, including complement and coagulation, as targets of the coronavirus proteome. To determine if conditions associated with dysregulation of the complement or coagulation systems impact adverse clinical outcomes associated with SARS-CoV-2 infection, we performed a retrospective observational study of 11,116 patients suspected of SARS-CoV-2 infection. We found that history of macular degeneration (a proxy for complement activation disorders) and history of coagulation disorders (thrombocytopenia, thrombosis, and hemorrhage) are risk factors for morbidity and mortality in SARS-CoV-2 infected patients – effects that could not be explained by age or sex. In addition, using data from the UK Biobank, we implemented a candidate driven approach to evaluate linkage between severe SARS-CoV-2 disease and genetic variation associated with complement and coagulation pathways. Among our findings, our scan identified an eQTL for CD55 (a negative regulator of complement activation) and SNPs in Complement Factor H (CFH) and Complement Component 4 Binding Protein Alpha (C4BPA), which play central roles in complement activation and innate immunity and were previously linked to Age Related Macular Degeneration (AMD) in a Genome-Wide Association Study (GWAS). In addition to providing evidence that complement function modulates SARS-CoV-2 infection outcome, the data point to several putative genetic markers of susceptibility. The results highlight the value of using a multi-modal analytical approach, combining molecular information from virus protein structure-function analysis with clinical informatics and genomics to reveal determinants and predictors of immunity, susceptibility, and clinical outcome associated with infection.

positive: Modeling the early phase of the Belgian COVID-19 epidemic using a stochastic compartmental model and studying its implied future trajectories Following the onset of the ongoing COVID-19 pandemic throughout the world, a large fraction of the global population is or has been under strict measures of physical distancing and quarantine, with many countries being in partial or full lockdown. These measures are imposed in order to reduce the spread of the disease and to lift the pressure on healthcare systems. Estimating the impact of such interventions as well as monitoring the gradual relaxing of these stringent measures is quintessential to understand how resurgence of the COVID-19 epidemic can be controlled for in the future. In this paper we use a stochastic age-structured discrete time compartmental model to describe the transmission of COVID-19 in Belgium. Our model explicitly accounts for age-structure by integrating data on social contacts to (i) assess the impact of the lockdown as implemented on March 13, 2020 on the number of new hospitalizations in Belgium; (ii) conduct a scenario analysis estimating the impact of possible exit strategies on potential future COVID-19 waves. More specifically, the aforementioned model is fitted to hospital admission data, data on the daily number of COVID-19 deaths and serial serological survey data informing the (sero)prevalence of the disease in the population while relying on a Bayesian MCMC approach. Our age-structured stochastic model describes the observed outbreak data well, both in terms of hospitalizations as well as COVID-19 related deaths in the Belgian population. Despite an extensive exploration of various projections for the future course of the epidemic, based on the impact of adherence to measures of physical distancing and a potential increase in contacts as a result of the relaxation of the stringent lockdown measures, a lot of uncertainty remains about the evolution of the epidemic in the next months.

positive: Identification of spatial variations in COVID-19 epidemiological data using K-Means clustering algorithm: a global perspective Background: Discerning spatial variations of COVID-19 through quantitative analysis operating on the geographically designated datasets relating to socio-demographics and epidemiological data facilitate strategy planning in curtailing the transmission of the disease and focus on articulation of necessary interventions in an informed manner. Methods: K-means clustering was employed on the available country-specific COVID-19 epidemiological data and the influential background characteristics. Country-specific case fatality rates and the average number of people tested positive for COVID-19 per every 10,000 population in each country were derived from the WHO COVID-19 situation report 107, and were used for clustering along with the background characteristics of proportion of countrys population aged >65 years and percentage GDP spent as public health expenditure. Results: The algorithm grouped the 89 countries into cluster 1 and Cluster 2 of sizes 54 and 35, respectively. It is apparent that Americas, European countries, and Australia formed a major part of cluster 2 with high COVID-19 case fatality rate, higher proportion of countrys population tested COVID-19 positive, higher percentage of GDP spent as public health expenditure, and greater percentage of population being more than 65 years of age. Conclusion: In spite of the positive correlation between high public health expenditure (%GDP) and COVID-19 incidence, case fatality rate, the immediate task ahead of most of the low and middle income countries is to strengthen their public health systems realizing that the correlation found in this study could be spurious in light of the underreported number of cases and poor death registration.

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

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

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

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

positive: Mortality surveillance during the COVID-19 pandemic

positive: Total predicted MHC-I epitope load is inversely associated with mortality from SARS-CoV-2 Polymorphism in MHC-I protein sequences across human populations significantly impacts their binding to viral peptides and alters T cell immunity to infection. Prioritization of MHC-I restricted viral epitopes remains a fundamental challenge for understanding adaptive immunity to SARS-CoV-2. Here, we present a consensus MHC-I binding prediction model, EnsembleMHC, based on the biochemical and structural basis of peptide presentation to aid the discovery of SARS-CoV-2 MHC-I peptides. We performed immunopeptidome predictions of SARS-CoV-2 proteins across 52 common MHC-I alleles identifying 658 high confidence peptides. Analysis of the resulting peptide-allele assignment distribution demonstrated significant variation across the allele panel up to an order of magnitude. Using MHC-I population-based allele frequencies, we estimated the average SARS-CoV-2 peptide population binding capacity across 21 individual countries. We have discovered a strong inverse association between the predicted population SARS-CoV-2 peptide binding capacity and overall mortality from SARS-CoV-2. Furthermore, we found that the consideration of only structural proteins produced a stronger association with observed death rate, highlighting their importance in protein-targeted immune responses. The 108 predicted SARS-CoV-2 structural protein peptides were shown to be derived from enriched regions in the originating protein, and present minimal risk for disruption by mutation. These results suggest that the immunologic fitness of both individuals and populations to generate class I-restricted T cell immunity to SARS-CoV-2 infection may impact clinical outcome from viral infection.

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

positive: Comorbidities, clinical signs and symptoms, laboratory findings, imaging features, treatment strategies, and outcomes in adult and pediatric patients with COVID-19: A systematic review and meta-analysis Introduction Since December 2019, a novel coronavirus (SARS-CoV-2) has triggered a world-wide pandemic with an enormous medical, societal, and economic toll. Thus, our aim was to gather all available information regarding comorbidities, clinical signs and symptoms, outcomes, laboratory findings, imaging features, and treatments in patients with coronavirus disease 2019 (COVID-19). Methods EMBASE, PubMed/ Medline, Scopus, and Web of Science were searched for studies published in any language between December 1st, 2019 and March 28th. Original studies were included if the exposure of interest was an infection with SARS-CoV-2 or confirmed COVID-19. The primary outcome was the risk ratio of comorbidities, clinical signs and symptoms, imaging features, treatments, outcomes, and complications associated with COVID-19 morbidity and mortality. We performed random-effects pairwise meta-analyses for proportions and relative risks, I2, Tau2, and Cochrane Q, sensitivity analyses, and assessed publication bias. Results: 148 met the inclusion criteria for the systematic review and meta-analysis with 12149 patients (5739 female) and a median age was 47.0 [35.0-64.6]. 617 patients died from COVID-19 and its complication, while 297 patients were reported as asymptomatic. Older age (SMD: 1.25 [0.78- 1.72]; p < 0.001), being male (RR = 1.32 [1.13-1.54], p = 0.005) and pre-existing comorbidity (RR = 1.69 [1.48-1.94]; p < 0.001) were identified as risk factors of in-hospital mortality. The heterogeneity between studies varied substantially (I2; range: 1.5-98.2%). Publication bias was only found in eight studies (Eggers test: p < 0.05). Conclusions: Our meta-analyses revealed important risk factors that are associated with severity and mortality of COVID-19.

positive: Number of International Arrivals Predicts Severity of the first Global Wave of the COVID-19 Pandemic Background: Reported death rates from different countries during the COVID-19 pandemic vary. Lack of universal testing and death underreporting make between-country comparisons difficult. The country-level determinants of COVID-19 mortality are unknown. Objective: Derive a measure of COVID-related death rates that is comparable across countries and identify its country-level predictors. Methods: An ecological study design of publicly available data was employed. Countries reporting >25 COVID-related deaths until May 1, 2020 were included. The outcome was the mean mortality rate from COVID-19, an estimate of the country-level daily increase in reported deaths during the ascending phase of the epidemic curve. Potential predictors assessed were most recently published Demographic parameters (population and population density, percentage population living in urban areas, median age, average body mass index, smoking prevalence), Economic parameters (Gross Domestic Product per capita; environmental parameters: pollution levels, mean temperature (January-April)), co-morbidities (prevalence of diabetes, hypertension and cancer), health systems parameters (WHO Health Index and hospital beds per 10,000 population and international arrivals). Multivariable linear regression was used to analyse the data. Results: Thirty-one countries were included. Of all country-level predictors included in the multivariable model, only total number of international arrivals was significantly associated with the mean death rate: Beta 0.3798 (95% Confidence Interval 0.2414, 0.5182), P <0.001. Conclusion: International travel was directly associated with the mortality slope and thus potentially the spread of COVID-19. Stopping international travel, particularly from affected areas, may be the most effective strategy to control COVID outbreak and prevent related deaths.

positive: Male mortality and the German response: lessons from COVID‐19 The current COVID‐19 outbreak has raised many questions, amongst them the higher mortality rates in men and the low overall mortality rates in Germany compared to other European countries. Here the authors explore some of the reasons behind both these phenomena and outline what we can learn from them for the future.

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: Mortality Factor Survey of Severe Acute Respiratory Syndrome in Taiwan SUMMARY Background Severe acute respiratory syndrome (SARS) is a new respiratory tract infectious disease caused by the highly contagious coronavirus (SARS-CoV). Its propagation and symptom progress are very rapid. This study evaluated the clinical characteristics, laboratory results and mortality factors of probable SARS cases. Methods This study was adopted with a retrospective research design to study probable SARS cases from the Chang Gung Memorial Hospital in Linkou and Kaoshiung from August 2003 to February 2004, with a total of 78 cases (average age, 44 years; standard deviation, 18 years; age range, 13–84 years) including 24 males (30.8%) and 54 females (69.2%). Results Most of the 78 cases involved nosocomial infection (56.4%). A total of 24 patients died, and the mortality rate was as high as 30.8%. Logistic regression analysis found that intubation (odds ratio, 115; p < 0.001) was the mortality forecast factor. Conclusion The mortality rate of intubation patients was 115 times higher than that of those who did not require intubation. Therefore, special care must be taken with SARS disease with severe infiltration chest X-ray images and respiratory distress. Positive medical treatment should be performed to lower the mortality rate.

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

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

positive: Coronavirus disease-2019 in cancer patients. A report of the first 25 cancer patients in a western country (Italy) Background: We describe cancer patients with coronavirus disease-2019 (COVID-19) infection treated at the Piacenza’s general hospital (north Italy). Materials & methods: Twenty-five cancer patients infected by COVID-19 admitted at the Piacenza’s general hospital from 21 February to 18 March 2020. Outcome from the infection were compared with infected noncancer patients. Results: Twenty patients (80%) were treated with antiviral therapy and hydroxychloroquine and five (20%) received hydroxychloroquine alone. Nine (36%) patients died, while 16 (64%) overcome the infection. In the control group the mortality was 16.13% and the overcome from infection was 83.87%. Conclusion: Mortality for COVID-19 was greater in cancer patients when compared with noncancer patients, worse prognosis for older age, women and patients treated with hydroxychloroquine alone. However, the comparisons did not reach statistical significance in most cases. This could be due to the small sample size that is the main limitation of the study.

positive: The importance of timing of a population level intervention on COVID-19 mortality COVID-19 poses an immense and immediate threat to global public health. Population level interventions (PLIs) impact this threat, with estimable large effects on reducing mortality. Many countries worldwide have currently zero/low mortality and many have yet to implement such PLIs. The importance of timing of PLI implementation on mortality outcomes is poorly understood. We extracted cumulative country-specific COVID-19 mortality for France, Germany, Italy, Spain and the UK to examine country-specific mortality trends and found that all five countries experienced COVID-19 mortality epidemics initially of exponential nature. We estimated the magnitude of effect on mortality of the nationwide PLI implemented on day 18 of Italy's mortality epidemic and assessed the importance of timing of PLI implementation by computing the effect of implementation of a PLI of this magnitude at various times on subsequent mortality. The nationwide PLI in Italy saved an estimated 6,170 lives by day 30 of the Italian epidemic. Implementing a PLI with this effect magnitude in a country of 60 million people on the day of the first death, and on days 7, 10, 14 and 17 thereafter, compared to implementation on day 18, resulted in substantially greater numbers of lives saved. Implementation on day 1 resulted in an additional 3,477 lives saved, 6,955 intensive care unit admissions and 52,162 hospital admissions prevented, beyond that achieved by implementation on day 18. PLI implementation earlier than day 18 substantially enhances benefit. Intervention on the day of the first mortality event in a country achieves the greatest benefit.

positive: Rethinking case fatality ratios for covid-19 from a data-driven viewpoint The case fatality ratio (CFR) for COVID-19 is difficult to estimate. One difficulty is due to ignoring or overestimating time delay between reporting and death. We claim that all of these cause large errors and artificial time dependence of the CFR. We find that for each country, there is a unique value of the time lag between reported cases and deaths versus time, that yields the optimal correlation between them is a specific sense. We find that the resulting corrected CFR (deaths shifted back by this time lag, divided by cases) is actually constant over many months, for many countries, but also for the entire world. This optimal time lag and constant CFR for each country can be found through a simple data driven algorithm. The traditional CFR (ignoring time lag) is spuriously time-dependent and its evolution is hard to quantify. Our corrected CFR is constant over time, therefore an important index of the pandemic in each country, and can be inferred from data earlier on, facilitating improved early estimates of COVID-19 mortality.

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

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

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

positive: Correlation Analysis Between Disease Severity and Inflammation-related Parameters in Patients with COVID-19 Pneumonia Aim: The new coronavirus pneumonia (COVID-19) outbreaking at the end of 2019 is highly contagious. Crude mortality rate reached 49% in critical patients. Inflammation matters on disease progression. This study analyzed blood inflammation indicators among mild, severe and critical patients, helping to identify severe or critical patients early. Methods: In this cross-sectional study, 100 patients were included and divided to mild, severe or critical groups. Correlation of peripheral blood inflammation-related indicators with disease criticality was analyzed. Cut-off values for critically ill patients were speculated through the ROC curve. Results：Significantly, disease severity were associated with age (R=-0.564, P<0.001), interleukin-2 receptor (IL2R) (R=-0.534, P<0.001), interleukin-6 (IL-6) (R=-0.535, P<0.001), interleukin-8 (IL-8) (R=-0.308, P<0.001), interleukin-10 (IL-10) (R=-0.422, P<0.001), tumor necrosis factor α (TNFα) (R=-0.322, P<0.001), C-reactive protein (CRP) (R=-0.604, P<0.001), ferroprotein (R=-0.508, P<0.001), procalcitonin (R=-0.650, P<0.001), white cell counts (WBC) (R=-0.54, P<0.001), lymphocyte counts (LC) (R=-0.56, P<0.001), neutrophil count (NC) (R=-0.585, P<0.001) and eosinophil counts (EC) (R=-0.299, P=0.01). Conclusion：With following parameters such as age >67.5 years, IL2R >793.5U/mL, CRP >30.7ng/mL, ferroprotein >2252μg/L, WBC>9.5*10^9/L or NC >7.305*10^9/L, the progress of COVID-19 to critical stage should be closely observed and possibly prevented. Inflammation is closely related to severity of COVID-19, and IL-6, TNFα and IL-8 might be promising therapeutic targets.

positive: Do Patients with Cancer Have a Poorer Prognosis of COVID-19? An Experience in New York City.

positive: High rates of 30-day mortality in patients with cirrhosis and COVID-19 BACKGROUND AND AIMS: Coronavirus disease (COVID-19) is a major worldwide threat for healthy individuals as well as for patients with comorbidities, but its impact on patients with cirrhosis is currently unknown. This study aimed at evaluating the impact of COVID-19 on the clinical outcome of these patients. METHODS: In this multicenter retrospective study, cirrhotic patients with confirmed Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection were enrolled between 1(st) and 31(th) March 2020. Clinical and biochemical data at COVID-19 and at the last outpatient visit were obtained through review of medical records. RESULTS: Fifty cirrhotic patients with confirmed SARS-CoV-2 infection were enrolled (age 67 years, 70% men, 38% virus-related, 52% previously compensated cirrhosis). At diagnosis, 64% of patients presented fever, 42% shortness of breath/polypnea, 22% encephalopathy, 96% needed hospitalization or prolonged an ongoing one. Respiratory-support was necessary in 71%, 52% received antivirals, 80% heparin. Serum albumin significantly decreased, while bilirubin, creatinine and prothrombin time significantly increased at COVID-19 diagnosis compared to last available data. The proportion of patients with MELD≥15 increased from 13% to 26% (p=0.037), acute-on-chronic liver failure and and de novo acute liver injury occurred in 14 (28%) and 10 patients, respectively. Seventeen patients died after a median of 10 (4-13) days from COVID-19 diagnosis, with a 30-day-mortality rate of 34%. Severity of lung and liver (according to CLIF-C, CLIF-OF and MELD scores) diseases independently predicted mortality. Mortality was significantly higher in hospitalized cirrhotics with COVID-19 than in those hospitalized for bacterial infections. CONCLUSION: COVID-19 is associated with liver function deterioration and elevated mortality in cirrhotic patients.

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

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

positive: The COVID-19 infection in Italy: a statistical study of an abnormally severe disease We statistically investigate the Coronavirus Disease 19 (hereinafter Covid-19) epidemics, which is particularly invasive in Italy. We show that the high apparent mortality (or Case Fatality Ratio, CFR) observed in Italy, as compared with other countries, is likely biased by a strong underestimation of infected cases. To give a more realistic estimate of the mortality of Covid-19, we use the most recent estimates of the IFR (Infection Fatality Ratio) of epidemic, based on the minimum observed CFR, and furthermore analyse data obtained from the ship Diamond Princess, a good representation of a laboratory case-study from an isolated system in which all the people have been tested. From such analyses we derive more realistic estimates of the real extension of the infection, as well as more accurate indicators of how fast the infection propagates. We then point out from the various explanations proposed, the dominant factors causing such an abnormal seriousness of the disease in Italy. Finally, we use the deceased data, the only ones estimated to be reliable enough, to predict the total number of infected people and the interval of time when the infection in Italy could stop.

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

positive: Correlation of population mortality of COVID-19 and testing coverage: a comparison among 36 OECD countries and Taiwan Although testing is widely regarded as critical to fighting the Covid-19 pandemic, what measure and level of testing best reflects successful infection control remains unresolved. Our aim was to compare the sensitivity of two testing metrics--population testing number and testing coverage--to population mortality outcomes and identify a benchmark for testing adequacy with respect to population mortality and capture of potential disease burden. This ecological study aggregated publicly available data through April 12 on testing and outcomes related to COVID-19 across 36 OECD (Organization for Economic Development) countries and Taiwan. All OECD countries and Taiwan were included in this population-based study as a proxy for countries with highly developed economic and healthcare infrastructure. Spearman correlation coefficients were calculated between the aforementioned metrics and following outcome measures: deaths per 1 million people, case fatality rate, and case proportion of critical illness. Fractional polynomials were used to generate scatter plots to model the relationship between the testing metrics and outcomes. Testing coverage, but not population testing number, was highly correlated with population mortality (rs= -0.79, P=5.975e-09 vs rs =- 0.3, P=0.05) and case fatality rate (rs= -0.67, P=9.067e-06 vs rs = -0.21, P=0.20). A testing coverage threshold of 15-45 signified adequate testing: below 15, testing coverage was associated with exponentially increasing population mortality, whereas above 45, increased testing did not yield significant incremental mortality benefit. Testing coverage was better than population testing number in explaining country performance and can be used as an early and sensitive indicator of testing adequacy and disease burden. This may be particularly useful as countries consider re-opening their economies.

positive: Epidemiological Characteristics of Coronavirus Disease 2019 (COVID-19) Patients in IRAN: A single Center Study • The majority of cases were in the age group of 50 to 60 years of old. • A total of 2964 cases of COVID-19 were investigated. • The male-to-female ratio was 1.93:1. • A significant effect of age, gender and comorbidities on the mortality. • The Case Fatality Rate among understudy cases was 8.06%.

positive: ICU and Ventilator Mortality Among Critically Ill Adults With Coronavirus Disease 2019 To determine mortality rates among adults with critical illness from coronavirus disease 2019. DESIGN: Observational cohort study of patients admitted from March 6, 2020, to April 17, 2020. SETTING: Six coronavirus disease 2019 designated ICUs at three hospitals within an academic health center network in Atlanta, Georgia, United States. PATIENTS: Adults greater than or equal to 18 years old with confirmed severe acute respiratory syndrome-CoV-2 disease who were admitted to an ICU during the study period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 217 critically ill patients, mortality for those who required mechanical ventilation was 35.7% (59/165), with 4.8% of patients (8/165) still on the ventilator at the time of this report. Overall mortality to date in this critically ill cohort is 30.9% (67/217) and 60.4% (131/217) patients have survived to hospital discharge. Mortality was significantly associated with older age, lower body mass index, chronic renal disease, higher Sequential Organ Failure Assessment score, lower Pao(2)/Fio(2) ratio, higher d-dimer, higher C-reactive protein, and receipt of mechanical ventilation, vasopressors, renal replacement therapy, or vasodilator therapy. CONCLUSIONS: Despite multiple reports of mortality rates exceeding 50% among critically ill adults with coronavirus disease 2019, particularly among those requiring mechanical ventilation, our early experience indicates that many patients survive their critical illness.

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: SARS-CoV-2 in Italy: Population Density correlates with Morbidity and Mortality. Since the beginning of the SARS-CoV-2/COVID-19 epidemic in China, elderly and multimorbid subjects showed a higher mortality rate. However, other factors could influence the mortality and the spread of contagion such as the population density. An archival research based on the Italian data stratified by region was performed in order to quantify the association between the population density, ageing index, number of positive cases, number of deaths, case-fatality rate, and medical equipment (gloves, masks, and ventilators). Results showed a significant positive linear relationship between the population density and cases, deaths, and case-fatality rate. No correlation with the ageing index was shown. Furthermore, we found a significant positive correlation between the number of medical supplies and population density, cases, and deaths. However, the medical supplies did not show any correlation with the case-fatality rate. Taken together, these findings suggest that the population density and the lack of medical equipment are key factors explaining morbidity and mortality of COVID-19 in Italy.

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: COVID-19 mortality rates in the European Union, Switzerland, and the UK: effect of timeliness, lockdown rigidity, and population density. BACKGROUND To date the European experience with COVID-19 mortality has been different to the observed in China and Asia. We aimed to forecast mortality trends in the 27 countries of the European Union (EU), plus Switzerland and the United Kingdom (UK), where lockdown dates and confinement interventions have been heterogeneous, and to explore its determinants. METHODS We have adapted our predictive model of COVID-19-related mortality, which rested on the observed mortality within the first weeks of the outbreak and the date of the respective lockdown in each country. It was applied in a training set of three countries (Italy, Germany and Spain), and then applied to the EU plus the UK and Switzerland. In addition, we explored the effects of timeliness and rigidity of the lockdown (on a five-step scale) and population density in our forecasts. We report r2, and percent variation of expected versus observed deaths, all following TRIPOD guidance. RESULTS We identified a homogeneous distribution of deaths, and found a median of 24 days after lockdown adoption to reach the maximum daily deaths. Strikingly, cumulative deaths up to April 25th, 2020 observed in Europe separated countries in three waves, according to the time lockdown measures were adopted following the onset of the outbreak: after a week, within a week, or even prior to the outbreak (r2=0.876). In contrast, no correlation neither with lockdown rigidity nor population density were observed. CONCLUSIONS The European experience confirms that early, effective interventions of 86 lockdown are fundamental to minimizing the COVID-19 death toll.

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

positive: Depletion of Alveolar Macrophages Ameliorates Virus-Induced Disease following a Pulmonary Coronavirus Infection Coronaviruses cause respiratory disease in humans that can range from mild to severe. However, the pathogenesis of pulmonary coronavirus infections is poorly understood. Mouse hepatitis virus type 1 (MHV-1) is a group 2 coronavirus capable of causing severe morbidity and mortality in highly susceptible C3H/HeJ mice. We have previously shown that both CD4 and CD8 T cells play a critical role in mediating MHV-1-induced disease. Here we evaluated the role of alveolar macrophages (AM) in modulating the adaptive immune response and subsequent disease. Depletion of AM using clodronate liposomes administered prior to MHV-1 infection was associated with a significant amelioration of MHV-1-induced morbidity and mortality. AM depletion resulted in a decreased number of virus-specific CD4 T cells in the lung airways. In addition, a significant increase in the frequency and total number of Tregs in the lung tissue and lung airways was observed following MHV-1 infection in mice depleted of AM. Our results indicate that AM play a critical role in modulating MHV-1-induced morbidity and mortality.

positive: Preliminary data on outcomes of SARS‐CoV‐2 infection in a Spanish single center cohort of kidney recipients Since the first cases of Coronavirus Disease 2019(COVID-19) were identified on December 12th , 2019, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection has dramatically spread worldwide becoming a pandemic with devastating consequences1 . This exponential increase in COVID-19 cases also includes vulnerable populations such as kidney recipients2,3 . Although scarce, preliminary information in this population suggests a serious course with a mortality of up to 25%4 . Herein, we report the outcomes of a cohort of 33 kidney transplant recipients from a single center focusing on hospital and intensive care (ICU) admission and mortality.

positive: Investigating the Determinants of High Case-Fatality Rate for Coronavirus Disease 2019 in Italy Case-Fatality Rate (CFR) for COVID-19 in Italy is apparently much higher than in other countries. Using data from Italy and other countries we evaluated the role of different determinants of this phenomenon. We found that the Italian testing strategy could explain an important part of the observed difference in CFR. In particular, the majority of patients that are currently tested in Italy have severe clinical symptoms that usually require hospitalization and this translates to a large CFR. We are confident that, once modifications in the testing strategy leading to higher population coverage are consistently adopted in Italy, CFR will realign with the values reported worldwide.

positive: Monitoring Transmissibility and Mortality of COVID-19 in Europe Abstract Objectives As a global pandemic is inevitable, real-time monitoring of transmission is vital for containing the spread of COVID-19. The main objective was to report real-time effective reproduction numbers (R(t)) case fatality rate (CFR). Methods Data were mainly obtained from WHO website, up to 9 March 2020. R(t) was estimated by exponential growth rate (EG) and time dependent (TD) methods. “R0” package in R was employed to estimate R(t) by fitting the existing epidemic curve. Both naïve CFR (nCFR) and adjust CFR (aCFR) were estimated. Results In EG method, R(t) was 3.27 [3.17-3.38] for Italy, 6.32 [5.72-6.99] for France, 6.07 [5.51-6.69] for Germany, 5.08 [4.51-5.74] for Spain. With TD method, the R value for March 9 was 3.10 [2.21-4.11] for Italy, 6.56 [2.04-12.26] for France, 4.43 [1.83-7.92] for Germany, and 3.95 [0-10.19] for Spain. Conclusions This study provides important findings on an early outbreak of COVID-19 in Europe. Due to the recent rapid increase in new cases of COVID-19, real-time monitoring of the transmissibility and mortality in Spain and France is a priority

positive: Epidemiological Determinants of Acute Respiratory Syndrome Coronavirus-2 Disease Pandemic and The Role of the Bacille-Calmette-Guerin Vaccine in Reducing Morbidity and Mortality This study analyzed the determinants of morbidity, mortality, and case fatality rate (CFR) of the ongoing pandemic of severe acute respiratory syndrome coronavirus-2 disease 2019 (COVID-19) Data for 210 countries and territories available in public domains were analyzed in relation to mandatory vaccination with Bacille-Calmette-Guerin (BCG), population density, median age of the country population, health care expenditure per capita, life expectancy at birth, healthy life expectancy, literacy rate, per capita gross domestic production adjusted to purchasing power (PPP), burden of tuberculosis (TB), acquired immunodeficiency disease caused by human immunodeficiency virus (HI V-AIDS), malaria, cardiovascular disease (CVD), neoplasm, diabetes, deaths due to energy-protein (food) deficiency (EPD), and per capita government spending on safe water and sanitation Mandatory BCG vaccination showed a highly significant (p<0 0001) negative correlation with COVID-19 morbidity (r = -0 62) and mortality (r = -0 58) rates, but no significant correlation with CFR The median age of the nation showed a significant (p<0 0001) positive correlation with COVID-19 morbidity (r= 0 40) and mortality (r = 0 34) rates, but no significant correlation with CFR The pandemic resulted in higher morbidity (r= 0 47, p<0 0001) and mortality (r= 0 25, p = 0 01) rates in countries with a higher PPP than in those with a lower PPP COVID-19 CFR and morbidity and mortality rates showed no significant correlation with population density, the burden of malaria or diabetes, or the level of spending on safe water and sanitation Only the burden of TB showed a positive correlation with CFR (r = 0 17, p = 0 05) However, COVID-19 morbidity showed a significant (p =0 05) negative correlation with the burden of TB, HI V-AIDS, CVD, and EPD Mortality and morbidity in COVID-19 patients showed a positive correlation with per capita health expenditure, life expectancy, the burden of neoplasia, and PPP

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

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

positive: Pseudo-Likelihood Based Logistic Regression for Estimating COVID-19 Infection and Case Fatality Rates by Gender, Race, and Age in California In emerging epidemics, early estimates of key epidemiological characteristics of the disease are critical for guiding public policy. In particular, identifying high risk population subgroups aids policymakers and health officials in combatting the epidemic. This has been challenging during the coronavirus disease 2019 (COVID-19) pandemic, because governmental agencies typically release aggregate COVID-19 data as marginal summary statistics of patient demographics. These data may identify disparities in COVID-19 outcomes between broad population subgroups, but do not provide comparisons between more granular population subgroups defined by combinations of multiple demographics. We introduce a method that overcomes the limitations of aggregated summary statistics and yields estimates of COVID-19 infection and case fatality rates --- key quantities for guiding public policy related to the control and prevention of COVID-19 --- for population subgroups across combinations of demographic characteristics. Our approach uses pseudo-likelihood based logistic regression to combine aggregate COVID-19 case and fatality data with population-level demographic survey data to estimate infection and case fatality rates for population subgroups across combinations of demographic characteristics. We illustrate our method on California COVID-19 data to estimate test-based infection and case fatality rates for population subgroups defined by gender, age, and race and ethnicity. Our analysis indicates that in California, males have higher test-based infection rates and test-based case fatality rates across age and race/ethnicity groups, with the gender gap widening with increasing age. Although elderly infected with COVID-19 are at an elevated risk of mortality, the test-based infection rates do not increase monotonically with age. LatinX and African Americans have higher test-based infection rates than other race/ethnicity groups. The subgroups with the highest 5 test-based case fatality rates are African American male, Multi-race male, Asian male, African American female, and American Indian or Alaska Native male, indicating that African Americans are an especially vulnerable California subpopulation.

positive: Factors associated with increased all-cause mortality during the COVID-19 pandemic in Italy BACKGROUND: The number of excess deaths in February-March 2020 in Italy, in comparison to the previous years, was considerably higher than recorded COVID19-related deaths. The present study is aimed at exploring the associations of excess mortality with some indices related to the epidemic and its management. METHODS: Data on all-cause mortality from February 20th to March 31st, in years from 2015 to 2020, and demographic, socioeconomic and healthcare organization data of each Italian region were obtained from Italian Institute of Statistics. Non-COVID19-Imputed Excess Mortality (NCIEM) was calculated as the difference between excess 2020 mortality and reported COVID19 mortality. The association of NCIEM with the rate of COVID-19 cases, COVID-19 mortality, and other potential moderators was assessed using linear regression models. RESULTS: The nationwide number of excess deaths, COVID-19 deaths was 26,701 and 13,710, respectively, with a difference of 12,991. NCIEM in different Regions showed a direct correlation with COVID-19 mortality (r2 = 0.61, p < 0.001) and total cases (r2 = 0.30, p = 0.012), and an inverse correlation with cases/total tests ratio (r2 = 0.49, p = 0.001). Direct correlations were also found with the proportion of institutionalized elderly, whereas inverse correlations were observed with prevalence of diabetes, cardiovascular mortality, and density of general practitioners. CONCLUSIONS: The impact of the COVID19 epidemic on all-cause mortality is considerably greater than that indicated by official counts of victims. Limited testing capacity and causes of death other than COVID19 could contribute to the increase in overall mortality rates.

positive: Estimating case fatality rates of COVID-19

positive: Analyzing COVID-19 pandemic for unequal distribution of tests, identified cases, deaths, and fatality rates in the top 18 countries BACKGROUND AND AIMS: COVID-19 pandemic has affected various countries differently due to variance in demographics, income level, health infrastructure, government response, control and enforcement, and cultural traits of different populations. This study aims to identify significant factors behind the unequal distribution of identified cases and deaths in different countries. Our study’s objective is comparative analysis and identification of relations between the spread of COVID-19 pandemic, population characteristics, and government response. METHODS: The top 18 countries worst hit by COVID-19 cases were identified. The data metrics, such as the number of cases, deaths, fatality rates, tests, average life expectancy, and population, were collected and consolidated. RESULTS: Countries with significant percentage of the older population are vulnerable to a high number of deaths due to COVID-19. Developed countries have higher per capita testing, whereas testing is less intensive in developing/underdeveloped countries. There is a consensus among health experts that COVID-19 has higher fatality rates for people above 60, however, with further age, this increases exponentially. Countries with higher life expectancy are also high-income countries, and the best course of action would be to provide specialized support to self-isolate for people of ages 75 and above. CONCLUSION: The behaviour of disease occurring at a large scale and interaction with different populations is studied to understand and differentiate the factors and measures that successfully inhibited the pandemic. The study benchmarks different countries based on their performance and efforts against the pandemic and provides some useful insights on the efficiency of their governance and potential to improve & ramp up their programs. The economic status and existing healthcare infrastructure as they are the key factors in determining the country’s ability to contain and minimize the losses from this pandemic.

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

positive: Limited Transmission of Turkey Coronavirus in Young Turkeys by Adult Alphitobius diaperinus (Coleoptera: Tenebrionidae) We examined the role of lesser mealworm, Alphitobius diaperinus (Panzer), in the transmission of an enteric disease of turkeys caused by a coronavirus. Turkey coronavirus (TCV) from two sources was studied, one isolate (NC95) was embryo propagated, the second was TCV infected material from turkeys diagnosed with poult enteritis mortality syndrome (PEMS). Beetles were fed virus-infected feces mixed with chicken feed. Transmission of virus was effectively halted by surface sterilization of the beetles. Turkey poults administered beetle homogenates infected with TCV+ PEMS that had not been surface sterilized had reduced weight gains and 50% mortality. Mortality and weight gains were not effected in the NC95 group. Virus isolation procedures were performed to determine NC95 viability at varying time intervals. Beetles were dissected and the guts removed 1, 12, and 24 h after the initial viral feeding. Whole beetles were also examined for comparison. Whole beetles and beetle guts were homogenized and injected into turkey eggs for embryo propagation. Direct immunofluorescence was used to determine the presence of TCV. A. diaperinus were capable of mechanical transmission of TCV. However, only turkey embryos receiving whole beetle and beetle gut homogenates within 1 h of feeding on the virus were positive for TCV. Laboratory studies demonstrating PEMS transmission by A. diaperinus are continuing.

positive: A systematic review and meta-analysis of cancer patients affected by a novel coronavirus BACKGROUND: Cancer patients with COVID-19 disease have been reported to have double the case fatality rate of the general population. MATERIALS AND METHODS: A systematic search of PubMed/MEDLINE, Embase, Cochrane Central, Google Scholar, and MedRxiv was done for studies on cancer patients with COVID-19. Pooled proportions were calculated for categorical variables. Odds ratio and forest plots were constructed for both primary and secondary outcomes. The random-effects model was used to account for heterogeneity between studies. RESULTS: This systematic review of 31 studies and meta-analysis of 181,323 patients from 26 studies involving 23,736 cancer patients is the largest meta-analysis to the best of our knowledge assessing outcomes in cancer patients affected by COVID-19. Our meta-analysis shows that cancer patients with COVID-19 have a higher likelihood of death (odds ratio, OR 2.54), which was largely driven by mortality among patients in China. Cancer patients were more likely to be intubated, although ICU admission rates were not statistically significant. Among cancer subtypes, the mortality was highest in hematological malignancies (OR 2.43) followed by lung cancer (OR 1.8). There was no association between receipt of a particular type of oncologic therapy and mortality. Our study showed that cancer patients affected by COVID-19 are a decade older than the normal population and have a higher proportion of co-morbidities. There was insufficient data to assess the association of COVID-directed therapy and survival outcomes in cancer patients. Despite the heterogeneity of studies and inconsistencies in reported variables and outcomes, these data could guide clinical practice and oncologic care during this unprecedented global health pandemic. CONCLUSION: Cancer patients with COVID-19 disease are at increased risk of mortality and morbidity. A more nuanced understanding of the interaction between cancer-directed therapies and COVID-19-directed therapies is needed. This will require uniform prospective recording of data, possibly in multi-institutional registry databases.

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

positive: Relationship between COVID-19 death toll doubling time and national BCG vaccination policy In this manuscript, we showed a statistically significant difference of the doubling times of the death toll between the group of countries with national universal Bacillus Calmette-Guerin (BCG) vaccination and the group without it for recent years. Based on a statistical test, the distributions of the doubling time of these two groups were significantly different (p=0.007). Miller et al. reported the relationship between BCG vaccination and mortality for COVID-19 based on deaths per million inhabitants. However, they did not take into account the differences in COVID-19 detection rates among the countries and the epidemic stages of the countries. Therefore we used a doubling time of the death toll as a more stable indicator instead. We also investigated the dependency of the BCG strains. Among the 42 BCG-vaccinated countries, the median doubling time of the eight countries using "Tokyo 172-1" strain at least partially (Japan, Iraq, Malaysia, South Korea, Philippines, Saudi Arabia, Pakistan, and Bangladesh) was 7.2 days, and that of the other 34 vaccinated countries was 5.5 days. Their distributions were also significantly different (p=0.026).

positive: Covid-19: Cancer mortality could rise at least 20% because of pandemic, study finds.

positive: Letalidad del COVID-19: ausencia de patrón epidemiológico./ [Case fatality rate of COVID-19: absence of epidemiological pattern] OBJECTIVE: Analyze a set of indicators to understand the variability of the evolution and impact of the COVID-19 epidemic in a set of selected countries. METHOD: Ecological study of a group of countries with more than 200 reported cases. Demographic variables, health expenditure variables, and variables about characteristics of health services were included as explanatory variables. and incidence, mortality and fatality rates have been analyzed as response variables. In addition, a relative fatality index has been created. Data are from international organizations. Spearman's correlation coefficient was used to estimate the magnitude of the associations. RESULTS: Number of tests and of medical professionals are associated with a higher incidence rate. Mortality and case fatality rate are not associated with demographic, health expenditure, or health services variables. CONCLUSION: Differences suggest a general underestimation of the magnitude of the epidemic. Improvement of case identification and effectiveness of epidemiological surveillance systems is necessary.

positive: Assumptions for disparities in case-fatality rates of coronavirus disease (COVID-19) across the globe In a short span, Coronavirus disease (COVID-19) has become the world pandemic by rapidly spreading almost to all the countries around the globe, irrespective of the continent, population size, economic status and healthcare system. Despite the number of cases increasing exponentially in most of the countries, there exist certain disparities in terms of case-fatality rates. As of April 24, 2020, the case-fatality rate of COVID-19 is about 7.0%, with 193,671 deaths and 2,761,121 confirmed cases around the world. Although the United States of America (USA), Spain, Italy, France, and Germany are the top-most affected counties in terms of confirmed cases; France, Italy and Spain are leading the list in terms of case-fatality rates. Therefore, through this mini-review, authors sought to brief on possible assumptions (five D's) that might contribute to the varying case-fatality rates among different countries across the globe.

positive: Assumptions for disparities in case-fatality rates of coronavirus disease (COVID-19) across the globe. In a short span, Coronavirus disease (COVID-19) has become the world pandemic by rapidly spreading almost to all the countries around the globe, irrespective of the continent, population size, economic status and healthcare system. Despite the number of cases increasing exponentially in most of the countries, there exist certain disparities in terms of case-fatality rates. As of April 24, 2020, the case-fatality rate of COVID-19 is about 7.0%, with 193,671 deaths and 2,761,121 confirmed cases around the world. Although the United States of America (USA), Spain, Italy, France, and Germany are the top-most affected counties in terms of confirmed cases; France, Italy and Spain are leading the list in terms of case-fatality rates. Therefore, through this mini-review, authors sought to brief on possible assumptions (five D's) that might contribute to the varying case-fatality rates among different countries across the globe.

positive: Oral Versus Aerosolized Ribavirin for the Treatment of Respiratory Syncytial Virus Infections in Hematopoietic Cell Transplant Recipients BACKGROUND: The use of oral ribavirin (RBV) for respiratory syncytial virus (RSV) infections is not well studied. With the drastic increase in the cost of aerosolized RBV, we aimed to compare outcomes of hematopoietic cell transplant (HCT) recipients treated with oral or aerosolized RBV for RSV infections. METHODS: We reviewed the records of 124 HCT recipients with RSV infections treated with oral or aerosolized RBV from September 2014 through April 2017. An immunodeficiency scoring index (ISI) was used to classify patients as low, moderate, or high risk for progression to lower respiratory infection (LRI) or death. RESULTS: Seventy patients (56%) received aerosolized RBV and 54 (44%) oral RBV. Both groups had a 27% rate of progression to LRI (P = 1.00). Mortality rates did not significantly differ between groups (30-day: aerosolized 10%, oral 9%, P = 1.00; 90-day: aerosolized 23%, oral 11%, P = .10). Classification and regression tree analysis identified ISI ≥7 as an independent predictor of 30-day mortality. For patients with ISI ≥7, 30-day mortality was significantly increased overall, yet remained similar between the aerosolized and oral therapy groups (33% for both). After propensity score adjustment, Cox proportional hazards models showed similar mortality rates between oral and aerosolized therapy groups (30-day: hazard ratio [HR], 1.12 [95% confidence interval {CI}, .345–3.65, P = .845). CONCLUSIONS: HCT recipients with RSV infections had similar outcomes when treated with aerosolized or oral RBV. Oral ribavirin may be an effective alternative to aerosolized RBV, with potential significant cost savings.

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

positive: COVID-19: Modelling Local Transmission and Morbidity effects to provide an estimate of overall Relative Healthcare Resource Impact by General Practice Granularity Introduction Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the name given to the 2019 novel coronavirus. COVID-19 is the name given to the disease associated with the virus. SARS-CoV-2 is a new strain of coronavirus that has not been previously identified in humans. Methods Two key factors were analysed which when multiplied together would give an estimate of relative demand on healthcare utilisation. These factors were case incidence and case morbidity. GP Practice data was used as this provided the most geographically granular source of published public population data. To analyse case incidence, the latest values for indicators that could be associated with infection transmission rates were collected from the Office of National Statistics (ONS) and Quality Outcome Framework (QOF) sources. These included population density, % age >16 at fulltime work/education, % age over 60, % BME ethnicity, social deprivation as IMD 2019, Location as latitude/longitude, and patient engagement as % self-confident in their own long term condition management. Average case morbidity was calculated by applying the international mortality Odds Ratio to the local population relevant age and disease prevalences and then summing and dividing by the equivalent national figure. To provide a comparative measure of overall healthcare resource impact, individual GP practice impact scores were compared against the median practice. Results The case incidence regression is a dynamic situation with the significance of specific factors moderating over time as the balance between external infection, community transmission and impact of mitigation measures feeds through to the number of cases. It showed that currently Urban, % Working and age >60 were the strongest determinants of case incidence. The local population comorbidity remains unchanged. The range of relative HC impact was wide with 80% of practices falling between 20%-250% of the national median. Once practice population numbers were included it showed that the top 33% of GP practices supporting 45% of the patient population would require 68% of COVID-19 healthcare resources. The model provides useful information about the relative impact of Covid-19 on healthcare workload at GP practice granularity in all parts of England. Conclusion Covid-19 is impacting on the utilisation of health and social care resources across the country. This model provides a method for predicting relative local levels of disease burden based on defined criteria and thereby providing a method for targeting limited (and perhaps soon to be scarce) care resources to optimise national, regional and local responses to the COVID-19 outbreak.

positive: Assessing the burden of COVID-19 in Canada Background: The burden of COVID-19 in Canada is unequally distributed geographically, with the largest number of cases and fatalities recorded in Quebec and Ontario while other provinces experienced limited outbreaks. To date, however, no study has assessed how provincial epidemics have unfolded in a comparative perspective. This is essential to calibrate projections of the future course of the epidemic and plan health care resources for the second wave of infections. Methods: Using newly released individual-level data collected by the Public Health Agency of Canada, we assess COVID-19-related morbidity and mortality across age and gender groups at the provincial level through a combination of demographic and survival analyses. Results: Quebec has the highest absolute and per capita number of COVID-19 confirmed positive cases, hospitalizations and fatalities in all age groups. In each province, a higher number of women than men test positive for the disease, especially above age 80. Yet consistently across age groups, infected men are more likely to be hospitalized and enter intensive care than women do. These gender differences in hospitalisation rates account for the higher case fatality risk due to COVID-19 among men compared to women. Interpretation: Although health care capacity across provinces has been sufficient to treat severe cases, we find that the main factor accounting for gender differences in COVID-19-related mortality is the need for hospitalization and intensive care, especially above age 80. This suggests a selection effect of severe cases requiring to be treated in a hospital setting that needs to be further investigated.

positive: Suicide Mortality and Coronavirus Disease 2019-A Perfect Storm?

positive: Coronavirus disease 19 in minority populations of Newark, New Jersey BACKGROUND: The purpose of this study is to report the clinical features and outcomes of Black/African American (AA) and Latino Hispanic patients with Coronavirus disease 2019 (COVID-19) hospitalized in an inter-city hospital in the state of New Jersey. METHODS: This is a retrospective cohort study of AA and Latino Hispanic patients with COVID-19 admitted to a 665-bed quaternary care, teaching hospital located in Newark, New Jersey. The study included patients who had completed hospitalization between March 10, 2020, and April 10, 2020. We reviewed demographics, socioeconomic variables and incidence of in-hospital mortality and morbidity. Logistic regression was used to identify predictor of in-hospital death. RESULTS: Out of 416 patients, 251 (60%) had completed hospitalization as of April 10, 2020. The incidence of In-hospital mortality was 38.6% (n = 97). Most common symptoms at initial presentation were dyspnea 39% (n = 162) followed by cough 38%(n = 156) and fever 34% (n = 143). Patients were in the highest quartile for population’s density, number of housing units and disproportionately fell into the lowest median income quartile for the state of New Jersey. The incidence of septic shock, acute kidney injury (AKI) requiring hemodialysis and admission to an intensive care unit (ICU) was 24% (n = 59), 21% (n = 52), 33% (n = 82) respectively. Independent predictors of in-hospital mortality were older age, lower serum Hemoglobin < 10 mg/dl, elevated serum Ferritin and Creatinine phosphokinase levels > 1200 U/L and > 1000 U/L. CONCLUSIONS: Findings from an inter-city hospital’s experience with COVID-19 among underserved minority populations showed that, more than one of every three patients were at risk for in-hospital death or morbidity. Older age and elevated inflammatory markers at presentation were associated with in-hospital death.

positive: Risk factors associated with mortality of COVID-19 in 2692 counties of the United States Background: The number of cumulative confirmed cases of COVID-19 in the United States has risen sharply since March. A county health ranking and roadmaps program has been established to identify factors associated with disparity in mobility and mortality of COVID-19 in all counties in the United States. Objective: To find out the risk factors associated with mortality of COVID-19 with various levels of prevalence. Design: A negative binomial design was applied to the county-level mortality counts of COVID-19 on April 15, 2020 in the United States. In this design, the infected counties were categorized into three levels of infections using clustering analysis based on time-variant cumulative confirmed cases from March 1 to April 15, 2020. Setting: United States Participants: COVID-19 patients in various counties of the United States from March 1 to April 15, 2020. Measurements: The county-level cumulative confirmed cases and mortality of COVID-19. Results. 2692 infected counties were assigned into three classes where the mild, moderate, and severe prevalence of infections were identified, respectively. Several risk factors are significantly associated with the mortality of COVID-19, where Hispanic (0.024, P=0.002), female (0.253, P=0.027), elder (0.218, P=0.017) and Native Hawaiian or other Pacific islander (2.032, P=0.027) individuals are more vulnerable to the mortality of COVID-19. More locations open to exercise (0.030, P=0.004), higher levels of air pollution (0.184, P=0.044), and segregation between non-White and White increased the mortality rate. Limitation: The study relied on mortality data on April 15, 2020. Conclusion. The mortality of COVID-19 depends on sex, ethnicity, and outdoor environment. The increasing awareness of these significant factors may lead to the reduction in the mortality rate 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: Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. Importance Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 pneumonia have not yet been well delineated. Objective To describe the clinical characteristics and outcomes in patients with COVID-19 pneumonia who developed acute respiratory distress syndrome (ARDS) or died. Design, Setting, and Participants Retrospective cohort study of 201 patients with confirmed COVID-19 pneumonia admitted to Wuhan Jinyintan Hospital in China between December 25, 2019, and January 26, 2020. The final date of follow-up was February 13, 2020. Exposures Confirmed COVID-19 pneumonia. Main Outcomes and Measures The development of ARDS and death. Epidemiological, demographic, clinical, laboratory, management, treatment, and outcome data were also collected and analyzed. Results Of 201 patients, the median age was 51 years (interquartile range, 43-60 years), and 128 (63.7%) patients were men. Eighty-four patients (41.8%) developed ARDS, and of those 84 patients, 44 (52.4%) died. In those who developed ARDS, compared with those who did not, more patients presented with dyspnea (50 of 84 [59.5%] patients and 30 of 117 [25.6%] patients, respectively [difference, 33.9%; 95% CI, 19.7%-48.1%]) and had comorbidities such as hypertension (23 of 84 [27.4%] patients and 16 of 117 [13.7%] patients, respectively [difference, 13.7%; 95% CI, 1.3%-26.1%]) and diabetes (16 of 84 [19.0%] patients and 6 of 117 [5.1%] patients, respectively [difference, 13.9%; 95% CI, 3.6%-24.2%]). In bivariate Cox regression analysis, risk factors associated with the development of ARDS and progression from ARDS to death included older age (hazard ratio [HR], 3.26; 95% CI 2.08-5.11; and HR, 6.17; 95% CI, 3.26-11.67, respectively), neutrophilia (HR, 1.14; 95% CI, 1.09-1.19; and HR, 1.08; 95% CI, 1.01-1.17, respectively), and organ and coagulation dysfunction (eg, higher lactate dehydrogenase [HR, 1.61; 95% CI, 1.44-1.79; and HR, 1.30; 95% CI, 1.11-1.52, respectively] and D-dimer [HR, 1.03; 95% CI, 1.01-1.04; and HR, 1.02; 95% CI, 1.01-1.04, respectively]). High fever (≥39 °C) was associated with higher likelihood of ARDS development (HR, 1.77; 95% CI, 1.11-2.84) and lower likelihood of death (HR, 0.41; 95% CI, 0.21-0.82). Among patients with ARDS, treatment with methylprednisolone decreased the risk of death (HR, 0.38; 95% CI, 0.20-0.72). Conclusions and Relevance Older age was associated with greater risk of development of ARDS and death likely owing to less rigorous immune response. Although high fever was associated with the development of ARDS, it was also associated with better outcomes among patients with ARDS. Moreover, treatment with methylprednisolone may be beneficial for patients who develop ARDS.

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

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

positive: Comorbidity and Sociodemographic determinants in COVID-19 Mortality in an US Urban Healthcare System Background: New York City is the US epicenter of the coronavirus disease 2019 (COVID-19) pandemic. Early international data indicated that comorbidity contributes significantly to poor prognosis and fatality in patients infected with SARS-CoV-2. It is not known to what degree medical comorbidity and sociodemographic determinants impact COVID-19 mortality in the US. Methods: Evaluation of de-identified electronic health records of 7,592 COVID-19 patients confirmed by SARS-CoV-2 lab tests in New York City. Medical comorbidites and outcome of mortality, and other covariates, including clinical, sociodemographic, and medication measures were assessed by bivariate and multivariate logistic regression models. Results: Of common comorbid conditions (hypertension, chronic kidney disease, chronic obstructive pulmonary disease, asthma, obesity, diabetes, HIV, cancer), when adjusted for covariates, chronic kidney disease remained significantly associated with increased odds of mortality. Patients who had more than one comorbidities, former smokers, treated with Azithromycin without Hydroxychloroquine, reside within the boroughs of Brooklyn and Queens Higher had higher odds of death. Conclusions: Increasing numbers of comorbid factors increase COVID-19 mortality, but several clinical and sociodemographic factors can mitigate risk. Continued evaluation of COVID-19 in large diverse populations is important to characterize individuals at risk and improve clinical outcomes.

positive: 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.

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

positive: Prevalence and fatality rates of COVID-19: What are the reasons for the wide variations worldwide?

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

positive: Health and Demographic Impact on COVID-19 Infection and Mortality in US Counties Introduction With the pandemic of COVID-19, the number of confirmed cases and related deaths are increasing in the US. We aimed to understand the potential impact of health and demographic factors on the infection and mortality rates of COVID-19 at the population level. Methods We collected total number of confirmed cases and deaths related to COVID-19 at the county level in the US from January 21, 2020 to April 23, 2020. We extracted health and demographic measures for each US county. Multivariable linear mixed effects models were used to investigate potential correlations of health and demographic characteristics with the infection and mortality rates of COVID-19 in US counties. Results Our models showed that several health and demographic factors were positively correlated with the infection rate of COVID-19, such as low education level and percentage of Black. In contrast, several factors, including percentage of smokers and percentage of food insecure, were negatively correlated with the infection rate of COVID-19. While the number of days since first confirmed case and the infection rate of COVID-19 were negatively correlated with the mortality rate of COVID-19, percentage of elders (65 and above) and percentage of rural were positively correlated with the mortality rate of COVID-19. Conclusions At the population level, health and demographic factors could impact the infection and mortality rates of COVID-19 in US counties.

positive: Standardization and Age-Distribution of COVID-19: Implications for Variability in Case Fatality and Outbreak Identification Background: Epidemiological data from the COVID-19 pandemic has demonstrated variability in attack rates by age, and country-to-country variability in case fatality ratio (CFR). Objective: To use direct and indirect standardization for insights into the impact of age-specific under-reporting on between-country variability in CFR, and apparent size of COVID-19 epidemics. Design: Post-hoc secondary data analysis (case studies), and mathematical modeling. Setting: China, global. Interventions: None. Measurements: Data were extracted from a sentinel epidemiological study by the Chinese Center for Disease Control (CCDC) that describes attack rates and CFR for COVID-19 in China prior to February 12, 2020. Standardized morbidity ratios (SMR) were used to impute missing cases and adjust CFR. Age-specific attack rates and CFR were applied to different countries with differing age structures (Italy, Japan, Indonesia, and Egypt), in order to generate estimates for CFR, apparent epidemic size, and time to outbreak recognition for identical age-specific attack rates. Results: SMR demonstrated that 50-70% of cases were likely missed during the Chinese epidemic. Adjustment for under-recognition of younger cases decreased CFR from 2.4% to 0.8% (assuming 50% case ascertainment in older individuals). Standardizing the Chinese epidemic to countries with older populations (Italy, and Japan) resulted in larger apparent epidemic sizes, higher CFR and earlier outbreak recognition. The opposite effect was demonstrated for countries with younger populations (Indonesia, and Egypt). Limitations: Secondary data analysis based on a single country at an early stage of the COVID-19 pandemic, with no attempt to incorporate second order effects (ICU saturation) on CFR. Conclusion: Direct and indirect standardization are simple tools that provide key insights into between-country variation in the apparent size and severity of COVID-19 epidemics.

positive: Regulation and Trust: 3-Month Follow-up Study on COVID-19 Mortality in 25 European Countries BACKGROUND: The outbreak of the coronavirus disease (COVID-19) has dramatically changed societies in 2020. Since the end of February, Europe has been hit particularly hard by COVID-19, but there are major country differences in both the spread of the virus and measures taken to stop the virus. Social psychological factors such as institutional trust could be important in understanding the development of the epidemic. OBJECTIVE: The aim of this study was to examine country variations of COVID-19 mortality in Europe by analyzing social risk factors explaining the spread of the disease, restrictions and control measures, and institutional trust. METHODS: The present study was based on a background analysis of European Social Survey data on 25 European countries (N=47,802). Multilevel mixed effects linear regression models focused on 84 days of the COVID-19 epidemic (January 22 to April 14, 2020) and modelled the daily COVID-19 mortality. Analysis focused on the impact of social relations, restrictions, and institutional trust within each country. RESULTS: The spread of the COVID-19 epidemic has been fast everywhere, but the findings revealed significant differences between countries in COVID-19 mortality. Perceived sociability predicted higher COVID-19 mortality. Major differences between the 25 countries were found in reaction times to the crisis. Late reaction to the crisis predicted later mortality figures. Institutional trust was associated with lower COVID-19 mortality. CONCLUSIONS: The analyses demonstrated the importance of societal and social psychological factors in the spread of the COVID-19 epidemic. By considering multiple perspectives, this study showed that country differences in Europe are major, and this will have an impact on how countries will cope with the ongoing crisis in the following months. The results indicated the importance of timely restrictions and cooperation with people.

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

positive: Strong Correlation Between Prevalence of Severe Vitamin D Deficiency and Population Mortality Rate from COVID-19 in Europe Background: SARS-CoV-2 virus causes a very wide range of COVID-19 disease severity in humans: from completely asymptomatic to fatal, and the reasons behind it are often not understood. There is some data that Vitamin D may have protective effect, so authors decided to analyze European country-wide data to determine if Vitamin D levels are associated with COVID-19 population death rate. Methods: To retrieve the Vitamin D levels data, authors analyzed the Vitamin D European population data compiled by 2019 ECTS Statement on Vitamin D Status published in the European Journal of Endocrinology. For the data set to used for analysis, only recently published data, that included general adult population of both genders ages 40-65 or wider, and must have included the prevalence of Vitamin D deficiency. Results: There were 10 countries data sets that fit the criteria and were analyzed. Severe Vitamin D deficiency was defined as 25(OH)D less than 25 nmol/L (10 ng/dL). Pearson correlation analysis between death rate per million from COVID-19 and prevalence of severe Vitamin D deficiency shows a strong correlation with r = 0.76, p = 0.01, indicating significant correlation. Correlation remained significant, even after adjusting for age structure of the population. Additionally, over time, correlation strengthened, and r coefficient asymptoticaly increased. Conclusions: Authors recommend universal screening for Vitamin D deficiency, and further investigation of Vitamin D supplementation in randomized control studies, which may lead to possible treatment or prevention of COVID-19.

positive: Characteristics, outcome and predictors of in-hospital mortality in an elderly population from a SARS-CoV-2 outbreak in a long-term care facility. Since December 2019, coronavirus disease 2019 (COVID-19) pandemic has spread from China all over the world, many COVID-19 outbreaks have been reported in long-term care facilities (LCTF). However, data on clinical characteristics and prognostic factors in such settings are scarce. We conducted a retrospective, observational cohort study to assess clinical characteristics and baseline predictors of mortality of COVID-19 patients hospitalized after an outbreak of SARS-CoV-2 infection in a LTCF. A total of 50 patients were included. Mean age was 80 years (SD, 12 years), and 24/50 (57.1%) patients were males. A total of 42/50 (84%) patients experienced symptoms of SARS-CoV-2 infection. The overall in-hospital mortality rate was 32%. In Cox regression, significant predictors of in-hospital mortality were: hypernatremia (HR 9.12), lymphocyte count <1000 cells/L (HR 7.45), cardiovascular diseases other than hypertension (HR 6.41), and higher levels of serum interleukin-6 (IL-6, pg/mL) (HR 1.005). Our study shows a high in-hospital mortality rate in a cohort of elderly patients with COVID-19 and hypernatremia, lymphopenia, CVD other than hypertension, and higher IL-6 serum levels were identified as independent predictors of in-hospital mortality. Further studies are necessary to better understand and confirm our findings in the setting of a LTCF outbreak of COVID-19.

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

positive: The effect of age on mortality in patients with Covid-19: a metanalysis with 611,583 subjects ABSTRACT Objectives Initial data on Covid-19 infection has pointed out a special vulnerability of elderly people. Design we performed a meta-analysis with available national reports at May 7th 2020 from China, Italy, Spain, United Kingdom and New York State. Analyses were performed by a random effects model and sensitivity analyses were performed for the identification of potential sources of heterogeneity. Setting and Participants: covid-19 positive patients reported in literature and national reports. Measures all-cause mortality by age. Results A total of 611,1583 subjects were analyzed and 141,745 (23.2%) had age ≥80. The percentage of octogenarians was different in the 5 registries being the lowest in China (3.2%) and the highest and the highest in UK and New York State. The overall mortality rate was 12.10% and it varied widely between countries being the lowest in China (3.1%) and the highest in UK (20.8%) and New York State (20.99%). Mortality was <1.1% in patients with age <50 and it increased exponentially after that age in the 5 national registries. As expected, the highest mortality rate was observed in patients ≥80 years old. All age groups had significantly higher mortality compared to the inmediatelly younger age group. The largest increase in mortality risk was observed in patients with age 60-69 compared to 50-59 (OR: 3.13 95% CI 2.61-3.76). Conclusions and implications this metanalysis with more than half-million of Covid-19 patients from different countries highlights the determinant effect of age on mortality with the relevant thresholds on age >50 and, especially, >60. Elderly patients should be priorized in the implementation of preventive measures.

positive: COVID-19: Spatial Analysis of Hospital Case-Fatality Rate in France When the population risk factors and reporting systems are similar, the assessment of the case-fatality (or lethality) rate (ratio of cases to deaths) represents a perfect tool for analyzing, understanding and improving the overall efficiency of the health system. The objective of this article is to estimate the influence of the hospital care system on lethality in metropolitan France during the inception of the COVID-19 epidemic, by analyzing the spatial variability of the hospital case-fatality rate between French districts. The results show that the higher case-fatality rates observed in certain districts are mostly related to the level of morbidity in the district, therefore to the overwhelming of the healthcare systems during the acute phases of the epidemic. However, the magnitude of this increase of case-fatality rate represents less than 10 per cent of the average case-fatality rate and cannot explain the magnitude of the variations in case-fatality rate reported by country by international organizations or information sites. These differences can only be explained by the systems for reporting cases and deaths, which, indeed, vary greatly from country to country, and not attributed to the care or treatment of patients, even during hospital stress due to epidemic peaks.

positive: Time for a culture change: understanding and reducing risk, morbidity and mortality from COVID-19 in those of black and minority ethnicity. Following a number of epidemics in the 21st century, including Ebola and Middle East respiratory syndrome, the SARS-COV-2 virus, causing COVID-19 disease, was declared a pandemic health emergency of international concern in January 2020.

positive: Controlled Avalanche: A Regulated Voluntary Exposure Approach for Addressing Covid19 Background: The ongoing Covid-19 pandemic has driven many countries to take radical suppression measures. While reducing mortality, these measures result in severe economic repercussions, and inhibit the development of herd immunity. Until an effective vaccine will be available, we propose an alternative approach, akin to avalanche control at ski resorts, a practice which intentionally triggers small avalanches in order to prevent a singular catastrophic one. Its main goal is to approach herd immunity faster than the current alternatives, with lower mortality rates and lower demand for critical health-care resources. According to this approach, individuals whose probability of developing serious health conditions is low (i.e. 20-49 years old with no comorbidities) will be offered the option to be voluntarily exposed to the virus under controlled supervision, and will then be issued 'immunity certificates' if they are confirmed to have developed SARS-CoV-2 antibodies. Methods: Using a compartmental model we examine the implications of the controlled avalanche (CA) strategy over the population in Israel. We compare four scenarios: in two scenarios the CA program is applied to the low-risk population (with the rest of the population subject to mitigation measures), followed by mitigation for the entire population or by uncontrolled spread. These are compared to mitigated and uncontrolled scenarios without the CA program. We discuss the economic, ethical and public health implications of the CA strategy. Findings: We show that compared to mitigation of the entire population, the CA strategy reduces the overall mortality by 43%, reduces the maximum number of people in need for ICUs by 62% and decreases the time required for release of 50% of the low-risk population by more than 2 months. Interpretation: This study suggests an ethically acceptable practice, that enables reaching herd immunity faster than the current alternatives, with low mortality and minimal economic damage.

positive: Influenza– and Respiratory Syncytial Virus–Associated Morbidity and Mortality in the Nursing Home Population Objectives: To estimate winter viral‐related morbidity and mortality in Tennessee nursing home residents during 4 consecutive years. Design: A retrospective cohort study. Setting: Three hundred eighty‐one Tennessee nursing homes. Participants: Nursing home residents. Measurements: Viral surveillance data were used to define three seasons: influenza (influenza and respiratory syncytial virus (RSV) cocirculating), RSV (RSV alone circulating), and non winter‐viral (neither virus circulating). Adjusted seasonal differences in rates of cardiopulmonary hospitalizations, antibiotic prescriptions, and deaths during these three seasons were calculated to estimate annual hospitalizations, courses of antibiotics, and deaths attributable to influenza and RSV from 1995 to 1999. Results: Nursing home residents had 81,885 person‐years of follow‐up. In the 63% of residents with comorbid conditions that increase influenza morbidity, influenza infection contributed to an estimated average of 28 hospitalizations, 147 courses of antibiotics, and 15 deaths per 1,000 persons annually. Similarly, RSV accounted for an annual average of 15 hospitalizations, 76 courses of antibiotics, and 17 deaths per 1,000 persons. Influenza and RSV accounted for 7% of cardiopulmonary hospitalizations and 9% of total deaths in high‐risk residents during the 4 study years. Absolute morbidity and mortality were lower in residents without identified comorbid conditions but accounted for 15% of hospitalizations and 14% of deaths. These estimates depend on the assumption that morbidity and mortality from other respiratory viruses were distributed evenly between the three defined seasons. Conclusion: Influenza and RSV substantially increased hospitalization rates, antibiotic use, and deaths in elderly nursing home residents each winter. These data should encourage persistent efforts toward disease prevention, and thoughtful study of vaccine development and delivery, diagnostic tools, and methods of prophylaxis and therapy.

positive: Prevalence, Severity and Mortality associated with COPD and Smoking in patients with COVID-19: A Rapid Systematic Review and Meta-Analysis BACKGROUND: Coronavirus disease 2019 (COVID-19) is an evolving infectious disease that dramatically spread all over the world in the early part of 2020. No studies have yet summarized the potential severity and mortality risks caused by COVID-19 in patients with chronic obstructive pulmonary disease (COPD), and we update information in smokers. METHODS: We systematically searched electronic databases from inception to March 24, 2020. Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Study quality was assessed using a modified version of the Newcastle-Ottawa Scale. We synthesized a narrative from eligible studies and conducted a meta-analysis using a random-effects model to calculate pooled prevalence rates and 95% confidence intervals (95%CI). RESULTS: In total, 123 abstracts were screened and 61 full-text manuscripts were reviewed. A total of 15 studies met the inclusion criteria, which included a total of 2473 confirmed COVID-19 patients. All studies were included in the meta-analysis. The crude case fatality rate of COVID-19 was 7.4%. The pooled prevalence rates of COPD patients and smokers in COVID-19 cases were 2% (95% CI, 1%-3%) and 9% (95% CI, 4%-14%) respectively. COPD patients were at a higher risk of more severe disease (risk of severity = 63%, (22/35) compared to patients without COPD 33.4% (409/1224) [calculated RR, 1.88 (95% CI, 1.4-2.4)]. This was associated with higher mortality (60%). Our results showed that 22% (31/139) of current smokers and 46% (13/28) of ex-smokers had severe complications. The calculated RR showed that current smokers were 1.45 times more likely [95% CI: 1.03-2.04] to have severe complications compared to former and never smokers. Current smokers also had a higher mortality rate of 38.5%. CONCLUSION: Although COPD prevalence in COVID-19 cases was low in current reports, COVID-19 infection was associated with substantial severity and mortality rates in COPD. Compared to former and never smokers, current smokers were at greater risk of severe complications and higher mortality rate. Effective preventive measures are required to reduce COVID-19 risk in COPD patients and current smokers.

positive: Monitoring trends and differences in COVID-19 case fatality rates using decomposition methods: Contributions of age structure and age-specific fatality The population-level case fatality rate (CFR) associated with COVID-19 varies substantially, both across countries and within countries over time. We analyze the contribution of two key determinants of the variation in the observed CFR: the age-structure of diagnosed infection cases and age-specific case-fatality rates. We use data on diagnosed COVID-19 cases and death counts attributable to COVID-19 by age for China, France, Germany, Italy, South Korea, Spain, and the United States. We calculate the CFR for each country at the latest data point and for Italy also over time. We use demographic decomposition to break the difference between CFRs into unique contributions arising from the age-structure of confirmed cases and the age-specific case-fatality. CFRs vary from 0.7% in Germany and 1.6% in South Korea to 8.6% in Spain and 10.6% in Italy. The age-structure of detected cases can explain a substantial proportion of cross-country variation in the CFR. For example, 57% of Spain's difference with respect to South Korea is explained by the observed cases being older. In Italy, the CFR increased from 4.2% to 10.6% between March 9 and March 29, 2020, and more than 95% of the change was due to increasing age-specific case fatality rates. The importance of the age-structure of infected cases likely reflects several factors, including different testing regimes and differences in transmission trajectories; while increasing age-specific case fatality rates indicate the worsening health outcomes of those infected with COVID-19. Our findings lend support to recommendations for data to be disaggregated by age, and potentially other variables, to facilitate a better understanding of population-level differences in CFRs. They also show the need for well designed seroprevalence studies to ascertain the extent to which differences in testing regimes drive differences in the age-structure of detected cases.

positive: Prevalence, Severity and Mortality associated with COPD and Smoking in patients with COVID-19: A Rapid Systematic Review and Meta-Analysis BACKGROUND: Coronavirus disease 2019 (COVID-19) is an evolving infectious disease that dramatically spread all over the world in the early part of 2020. No studies have yet summarized the potential severity and mortality risks caused by COVID-19 in patients with chronic obstructive pulmonary disease (COPD), and we update information in smokers. METHODS: We systematically searched electronic databases from inception to March 24, 2020. Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Study quality was assessed using a modified version of the Newcastle-Ottawa Scale. We synthesized a narrative from eligible studies and conducted a meta-analysis using a random-effects model to calculate pooled prevalence rates and 95% confidence intervals (95%CI). RESULTS: In total, 123 abstracts were screened and 61 full-text manuscripts were reviewed. A total of 15 studies met the inclusion criteria, which included a total of 2473 confirmed COVID-19 patients. All studies were included in the meta-analysis. The crude case fatality rate of COVID-19 was 7.4%. The pooled prevalence rates of COPD patients and smokers in COVID-19 cases were 2% (95% CI, 1%–3%) and 9% (95% CI, 4%–14%) respectively. COPD patients were at a higher risk of more severe disease (risk of severity = 63%, (22/35) compared to patients without COPD 33.4% (409/1224) [calculated RR, 1.88 (95% CI, 1.4–2.4)]. This was associated with higher mortality (60%). Our results showed that 22% (31/139) of current smokers and 46% (13/28) of ex-smokers had severe complications. The calculated RR showed that current smokers were 1.45 times more likely [95% CI: 1.03–2.04] to have severe complications compared to former and never smokers. Current smokers also had a higher mortality rate of 38.5%. CONCLUSION: Although COPD prevalence in COVID-19 cases was low in current reports, COVID-19 infection was associated with substantial severity and mortality rates in COPD. Compared to former and never smokers, current smokers were at greater risk of severe complications and higher mortality rate. Effective preventive measures are required to reduce COVID-19 risk in COPD patients and current smokers.

positive: Clinical Characteristics, Associated Factors, and Predicting COVID-19 Mortality Risk: A Retrospective Study in Wuhan, China Introduction Coronavirus disease 2019 (COVID-19) has become a serious global pandemic. This study investigates the clinical characteristics and risk factors for COVID-19 mortality, and establishes a novel scoring system to predict mortality risk in COVID-19 patients. Methods A cohort of 1,663 hospitalized COVID-19 patients in Wuhan, China, of whom 212 died and 1,252 recovered, were included in the present study. Demographic, clinical, and laboratory data on admission were collected from electronic medical records between January 14, 2020, and February 28, 2020. Clinical outcomes were collected until March 26, 2020. Multivariable logistic regression was used to explore the association between potential risk factors and COVID-19 mortality. The receiver operating characteristic curve was used to predict COVID-19 mortality risk. All analyses were conducted in April 2020. Results Multivariable regression showed increased odds of COVID-19 mortality associated with older age (OR=2.15, 95% CI=1.35, 3.43), male sex (OR=1.97, 95% CI=1.29, 2.99), history of diabetes (OR=2.34, 95% CI=1.45, 3.76), lymphopenia (OR=1.59, 95% CI=1.03, 2.46), and increased procalcitonin (OR=3.91, 95% CI=2.22, 6.91, per SD increase) on admission. Spline regression analysis indicated that the correlation between procalcitonin levels and COVID-19 mortality was nonlinear (p=0.0004 for nonlinearity). The area under the receiver operating curve of the COVID-19 mortality risk was 0.765 (95% CI=0.725, 0.805). Conclusions The independent risk factors for COVID-19 mortality included older age, male sex, history of diabetes, lymphopenia, and increased procalcitonin, which could help clinicians to identify COVID-19 patients with poor prognosis at an earlier stage. The COVID-19 mortality risk score model may assist clinicians in reducing COVID-19-related mortality by implementing better strategies for more effective use of limited medical resources.

positive: [Democracy and Covid-19 mortality in Europe.] OBJECTIVE: In Europe there is a great variability in mortality by Covid-19 among different countries While some countries, such as Greece, Belarus or Ukraine, have a mortality rate of less than 5 cases/100,000 inhabitants, other countries such as Belgium, Spain or the United Kingdom have a mortality rate of well over 50 cases/100,000 inhabitants It is generally considered that the reason for this variability is multifactorial (including political reasons), but there are few studies that associate factors related to this variability The objective of this work was to analyse political risk factors/markers that could explain the variability in mortality due to Covid-19 among different European countries METHODS: This is a retrospective, multinational, ecological study based on the exploitation of the database provided by the European Centre for Disease Prevention and Control which collects daily information worldwide on new cases and deaths The accumulated mortality of Covid-19 in European countries (with more than 100 deaths on 01/05/2020) was calculated up to 29/05/2020 Political variables were compiled from different sources in the countries included in the study The variables analysed were: the democracy index and the different factors included in it, the country's political system and the country's corruption index On the other hand, specific political measures implemented in the different countries were collected, such as the number of days elapsed from the notification of the first infected person to 100 infected persons, to lockdown, to the closure of schools or the cancelation of meetings The number of people infected up to the date of lockdown was also registered For the statistical analysis of the association between the dependent variable (mortality) and the factors studied, correlation index were calculated, and the association was studied through univariate and multivariate linear regression models RESULTS: At May 1 2020, 27 European countries had at least 100 deaths The mean mortality was 19 83 cases/100,000 inhabitants (SD 22 4) and a median of 7 95 Mortality varied from a minimum of 1 49 cases/100,000 population in Ukraine to 82 19 cases/100,000 population in Belgium About factors analyzed both the democracy index (as well as the factors included in it), the political system (full democracy vs no) and the corruption index were statistically associated with mortality Also, the time until the implementation of the political measures was associated with mortality CONCLUSIONS: In Europe, there is a west to east (from highest to lowest) gradient in the mortality of Covid-19 Some of the observed mortality variability can be explained by political factors

positive: Cross-Country Age Disparities in COVID-19 Cases with Hospitalization, ICU Usage, and Morbidity In this paper, we examine cross-country differences, in terms of the age distribution of symptomatic cases, hospitalizations, intensive care unit (ICU) cases, and fatalities due to the novel COVID-19. By calculating conditional probabilities, we bridge country-level incidence data gathered from different countries and attribute the variability in data to country demographics. We then provide case, hospitalization, ICU, and fatality estimates for a comprehensive list of countries using the existing data from a variety of countries.

positive: Patient-Led COVID-19 Triage Systems and Case Fatality Rates: A Comparative Study Between Singapore, Japan, Norway, the USA and the UK. Introduction: The case fatality rate from COVID-19 differs markedly around the world. There are likely a number of factors one can attribute to such disparity, not least of which is differing healthcare models and approaches. Here, we examine the COVID-19 related health advice issued by six different countries, specifically examining the patient-led triage pathways in each country. Methods: A simulation study was conducted on current, nationwide, patient-led triage systems from three countries with low case fatality rates (Singapore, Norway and Japan) and two countries with high case fatality rates (the USA and the UK). 36 case scenarios were designed to imitate common presentations of COVID-19 with varying degrees of severity. These scenarios were then fed into each countrys patient-led triage system. The advice for each scenario was recorded and then compared. Results: Patient-led triage systems from Singapore, Japan and Norway maintained a low threshold for advising clinical contact for patients with possible COVID-19 (88 to 100% of cases were referred). Patient-led triage systems from the USA and the UK maintained high thresholds for advising contact with either call centre support or clinical contact (28 and 33% of cases were referred, respectively), and triaged the majority of cases home with no further healthcare input. There was a strong inverse correlation between percentage of cases referred and the nations case fatality rate (Pearsons Correlation = -0.642, p = 0.01). Conclusion: In this simulation study, countries with low case fatality rates - Singapore, Norway and Japan -, performed well, successfully identifying severe COVID-19 and triaging such cases to medical care. The USA triage system (CDCs Coronavirus Self-Checker) and the UKs triage system (NHS 111 online) performed poorly, failing to identify Severe COVID-19 infection and sepsis in the case simulations, and triaging the majority of cases to self-care with no further healthcare input. Such poorly performing triage systems are likely to be contributing to the high case fatality rates in the US and the UK.

positive: Clinical characteristics and outcomes of hospitalised patients with COVID-19 treated in Hubei (epicentre) and outside Hubei (non-epicentre): a nationwide analysis of China BACKGROUND: During the outbreak of coronavirus disease 2019 (COVID-19), consistent and considerable differences in disease severity and mortality rate of patients treated in Hubei province compared to those in other parts of China have been observed. We sought to compare the clinical characteristics and outcomes of patients being treated inside and outside Hubei province, and explore the factors underlying these differences. METHODS: Collaborating with the National Health Commission, we established a retrospective cohort to study hospitalised COVID-19 cases in China. Clinical characteristics, the rate of severe events and deaths, and the time to critical illness (invasive ventilation or intensive care unit admission or death) were compared between patients within and outside Hubei. The impact of Wuhan-related exposure (a presumed key factor that drove the severe situation in Hubei, as Wuhan is the epicentre as well the administrative centre of Hubei province) and the duration between symptom onset and admission on prognosis were also determined. RESULTS: At the data cut-off (31 January 2020), 1590 cases from 575 hospitals in 31 provincial administrative regions were collected (core cohort). The overall rate of severe cases and mortality was 16.0% and 3.2%, respectively. Patients in Hubei (predominantly with Wuhan-related exposure, 597 (92.3%) out of 647) were older (mean age 49.7 versus 44.9â years), had more cases with comorbidity (32.9% versus 19.7%), higher symptomatic burden, abnormal radiologic manifestations and, especially, a longer waiting time between symptom onset and admission (5.7 versus 4.5â days) compared with patients outside Hubei. Patients in Hubei (severe event rate 23.0% versus 11.1%, death rate 7.3% versus 0.3%, HR (95% CI) for critical illness 1.59 (1.05-2.41)) have a poorer prognosis compared with patients outside Hubei after adjusting for age and comorbidity. However, among patients outside Hubei, the duration from symptom onset to hospitalisation (mean 4.4 versus 4.7â days) and prognosis (HR (95%) 0.84 (0.40-1.80)) were similar between patients with or without Wuhan-related exposure. In the overall population, the waiting time, but neither treated in Hubei nor Wuhan-related exposure, remained an independent prognostic factor (HR (95%) 1.05 (1.01-1.08)). CONCLUSION: There were more severe cases and poorer outcomes for COVID-19 patients treated in Hubei, which might be attributed to the prolonged duration of symptom onset to hospitalisation in the epicentre. Future studies to determine the reason for delaying hospitalisation are warranted.

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: Severe SARS-CoV-2 infections: practical considerations and management strategy for intensivists

positive: Mortality rate and gender differences in COVID-19 patients dying in Italy: A comparison with other countries

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

positive: Clinical Features of 69 Cases with Coronavirus Disease 2019 in Wuhan, China BACKGROUND: From December 2019 to February 2020, 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a serious outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China. Related clinical features are needed. METHODS: We reviewed 69 patients who were hospitalized in Union hospital in Wuhan between January 16 to January 29, 2020. All patients were confirmed to be infected with SARS-CoV-2 and the final date of follow-up was February 4, 2020. RESULTS: The median age of 69 enrolled patients was 42.0 years (IQR 35.0-62.0), and 32 patients (46%) were men. The most common symptoms were fever (60[87%]), cough (38[55%]), and fatigue (29[42%]). Most patients received antiviral therapy (66 [98.5%] of 67 patients) and antibiotic therapy (66 [98.5%] of 67 patients). As of February 4, 2020, 18 (26.9%) of 67 patients had been discharged, and five patients had died, with a mortality rate of 7.5%. According to the lowest SpO(2) during admission, cases were divided into the SpO(2)≥90% group (n=55) and the SpO(2)<90% group (n=14). All 5 deaths occurred in the SpO(2)<90% group. Compared with SpO(2)≥90% group, patients of the SpO(2)<90% group were older, and showed more comorbidities and higher plasma levels of IL6, IL10, lactate dehydrogenase, and c reactive protein. Arbidol treatment showed tendency to improve the discharging rate and decrease the mortality rate. CONCLUSIONS: COVID-19 appears to show frequent fever, dry cough, and increase of inflammatory cytokines, and induced a mortality rate of 7.5%. Older patients or those with underlying comorbidities are at higher risk of death.

positive: Racial and Ethnic Disparities in Population Level Covid-19 Mortality Background: Current reporting of Covid-19 mortality data by race and ethnicity across the United States could bias our understanding of population-mortality disparities. Moreover, stark differences in age distribution by race and ethnicity groups are seldom accounted for in analyses. Methods: To address these gaps, we conducted a cross-sectional study using publicly-reported Covid-19 mortality data to assess the quality of race and ethnicity data (Black, Latinx, white), and estimated age-adjusted disparities using a random effects meta-analytic approach. Results: We found only 28 states, and NYC, reported race and ethnicity-stratified Covid-19 mortality along with large variation in the percent of missing race and ethnicity data by state. Aggregated relative risk of death estimates for Black compared to the white population was 3.57 (95% CI: 2.84-4.48). Similarly, Latinx population displayed 1.88 (95% CI: 1.61-2.19) times higher risk of death than white patients. Discussion: In states providing race and ethnicity data, we identified significant population-level Covid-19 mortality disparities. We demonstrated the importance of adjusting for age differences across population groups to prevent underestimating disparities in younger population groups. The availability of high-quality and comprehensive race and ethnicity data is necessary to address factors contributing to inequity in Covid-19 mortality.

positive: Denominator matters in estimating COVID-19 mortality rates

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

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: Spatial Disparities in Coronavirus Incidence and Mortality in the United States: An Ecological Analysis as of May 2020 PURPOSE: This ecological analysis investigates the spatial patterns of the COVID‐19 epidemic in the United States in relation to socioeconomic variables that characterize US counties. METHODS: Data on confirmed cases and deaths from COVID‐19 for 2,814 US counties were obtained from Johns Hopkins University. We used Geographic Information Systems (GIS) to map the spatial aspects of this pandemic and investigate the disparities between metropolitan and nonmetropolitan communities. Multiple regression models were used to explore the contextual risk factors of infections and death across US counties. We included population density, percent of population aged 65+, percent population in poverty, percent minority population, and percent of the uninsured as independent variables. A state‐level measure of the percent of the population that has been tested for COVID‐19 was used to control for the impact of testing. FINDINGS: The impact of COVID‐19 in the United States has been extremely uneven. Although densely populated large cities and their surrounding metropolitan areas are hotspots of the pandemic, it is counterintuitive that incidence and mortality rates in some small cities and nonmetropolitan counties approximate those in epicenters such as New York City. Regression analyses support the hypotheses of positive correlations between COVID‐19 incidence and mortality rates and socioeconomic factors including population density, proportions of elderly residents, poverty, and percent population tested. CONCLUSIONS: Knowledge about the spatial aspects of the COVID‐19 epidemic and its socioeconomic correlates can inform first responders and government efforts. Directives for social distancing and to “shelter‐in‐place” should continue to stem the spread of COVID‐19.

positive: Clinical outcomes of 402 patients with COVID‐2019 from a single center in Wuhan, China The outbreak of SARS‐CoV‐2 has become a pandemic with significant mortality. Published studies describing clinical characteristics of the disease contain small cohorts from individual centers or larger series consisting of mixed series from multiple different hospitals. We report here analyses of mortality and disease severity among 402 patients from a single hospital. The cohort includes 297 patients with confirmed and 105 with clinical diagnosis. The latter group consists of cases with inconclusive nucleic acid test but meeting the criteria for clinical diagnosis. Data are compared between genders and among different age groups. The overall case fatality is 5.2%. However, age at 70 years or older is associated with a significantly higher mortality (17.8%) and higher rate of severe and critical illness (57.5%). Case fatality is 8% in patients 50 years of age or older, and 1.2% in those younger than 50 years. In addition, case fatality is 7.6% in male patients, as opposed to 2.9% in females, demonstrating a clear gender difference. This article is protected by copyright. All rights reserved.

positive: Ethnic and regional variation in hospital mortality from COVID-19 in Brazil Background: The COVID-19 pandemic is quickly spreading throughout Brazil, which is rapidly ascending the ranking of countries with the highest number of cases and deaths. A particularly unstable federal regime and fragile socioeconomic situation is likely to have contributed to the impact of the disease. Amid this crisis there is substantial concern in the possible socioeconomic, geopolitical and ethnic inequity of the impact of COVID-19 on the country's particularly diverse population. Methods: We performed a cross-sectional observational study of COVID-19 hospital mortality using observational data from the SIVEP-Gripe dataset. We present descriptive statistics to quantify the COVID-19 pandemic in Brazil. We assess the importance of regional factors such as education, income and health either on a state-by-state basis or by splitting Brazil into a North and a Central-South region. Mixed-effects survival analysis was used to estimate the effects of ethnicity and comorbidity at an individual level in the context of regional variation. Findings: Our results show that, compared to branco comparators, hospitalised pardo and preto Brazilians have significantly higher risk of mortality, with hazard ratios and 95% CI of 1.47 (1.33-1.58) and 1.32 (1.15-1.52), respectively. In particular, pardo ethnicity was the second most important risk factor (after age). We also found that hospitalised Brazilians in North regions tend to have more comorbidities than in the Central-South, with similar proportions between the various ethnic groups. Finally, we found that states in the North have a higher hazard ratio as compared to the Central-South, and that Rio de Janeiro obtained one of the highest hazard ratios, similar to the ones of the more underdeveloped Pernambuco and Amazonas. Interpretation: Our results can be interpreted according to the interplay of two independent, but correlated, effects: i) mortality by COVID-19 increases going North (vertical effect), ii) mortality increases for the pardo and preto population (horizontal effect). We speculate that the vertical effect is driven by increasing levels of comorbidity in Northern regions where levels of socioeconomic development are lower, whereas the horizontal effect may be related to lower levels of healthcare access or availability (including intensive care) for pardo and preto Brazilians. For most states the vertical and horizontal effects are correlated giving a larger cumulative mortality. However, Rio de Janeiro was found to be an outlier to this trend: It has an ethnicity composition (horizontal effect) similar to the states in the North region, despite high levels of socioeconomic development (vertical effect). Our analysis motivates an urgent effort on the part of Brazilian authorities to consider how the national response to COVID-19 can better protect pardo and preto Brazilians as well as the population of poorer states from their higher death risk from SARS-CoV-2 infection.

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

positive: Evaluating the determinants of COVID-19 mortality: A cross-country study As the COVID-19 pandemic has spread to the entire world, a race to understand the virus and to find an effective and safe vaccine or treatment has triggered interest in the factors contributing to mortality. For instance, some studies have suggested that the BCG vaccine could protect from COVID-19 and nicotine patches could be therapeutic against the virus. This study makes use of data for about 140 countries to evaluate the determinants of COVID-19 mortality. It finds that a country's share of spending on health care (as a measure of a country's effectiveness in tracking, recording, and reporting COVID-19 deaths) is positively associated with COVID-19 deaths. It also finds that the share of people above 65 years of age, obesity, and urbanization are all positively associated with COVID-19 mortality. There is no evidence that BCG vaccination, smoking prevalence, and PM25 pollution have any link to COVID-19 mortality. These estimation results are robust to alternative specifications and after controlling for confounding factors and excluding outliers. Policymakers should allocate resources towards the protection of the elderly and those suffering from underlying conditions such as obesity. They should also exercise caution about administering nicotine patches or the BCG vaccine to fight COVID-19 without the backing of concrete scientific evidence.

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

positive: Real estimates of mortality following COVID-19 infection

positive: Epidemiologic Features of 135 Patients With Coronavirus Disease (COVID-19) in Tianjin, China OBJECTIVE: This study describes the epidemiologic features of an outbreak of the coronavirus disease (COVID-19) in Tianjin caused by a novel coronavirus and provides the scientific basis for prevention and control measures. METHODS: Data from COVID-19 cases were collected from daily notifications given to the National Health Commission of the People’s Republic of China and Tianjin Health Committee. All of the data were analyzed with SPSS, version 24.0 software (IBM Corp, Armonk, NY). RESULTS: As of February 24, 2020, there have been 135 confirmed cases, 3 deaths, and 87 recoveries in Tianjin, China. The incidence of COVID-19 was 8.65/1 000 000 with a 2.22% case fatality rate. Regarding geographic distribution, the incidence was 8.82 per 1 000 000 in urban areas and 8.00 per 1 000 000 in suburbs. During the early stage of the epidemic, most cases came from urban areas and in patients with a history of sojourning in Hubei Province. The majority of patients were 31–70 years old (75.97%). A familial clustering was the most important characteristic of COVID-19 (accounting for 74.81%). CONCLUSIONS: Current information suggests that people are generally susceptible to COVID-19, which has shown a familial clustering in Tianjin.

positive: The Correlation of Comorbidities on the Mortality in Patients with COVID-19: an Observational Study Based on the Korean National Health Insurance Big Data BACKGROUND: Mortality of coronavirus disease 2019 (COVID-19) is a major concern for quarantine departments in all countries. This is because the mortality of infectious diseases determines the basic policy stance of measures to prevent infectious diseases. Early screening of high-risk groups and taking action are the basics of disease management. This study examined the correlation of comorbidities on the mortality of patients with COVID-19. METHODS: We constructed epidemiologic characteristics and medical history database based on the Korean National Health Insurance Service Big Data and linked COVID-19 registry data of Korea Centers for Disease Control & Prevention (KCDC) for this emergent observational cohort study. A total of 9,148 patients with confirmed COVID-19 were included. Mortalities by sex, age, district, income level and all range of comorbidities classified by International Classification of Diseases-10 based 298 categories were estimated. RESULTS: There were 3,556 male confirmed cases, 67 deaths, and crude death rate (CDR) of 1.88%. There were 5,592 females, 63 deaths, and CDR of 1.13%. The most confirmed cases were 1,352 patients between the ages of 20 to 24, followed by 25 to 29. As a result of multivariate logistic regression analysis that adjusted epidemiologic factors to view the risk of death, the odds ratio of death would be hemorrhagic conditions and other diseases of blood and blood-forming organs 3.88-fold (95% confidence interval [CI], 1.52–9.88), heart failure 3.17-fold (95% CI, 1.88–5.34), renal failure 3.07-fold (95% CI, 1.43–6.61), prostate malignant neoplasm 2.88-fold (95% CI, 1.01–8.22), acute myocardial infarction 2.38-fold (95% CI, 1.03–5.49), diabetes was 1.82-fold (95% CI, 1.25–2.67), and other ischemic heart disease 1.71-fold (95% CI, 1.09–2.66). CONCLUSION: We hope that this study could provide information on high risk groups for preemptive interventions. In the future, if a vaccine for COVID-19 is developed, it is expected that this study will be the basic data for recommending immunization by selecting those with chronic disease that had high risk of death, as recommended target diseases for vaccination.

positive: Scaling COVID-19 against inequalities: should the policy response consistently match the mortality challenge? Background The mortality impact of COVID-19 has thus far been described in terms of crude death counts. We aimed to calibrate the scale of the modelled mortality impact of COVID-19 using age-standardised mortality rates and life expectancy contribution against other, socially-determined, causes of death in order to inform governments and the public. Methods We compared mortality attributable to suicide, drug poisoning and socioeconomic inequality with estimates of mortality from an infectious disease model of COVID-19. We calculated age-standardised mortality rates and life expectancy contributions for the UK and its constituent nations. Results Mortality from a fully unmitigated COVID-19 pandemic is estimated to be responsible for a negative life expectancy contribution of -5.96 years for the UK. This is reduced to -0.33 years in the fully mitigated scenario. The equivalent annual life expectancy contributions of suicide, drug poisoning and socioeconomic inequality-related deaths are -0.25, -0.20 and -3.51 years respectively. The negative impact of fully unmitigated COVID-19 on life expectancy is therefore equivalent to 24 years of suicide deaths, 30 years of drug poisoning deaths, and 1.7 years of inequality-related deaths for the UK. Conclusion Fully mitigating COVID-19 is estimated to prevent a loss of 5.63 years of life expectancy for the UK. Over 10 years there is a greater negative life expectancy contribution from inequality than around six unmitigated COVID-19 pandemics. To achieve long-term population health improvements it is therefore important to take this opportunity to introduce post-pandemic economic policies to build back better.

positive: Mortality impacts of the coronavirus disease (COVID-19) outbreak by sex and age: rapid mortality surveillance system, Italy, 1 February to 18 April 2020 Data from the rapid mortality surveillance system in 19 major Italian cities were used to carry out a timely assessment of the health impact of the COVID-19 epidemic. By 18 April, a + 45% excess in mortality was observed, with a higher impact in the north of the country (+ 76%). The excess was greatest among men, with an increasing trend by age. Surveillance data can be used to evaluate the lockdown and re-opening phases.

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

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

positive: COVID: How to explain differences in lethality between different populations?

positive: The role of essential organ-based comorbidities in the prognosis of COVID-19 infection patients Objectives: To assess the role of essential organ-based comorbidities in the prognosis of COVID-19 patients. Methods: All consecutive patients diagnosed with COVID-19 admitted to the Zhongnan Hospital of Wuhan University from 11 January to 16 March 2020 were enrolled in this retrospective cohort study. Results: A total of 212 COVID-19 patients were included. COVID-19 patients with heart, liver and kidneycomorbidity, compared to patients without related comorbidities, were more likely to have cardiac injuries [9.1%(3/33) vs 2.2%(4/179), P = 0.043], liver injuries [13.0%(3/23) vs 3.2%(6/189), P = 0.027], kidney injury [54.5%(6/11) vs 2.0%(4/201), P < 0.001], and higher risk of mortality [Heart-comorbidity: 6.1%(2/33) vs 0.6%(1/179), P = 0.014; Liver-comorbidity: 8.7%(2/23) vs 0.5%(1/189), P = 0.002; Kidney-comorbidity: 27.3%(3/11) vs 1.0%(2/201), P < 0.001. Mortality was higher in patients with more severe Grade of organ injuries [Heart-injury: P = 0.044; Liver-injury: P = 0.020; Kidney-injury: P = 0.030]. Conclusion: Male, older, co-existing of heart, liver, and kidney comorbidities, especially those with severe Grade organ injuries, had a poor prognosis after SARS-CoV-2 infection.

positive: Clinical and demographic characteristics of patients dying from COVID‐19 in Italy versus China Coronavirus disease 2019 (COVID‐19), an infectious outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2),(1) has now progressed to global pandemic.(2) Besides the compelling need to understand the novel biological pathways underlying the virulence and pathogenicity of SARS‐CoV‐2 in humans to enable the development of appropriate interventions and therapies,(3,4) the noticeable difference in mortality rates between Asian and European populations is one of the most significant issues demanding the attention of biologists, epidemiologists and clinicians around the world. This article is protected by copyright. All rights reserved.

positive: Tuberculosis, COVID-19 and migrants: preliminary analysis of deaths occurring in 69 patients from two cohorts Abstract Little is known about the relationship between the COVID-19 and tuberculosis (TB). The aim of this study is to describe a group of patients who died with TB (active disease or sequelae) and COVID-19 in two cohorts. Data from 49 consecutive cases in 8 countries (cohort A) and 20 hospitalized patients with TB and COVID-19 (cohort B) were analysed and patients who died were described. Demographic and clinical variables were retrospectively collected, including co-morbidities and risk factors for TB and COVID-19 mortality. Overall, 8 out of 69 (11.6%) patients died, 7 from cohort A (14.3%) and one from cohort B (5%). Out of 69 patients 43 were migrants, 26/49 (53.1%) in cohort A and 17/20 (85.0%) in cohort B. Migrants: 1) were younger than natives; in cohort A the median (IQR) age was 40 (27-49) VS. 66 (46-70) years, whereas in cohort B 37 (27-46) VS. 48 (47-60) years; 2) had a lower mortality rate than natives (1/43, 2.3% versus 7/26, 26.9%; p-value: 0.002); 3) had fewer co-morbidities than natives (23/43, 53.5 % versus 5/26- 19.2%) natives; p-value: 0.005). The study findings show that: 1) mortality is likely to occur in elderly patients with co-morbidities; 2) TB might not be a major determinant of mortality and 3) migrants had lower mortality, probably because of their younger age and lower number of co-morbidities. However, in settings where advanced forms of TB frequently occur and are caused by drug-resistant strains of M. tuberculosis, higher mortality rates can be expected in young individuals.

positive: The Italian Outbreak of COVID-19: Conditions, Contributors, and Concerns

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 COVID-19 epidemic, its mortality, and the role of non-pharmaceutical interventions COVID-19 has developed into a pandemic, hitting hard on our communities. As the pandemic continues to bring health and economic hardship, keeping mortality as low as possible will be the highest priority for individuals; hence governments must put in place measures to ameliorate the inevitable economic downturn. The course of an epidemic may be defined by a series of key factors. In the early stages of a new infectious disease outbreak, it is crucial to understand the transmission dynamics of the infection. The basic reproduction number (R(0)), which defines the mean number of secondary cases generated by one primary case when the population is largely susceptible to infection (‘totally naïve’), determines the overall number of people who are likely to be infected, or, more precisely, the area under the epidemic curve. Estimation of changes in transmission over time can provide insights into the epidemiological situation and identify whether outbreak control measures are having a measurable effect. For R(0) > 1, the number infected tends to increase, and for R(0) < 1, transmission dies out. Non-pharmaceutical strategies to handle the epidemic are sketched and based on current knowledge, the current situation is sketched and scenarios for the near future discussed.

positive: Excess Out-Of-Hospital Mortality and Declining Oxygen Saturation: The Sentinel Role of EMS Data in the COVID-19 Crisis in Tijuana, Mexico OBJECTIVE: Emergency medical services (EMS) may serve as a key source of real-time data about the evolving health of COVID-19 affected populations, especially in low-and-middle-income countries (LMICs) with less rapid and reliable vital statistic registration systems. Although official COVID-19 statistics in Mexico report almost exclusively in-hospital mortality events, excess out-of-hospital mortality has been identified in other settings, including one EMS study in Italy that showed a 58% increase. EMS and hospital reports from several countries have suggested that silent hypoxemia—low oxygen saturation (SpO2) in the absence of dyspnea—is associated with COVID-19 outbreaks. It is unclear, however, how these phenomena can be generalized to LMICs. We assess how EMS data can be used in a sentinel capacity in Tijuana, a city on the Mexico-United States border with earlier exposure to COVID-19 than many LMIC settings. METHODS: We calculated numbers of weekly out-of-hospital deaths and respiratory cases seen by EMS in Tijuana, and estimate the difference between peak-epidemic rates (during April 14(th)-May 11(th)) and forecasted 2014–2019 trends. Results were compared with official COVID-19 statistics, stratified by neighborhood socioeconomic status (SES), and examined for changing demographic or clinical features, including mean (SpO2). RESULTS: An estimated 194.7 (95%CI: 135.5–253.9) excess out-of-hospital deaths events occurred, representing an increase of 145% (70%−338%) compared to forecasted trends. During the same window, only 8 COVID-19-positive, out-of-hospital deaths were reported in official statistics. This corresponded with a rise in respiratory cases of 274% (119%−1142%), and a drop in mean SpO2 to 77.7%, from 90.2% at baseline. The highest out-of-hospital death rates were observed in low-SES areas, although respiratory cases were more concentrated in high-SES areas. CONCLUSIONS: EMS systems may play an important sentinel role in monitoring excess out-of-hospital mortality and other trends during the COVID-19 crisis in LMICs. Using EMS data, we observed increases in out-of-hospital deaths in Tijuana that were nearly threefold greater magnitude than increases reported using EMS data in Italy. Increased testing in out-of-hospital settings may be required to determine if excess mortality is being driven by COVID-19 infection, health system saturation, or patient avoidance of healthcare. We also found evidence of worsening rates of hypoxemia among respiratory patients seen by EMS, suggesting a rise in silent hypoxemia, which should be met with increased detection and clinical management efforts. Finally, we observed that social disparities in out-of-hospital death that warrant monitoring and amelioration.

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

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

positive: Associations of Global Country Profiles and Modifiable Risk Factors with COVID-19 Cases and Deaths Modifiable risk factors affect SARS-CoV-2 infection and mortality raising the possibility that lifestyle modification could play a role. This has not been studied at a global level. We analysed publicly available data from countries reporting COVID-19 cases and deaths. Associations of modifiable risk factors with total cases and excess deaths were determined with and without adjustment for confounders. 4,670,832 cases and 311,384 deaths were reported by 181 countries by 18th May 2020. Wealthier countries had the greatest caseload. Obesity was the primary modifiable risk factor for infection and greater age, male sex, physical inactivity and low salt consumption were associated with excess deaths. Obesity was less influential on mortality than physical inactivity. Globally, obesity confers vulnerability to SARS-CoV-2 infection and physical inactivity likely explains the greater mortality in the obese. High salt consumption may induce reductions in tissue ACE2 expression and subsequently reduce mortality rates.

positive: Why Do COVID-19 Fatality Rates Differ Across Countries? An Explorative Cross-country Study Based on Select Indicators In this article, we analyse the factors that determine the fatality rates across 29 economies spread across both the developing and developed world. Recent emerging literature and expert opinions in popular media have indicated various factors that may explain cross-country difference in fatality rates. These factors range from access to public health infrastructure, BCG vaccination policies, demographic structure, restrictive policy interventions and the weather. In addition, articles are examining different kinds of fatality rates that can be explained. Progressing beyond fragmented databases and anecdotal evidence, we have developed a database for such factors, have explored various econometric models to test the explanatory power of these factors in explaining several kinds of fatality rates. Based on available data, our study reveals that factors such as public health system, population age structure, poverty level and BCG vaccination are powerful contributory factors in determining fatality rates. Interactions between factors such as poverty level and BCG vaccination provide interesting insights into the complex interplay of factors. Our analysis suggests that poor citizens’ access to the public healthcare system are worse in many countries irrespective of whether they are developed or developing countries.

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

positive: Acute renal impairment in coronavirus-associated severe acute respiratory syndrome Acute renal impairment in coronavirus-associated severe acute respiratory syndrome. Background Severe acute respiratory syndrome (SARS) is a newly emerged infection from a novel coronavirus (SARS-CoV). Apart from fever and respiratory complications, acute renal impairment has been observed in some patients with SARS. Herein, we describe the clinical, pathologic, and laboratory features of the acute renal impairment complicating this new viral infection. Methods We conducted a retrospective analysis of the plasma creatinine concentration and other clinical parameters of the 536 SARS patients with normal plasma creatinine at first clinical presentation, admitted to two regional hospitals following a major outbreak in Hong Kong in March 2003. Kidney tissues from seven other patients with postmortem examinations were studied by light microscopy and electron microscopy. Results Among these 536 patients with SARS, 36 (6.7%) developed acute renal impairment occurring at a median duration of 20 days (range 5–48 days) after the onset of viral infection despite a normal plasma creatinine level at first clinical presentation. The acute renal impairment reflected the different prerenal and renal factors that exerted renal insult occurring in the context of multiorgan failure. Eventually, 33 SARS patients (91.7%) with acute renal impairment died. The mortality rate was significantly higher among patients with SARS and acute renal impairment compared with those with SARS and no renal impairment (91.7% vs. 8.8%) (P < 0.0001). Renal tissues revealed predominantly acute tubular necrosis with no evidence of glomerular pathology. The adjusted relative risk of mortality associated with the development of acute renal impairment was 4.057 (P < 0.001). By multivariate analysis, acute respiratory distress syndrome and age were the most significant independent risk factors predicting the development of acute renal impairment in SARS. Conclusion Acute renal impairment is uncommon in SARS but carries a high mortality. The acute renal impairment is likely to be related to multi-organ failure rather than the kidney tropism of the virus. The development of acute renal impairment is an important negative prognostic indicator for survival with SARS.

positive: Patterns of COVID-19 related excess mortality in the municipalities of Northern Italy The Coronavirus Disease 2019 (COVID-19) spatial distribution in Italy is inhomogeneous, because of its ways of spreading from the initial hotspots. The impact of COVID-19 on mortality has been described at the regional level, while less is known about mortality in demographic subgroups within municipalities. We aimed to describe the excess mortality (EM) due to COVID-19 in the three most affected Italian regions, by estimating EM in subgroups defined by gender and age classes within each municipality from February 23 to March 31, 2020. EM varied widely among municipalities even within the same region; it was similar between genders for the [≥]75 age group, while in the other age groups it was higher in males. Thus, nearby municipalities may show a different mortality burden despite being under common regional health policies, possibly as a result of policies adopted both at the regional and at the municipality level.

positive: Age could be driving variable SARS-CoV-2 epidemic trajectories worldwide Background Current geographic spread of documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections shows heterogeneity. This study explores the role of age in potentially driving differentials in infection spread, epidemic potential, and rates of disease severity and mortality across countries. Methods An age-stratified deterministic mathematical model that describes SARS-CoV-2 transmission dynamics was applied to 159 countries and territories with a population ≥1 million. Results Assuming worst-case scenario for the pandemic, the results indicate that there could be stark regional differences in epidemic trajectories driven by differences in the distribution of the population by age. In the African Region (median age: 18.9 years), the median R0 was 1.05 versus 2.05 in the European Region (median age: 41.7 years), and the median (per 100 persons) for the infections rate was 22.5 (versus 69.0), for severe and/or critical disease cases rate was 3.3 (versus 13.0), and for death rate was 0.5 (versus 3.9). Conclusions Age could be a driver of variable SARS-CoV-2 epidemic trajectories worldwide. Countries with sizable adult and/or elderly populations and smaller children populations may experience large and rapid epidemics in absence of interventions. Meanwhile, countries with predominantly younger age cohorts may experience smaller and slower epidemics. These predictions, however, should not lead to complacency, as the pandemic could still have a heavy toll nearly everywhere.

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

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

positive: Estimating the Size of High-risk Populations for COVID-19 Mortality across 442 US Cities A variety of predisposing factors have been associated with serious illness and death from COVID-19. Understanding the distribution of risks associated with these factors by local communities can provide important opportunities for targeting interventions. We characterize the distribution of risk for COVID-19 mortality for populations at large across 442 US cities, by utilizing recently published estimates of risk associated with age, gender, ethnicity, social deprivation and 12 health conditions from a very large UK-based study, combined with the information available on prevalence and co-occurrence of these factors in the US through a variety of population-based public databases. We estimate that across all the cities, an underlying weighted risk-score can identify a total of approximately 12.65 million, 4.09 million and 1.34 million individuals who are at 2-, 5- and 10-fold higher risk, respectively, compared to the average risk for the US population. The percentage of population which exceed the respective risk thresholds varies across the cities in the range (1st-99th percentile), 3.6%-20.1%, 0.7%-8.0% and 0.1%-3.2%, respectively. The percentage of deaths within a city that are expected to occur above these risk-thresholds varies in the range of 20.1%-53.5%, 8.5%-38.2% and 2.9%-25.4%, respectively. Our analysis can provide guidance to national and local policy makers regarding resources needed to protect the most vulnerable populations in these communities, and how much utility such interventions may have in reducing the total population burden of death.

positive: Municipality- level predictors of COVID-19 mortality in Mexico: a cautionary tale Background. Inequalities and burden of comorbidities of the Coronavirus disease 2019 (COVID-19) vary importantly inside the countries. We aimed to analyze the Municipality-level factors associated with a high COVID-19 mortality rate of in Mexico. Methods. We retrieved information from 142,643 cumulative confirmed symptomatic cases and 18,886 deaths of COVID-19 as of June 20th, 2020 from the publicly available database of the Ministry of Health of Mexico. Public official data of the most recent census and surveys of the country were used to adjust a negative binomial regression model with the quintiles (Q) of the distribution of sociodemographic and health outcomes among 2,457 Municipality-level. Expected Mortality Rates (EMR), Incidence Rate Ratios (IRR) and 95% Confidence Intervals are reported. Results. Factors associated with high MR of COVID-19, relative to Quintile 1 (Q1), were; diabetes prevalence (Q4, IRR=2.60), obesity prevalence (Q5, IRR=1.93), diabetes mortality rate (Q5, IRR=1.58), proportion of indigenous population (Q2, IRR=1.68), proportion of economically active population (Q5, IRR=1.50), density of economic units that operate essential activities (Q4, IRR=1.54) and population density (Q5, IRR=2.12). We identified 1,351 Municipality-level without confirmed COVID-19 deaths, of which, 202 had nevertheless high (Q4, Mean EMR= 8.0 deaths per 100,000) and 82 very high expected COVID-19 mortality (Q5, Mean EMR= 13.8 deaths per 100,000). Conclusion. This study identified 1,351 Municipality-level of Mexico that, in spite of not having confirmed COVID-19 deaths yet, share characteristics that could eventually lead to a high mortality scenario later in the epidemic and warn against premature easing of mobility restrictions. Local information should be used to reinforce strategies of prevention and control of outbreaks in communities vulnerable to COVID-19. Keywords: COVID-19; risk factors; social determinants; health determinants; Municipality-level; counties.

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

positive: 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: Disparities in Age-Specific Morbidity and Mortality from SARS-CoV-2 in China and the Republic of Korea We analyzed age- and sex-specific morbidity and mortality data from SARS-COV-2 pandemic in China and Republic of Korea (ROK). Data from China exhibit a standard Gaussian distribution with peak morbidity in the 50-59 years cohort, while the ROK data have a bimodal distribution with highest morbidity in the 20-29 years cohort.

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

positive: Likelihood of survival of coronavirus disease 2019

positive: Mortality Rates of Patients with Proximal Femoral Fracture in a Worldwide Pandemic: Preliminary Results of the Spanish HIP-COVID Observational Study. BACKGROUND The outbreak of coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), in December 2019 in Wuhan, People's Republic of China, has developed into an unprecedented pandemic with enormous pressure on health-care providers around the world. A higher mortality rate has been described in older infected individuals. Patients with hip fracture are a particularly vulnerable population during this pandemic because older age is associated with a higher mortality rate. Our aim was to describe the early mortality rate and demographic variables in a hip fracture sample population in Spain during the coronavirus pandemic. METHODS This is a multicenter, observational, retrospective, descriptive study. We collected data from 13 major hospitals in Spain from the beginning of the national state of alarm (declared on March 14, 2020, by the Spanish government) until the end of our study period on April 4, 2020. All patients who were ≥65 years of age, presented to the Emergency Department of the participating hospitals during this period with a diagnosis of proximal femoral fracture, and had a minimum follow-up of 10 days were included in the cohort. In addition to mortality, demographic and other potential prognostic variables were also collected. RESULTS In this study, 136 patients with a hip fracture were included. Of these patients, 124 underwent a surgical procedure and 12 were managed nonoperatively. The total mortality rate was 9.6%. Sixty-two patients were tested for COVID-19, with 23 patients being positive. The mortality rate for these 23 patients was 30.4% (7 of 23 patients) at a mean follow-up of 14 days. The mortality rate was 10.3% (4 of 39) for patients who had been tested and had a negative result and 2.7% (2 of 74) for patients who had not been tested. Of the 12 patients who were managed nonoperatively, 8 (67%) died, whereas, of the 124 patients who were surgically treated, 5 (4%) died. Results differed among centers. CONCLUSIONS There is a higher mortality rate in patients with a hip fracture and an associated positive test for COVID-19. LEVEL OF EVIDENCE Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

positive: Hypertension and coronavirus disease 2019 mortality

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

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

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

positive: Official Data and Analytical Forecasts: Differences and Similarities Among Coronavirus Disease (COVID-19) Confirmed Cases and Deaths

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

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

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

positive: Clinical outcomes of 402 patients with COVID-2019 from a single center in Wuhan, China The outbreak of SARS-CoV-2 has become a pandemic with significant mortality. Published studies described clinical characteristics of the disease contain small cohorts from individual centers or larger series consisting of mixed series from multiple different hospitals. We report here analyses of mortality and disease severity among 402 patients from a single hospital. The cohort includes 297 patients with confirmed and 105 with clinical diagnosis. The latter group consists of cases with inconclusive nucleic acid test but meeting the criteria for clinical diagnosis. Data are compared between sexes and among different age groups. The overall case fatality is 5.2%. However, age at 70 years or older is associated with a significantly higher mortality (17.8%) and higher rate of severe and critical illness (57.5%). Case fatality is 8% in patients 50 years of age or older, and 1.2% in those younger than 50 years. In addition, case fatality is 7.6% in male patients, as opposed to 2.9% in females, demonstrating a clear sex difference.

positive: Age separation dramatically reduces COVID-19 mortality rate in a computational model of a large population COVID-19 pandemic has caused a global lock down in many countries throughout the world. Faced with a new reality, and until a vaccine or efficient treatment is found, humanity must figure out ways to keep economy going on one hand, yet keep the population safe on the other hand, especially those that are susceptible to this virus. Here we use a network simulation, with parameters that were drawn from what is known about the virus, to explore 5 different scenarios of partial lock down release. We find that separating age groups by reducing interactions between age groups, protects the general population and reduces mortality rates. Furthermore, addition of new connections within the same age group to compensate for the lost connections outside the age group, still has a strong beneficial influence and reduces the total death toll by 66%. While complete isolation from society may be the most protective scenario for the elderly population, it would have an emotional and possibly cognitive impact that might outweigh its benefit. We therefore propose creating age-related social recommendations or even restrictions, thereby allowing social connections but still strong protection for the older population.

positive: Estimating the instant case fatality rate of COVID-19 in China OBJECTIVE: The outbreak of coronavirus disease 2019 (COVID-19) in China has been basically controlled. However, the global epidemic of COVID-19 is worsening. We established a method to estimate the instant case fatality rate (CFR) and cure rate of COVID-19 in China. METHODS: A total of 82 735 confirmed cases released officially by the Chinese authorities from December 8, 2019 to April 18, 2020 were collected. The estimated diagnosis dates of deaths and cured cases were calculated based on the median cure time or median death time of individual cases. Following this, the instant CFR was calculated according to the number of deaths and cured cases on the same estimated diagnosis date. RESULTS: In China, the instant CFR of COVID-19 was 3.8-14.6% from January 1 to January 17; it then declined gradually and stabilized at 5.7% in April. The average CFR in China was 6.1±2.9%, while the CFR was 1.0±0.4% in China except Hubei Province. The cure rate of COVID-19 was 93.9±2.9% in China, and stabilized at 94.3%, while it was 99.0±0.4% in China except Hubei Province. CONCLUSIONS: The instant CFR of COVID-19 in China overall was much higher than that in China except Hubei Province. The CFR of COVID-19 in China was underestimated.

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

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

positive: Understanding and Interpretation of Case Fatality Rate of Coronavirus Disease 2019

positive: Early dinner or "dinner like a pauper": Evidence, the habitual time of the largest meal of the day - dinner - is predisposing to severe COVID-19 outcome - death. COVID-19 and metabolic syndrome are devastating pandemics. Effective control of metabolic parameters and their dysfunction may help prevent or minimize the acute and devastating effects of SARS-CoV-2 by reducing the local inflammatory response and blocking the entry of the virus into cells. With such consideration in mind, we gathered data from dietary surveys conducted in nine European countries to explore the relationship between actual clock hour of the large dinner meal and also interval in minutes between it and sunset in the respective countries and death rate above the median rate of per one million people as an index of mortality due to COVID-19 infection. Clock time of the dinner meal varied between 16:00 and 21:00 h across the European counties sampled, and the correlation between dinner mealtime and death rate was strongly correlated, R = 0.7991 (two-tailed p = 0.0098), with R 2 explaining 63% of the variation within the data. This strong linear positive correlation indicates that the later the clock time of the dinner meal, the higher is the death rate (and vice versa). The relationship between meal timing in reference to sunset, utilized as a gross surrogate marker of the activity/rest synchronizer of circadian rhythms, and death rate was negative and even slightly stronger, R = -0.8025 (two-tailed p = 0.0092), with R 2 explaining 64% of the variation within the data. This strong linear negative correlation indicates that the shorter the interval between the dinner meal and sunset, i.e., the closer the time of the largest meal of the day to bedtime, the greater is the death rate (and vice versa). Our preliminary approach to nighttime eating, in terms of the day's largest caloric intake, as a risk factor for the predisposing conditions of obesity, metabolic syndrome, type 2 diabetes, and other commonly associated comorbidities of being overweight, and death from COVID-19 infection reveals strong correlation with the time of the dinner meal, both in terms of its actual clock and circadian time.

positive: Racial, Economic and Health Inequality and COVID-19 Infection in the United States Abstract Background: There is preliminary evidence of racial and social-economic disparities in the population infected by and dying from COVID-19. The goal of this study is to report the associations of COVID-19 with respect to race, health and economic inequality in the United States. Methods: We performed a cross-sectional study of the associations between infection and mortality rate of COVID-19 and demographic, socioeconomic and mobility variables from 369 counties (total population: 102,178,117 [median: 73,447, IQR: 30,761-256,098]) from the seven most affected states (Michigan, New York, New Jersey, Pennsylvania, California, Louisiana, Massachusetts). Findings: The risk factors for infection and mortality are different. Our analysis shows that counties with more diverse demographics, higher population, education, income levels, and lower disability rates were at a higher risk of COVID-19 infection. However, counties with higher disability and poverty rates had a higher death rate. African Americans were more vulnerable to COVID-19 than other ethnic groups (1,981 African American infected cases versus 658 Whites per million). Data on mobility changes corroborate the impact of social distancing. Interpretation: The observed inequality might be due to the workforce of essential services, poverty, and access to care. Counties in more urban areas are probably better equipped at providing care. The lower rate of infection, but a higher death rate in counties with higher poverty and disability could be due to lower levels of mobility, but a higher rate of comorbidities and health care access. Keywords: Healthcare Disparities, Health Status Disparities, Socioeconomic Factors, COVID-19, Economic Inequality, Racial Disparity, United States, Population-Based Analysis.

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

positive: Covid-19 and Population Age Structure Epidemiological studies suggest that age distribution of a population has a non-trivial effect on how morbidity rates, mortality rates and case fatality rates (CFR) vary when there is an epidemic or pandemic. We look at the empirical evidence from a large cohort of countries to see the sensitivity of Covid-19 data to their respective median ages. The insights that emerge could be used to control for age structure effects while investigating other factors like cross-protection, co-morbidities, etc.

positive: The Correlation of Comorbidities on the Mortality in Patients with COVID-19: an Observational Study Based on the Korean National Health Insurance Big Data BACKGROUND: Mortality of coronavirus disease 2019 (COVID-19) is a major concern for quarantine departments in all countries. This is because the mortality of infectious diseases determines the basic policy stance of measures to prevent infectious diseases. Early screening of high-risk groups and taking action are the basics of disease management. This study examined the correlation of comorbidities on the mortality of patients with COVID-19. METHODS: We constructed epidemiologic characteristics and medical history database based on the Korean National Health Insurance Service Big Data and linked COVID-19 registry data of Korea Centers for Disease Control & Prevention (KCDC) for this emergent observational cohort study. A total of 9,148 patients with confirmed COVID-19 were included. Mortalities by sex, age, district, income level and all range of comorbidities classified by International Classification of Diseases-10 based 298 categories were estimated. RESULTS: There were 3,556 male confirmed cases, 67 deaths, and crude death rate (CDR) of 1.88%. There were 5,592 females, 63 deaths, and CDR of 1.13%. The most confirmed cases were 1,352 patients between the ages of 20 to 24, followed by 25 to 29. As a result of multivariate logistic regression analysis that adjusted epidemiologic factors to view the risk of death, the odds ratio of death would be hemorrhagic conditions and other diseases of blood and blood-forming organs 3.88-fold (95% confidence interval [CI], 1.52-9.88), heart failure 3.17-fold (95% CI, 1.88-5.34), renal failure 3.07-fold (95% CI, 1.43-6.61), prostate malignant neoplasm 2.88-fold (95% CI, 1.01-8.22), acute myocardial infarction 2.38-fold (95% CI, 1.03-5.49), diabetes was 1.82-fold (95% CI, 1.25-2.67), and other ischemic heart disease 1.71-fold (95% CI, 1.09-2.66). CONCLUSION: We hope that this study could provide information on high risk groups for preemptive interventions. In the future, if a vaccine for COVID-19 is developed, it is expected that this study will be the basic data for recommending immunization by selecting those with chronic disease that had high risk of death, as recommended target diseases for vaccination.

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

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

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

positive: Estimating the Case Fatality Risk of COVID-19 using Cases from Outside China There is large uncertainty around the case fatality risk (CFR) for COVID-19 in China. Therefore, we considered symptomatic cases outside of China (countries/settings with 20+ cases) and the proportion who are in intensive care units (4.0%, 14/349 on 13 February 2020). Given what is known about CFRs for ICU patients with severe respiratory conditions from a meta-analysis, we estimated a CFR of 1.37% (95%CI: 0.57% to 3.22%) for COVID-19 cases outside of China.

positive: The many estimates of the COVID-19 case fatality rate

positive: Identification and Analysis of Shared Risk Factors in Sepsis and High Mortality Risk COVID-19 Patients BACKGROUND Coronavirus disease 2019 (COVID-19) is a novel coronavirus strain disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease is highly transmissible and severe disease including viral sepsis has been reported in up to 16% of hospitalized cases. The admission characteristics associated with increased odds of hospital mortality among confirmed cases of COVID-19 include severe hypoxia, low platelet count, elevated bilirubin, hypoalbuminemia and reduced glomerular filtration rate. These symptoms correlate highly with severe sepsis cases. The diseases also share similar co-morbidity risks including dementia, type 2 diabetes mellitus, coronary heart disease, hypertension and chronic renal failure. Sepsis has been observed in up to 59% of hospitalized COVID-19 patients. It is highly desirable to identify risk factors and novel therapy/drug repurposing avenues for late-stage severe COVID-19 patients. This would enable better protection of at-risk populations and clinical stratification of COVID-19 patients according to their risk for developing life threatening disease. METHODS As there is currently insufficient data available for confirmed COVID-19 patients correlating their genomic profile, disease severity and outcome, co-morbidities and treatments as well as epidemiological risk factors (such as ethnicity, blood group, smoking, BMI etc.), a direct study of the impact of host genomics on disease severity and outcomes is not yet possible. We therefore ran a study on the UK Biobank sepsis cohort as a surrogate to identify sepsis associated signatures and genes, and correlated these with COVID-19 patients. Sepsis is itself a life-threatening inflammatory health condition with a mortality rate of approximately 20%. Like the initial studies for COVID-19 patients, standard genome wide association studies (GWAS) have previously failed to identify more than a handful of genetic variants that predispose individuals to developing sepsis. RESULTS We used a combinatorial association approach to analyze a sepsis population derived from UK Biobank. We identified 70 sepsis risk-associated genes, which provide insights into the disease mechanisms underlying sepsis pathogenesis. Many of these targets can be grouped by common mechanisms of action such as endothelial cell dysfunction, PI3K/mTOR pathway signaling, immune response regulation, aberrant GABA and neurogenic signaling. CONCLUSION This study has identified 70 sepsis related genes, many of them for the first time, that can reasonably be considered to be potentially relevant to severe COVID-19 patients. We have further identified 59 drug repurposing candidates for 13 of these targets that can be used for the development of novel therapeutic strategies to increase the survival rate of patients who develop sepsis and potentially severe COVID-19.

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

positive: Characteristics and Clinical Outcomes of COVID‐19 Patients in an Underserved‐Inner City Population: A Single Tertiary Center Cohort BACKGROUND: There is limited information describing the characteristics and clinical outcomes of patients infected with coronavirus disease 2019 (COVID‐19) especially those in underserved urban area with minority population in the United States. METHODS: This is a retrospective single center study for patients who were admitted with COVID‐19 infection. Data collection was from March 1 through April 24,2020. Demographic, clinical, laboratory, and treatment data were presented using descriptive statistics and frequencies. Chi‐square test and multivariate logistic regression were used to determine association of risk factors and clinical outcomes. RESULTS: A total of 242 inpatients were included with a mean age of 66 ±14.75 (±SD). 50% were female and 70% were African American. Comorbidities included hypertension (74%), diabetes mellitus (49%), and 19% had either COPD or asthma. Older age was associated with higher risk of inpatient death OR 1.056 [95% CI 1.023 to 1.090; p=0.001]. Inpatient mortality occurred in 70% who needed mechanical ventilation (OR: 29.51; 95% CI: 13.28‐65.60; p<0.0001), 58% who required continuous renal replacement therapy/hemodialysis (CRRT/HD) (OR: 6.63; 95% CI: 2.74‐16.05; p<0.0001), and 69% who needed vasopressors (OR: 30.64; 95% CI: 13.56 to 69.20; p<0.0001). Amongst biomarkers of disease severity, only baseline CRP levels (145±116 mg/L) were associated with mortality OR 1.008 [95% CI 1.003 to 1.012; p=0.002]. CONCLUSION: Majority of hospitalized patients had hypertension and diabetes. Older age was an independent risk factor for inpatient mortality. Requirement of mechanical ventilation, vasopressor use, and CRRT/HD were associated significantly with inpatient mortality. Higher baseline CRP was significantly associated with inpatient death. This article is protected by copyright. All rights reserved.

positive: Mortality rate and estimate of fraction of undiagnosed COVID-19 cases in the US in March and April 2020 We use a simple model to derive a mortality probability distribution for a patient as a function of days since diagnosis (considering diagnoses made between 25 February and 29 March 2020). The peak of the mortality probability is the 13th day after diagnosis. The overall shape and peak location of this probability curve are similar to the onset-to-death probability distribution in a case study using Chinese data. The total mortality probability of a COVID-19 patient in the US diagnosed between 25 February and 29 March is about 21%. We speculate that this high value is caused by severe under-testing of the population to identify all COVID-19 patients. With this probability, and an assumption that the true probability is 2.4%, we estimate that 89% of all SARS-CoV-2 infection cases were not diagnosed during this period. When the same method is applied to data extended to 25 April, we found that the total mortality probability of a patient diagnosed in the US after 1 April is about 6.4%, significantly lower than for the earlier period. We attribute this drop to increasingly available tests. Given the assumption that the true mortality probability is 2.4%, we estimate that 63% of all SARS-CoV-2 infection cases were not diagnosed during this period (1 - 25 April).

positive: Acute Physiology and Chronic Health Evaluation II Score as a Predictor of Hospital Mortality in Patients of Coronavirus Disease 2019 OBJECTIVES: Coronavirus disease 2019 has emerged as a major global health threat with a great number of deaths in China. We aimed to assess the association between Acute Physiology and Chronic Health Evaluation II score and hospital mortality in patients with coronavirus disease 2019, and to compare the predictive ability of Acute Physiology and Chronic Health Evaluation II score, with Sequential Organ Failure Assessment score and Confusion, Urea, Respiratory rate, Blood pressure, Age 65 (CURB65) score. DESIGN: Retrospective observational cohort. SETTING: Tongji Hospital in Wuhan, China. SUBJECTS: Confirmed patients with coronavirus disease 2019 hospitalized in the ICU of Tongji hospital from January 10, 2020, to February 10, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 178 potentially eligible patients with symptoms of coronavirus disease 2019, 23 patients (12.92%) were diagnosed as suspected cases, and one patient (0.56%) suffered from cardiac arrest immediately after admission. Ultimately, 154 patients were enrolled in the analysis and 52 patients (33.77%) died. Mean Acute Physiology and Chronic Health Evaluation II score (23.23 ± 6.05) was much higher in deaths compared with the mean Acute Physiology and Chronic Health Evaluation II score of 10.87 ± 4.40 in survivors (p < 0.001). Acute Physiology and Chronic Health Evaluation II score was independently associated with hospital mortality (adjusted hazard ratio, 1.07; 95% CI, 1.01-1.13). In predicting hospital mortality, Acute Physiology and Chronic Health Evaluation II score demonstrated better discriminative ability (area under the curve, 0.966; 95% CI, 0.942-0.990) than Sequential Organ Failure Assessment score (area under the curve, 0.867; 95% CI, 0.808-0.926) and CURB65 score (area under the curve, 0.844; 95% CI, 0.784-0.905). Based on the cut-off value of 17, Acute Physiology and Chronic Health Evaluation II score could predict the death of patients with coronavirus disease 2019 with a sensitivity of 96.15% and a specificity of 86.27%. Kaplan-Meier analysis showed that the survivor probability of patients with coronavirus disease 2019 with Acute Physiology and Chronic Health Evaluation II score less than 17 was notably higher than that of patients with Acute Physiology and Chronic Health Evaluation II score greater than or equal to 17 (p < 0.001). CONCLUSIONS: Acute Physiology and Chronic Health Evaluation II score was an effective clinical tool to predict hospital mortality in patients with coronavirus disease 2019 compared with Sequential Organ Failure Assessment score and CURB65 score. Acute Physiology and Chronic Health Evaluation II score greater than or equal to 17 serves as an early warning indicator of death and may provide guidance to make further clinical decisions.

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

positive: Why case fatality ratios can be misleading: individual- and population-based mortality estimates and factors influencing them Different ways of calculating mortality during epidemics have yielded very different results, particularly during the current COVID-19 pandemic. For example, the "CFR" has been interchangeably called the case fatality ratio, case fatality rate, and case fatality risk, often without standard mathematical definitions. The most commonly used CFR is thecase fatality ratio, typically constructed using the estimated number of deaths to date divided by the estimated total number of confirmed infected cases to date. How does this CFR relate to an infected individual's probability of death? To explore such issues, we formulate both a survival probability model and an associated infection duration-dependent SIR model to define individual- and population-based estimates of dynamic mortality measures to show that neither of these are directly represented by the case fatality ratio. The key parameters that affect the dynamics of different mortality estimates are the incubation period and the time individuals were infected before confirmation of infection. Using data on the recent SARS-CoV-2 outbreaks, we estimate and compare the different dynamic mortality estimates and highlight their differences. Informed by our modeling, we propose more systematic methods to determine mortality during epidemic outbreaks and discuss sensitivity to confounding effects and uncertainties in the data such as undertesting and heterogeneous populations.

positive: A systematic review and meta-analysis of published research data on COVID-19 infection-fatality rates Introduction: An important unknown during the COVID-19 pandemic has been the infection-fatality rate (IFR). This differs from the case-fatality rate (CFR) as an estimate of the number of deaths as a proportion of the total number of cases, including those who are mild and asymptomatic. While the CFR is extremely valuable for experts, IFR is increasingly being called for by policy-makers and the lay public as an estimate of the overall mortality from COVID-19. Methods: Pubmed and Medrxiv were searched using a set of terms and Boolean operators on 25/04/2020. Articles were screened for inclusion by both authors. Meta-analysis was performed in Stata 15.1 using the metan command, based on IFR and confidence intervals extracted from each study. Google/Google Scholar was used to assess the grey literature relating to government reports. Results: After exclusions, there were 13 estimates of IFR included in the final meta-analysis, from a wide range of countries, published between February and April 2020. The meta-analysis demonstrated a point-estimate of IFR of 0.75% (0.49-1.01%) with significant heterogeneity (p<0.001). Conclusion: Based on a systematic review and meta-analysis of published evidence on COVID-19 until the end of April, 2020, the IFR of the disease across populations is 0.75% (0.49-1.01%). However, due to very high heterogeneity in the meta-analysis, it is difficult to know if this represents the "true" point estimate. It is likely that different places will experience different IFRs. More research looking at age-stratified IFR is urgently needed to inform policy-making on this front.

positive: Status of SARS-CoV-2 infection in patients on renal replacement therapy Report of the COVID-19 Registry of the Spanish Society of Nephrology (SEN) Summary The recent appearance of the SARS-CoV-2 coronavirus pandemic has had a significant impact on the general population. Patients on renal replacement therapy (RRT) have not been unaware of this situation and due to their characteristics they are especially vulnerable. We present the results of the analysis of the COVID-19 Registry of the Spanish Society of Nephrology. Material and methods The Registry began operating on March 18th, 2020. It collects epidemiological variables, contagion and diagnosis data, signs and symptoms, treatments and outcomes. It is an “online” registry. Patients were diagnosed with SARS-Cov-2 infection based on the results of the PCR of the virus, carried out both in patients who had manifested compatible symptoms or had suspicious signs, as well as in those who had undergone screening after some contact. acquainted with another patient. Results As of April 11, the Registry had data on 868 patients, from all the Autonomous Communities. The most represented form of TRS is in-center hemodialysis (ICH) followed by transplant patients. Symptoms are similar to the general population. A very high percentage (85%) required hospital admission, 8% in intensive care units. The most used treatments were hydroxychloroquine, lopinavir-ritonavir, and steroids. Mortality is high and reaches 23%; deceased patients were more frequently on ICH, developed pneumonia more frequently, and received less frequently lopinavir-ritonavir and steroids. Age and pneumonia were independently associated with the risk of death. Conclusions SARS-CoV-2 infection already affects a significant number of Spanish patients on RRT, mainly those on ICH, hospitalization rates are very high and mortality is high; age and the development of pneumonia are factors associated with mortality.

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

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

positive: As COVID-19 cases, deaths and fatality rates surge in Italy, underlying causes require investigation COVID-19 case fatalities surged during the month of March 2020 in Italy, reaching over 10,000 by 28 March 2020. This number exceeds the number of fatalities in China (3,301) recorded from January to March, even though the number of diagnosed cases was similar (85,000 Italy vs. 80,000 China). Case Fatality Rates (CFR) could be somewhat unreliable because the estimation of total case numbers is limited by several factors, including insufficient testing and limitations in test kits and materials, such as NP swabs and PPE for testers. Sero prevalence of SARS-CoV-2 antibodies may help in more accurate estimations of the total number of cases. Nevertheless, the disparity in the differences in the total number of fatalities between Italy and China suggests investigation into several factors, such as demographics, sociological interactions, availability of medical equipment (ICU beds and PPE), variants in immune proteins (e.g., HLA, IFNs), past immunity to related CoVs, and mutations in SARS-CoV-2, could impact survival of severe COVID-19 illness survival and the number of case fatalities.

positive: Androgenic hormones and the excess male mortality observed in COVID-19 patients: new convergent data

positive: ICU and Ventilator Mortality Among Critically Ill Adults With Coronavirus Disease 2019 OBJECTIVES: To determine mortality rates among adults with critical illness from coronavirus disease 2019. DESIGN: Observational cohort study of patients admitted from March 6, 2020, to April 17, 2020. SETTING: Six coronavirus disease 2019 designated ICUs at three hospitals within an academic health center network in Atlanta, Georgia, United States. PATIENTS: Adults greater than or equal to 18 years old with confirmed severe acute respiratory syndrome-CoV-2 disease who were admitted to an ICU during the study period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 217 critically ill patients, mortality for those who required mechanical ventilation was 35.7% (59/165), with 4.8% of patients (8/165) still on the ventilator at the time of this report. Overall mortality to date in this critically ill cohort is 30.9% (67/217) and 60.4% (131/217) patients have survived to hospital discharge. Mortality was significantly associated with older age, lower body mass index, chronic renal disease, higher Sequential Organ Failure Assessment score, lower PaO2/FIO2 ratio, higher D-dimer, higher C-reactive protein, and receipt of mechanical ventilation, vasopressors, renal replacement therapy, or vasodilator therapy. CONCLUSIONS: Despite multiple reports of mortality rates exceeding 50% among critically ill adults with coronavirus disease 2019, particularly among those requiring mechanical ventilation, our early experience indicates that many patients survive their critical illness.

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: COVID-19 Propagation and Mortality in a Two-Part Population There has recently emerged a striking consistency to the mortality from SARS-CoV-2, as a fraction of population, across many nations. We have constructed a model for the spread of the virus that reproduces this phenomenon via inclusion of two (or more) categories of susceptibility to the virus. In the simplest case, the population is given a smaller fraction of 10-20% with higher susceptibility and the balance of 80-90% with lower susceptibility. Susceptibility is taken to include the level of immunity to the virus combined with the societal circumstances of certain smaller groups within a population. This is programmed numerically by considering a realistic random rate of contacts, together with an assumed constant viral genome. The remaining major variable is the societal response of nations to the outbreak, with earlier or later application of various degrees of lockdown, tracing and sanitation. China, South Korea and other nations, including Germany, have stopped or greatly slowed the spread of the disease before it could run its course through a whole population. Using this model the extent of progress toward herd immunity is discussed, with an in-principle estimate of the remaining toll to be experienced.

positive: Early estimation of the case fatality rate of COVID-19 in mainland China: a data-driven analysis. Background An ongoing outbreak of pneumonia caused by a novel coronavirus [severe acute respiratory syndrome coronavirus (SARS-CoV)-2], named COVID-19, hit a major city of China, Wuhan in December 2019 and subsequently spread to other provinces/regions of China and overseas. Several studies have been done to estimate the basic reproduction number in the early phase of this outbreak, yet there are no reliable estimates of case fatality rate (CFR) for COVID-19 to date. Methods In this study, we used a purely data-driven statistical method to estimate the CFR in the early phase of the COVID-19 outbreak. Daily numbers of laboratory-confirmed COVID-19 cases and deaths were collected from January 10 to February 3, 2020 and divided into three clusters: Wuhan city, other cities of Hubei province, and other provinces of mainland China. Simple linear regression model was applied to estimate the CFR from each cluster. Results We estimated that CFR during the first weeks of the epidemic ranges from 0.15% (95% CI: 0.12-0.18%) in mainland China excluding Hubei through 1.41% (95% CI: 1.38-1.45%) in Hubei province excluding the city of Wuhan to 5.25% (95% CI: 4.98-5.51%) in Wuhan. Conclusions Our early estimates suggest that the CFR of COVID-19 is lower than the previous coronavirus epidemics caused by SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV).

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

positive: Immune Predictors of Mortality After Ribonucleic Acid Virus Infection BACKGROUND: Virus infections result in a range of clinical outcomes for the host, from asymptomatic to severe or even lethal disease. Despite global efforts to prevent and treat virus infections to limit morbidity and mortality, the continued emergence and re-emergence of new outbreaks as well as common infections such as influenza persist as a health threat. Challenges to the prevention of severe disease after virus infection include both a paucity of protective vaccines as well as the early identification of individuals with the highest risk that may require supportive treatment. METHODS: We completed a screen of mice from the Collaborative Cross (CC) that we infected with influenza, severe acute respiratory syndrome-coronavirus, and West Nile virus. RESULTS: The CC mice exhibited a range of disease manifestations upon infections, and we used this natural variation to identify strains with mortality after infection and strains exhibiting no mortality. We then used comprehensive preinfection immunophenotyping to identify global baseline immune correlates of protection from mortality to virus infection. CONCLUSIONS: These data suggest that immune phenotypes might be leveraged to identify humans at highest risk of adverse clinical outcomes upon infection, who may most benefit from intensive clinical interventions, in addition to providing insight for rational vaccine design.

positive: Connecting BCG Vaccination and COVID-19: Additional Data The reasons for a wide variation in severity of coronavirus disease 2019 (COVID-19) across the affected countries of the world are not known. Two recent studies have suggested a link between the BCG vaccination policy and the morbidity and mortality due to COVID-19. In the present study we compared the impact of COVID-19 in terms of case fatality rates (CFR) between countries with high disease burden and those with BCG revaccination policies presuming that revaccination practices would have provided added protection to the population against severe COVID-19. We found a significant difference in the CFR between the two groups of countries. Our data further supports the view that universal BCG vaccination has a protective effect on the course of COVID-19 probably preventing progression to severe disease and death. Clinical trials of BCG vaccine are urgently needed to establish its beneficial role in COVID-19 as suggested by the epidemiological data, especially in countries without a universal BCG vaccination policy. Keywords: COVID-19, BCG vaccination, case fatality ratio, mortality, low resource countries

positive: Time for a culture change: understanding and reducing risk, morbidity and mortality from COVID-19 in those of black and minority ethnicity Following a number of epidemics in the 21st century, including Ebola and Middle East respiratory syndrome, the SARS-COV-2 virus, causing COVID-19 disease, was declared a pandemic health emergency of international concern in January 2020.

positive: Analyzing COVID-19 pandemic for unequal distribution of tests, identified cases, deaths, and fatality rates in the top 18 countries BACKGROUND AND AIMS: COVID-19 pandemic has affected various countries differently due to variance in demographics, income level, health infrastructure, government response, control and enforcement, and cultural traits of different populations. This study aims to identify significant factors behind the unequal distribution of identified cases and deaths in different countries. Our study's objective is comparative analysis and identification of relations between the spread of COVID-19 pandemic, population characteristics, and government response. METHODS: The top 18 countries worst hit by COVID-19 cases were identified. The data metrics, such as the number of cases, deaths, fatality rates, tests, average life expectancy, and population, were collected and consolidated. RESULTS: Countries with significant percentage of the older population are vulnerable to a high number of deaths due to COVID-19. Developed countries have higher per capita testing, whereas testing is less intensive in developing/underdeveloped countries. There is a consensus among health experts that COVID-19 has higher fatality rates for people above 60, however, with further age, this increases exponentially. Countries with higher life expectancy are also high-income countries, and the best course of action would be to provide specialized support to self-isolate for people of ages 75 and above. CONCLUSION: The behaviour of disease occurring at a large scale and interaction with different populations is studied to understand and differentiate the factors and measures that successfully inhibited the pandemic. The study benchmarks different countries based on their performance and efforts against the pandemic and provides some useful insights on the efficiency of their governance and potential to improve & ramp up their programs. The economic status and existing healthcare infrastructure as they are the key factors in determining the country's ability to contain and minimize the losses from this pandemic.

positive: Impacto de la COVID-19 en la mortalidad de la comunidad autónoma de Castilla y León ABSTRACT Objective: To estimate the increase in mortality associated with the SARS-CoV-2 coronavirus pandemic in the autonomous community of Castilla y León (Spain). Method: Ecological study based on population and death data for the months of March 2016 to 2020 in Castilla y León. The general and provincial standardized rates, the relative risks of the year 2020 with respect to previous years and the risks adjusted by sex, periods and province, using Poisson regression, were calculated. Trend analysis was performed using joinpoint linear regression. Results: An increase in mortality was observed in March 2020 with respect to previous years, with an increase of 39% for men (relative risk [RR]: 1.39; 95% confidence interval [95%CI]: 1.32-1.47) and 28% for women (RR: 1.28; 95%CI: 1.21-1.35). The model predicts excess mortality of 775 deaths. In the trend analysis there is a significant turning point in 2019 in men, globally and for almost all provinces. The increase in mortality is general, although heterogeneous by sex, age group and province. Conclusions: Although the observed increase in mortality cannot be totally attributed to the disease, it is the best estimate we have of the real impact on deaths directly or indirectly related to it. The number of declared deaths only reaches two thirds of the increase in mortality observed.

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

positive: Early dinner or "dinner like a pauper": Evidence, the habitual time of the largest meal of the day - dinner - is predisposing to severe COVID-19 outcome - death COVID-19 and metabolic syndrome are devastating pandemics. Effective control of metabolic parameters and their dysfunction may help prevent or minimize the acute and devastating effects of SARS-CoV-2 by reducing the local inflammatory response and blocking the entry of the virus into cells. With such consideration in mind, we gathered data from dietary surveys conducted in nine European countries to explore the relationship between actual clock hour of the large dinner meal and also interval in minutes between it and sunset in the respective countries and death rate above the median rate of per one million people as an index of mortality due to COVID-19 infection. Clock time of the dinner meal varied between 16:00 and 21:00 h across the European counties sampled, and the correlation between dinner mealtime and death rate was strongly correlated, R = 0.7991 (two-tailed p = 0.0098), with R 2 explaining 63% of the variation within the data. This strong linear positive correlation indicates that the later the clock time of the dinner meal, the higher is the death rate (and vice versa). The relationship between meal timing in reference to sunset, utilized as a gross surrogate marker of the activity/rest synchronizer of circadian rhythms, and death rate was negative and even slightly stronger, R = -0.8025 (two-tailed p = 0.0092), with R 2 explaining 64% of the variation within the data. This strong linear negative correlation indicates that the shorter the interval between the dinner meal and sunset, i.e., the closer the time of the largest meal of the day to bedtime, the greater is the death rate (and vice versa). Our preliminary approach to nighttime eating, in terms of the day's largest caloric intake, as a risk factor for the predisposing conditions of obesity, metabolic syndrome, type 2 diabetes, and other commonly associated comorbidities of being overweight, and death from COVID-19 infection reveals strong correlation with the time of the dinner meal, both in terms of its actual clock and circadian time.

positive: Risk Factors for Mortality in Patients with COVID-19 in New York City BACKGROUND: New York City emerged as an epicenter of the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVE: To describe the clinical characteristics and risk factors associated with mortality in a large patient population in the USA. DESIGN: Retrospective cohort study. PARTICIPANTS: 6493 patients who had laboratory-confirmed COVID-19 with clinical outcomes between March 13 and April 17, 2020, who were seen in one of the 8 hospitals and/or over 400 ambulatory practices in the New York City metropolitan area MAIN MEASURES: Clinical characteristics and risk factors associated with in-hospital mortality. KEY RESULTS: A total of 858 of 6493 (13.2%) patients in our total cohort died: 52/2785 (1.9%) ambulatory patients and 806/3708 (21.7%) hospitalized patients. Cox proportional hazard regression modeling showed an increased risk of in-hospital mortality associated with age older than 50 years (hazard ratio [HR] 2.34, CI 1.47-3.71), systolic blood pressure less than 90 mmHg (HR 1.38, CI 1.06-1.80), a respiratory rate greater than 24 per min (HR 1.43, CI 1.13-1.83), peripheral oxygen saturation less than 92% (HR 2.12, CI 1.56-2.88), estimated glomerular filtration rate less than 60 mL/min/1.73m2 (HR 1.80, CI 1.60-2.02), IL-6 greater than 100 pg/mL (HR 1.50, CI 1.12-2.03), D-dimer greater than 2 mcg/mL (HR 1.19, CI 1.02-1.39), and troponin greater than 0.03 ng/mL (HR 1.40, CI 1.23-1.62). Decreased risk of in-hospital mortality was associated with female sex (HR 0.84, CI 0.77-0.90), African American race (HR 0.78 CI 0.65-0.95), and hydroxychloroquine use (HR 0.53, CI 0.41-0.67). CONCLUSIONS: Among patients with COVID-19, older age, male sex, hypotension, tachypnea, hypoxia, impaired renal function, elevated D-dimer, and elevated troponin were associated with increased in-hospital mortality and hydroxychloroquine use was associated with decreased in-hospital mortality.

positive: A Covid-19 case mortality rate without time delay systematics Concerning the two approaches to the Covid-19 case mortality rate published in the literature, namely computing the ratio of (a) the daily number of deaths to a time delayed daily number of confirmed infections; and (b) the cumulative number of deaths to confirmed infections up to a certain time, both numbers having been acquired in the middle of an outbreak, it is shown that each suffers from systematic error of a different source. We further show that in the absence of detailed knowledge of the time delay distribution of (a), the true case mortality rate is obtained by pursuing method (b) at the end of the outbreak when the fate of every case has decisively been rendered. The approach is then employed to calculate the mean case mortality rate of 13 regions of China where every case has already been resolved. This leads to a mean rate of 0.527 +/- 0.001 %.

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

positive: Clinical determinants for fatality of 44,672 patients with COVID-19

positive: Characteristics, comorbidities, 30-day outcome and in-hospital mortality of patients hospitalised with COVID-19 in a Swiss area - a retrospective cohort study. BACKGROUND Since its first description in December 2019, coronavirus disease 19 (COVID-19) has spread worldwide. There is limited information about presenting characteristics and outcomes of Swiss patients requiring hospitalisation. Furthermore, outcomes 30 days after onset of symptoms and after hospital discharge have not been described. AIMS To describe the clinical characteristics, outcomes 30 days after onset of symptoms and in-hospital mortality of a cohort of patients hospitalised for COVID-19 in a Swiss area. METHODS In this retrospective cohort study, we included all inpatients hospitalised with microbiologically confirmed COVID-19 between 1 March and 12 April 2020 in the public hospital network of a Swiss area (Fribourg). Demographic data, comorbidities and outcomes were recorded. Rate of potential hospital-acquired infection, outcomes 30 days after onset of symptoms and in-hospital mortality are reported. RESULTS One hundred ninety-six patients were included in the study. In our population, 119 (61%) were male and the median age was 70 years. Forty-nine patients (25%) were admitted to the intensive care unit (ICU). The rate of potential hospital-acquired infection was 7%. Overall, 30 days after onset of symptoms 117 patients (60%) had returned home, 23 patients (12%) were in a rehabilitation facility, 18 patients (9%) in a medical ward, 6 patients (3%) in ICU and 32 (16%) patients had died. Among patients who returned home within 30 days, 73 patients (63%) reported persistent symptoms. The overall in-hospital mortality was 17%. CONCLUSION We report the first cohort of Swiss patients hospitalised with COVID-19. Thirty days after onset of the symptoms, 60% had returned home. Among them, 63% still presented symptoms. Studies with longer follow-up are needed to document long-term outcomes in patients hospitalised with COVID-19.

positive: Prevalence and mortality in ß-thalassaemias due to outbreak of novel coronavirus disease (COVID-19): the nationwide Iranian experience

positive: Biological and Epidemiological Trends in the Prevalence and Mortality due to Outbreaks of Novel Coronavirus COVID-19 Abstract The novel coronavirus (Covid-19) infection outbreak has posed a major threat to international health system and economy. This study is aimed at investigating the biological and epidemiological trends in the prevalence and mortality due to outbreaks of novel coronavirus (COVID-19) infections. The data on the global outbreak of COVID-19, were obtained from World Health Organization (WHO), Worldometer, Centers for Disease Control and Prevention (CDC), and research institutes. The information was also recorded from research documents published in global scientific journals indexed in Pub Med and Institute of Scientific Information (ISI) Web of Science on the trends in the prevalence and mortality due to COVID-19 infection outbreaks. The results show rising trends in the transmission, prevalence and mortality rate due to coronavirus COVID-19. During the period of December 29, 2019 through March 31, 2020, it has infected 750890 people worldwide, resulting in 36405 deaths with a mortality rate of 4.84%. The infections were more frequent among male gender with above 60 years of age. The mean growth rate index for total number of cases from January 23 to March 31, 2020 was 1.20 and growth rate index for mortality rate was 1.12. There was a positive association between the prevalence and mortality rate (R2=0.996). The novel coronavirus COVID-19 is highly contagious and has affected a large number of people worldwide. It is still spreading with mutable prevalence and mortality outbreak trends. The global health officials have taken priority measures to prevent the further outbreaks of this emerging pathogen across the globe. However, the rising number of cases and mortality risk estimates are demonstrating that enhanced public health mediations, good hygienic conditions, social distancing and movement limitations may control the COVID-19 epidemics.

positive: Analysis of mortality in patients of COVID-19: clinical and laboratory parameters Several reports on epidemiological and clinical features of the 2019 coronavirus disease (COVID-19) had been published. However, mortality and morbidity analysis, important for better understanding of the pathogenesis of this disease, are scarce. We examine the clinical and laboratory features of 14 patients who died of COVID-19. The cohort consisted of 11 male and 3 female patients; nine patients aged 70 years or above, and nearly all had underlying diseases. Fever with bilateral pneumonia was the main manifestation. Most patients had consolidations combined with ground glass opacity (GGO) on chest CT scan. Laboratory tests showed lymphocytopenia in 10 patients, high blood glucose in 11, GGT in 5 of the 14 patients, and high LDH in 5 of 6 patients tested. In addition, patients in this cohort had high level of cytokines such as interleukin 6 in all 8 patients tested. The clinical and laboratory parameters in the cohort of fatal cases may be incorporated into future clinical prognosis models, and will be of help in understanding the pathogenesis of this disease.

positive: Gender-Based Disparities in COVID-19: Clinical Characteristics and Propensity-matched Analysis of Outcomes Importance COVID-19 epidemiological data show higher mortality rates among males compared to females. However, it remains unclear if the disparity in mortality is due to gender differences in high-risk characteristics. Objective To study the clinical characteristics of a large and diverse cohort of COVID-19 patients stratified by gender and determine the outcomes after matching for age and other high-risk characteristics. Design Retrospective cohort between January 20, 2020, and April 15, 2020 Setting TriNetX COVID-19 Research Network consisting of multiple healthcare organizations (HCOs) predominantly in the United States Participants and Exposure A cohort of male and female patients > 10 years of age diagnosed with COVID-19 identified with real-time analyses of electronic medical records of patients from participating HCOs. A 1:1 propensity score matching of cohorts was performed for age, race, nicotine use, and all possible confounding comorbidities. Main Outcome Risk of mortality, hospitalization and mechanical ventilation within 30 days after the diagnosis of COVID-19 Results A total of 5980 males and 7730 females diagnosed with COVID-19 were identified. Males were significantly older than females (54.9 (18.3) vs. 50.9 (18.4), p-value <0.0001). There were significant differences in patient characteristics, but after propensity matching, both groups (N=5350 each group) were balanced. Males had a significantly higher risk for mortality both before (Risk Ratio (RR) 2.1, 95% CI 1.8-2.4) and after matching (RR 1.4, 95% CI 1.2-1.7). Similarly, the risk of hospitalization (RR 1.3, 95%CI 1.2-1.4) and mechanical ventilation (RR 1.71, 95% CI 1.3-2.3) was significantly higher in males even after matching. On subanalysis, males age > 50 had higher mortality than matched females of similar age (RR 1.6, 95% CI 1.4-1.8), whereas the risk of mortality in matched groups < 40 years was similar (RR 1.00, 95% CI 0.4-2.4). Conclusion In conclusion, males are more severely affected and have higher mortality from COVID-19. This gender-specific risk is especially more pronounced in advanced age. Gender disparity in poor outcomes can only be partially explained by differences in high-risk behavior and comorbidities. Further research is needed to understand the causes of this disparity.

positive: Disparities in Age-Specific Morbidity and Mortality from SARS-CoV-2 in China and the Republic of Korea We analyzed age- and sex-specific morbidity and mortality data from SARS-COV-2 pandemic in China and Republic of Korea (ROK). Data from China exhibit a Gaussian distribution with peak morbidity in the 50-59 years cohort, while the ROK data have a bimodal distribution with highest morbidity in the 20-29 years cohort.

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 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: Racial Inequalities in Mortality from Coronavirus: The Tip of the Iceberg

positive: COVID-19 death rates by age and sex and the resulting mortality vulnerability of countries and regions in the world The growing number of series on COVID-19 deaths classified by age and sex, released by national health authorities, has allowed us to compute age and sex patterns of its mortality, based on 183,619 deaths from Western Europe and the USA. We highlight the specific age schedule of COVID-19 mortality and its pronounced excess male mortality and we then apply these COVID-19 death rates to world populations, in 2020. Our results underscore that considerable variations exist between world regions, as concerns the potential impact of COVID-19 mortality, because of their demographic structures. When compared to younger countries in Sub-Saharan Africa, the vulnerability to COVID-19 mortality is shown to be 17 times higher in several industrialized countries of East Asia and Europe. There is a high correlation (r2= .44) between demographic vulnerability to COVID-19 mortality and current COVID-19 death rates.

positive: If long-term suppression is not possible, how do we minimize mortality for COVID-19 and other emerging infectious disease outbreaks? If COVID-19 containment policies fail and social distancing measures cannot be sustained until vaccines becomes available, the next best approach is to use interventions that reduce mortality and prevent excess infections while allowing low-risk individuals to acquire immunity through natural infection until population level immunity is achieved. In such a situation, allowing some infections to occur in lower-risk groups might lead to an overall greater reduction in mortality than trying to protect everyone equally.

positive: Lower mortality of COVID-19 by early recognition and intervention: experience from Jiangsu Province

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

positive: The Role of Vitamin D in Suppressing Cytokine Storm in COVID-19 Patients and Associated Mortality The authors have withdrawn this manuscript because they have noticed idiosyncrasies in the reporting of 25(OH)D data across different countries. Therefore, the authors do not wish this work to be cited until after this issue is addressed. If you have any questions, please contact the corresponding author.

positive: 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.

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: COVID-19: a potential public health problem for homeless populations

positive: Mortality of the COVID-19 outbreak in Sweden in relation to previous severe disease outbreaks Influenza viruses have caused disease outbreaks in human societies for a long time. Influenza often has rapid onset and relatively short duration, both in the individual and in the population. The case fatality rate varies for different strains of the virus, as do the effects on total mortality. Outbreaks related to coronavirus infections have recently become a global concern but much less is known about the dynamics of these outbreaks and their effects on mortality. In this work, disease outbreaks in Sweden, in the time period of 1860-2020, are characterized and compared to the currently ongoing COVID-19 outbreak. The focus is on outbreaks with a sharp increase in all-cause mortality. Outbreak onset is defined as the time point when deaths counts starts to increase consistently for a period of 10 days. The duration of the outbreak is defined as the time period in which mortality rates are elevated. Excess mortality is estimated by standard methods. In total there were 15 outbreaks detected in the time period, the first 14 were likely caused by influenza virus infections, the last by SARS-CoV-2. The mortality dynamics of the SARS-CoV-2 outbreak is shown to be similar to outbreaks due to influenza virus, and in terms of the number of excess deaths, might become the worst outbreak since the 'Spanish flu' of 1918-1919.

positive: Case fatality risk of novel coronavirus diseases 2019 in China Objective The outbreak of novel coronavirus disease 2019 (COVID-19) imposed a substantial health burden in mainland China and remains a global epidemic threat. Our objectives are to assess the case fatality risk (CFR) among COVID-19 patients detected in mainland China, stratified by clinical category and age group. Method We collected individual information on laboratory-confirmed COVID-19 cases from publicly available official sources from December 29, 2019 to February 23, 2020. We explored the risk factors associated with mortality. We used methods accounting for right-censoring and survival analyses to estimate the CFR among detected cases. Results Of 12,863 cases reported outside Hubei, we obtained individual records for 9,651 cases, including 62 deaths and 1,449 discharged cases. The deceased were significantly older than discharged cases (median age: 77 vs 39 years, p<0.001). 58% (36/62) were male. Older age (OR 1.18 per year; 95%CI: 1.14 to 1.22), being male (OR 2.02; 95%CI: 1.02 to 4.03), and being treated in less developed economic regions (e.g., West and Northeast vs. East, OR 3.93; 95%CI: 1.74 to 8.85) were mortality risk factors. The estimated CFR was 0.89-1.24% among all cases. The fatality risk among critical patients was 2-fold higher than that among severe and critical patients, and 24-fold higher than that among moderate, severe and critical patients. Conclusions Our estimates of CFR based on laboratory-confirmed cases ascertained outside of Hubei suggest that COVID-19 is not as severe as severe acute respiratory syndrome and Middle East respiratory syndrome, but more similar to the mortality risk of 2009 H1N1 influenza pandemic in hospitalized patients. The fatality risk of COVID-19 is higher in males and increases with age. Our study improves the severity assessment of the ongoing epidemic and can inform the COVID-19 outbreak response in China and beyond.

positive: A scaling approach to estimate the COVID-19 infection fatality ratio from incomplete data SARS-CoV-2 has disrupted the life of billions of people around the world since the first outbreak was officially declared in China at the beginning of 2020. Yet, important questions such as how deadly it is or its degree of spread within different countries remain unanswered. In this work, we exploit the 'universal' growth of the mortality rate with age observed in different countries since the beginning of their respective outbreaks, combined with the results of the antibody prevalence tests in the population of Spain, to unveil both unknowns. We validate these results with an analogous antibody rate survey in the canton of Geneva, Switzerland. We also argue that the official number of deaths over 70 years old is importantly underestimated in most of the countries, and we use the comparison between the official records with the number of deaths mentioning COVID-19 in the death certificates to quantify by how much. Using this information, we estimate the fatality infection ratio (IFR) for the different age segments and the fraction of the population infected in different countries assuming a uniform exposure to the virus in all age segments. We also give estimations for the non-uniform IFR using the sero-epidemiological results of Spain, showing a very similar growth of the fatality ratio with age. Only for Spain, we estimate the probability (if infected) of being identified as a case, being hospitalized or admitted in the intensive care units as function of age. In general, we observe a nearly exponential growth of the fatality ratio with age, which anticipates large differences in total IFR in countries with different demographic distributions, with numbers that range from 1.82% in Italy, to 0.62% in China or even 0.14% in middle Africa.

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

positive: Analysis of Austrian COVID-19 deaths by age and sex We analyze the age and sex distribution of the reported COVID-19 deaths in Austria. In accordance with international studies, the Austrian data also suggests that the risk of death increases substantially with age. The observed age dependency of the proportions of registered COVID-19 deaths in relation to the population sizes in the age groups is approximately exponential, similar to the age dependency of the general age specific mortality rate. Furthermore, we compare the general age specific mortality rate in Austria with the estimates of the SARS-CoV‑2 infection fatality rate by Ferguson et al. (2020). The parallels to the general age specific mortality rates do not imply that COVID-19 does not pose an additional risk. On the contrary, it follows from the structure and magnitude of the infection fatality rate that it is substantial, especially for higher age groups. However, since in many cases persons with severe pre-existing conditions are affected, it is not yet possible to estimate what effects COVID-19 will have on life expectancy.

positive: A Comparison of Mortality-related Risk Factors of COVID-19, SARS, and MERS: A Systematic Review and Meta-analysis Objective: Coronavirus Disease 2019 (COVID-19) is a pandemic. This systematic review compares mortality risk factors including clinical, demographic and laboratory features of COVID-19, Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The aim is to provide new strategies for COVID-19 prevention and treatment. Methods: We performed a systematic review with meta-analysis, using five databases to compare the predictors of death for COVID-19, SARS and MERS. A random-effects model meta-analysis calculated odds ratios (OR) and 95% confidence intervals (95% CI). Results: 845 articles up through 11/4/2020 were retrieved, but only 28 studies were included in this meta-analysis. The results showed that males had a higher likelihood of death than females (OR = 1.82, 95% CI 1.56-2.13). Age (OR = 7.86, 95% CI 5.46-11.29), diabetes comorbidity (OR = 3.73, 95% CI 2.35-5.90), chronic lung disease (OR = 3.43, 95% CI 1.80-6.52) and hypertension (OR = 3.38, 95% CI 2.45-4.67) were the mortality risk factors. The laboratory indicators lactic dehydrogenase (OR = 37.52, 95% CI 24.68-57.03), C-reactive protein (OR = 12.11, 95% CI 5.24-27.98), and neutrophils (OR = 17.56, 95% CI 10.67-28.90) had stronger correlations with COVID-19 mortality than with SARS or MERS mortality. Consolidation and ground-glass opacity imaging features were similar among COVID-19, SARS, and MERS patients. Conclusions: COVID-19’s mortality factors are similar to those of SARS and MERS. Age and laboratory indicators could be effective predictors of COVID-19 mortality outcomes.

positive: Coronavirus Disease (COVID-19) Pandemic: An Overview of Systematic Reviews Background: Navigating the rapidly growing body of scientific literature on the SARS-CoV-2 pandemic is challenging and ongoing critical appraisal of this output is essential. We aimed to collate and summarize all published systematic reviews on the coronavirus disease (COVID-19). Methods: Nine databases (Medline, EMBASE, Cochrane Library, CINAHL, Web of Sciences, PDQ-Evidence, WHO's Global Research, LILACS and Epistemonikos) were searched from December 1, 2019 to March 24, 2020. Systematic reviews analyzing primary studies of COVID-19 were included. Two authors independently undertook screening, selection, extraction (data on clinical symptoms, prevalence, pharmacological and non-pharmacological interventions, diagnostic test assessment, laboratory and radiological findings) and quality assessment (AMSTAR 2). Meta-analysis on prevalence of clinical outcomes was performed. Results: Eighteen systematic reviews were included; one was empty. Using AMSTAR 2, confidence in the results of 13 reviews was rated as "critically low", one as "low", one as "moderate" and two as "high". Symptoms of COVID-19 were (range values of point estimates): fever (82-95%), cough with or without sputum (58-72%), dyspnea (26-59%), myalgia or muscle fatigue (29-51%), sore throat (10-13%), headache (8-12%) and gastrointestinal complaints (5-9%). Severe symptoms were more common in men. Elevated C-reactive protein (associated with lymphocytopenia) and lactate dehydrogenase, and slightly elevated aspartate and alanine aminotransferase, were commonly described. Thrombocytopenia and elevated levels of procalcitonin and cardiac troponin I were associated with severe disease. Chest imaging described a frequent pattern of uni- or bilateral multilobar ground-glass opacity. Only one review investigated the impact of medication (chloroquine) but found no verifiable clinical data. All-cause mortality ranged from 0.3% to 14%. Conclusions: Confidence in the results of most reviews was "critically low". Future studies and systematic reviews should adhere to established methodologies. The majority of included systematic reviews were hampered by imprecise search strategy and no previous protocol submission. Protocol registration: This is an extension of a PROSPERO protocol (CRD42020170623); protocol available on Open Science Framework (https://osf.io/6xtyw).

positive: The role of economic structural factors in determining pandemic mortality rates: Evidence from the COVID-19 outbreak in France Abstract Among the majority of research on individual factors leading to coronavirus mortality, age has been identified as a dominant factor. Health and other individual factors including gender, comorbidity, ethnicity and obesity have also been identified by other studies. In contrast, we examine the role of economic structural factors on COVID-19 mortality rates. Particularly, focusing on a densely populated region of France, we document evidence that higher economic “precariousness indicators” such as unemployment and poverty rates, lack of formal education and housing are important factors in determining COVID-19 mortality rates. Our study will help inform policy makers regarding the role of economic factors in managing pandemics.

positive: COVID-19 FATALITY RISK: WHY IS AUSTRALIA LOWER THAN SOUTH KOREA? Background: As the Covid-19 virus epidemic spreads, it is important to establish reliable estimates of fatality hazard rates. Australia and South Korea are ideal candidates for detailed consideration. Both have completed the first wave of the epidemic, they have extensive Covid-19 testing and tracking programs so that confirmed case load data are reliable, and neither country has had any significant case load stress in their hospital systems. Methods: For each country, mortality hazard models were estimated using a parameterized distributed lag model where the number of daily deaths was dependent on the number of confirmed cases in each of the preceding six weeks. Age cohort CFRs were also examined. Findings: We observed major difference in the mortality rates when comparing South Korea to Australia in both the simple age adjusted fatality rates and in the disease hazard curve. On a like-for-like basis, the CFR for South Korea appears to be close to double the Australian rate (aggregate; 2.4% vs 1.4%). Interpretation: Neither differences in the time pattern of the peaking of the case load of confirmed cases, nor differences in the size of age cohorts of confirmed cases explain the difference in mortality observed. We discuss possible explanations that point the way for further investigation. Funding: nil.

positive: Asymptomatic transmission and the infection fatality risk for COVID-19: Implications for school reopening Asymptomatic infection occurs for numerous respiratory viral diseases, including influenza and COVID-19. We seek to clarify confusion in three areas: age-specific risks of transmission and/or disease; various definitions for the COVID-19 “mortality rate”, each useful for specific purposes; and implications for student return strategies from pre-school through university settings.

positive: Letalidad del COVID-19: ausencia de patrón epidemiológico ABSTRACT Objective: Analyze a set of indicators to understand the variability of the evolution and impact of the COVID-19 epidemic in a set of selected countries. Method: Ecological study of a group of countries with more than 200 reported cases. Demographic variables, health expenditure variables, and variables about characteristics of health services were included as explanatory variables. and incidence, mortality and fatality rates have been analyzed as response variables. In addition, a relative fatality index has been created. Data are from international organizations. Spearman's correlation coefficient was used to estimate the magnitude of the associations. Results: Number of tests and of medical professionals are associated with a higher incidence rate. Mortality and case fatality rate are not associated with demographic, health expenditure, or health services variables. Conclusion: Differences suggest a general underestimation of the magnitude of the epidemic. Improvement of case identification and effectiveness of epidemiological surveillance systems is necessary.

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

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

positive: Rotaviral and Coronaviral Diarrhea Rotaviruses and coronaviruses are very common causes of calfhood diarrhea throughout the world. Rotaviral and coronaviral infections in neonatal calves can produce a severe diarrhea of high morbidity but of variable mortality depending upon secondary bacterial infections and electrolyte imbalances. Laboratory diagnosis of rotaviral and coronaviral diarrhea is mostly done by detection of virus particles or virus antigens in fecal specimens. The sample of choice for these diagnostic tests is a fresh fecal sample collected directly from the calf as close as possible to the onset of diarrhea.

positive: Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970-2016: a systematic analysis for the Global Burden of Disease Study 2016. BACKGROUND Detailed assessments of mortality patterns, particularly age-specific mortality, represent a crucial input that enables health systems to target interventions to specific populations. Understanding how all-cause mortality has changed with respect to development status can identify exemplars for best practice. To accomplish this, the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) estimated age-specific and sex-specific all-cause mortality between 1970 and 2016 for 195 countries and territories and at the subnational level for the five countries with a population greater than 200 million in 2016. METHODS We have evaluated how well civil registration systems captured deaths using a set of demographic methods called death distribution methods for adults and from consideration of survey and census data for children younger than 5 years. We generated an overall assessment of completeness of registration of deaths by dividing registered deaths in each location-year by our estimate of all-age deaths generated from our overall estimation process. For 163 locations, including subnational units in countries with a population greater than 200 million with complete vital registration (VR) systems, our estimates were largely driven by the observed data, with corrections for small fluctuations in numbers and estimation for recent years where there were lags in data reporting (lags were variable by location, generally between 1 year and 6 years). For other locations, we took advantage of different data sources available to measure under-5 mortality rates (U5MR) using complete birth histories, summary birth histories, and incomplete VR with adjustments; we measured adult mortality rate (the probability of death in individuals aged 15-60 years) using adjusted incomplete VR, sibling histories, and household death recall. We used the U5MR and adult mortality rate, together with crude death rate due to HIV in the GBD model life table system, to estimate age-specific and sex-specific death rates for each location-year. Using various international databases, we identified fatal discontinuities, which we defined as increases in the death rate of more than one death per million, resulting from conflict and terrorism, natural disasters, major transport or technological accidents, and a subset of epidemic infectious diseases; these were added to estimates in the relevant years. In 47 countries with an identified peak adult prevalence for HIV/AIDS of more than 0·5% and where VR systems were less than 65% complete, we informed our estimates of age-sex-specific mortality using the Estimation and Projection Package (EPP)-Spectrum model fitted to national HIV/AIDS prevalence surveys and antenatal clinic serosurveillance systems. We estimated stillbirths, early neonatal, late neonatal, and childhood mortality using both survey and VR data in spatiotemporal Gaussian process regression models. We estimated abridged life tables for all location-years using age-specific death rates. We grouped locations into development quintiles based on the Socio-demographic Index (SDI) and analysed mortality trends by quintile. Using spline regression, we estimated the expected mortality rate for each age-sex group as a function of SDI. We identified countries with higher life expectancy than expected by comparing observed life expectancy to anticipated life expectancy on the basis of development status alone. FINDINGS Completeness in the registration of deaths increased from 28% in 1970 to a peak of 45% in 2013; completeness was lower after 2013 because of lags in reporting. Total deaths in children younger than 5 years decreased from 1970 to 2016, and slower decreases occurred at ages 5-24 years. By contrast, numbers of adult deaths increased in each 5-year age bracket above the age of 25 years. The distribution of annualised rates of change in age-specific mortality rate differed over the period 2000 to 2016 compared with earlier decades: increasing annualised rates of change were less frequent, although rising annualised rates of change still occurred in some locations, particularly for adolescent and younger adult age groups. Rates of stillbirths and under-5 mortality both decreased globally from 1970. Evidence for global convergence of death rates was mixed; although the absolute difference between age-standardised death rates narrowed between countries at the lowest and highest levels of SDI, the ratio of these death rates-a measure of relative inequality-increased slightly. There was a strong shift between 1970 and 2016 toward higher life expectancy, most noticeably at higher levels of SDI. Among countries with populations greater than 1 million in 2016, life expectancy at birth was highest for women in Japan, at 86·9 years (95% UI 86·7-87·2), and for men in Singapore, at 81·3 years (78·8-83·7) in 2016. Male life expectancy was generally lower than female life expectancy between 1970 and 2016, and the gap between male and female life expectancy increased with progression to higher levels of SDI. Some countries with exceptional health performance in 1990 in terms of the difference in observed to expected life expectancy at birth had slower progress on the same measure in 2016. INTERPRETATION Globally, mortality rates have decreased across all age groups over the past five decades, with the largest improvements occurring among children younger than 5 years. However, at the national level, considerable heterogeneity remains in terms of both level and rate of changes in age-specific mortality; increases in mortality for certain age groups occurred in some locations. We found evidence that the absolute gap between countries in age-specific death rates has declined, although the relative gap for some age-sex groups increased. Countries that now lead in terms of having higher observed life expectancy than that expected on the basis of development alone, or locations that have either increased this advantage or rapidly decreased the deficit from expected levels, could provide insight into the means to accelerate progress in nations where progress has stalled. FUNDING Bill & Melinda Gates Foundation, and the National Institute on Aging and the National Institute of Mental Health of the National Institutes of Health.

positive: COVID-19 Pandemic: Marked Global Disparities in Fatalities According to Geographic Location and Universal Health Care Since its outbreak, COVID-19 pandemic has been the biggest global concern with exponentially increasing number of cases and associated deaths across all habitable continents. Various countries around the world with their diverse health care systems, have responded to the pandemic in very distinctive ways. In this paper, we: compared COVID-19 mortality rates across global geographic regions; and assessed differences in COVID-19-related case fatality rate (CFR) based on presence or absence of Universal Health Coverage (UHC). We found that as of May 6, 2020, Europe had experienced the highest CFR globally of 9.6%, followed by 5.9% in North America. Although the pandemic originated in Asia, the continent ranked second to the last in terms of CFR (3.5%). Countries with UHC had lower number of cases of 37.6%, but the CFR of countries with UHC was twice that of countries without UHC (10.5% versus 4.9%). In conclusion, UHC does not appear to protect against mortality in a pandemic environment such as with COVID-19.

positive: COVID-19 excess deaths in the United States during April 2020 Background: Some have claimed that the number of COVID-19 deaths is not much greater than would be experienced in the usual course of events. We sought to estimate the number of deaths due to COVID-19 in the United States during April 2020 and compare that to the number of expected deaths in the same time period. Methods: The Institute for Health Metrics and Evaluation (IHME) predicts that 67,212 COVID-19 deaths will occur during April 2020. To obtain the number of excess COVID-19 deaths, we multiplied published infection fatality rates by age by population numbers to obtain assumed infection rates. We then subtracted the expected number of deaths calculated using life table mortality rates. Results: During April 2020 there may be 61,690 to 62,526 excess deaths. Population infection rates of 3.6% to 4.3% by mid-April 2020 would generate the number of COVID-19 deaths predicted by IHME. Conclusions: During April 2020 over 90% of the COVID-19 deaths can be classified as excess deaths. These deaths would normally occur over 11.2 to 13.3 months instead of being concentrated in 1 month.

positive: Ethnic disparities in COVID-19 mortality: are comorbidities to blame?

positive: The COVID-19 mortality effects of underlying health conditions in India: a modelling study Objective: To model how known COVID-19 comorbidities will affect mortality rates and the age distribution of mortality in a large lower middle income country (India), as compared with a high income country (England), and to identify which health conditions drive any differences. Design: Modelling study. Setting: England and India. Participants: 1,375,548 respondents aged 18 to 99 to the District Level Household Survey-4 and Annual Health Survey in India. Additional information on health condition prevalence on individuals aged 18 to 99 was obtained from the Health Survey for England and the Global Burden of Diseases, Risk Factors, and Injuries Studies (GBD). Main outcome measures: The primary outcome was the proportional increase in age-specific mortality in each country due to the prevalence of each COVID-19 mortality risk factor (diabetes, hypertension, obesity, chronic heart disease, respiratory illness, kidney disease, liver disease, and cancer, among others). The combined change in overall mortality and the share of deaths under 60 from the combination of risk factors was estimated in each country. Results: Relative to England, Indians have higher rates of diabetes (10.6% vs. 8.5%), chronic respiratory disease (4.8% vs. 2.5%), and kidney disease (9.7% vs. 5.6%), and lower rates of obesity (4.4% vs. 27.9%), chronic heart disease (4.4% vs. 5.9%), and cancer (0.3% vs. 2.8%). Population COVID-19 mortality in India relative to England is most increased by diabetes (+5.4%) and chronic respiratory disease (+2.3%), and most reduced by obesity (-9.7%), cancer (-3.2%), and chronic heart disease (-1.9%). Overall, comorbidities lower mortality in India relative to England by 9.7%. Accounting for demographics and population health explains a third of the difference in share of deaths under age 60 between the two countries. Conclusions: Known COVID-19 health risk factors are not expected to have a large effect on aggregate mortality or its age distribution in India relative to England. The high share of COVID-19 deaths from people under 60 in low- and middle-income countries (LMICs) remains unexplained. Understanding mortality risk associated with health conditions prevalent in LMICs, such as malnutrition and HIV/AIDS, is essential for understanding differential mortality. Keywords: COVID-19, India, low- and middle-income countries, comorbidity

positive: How Large Was the Mortality Increase Directly and Indirectly Caused by the COVID-19 Epidemic? An Analysis on All-Causes Mortality Data in Italy Objective: Overall mortality is a relevant indicator of the population burden during an epidemic. It informs on both undiagnosed cases and on the effects of health system disruption. Methods: We aimed at evaluating the extent of the total death excess during the COVID-19 epidemic in Italy. Data from 4433 municipalities providing mortality reports until April 15th, 2020 were included for a total of 34.5 million residents from all Italian regions. Data were analyzed by region, sex and age, and compared to expected from 2015-2019. Results: In both genders, overall mortality was stable until February 2020 and abruptly increased from March 1st onwards. Within the municipalities studied, 77,339 deaths were observed in the period between March 1st to April 15th, 2020, in contrast to the 50,822.6 expected. The rate ratio was 1.11 before age 60 and 1.55 afterwards. Both sexes were affected. The excess was greater in the regions most affected by COVID-19 but always exceeded the deaths attributed to COVID-19. The extrapolation to the total Italian population suggests an excess of 45,033 deaths in the study period, while the number of COVID-19 deaths was 21,046. Conclusion: Our paper shows a large death excess during the COVID-19 epidemic in Italy; greater than the number attributed to it. Possible causes included both the undetected cases and the disruption of the Health Service organization. Timely monitoring of overall mortality based on unbiased nationwide data is an essential tool for epidemic control.

positive: Why estimating population-based case fatality rates during epidemics may be misleading Different ways of calculating mortality ratios during epidemics can yield widely different results, particularly during the COVID-19 pandemic. We formulate both a survival probability model and an associated infection duration-dependent SIR model to define individual- and population-based estimates of dynamic mortality ratios. The key parameters that affect the dynamics of the different mortality estimates are the incubation period and the length of time individuals were infected before confirmation of infection. We stress that none of these ratios are accurately represented by the often misinterpreted case fatality ratio (CFR), the number of deaths to date divided by the total number of infected cases to date. Using available data on the recent SARS-CoV-2 outbreaks and simple assumptions, we estimate and compare the different dynamic mortality ratios and highlight their differences. Informed by our modeling, we propose a more systematic method to determine mortality ratios during epidemic outbreaks and discuss sensitivity to confounding effects and errors in the data.

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

positive: Climatic factors influence COVID-19 outbreak as revealed by worldwide mortality The COVID-19 outbreak is triggering a global crisis that is challenging governments, health systems and the scientific community worldwide. A central question in the COVID-19 pandemic is whether climatic factors modulate its progression. This information is key to epidemiologists and healthcare decision-makers for improving their management plans. Previous attempts to assess the impact of climatic parameters have yielded ambiguous results, either because they were using geographically or temporally restricted data, or because they were comparing infection rates across countries, which were measured differently depending on local screening strategies. In March 2020, the spread of COVID-19 dramatically increased the number of countries recording deaths, providing an opportunity to use mortality rate, which is measured more homogeneously across countries than infection rates, as a descriptor of the COVID-19 outbreak over a large latitudinal range. Here, using data recorded in 208 territories from 88 countries, we show that mortality rate is negatively influenced by warmer air temperature and positively affected by higher relative humidity. Each additional Celsius degree decreases mortality rate by ~4%, while a 1% increase in relative humidity raises mortality rate by ~2%. Temperature is positively correlated with UV-index, for which one unit of increase results in a ~15% decrease in the mortality rate. We also show that other factors contribute to the dynamics of the COVID-19 outbreak, such as the proportion of vulnerable age classes in the population, access to a non-overwhelmed health system, as well as governmental travel restrictions for controlling the spread of the disease. All of them are critical factors impacting the mortality rate of COVID-19. The influence of climatic factors is a warning to all southern hemisphere countries where winter is coming soon. Northern hemisphere countries should also be warned that climatic factors alone will likely not be sufficient to contain the disease.

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

positive: Has mortality due to other causes increased during the Covid-19 pandemic? Early evidence from England and Wales Background: The Covid-19 pandemic has claimed many lives in the UK and globally. The objective of this paper is to study whether the novel coronavirus has also been associated with an increase in deaths in England and Wales for those who have not contracted the disease. Reasons behind this may include avoiding visits to hospitals or GPs, and the effects of the lockdown. Methods: I used weekly ONS data on the number of deaths that did not involve covid-19 over the period 2015-2020. Simply observing trends is not sufficient as spikes in deaths may occasionally occur. I thus followed a differences-in-differences econometric approach to study whether there was a relative increase in non-covid-19 deaths during the pandemic, compared to a control. As an additional approach, an interrupted time series model was also used. Results: Results suggest that there were an additional 531 non-covid-19 deaths in England and Wales since the outbreak of the pandemic, compared to what would have otherwise been expected [diff-in-diff interaction coeff: 531.11; 95%CI: 125.65 to 936.57]. This is confirmed by the interrupted time series model. Discussion: The health effects of covid-19 do not seem to be limited only to patients suffering from the disease, as the number of deaths for those who did not contract covid-19 has also demonstrated an absolute and relative increase. Analysing the cause of death for non-covid-19 deaths will shed light upon the reasons for the increase in such deaths and will help design appropriate policy responses to save lives.

positive: Diabetes increases the mortality of patients with COVID-19: a meta-analysis AIMS: Nowadays, the ongoing pandemic of COVID-19 caused by the novel coronavirus Syndrome-Coronavirus-2 (SARS-CoV-2) is an emerging, rapidly evolving situation. Complications such as hypertension, diabetes, COPD, cardiovascular disease, and cerebrovascular disease are major risk factors for patients with COVID-19. METHODS: No meta-analysis has explored if or not diabetes related to mortality of patients with COVID-19. Therefore, this meta-analysis first aims to explore the possible clinical mortality between diabetes and COVID-19, analyze if diabetes patients infected with SARS-CoV-2 are exposed to the worst clinical prognostic risk, and to evaluate the reliability of the evidence. RESULTS: Our results showed a close relationship between diabetes and mortality of COVID-19, with a pooled OR of 1.75 (95% CI 1.31–2.36; P = 0.0002). The pooled data were calculated with the fixed effects model (FEM) as no heterogeneity appeared in the studies. Sensitivity analysis showed that after omitting any single study or converting a random effect model to FEM, the main results still held. CONCLUSIONS: Our meta-analysis showed that diabetes increases the mortality of patients with COVID-19. These results indicated the disturbance of blood glucose in the COVID-19 patients. More importantly, this meta-analysis grades the reliability of evidence for further basic and clinical research into the diabetes dysfunction in COVID-19 patients.

positive: Global years of life lost to COVID-19 Understanding the mortality impact of COVID-19 requires not only counting the dead, but analyzing how premature the deaths are. We calculate years of life lost (YLL) across 42 countries due to COVID-19 attributable deaths, and also conduct an analysis based on estimated excess deaths. As of June 13th 2020, YLL in heavily affected countries are 2 to 6 times the average seasonal influenza; over two thirds of the YLL result from deaths in ages below 75 and one quarter from deaths below 55; and men have lost 47% more life years than women. The results confirm the large mortality impact of COVID-19 among the elderly. They also call for heightened awareness in devising policies that protect vulnerable demographics losing the largest number of life-years.

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

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

positive: Effects of temperature variation and humidity on the mortality of COVID-19 in Wuhan Object Meteorological parameters are the important factors influencing the infectious diseases like severe acute respiratory syndrome (SARS). This study aims to explore the association between coronavirus disease (COVID-19) death and weather parameters. Methods In this study, we collected the daily death number of COVID-19, meteorological and air pollutant data from 20 January, 2020 to 29 February, 2020 in Wuhan, China. Then, the generalized additive model was applied to explore the impact of temperature, humidity and diurnal temperature range on daily mortality of COVID-19. Results There were in total 2299 COVID-19 mortality counts in Wuhan. A positive association with COVID-19 mortality was observed for diurnal temperature range (r = 0.44), but negative association for relative humidity (r = -0.32). In addition, each 1 unit increase in diurnal temperature range was only associated with a 2.92% (95% CI: 0.61%, 5.28%) increase in COVID-19 mortality at lag 3. However, both per 1 unit increase of temperature and absolute humidity were related to the decreased COVID-19 mortality at lag 3 and lag 5, respectively. Conclusion In summary, this study suggests the temperature variation and humidity may be important factors affecting the COVID-19 mortality.

positive: Ethnicity and COVID-19: an urgent public health research priority

positive: Mortality Rates of Patients with Proximal Femoral Fracture in a Worldwide Pandemic: Preliminary Results of the Spanish HIP-COVID Observational Study BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), in December 2019 in Wuhan, People's Republic of China, has developed into an unprecedented pandemic with enormous pressure on health-care providers around the world. A higher mortality rate has been described in older infected individuals. Patients with hip fracture are a particularly vulnerable population during this pandemic because older age is associated with a higher mortality rate. Our aim was to describe the early mortality rate and demographic variables in a hip fracture sample population in Spain during the coronavirus pandemic. METHODS: This is a multicenter, observational, retrospective, descriptive study. We collected data from 13 major hospitals in Spain from the beginning of the national state of alarm (declared on March 14, 2020, by the Spanish government) until the end of our study period on April 4, 2020. All patients who were ≥65 years of age, presented to the Emergency Department of the participating hospitals during this period with a diagnosis of proximal femoral fracture, and had a minimum follow-up of 10 days were included in the cohort. In addition to mortality, demographic and other potential prognostic variables were also collected. RESULTS: In this study, 136 patients with a hip fracture were included. Of these patients, 124 underwent a surgical procedure and 12 were managed nonoperatively. The total mortality rate was 9.6%. Sixty-two patients were tested for COVID-19, with 23 patients being positive. The mortality rate for these 23 patients was 30.4% (7 of 23 patients) at a mean follow-up of 14 days. The mortality rate was 10.3% (4 of 39) for patients who had been tested and had a negative result and 2.7% (2 of 74) for patients who had not been tested. Of the 12 patients who were managed nonoperatively, 8 (67%) died, whereas, of the 124 patients who were surgically treated, 5 (4%) died. Results differed among centers. CONCLUSIONS: There is a higher mortality rate in patients with a hip fracture and an associated positive test for COVID-19. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

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: Estimates of COVID-19 case-fatality risk from individual-level data When calculated from aggregate data on confirmed cases and deaths, the case-fatality risk (CFR) is a simple ratio between the former and the latter, which is prone to numerous biases. With individual-level data, the CFR can be estimated as a true measure of risk as the proportion of incidence for the disease. We present the first estimates of the CFR for COVID-19 by age and sex based on event history modelling of the risk of dying among confirmed positive individuals in the Canadian province of Ontario, which maintains one of the few individual-level datasets on COVID-19 in the world.

positive: Use of excess mortality associated with the COVID-19 epidemic as an epidemiological surveillance strategy - preliminary results of the evaluation of six Brazilian capitals In early 2020, the World Health Organization (WHO) recognized the pandemic situation of the new coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2), which causes Coronavirus Disease-2019 (COVID-19). In Brazil by the end of April 2020, another 110 thousand cases and 5,000 deaths had been confirmed. The scarcity of laboratory resources and overload of the care network, added to the broad clinical spectrum of the disease, can make it difficult to capture all mortality from this disease through epidemiological surveillance based on individual notification of cases. The aim of this study was to evaluate the excess of deaths in Brazilian capitals with the highest incidence of COVID-19, as a way of validating the method, we also evaluated a capital with low incidence. We assessed weekly mortality from all causes during the year 2020, up to the epidemiological week 17, compared with the previous year. The data were obtained through the National Civil Registry Information Center (CNIRC, acronym in Portuguese). We estimate the expected mortality and the 95% confidence interval by projecting the observed mortality in 2019 for the population of 2020. In the five capitals with the highest incidences it was possible to identify excess deaths in the pandemic period, the age group most affected were those over 60 years old, 31% of the excess deaths occurred in the population between 20 and 59 years old. There was a strong correlation (r = 0.94) between the excess of deaths in each city and the number of deaths confirmed by epidemiological surveillance. There was no excess of deaths in the capital with the lowest incidence, nor among the population under 20 years old. We estimate that epidemiological surveillance managed to capture only 52% of all mortality associated with the COVID-19 pandemic in the cities studied. Considering the simplicity of the method, its low cost and reliability for assessing the real burden of the disease, we believe that the assessment of excess mortality associated with the COVID-19 pandemic should be widely used as a complementary tool to regular epidemiological surveillance and its use should be encouraged by WHO.

positive: Clinical Characteristics of Hospitalized Covid-19 Patients in New York City ABSTRACT Background: The coronavirus 2019 (Covid-19) pandemic is a global public health crisis, with over 1.6 million cases and 95,000 deaths worldwide. Data are needed regarding the clinical course of hospitalized patients, particularly in the United States. Methods Demographic, clinical, and outcomes data for patients admitted to five Mount Sinai Health System hospitals with confirmed Covid-19 between February 27 and April 2, 2020 were identified through institutional electronic health records. We conducted a descriptive study of patients who had in-hospital mortality or were discharged alive. Results A total of 2,199 patients with Covid-19 were hospitalized during the study period. As of April 2nd, 1,121 (51%) patients remained hospitalized, and 1,078 (49%) completed their hospital course. Of the latter, the overall mortality was 29%, and 36% required intensive care. The median age was 65 years overall and 75 years in those who died. Pre-existing conditions were present in 65% of those who died and 46% of those discharged. In those who died, the admission median lymphocyte percentage was 11.7%, D-dimer was 2.4 ug/ml, C-reactive protein was 162 mg/L, and procalcitonin was 0.44 ng/mL. In those discharged, the admission median lymphocyte percentage was 16.6%, D-dimer was 0.93 ug/ml, C-reactive protein was 79 mg/L, and procalcitonin was 0.09 ng/mL. Conclusions This is the largest and most diverse case series of hospitalized patients with Covid-19 in the United States to date. Requirement of intensive care and mortality were high. Patients who died typically had pre-existing conditions and severe perturbations in inflammatory markers.

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

positive: BCG vaccination and socioeconomic variables vs Covid-19 global features: clearing up a controversial issue Background: The Covid-19 pandemic is characterized by extreme variability in the outcome distribution and mortality rates across different countries. Some recent studies suggested an inverse correlation with BCG vaccination at population level, while others denied this hypothesis. In order to address this controversial issue, we performed a strict epidemiological study collecting data available on a global scale, considering additional variables such as cultural-political factors and adherence to other vaccination coverages. Methods: Data on 121 countries, accounting for about 99% of Covid-19 cases and deaths globally, were from John's Hopkins Coronavirus Resource Center, World Bank, International Monetary Fund, United Nations, Human Freedom Report, and BCG Atlas. Statistical models used were Ordinary Least Squares, Tobit and Fractional Probit, implemented on Stata/MP16 software. Results: Based on our results, countries where BCG vaccination is or has been mandated in the last decades have seen a drastic reduction in Covid-19 diffusion (-80% on average) and mortality (-50% on average), even controlling for relative wealth of countries and their governmental health expenditure. A significant contribution to this reduction (respectively -50% and -13% on average) was also associated to the outbreak onset during summer, suggesting a possible influence of seasonality. Other variables turned out to be associated, though to a lesser extent. Conclusions: Relying on a very large dataset and a wide array of control variables, our study confirms a strong and robust association between Covid-19 diffusion and mortality with BCG vaccination and a set socio-economic factors, opening new perspectives for clinical speculations and public health policies.

positive: Ethnicity and risk of death in patients hospitalised for COVID-19 infection: an observational cohort study in an urban catchment area Objectives. To determine if specific ethnic groups are at higher risk of mortality from COVID19 infection. Design. Retrospective cohort study Setting. University Hospitals Birmingham NHS Foundation Trust (UHB) in Birmingham, UK Participants. Patients with confirmed SARS CoV 2 infection requiring admission to UHB between 10th March 2020 and 17th April 2020 Exposure. Ethnicity Main outcome measures. Standardised Admission Ratio (SAR) and Standardised Mortality Ratio (SMR) for each ethnicity was calculated using observed sex specific age distributions of COVID19 admissions/deaths and 2011 census data for Birmingham/Solihull. Hazard Ratio (aHR) for mortality was estimated for each ethnic group with white population as reference group, using Cox proportional hazards model adjusting for age, sex, social deprivation and co-morbidities, and propensity score matching. Results. 2217 patients admitted to UHB with a proven diagnosis of COVID19 were included. 58.2% were male, 69.5% White and the majority (80.2%) had co morbidities. 18.5% were of South Asian ethnicity, and these patients were more likely to be younger (median age 61 years vs.77 years), have no co morbidities (27.8% vs. 16.6%) but a higher prevalence of diabetes mellitus (48.0% vs 28.2%) than White patients. SAR and SMR suggested more admissions and deaths in South Asian patients than would be predicted. South Asian patients were also more likely to present with severe disease despite no delay in presentation since symptom onset. South Asian ethnicity was associated with an increased risk of death; both by Cox regression (Hazard Ratio 1.66 (95%CI 1.32 to 2.10)) after adjusting for age, sex, deprivation and comorbidities and by propensity score matching, (Hazard ratio 1.68 (1.33 to 2.13), using the same factors but categorising ethnicity into South Asian or not. Conclusions. Current evidence suggests those of South Asian ethnicity may be at risk of worse COVID19 outcomes, further studies need to establish the underlying mechanistic pathways.

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: Monitoring the Covid-19 epidemics in Italy from mortality data The mortality data can be used as an alternative source to monitor the status of Covid-19. We have studied a dataset including deaths up to the fourth week of April. There is a large excess, more pronounced at the beginning of the pandemic, showing a difference in age and gender compared to the Covid-19-confirmed cases. The study indicates that mortality information can be used to provide a less biased time profile of the pandemic.

positive: Epidemiology of 2019 novel coronavirus in Jiangsu Province, China after wartime control measures: A population-level retrospective study Abstract Background A novel coronavirus emerged in China in December 2019, and human-to-human transmission was previously identified. This study aimed to compare the epidemiological characteristics in Jiangsu Province and assess whether so-called wartime control measures changed the trend of coronavirus disease 2019 (COVID-19) in the province. Methods Epidemiological data were obtained from the websites of China's Bureau of Health and the People's Government of Jiangsu Province and informal online sources from January 22 to February 20, 2020. Results The cumulative number of patients in Jiangsu Province (over 79 million people) was 613. The number of daily confirmed new cases reached the inflection point on January 31 with the maximum of 39 cases. The temporal number of patients peaked from January 29 to February 9. The proportion of confirmed cases who were residents or travelers to Hubei Province was 100.0%–58.8% before January 31 and then gradually declined. The proportion of close contacts increased gradually from January 27 to February 17. The geographical distribution of COVID-2019 cases showed that all 13 cites reported confirmed new cases after only five days of the first confirmed new case in Suzhou. The cases were concentrated in Nanjing, Suzhou, and Xuzhou with a high population density (over eight million people). The epidemiological features of COVID-2019 cases in Wuxi, Jiangsu showed that seven confirmed cases were tourists from others areas beyond Hubei Province. The longest incubation period of COVID-2019 was 19 days based on the onset of laboratory-confirmed cases. Conclusion The number of daily confirmed new cases in Jiangsu Province peaked around January 31 and then declined. This result emphasized that wartime control measures, such as putting cities on lockdown to limit population mobility in Jiangsu Province, resulted in dramatic reductions in COVID-19 cases.

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

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

positive: Improved measurement of racial/ethnic disparities in COVID-19 mortality in the United States Different estimation methods produce diverging accounts of racial/ethnic disparities in COVID-19 mortality in the United States. The Center for Disease Control's decision to present the racial/ethnic distribution of COVID-19 deaths at the state level alongside the weighted racial/ethnic distribution of the counties within each state reporting those death -- in effect, a geographic adjustment -- makes it seem that Whites have the highest death rates. Age adjustment procedures used by others, including the New York City Department of Health and Mental Hygiene, lead to the opposite conclusion that Blacks and Hispanics are dying from COVID-19 at higher rates than Whites. In this paper, we use indirect standardization methods to adjust per capita death rates for both age and geography simultaneously, avoiding the one-sided adjustment procedures currently in use. Using CDC data, we find age-and-place-adjusted COVID-19 death rates are 80% higher for Blacks and over 50% higher for Hispanics, relative to Whites, on a national level. State-specific estimates show wide variation in mortality disparities. Comparison with nonepidemic mortality reveals potential roles for preexisting health disparities and differential rates of infection and care.

positive: Estimating the real-time case fatality rate of COVID-19 using Poisson mixtures model Importance: The case fatality rate (CFR) estimation during the early stage of a disease outbreak is important, but the current estimation methods are heavily biased. Objective: We proposed using a Poisson mixtures model that utilized requires data of deaths, recoveries, and total confirmed cases recorded in each day since the outbreak of a population. Design: We collected data of deaths, recoveries, and total confirmed cases of COVID-19 in Hubei Province, China, and other parts of China up to 10th April 2020. Main Outcome(s) and Measure(s): The CFR of COVID-19 was estimated by minimizing the chi-square goodness-of-fit statistic. Results: Our proposed CRF estimates for Hubei Province became stable on 5th February in the range of 4.5% to 7.0% at which the simple CFR estimators overestimated the actual CFR by more than five folds, and that for the other parts of China (1.5% to 1.6%) were all very close to the actual CFR on the first day of CFR estimation (25th January) at which the simple CFRs were in the range between 15% and 35%. Conclusions and Relevance: Our CFR estimates for Hubei Province and other parts of China were superior to the simple CFR estimators.

positive: Estimation of Tunisia COVID-19 infected cases based on mortality rate Estimating the number of people affected by COVID-19 is crucial in deciding which public health policies to follow. The authorities in different countries carry out mortality counts. We propose that the mortality reported in each country can be used to create an index of the number of actual cases at a given time. The specificity of whether or not deaths are rapid or not by COVID-19 also affects the number of actual cases. The number of days between the declaration of illness and death varies between 12 and 18 days. For a delay of 18 days, and using an estimated mortality rate of 2%, the number of cases in April 2020 in Tunisia would be 5 580 people. The pessimistic scenario predicts 22 320 infected people, and the most optimistic predicts 744 (which is the number of reported cases on April 12, 2020). Modeling the occurrence of COVID-19 cases is critical to assess the impact of policies to prevent the spread of the virus.

positive: Comparative Global Epidemiological Investigation of SARS-CoV-2 and SARS-CoV Diseases Using Meta-MUMS Tool Through Incidence, Mortality, and Recovery Rates COVID-19 is a novel coronavirus that was reported by the world health organization in late December 2019. As an unexplained respiratory disease epidemic, which is similar to respiratory syndrome coronavirus SARS-CoV, it rapidly spread all over the world. The study aims to compare several parameters of COVID-19 and SARS-CoV infectious diseases in terms of incidence, mortality, and recovery rates. The publicly available dataset Worldometer (extracted on April 5, 2020) confirmed by WHO report was available for meta-analysis purposes using the Meta-MUMS tool. And, the reported outcomes of the analysis used a random-effects model to evaluate the event rate, and risk ratios thorough subgroup analysis forest plots. Seventeen countries for COVID-19 and eight countries of SARS infections, including COVID-19 group n = 1124243, and SARS-CoV group n = 8346, were analyzed. In this meta-analysis, a random effect model of relations of incidence, mortality, and recovery rates of COVID-19 and SARS world infections were determined. The meta-analysis and forest plots of two viral world infections showed that the incidence rate of COVID-19 infection is more than SARS infections, while recovery and mortality event rates of SARS-CoV are more than COVID-19 infection. And subgroup analysis showed that the mortality and recovery rates were higher in both SARS-CoV wand COVID-19 in comparison to incidence and mortality rates, respectively. In conclusion, the meta-analysis approach on the abovementioned dataset revealed the epidemiological and statistical analyses for comparing COVID-19 and SARS-CoV outbreaks.

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: Estimating the Global Infection Fatality Rate of COVID-19 COVID-19 has become a global pandemic, resulting in nearly three hundred thousand deaths distributed heterogeneously across countries. Estimating the infection fatality rate (IFR) has been elusive due to the presence of asymptomatic or mildly symptomatic infections and lack of testing capacity. We analyze global data to derive the IFR of COVID-19. Estimates of COVID-19 IFR in each country or locality differ due to variable sampling regimes, demographics, and healthcare resources. We present a novel statistical approach based on sampling effort and the reported case fatality rate of each country. The asymptote of this function gives the global IFR. Applying this asymptotic estimator to cumulative COVID-19 data from 139 countries reveals a global IFR of 1.04% (CI: 0.77%,1.38%). Deviation of countries' reported CFR from the estimator does not correlate with demography or per capita GDP, suggesting variation is due to differing testing regimes or reporting guidelines by country. Estimates of IFR through seroprevalence studies and point estimates from case studies or sub-sampled populations are limited by sample coverage and cannot inform a global IFR, as mortality is known to vary dramatically by age and treatment availability. Our estimated IFR aligns with many previous estimates and is the first attempt at a global estimate of COVID-19 IFR.

positive: Explaining national differences in the mortality of Covid-19: individual patient simulation model to investigate the effects of testing policy and other factors on apparent mortality. There has been extensive speculation on the apparent differences in mortality between countries reporting on the confirmed cases and deaths due to Covid-19. A number of explanations have been suggested, but there is no clear evidence about how apparent fatality rates may be expected to vary with the different testing regimes, admission policies and other variables. An individual patient simulation model was developed to address this question. Parameters and sensitivity analysis based upon recent international data sources for Covid-19 and results were averaged over 100 iterations for a simulated cohort of over 500,000 patients. Different testing regimes for Covid-19 were considered; testing admitted patients only, various rates of community testing of symptomatic cases and active contact-tracing and screening. In the base case analysis, apparent mortality ranged from 10.5% under a policy of testing only admitted patients to 0.4% with intensive contact tracing and community testing. These findings were sensitive to assumptions regarding admission rates and the rate of spread, with more selective admission policies and suppression of spread increasing the apparent mortality and the potential for apparent mortality rates to exceed 18% under some circumstances. Under all scenarios the proportion of patients tested in the community had the greatest impact on apparent mortality. Whilst differences in mortality due to health service and demographic factors cannot be excluded, the current international differences in reported mortality are all consistent with differences in practice regarding screening, community testing and admission policies.

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

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

positive: Demographic science aids in understanding the spread and fatality rates of COVID-19 Governments around the world must rapidly mobilize and make difficult policy decisions to mitigate the COVID-19 pandemic. Because deaths have been concentrated at older ages, we highlight the important role of demography, particularly how the age structure of a population may help explain differences in fatality rates across countries and how transmission unfolds. We examine the role of age structure in deaths thus far in Italy and South Korea and illustrate how the pandemic could unfold in populations with similar population sizes but different age structures, showing a dramatically higher burden of mortality in countries with older versus younger populations. This powerful interaction of demography and current age-specific mortality for COVID-19 suggests that social distancing and other policies to slow transmission should consider both the age composition of local and national contexts as well as the social connectedness of older and younger generations. We also call for countries to provide case and fatality data disaggregated by age and sex to improve real-time targeted nowcasting.

positive: Age-dependent risks of Incidence and Mortality of COVID-19 in Hubei Province and Other Parts of China New coronavirus SARS-CoV-2 poses a big challenge for global public health in early 2020. Coronavirus Disease 2019 (COVID-19) caused by the virus rapidly spreads all over the world and takes thousands of lives in just two months. It is critical to refine the incidence and mortality risks of COVID-19 for the effective management of the general public and patients in the outbreak. In this report, we investigate the incidence and mortality risks of the infection by analyzing the age composition of 5319 infected patients, 76 fatal cases, and 1,144,648 individuals of the general public in China. Our result shows a relatively low incidence risk for young people but a very high mortality risk for seniors. Notably, mortality risk could be as high as 0.48 for people older than 80 years. Furthermore, our study suggests that a good medical service can effectively reduce the mortality rate of the viral infection to 1% or less.

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

positive: Prevalence of comorbidities in cases of Middle East respiratory syndrome coronavirus: a retrospective study The Middle East respiratory syndrome coronavirus (MERS-CoV) is a life-threatening respiratory disease with a high case fatality rate; however, its risk factors remain unclear. We aimed to explore the influence of demographic factors, clinical manifestations and underlying comorbidities on mortality in MERS-CoV patients. Retrospective chart reviews were performed to identify all laboratory-confirmed cases of MERS-COV infection in Saudi Arabia that were reported to the Ministry of Health of Saudi Arabia between 23 April 2014 and 7 June 2016. Statistical analyses were conducted to assess the effect of sex, age, clinical presentation and comorbidities on mortality from MERS-CoV. A total of 281 confirmed MERS-CoV cases were identified: 167 (59.4%) patients were male and 55 (20%) died. Mortality predominantly occurred among Saudi nationals and older patients and was significantly associated with respiratory failure and shortness of breath. Of the 281 confirmed cases, 160 (56.9%) involved comorbidities, wherein diabetes mellitus, hypertension, ischemic heart disease, congestive heart failure, end-stage renal disease and chronic kidney disease were significantly associated with mortality from MERS-CoV and two or three comorbidities significantly affected the fatality rates from MERS-CoV. The findings of this study show that old age and the existence of underlying comorbidities significantly increase mortality from MERS-CoV.

positive: Las estadísticas sanitarias y la invisibilidad por sexo y de género durante la epidemia de COVID-19./ [Health statistics and invisibility by sex and gender during the COVID-19 epidemic] Reports on COVID-19 from the Spanish Health Ministry are valuable, but incomplete, with the perverse effect that the susceptibility to COVID-19 by sex is unclear. Prevalence of COVID-19 by sexes differs between countries. The trend in Spain shows an unequal pattern, initially more frequent in men, but women outnumbered them from March 31, after two weeks lockdown. Infections are more frequent in women than in men in close contact with probable/confirmed COVID-19 cases. Consistent with deaths in men, they are hospitalized more frequently than women: Significant gender differences in signs/symptoms can drive this pattern, already observed in other pathologies. In late April, excess mortality is the same in women (67%) than in men (66%). But, lack of exhaustive information on deaths from COVID-19 in non-hospitalized patients may contribute to lower notification of deaths in women. Invisibility of data by sex and gender is probably affecting negatively women with COVID -19 more than men.

positive: Age- and sex-specific total mortality impacts of the early weeks of the Covid-19 pandemic in England and Wales: Application of a Bayesian model ensemble to mortality statistics Background: The Covid-19 pandemic affects mortality directly through infection as well as through changes in the social, environmental and healthcare determinants of health. The impacts on mortality are likely to vary, in both magnitude and timing, by age and sex. Our aim was to estimate the total mortality impacts of the pandemic, by sex, age group and week. Methods: We developed an ensemble of 16 Bayesian models that probabilistically estimate the weekly number of deaths that would be expected had the Covid-19 pandemic not occurred. The models account for seasonality of death rates, medium-long-term trends in death rates, the impact of temperature on death rates, association of death rates in each week on those in preceding week(s), and the impact of bank holidays. We used data from January 2010 through mid-February 2020 (i.e., week starting 15th February 2020) to estimate the parameters of each model, which was then used to predict the number of deaths for subsequent weeks as estimates of death rates if the pandemic had not occurred. We subtracted these estimates from the actual reported number of deaths to measure the total mortality impact of the pandemic. Results: In the week that began on 21st March, the same week that a national lockdown was put in place, there was a >92% probability that there were more deaths in men and women aged [≥]45 years than would occur in the absence of the pandemic; the probability was 100% from the subsequent week. Taken over the entire period from mid-February to 8th May 2020, there were an estimated [~] 49,200 (44,700-53,300) or 43% (37-48) more deaths than would be expected had the pandemic not taken place. 22,900 (19,300-26,100) of these deaths were in females (40% (32-48) higher than if there had not been a pandemic), and 26,300 (23,800-28,700) in males (46% (40-52) higher). The largest number of excess deaths occurred among women aged >85 years (12,400; 9,300-15,300), followed by men aged >85 years (9,600; 7,800-11,300) and 75-84 years (9,000; 7,500-10,300). The cause of death assigned to the majority (37,295) of these excess deaths was Covid-19. There was nonetheless a >99.99% probability that there has been an increase in deaths assigned to other causes in those aged [≥]45 years. However, by the 8th of May, the all-cause excess mortality had become virtually equal to deaths assigned to Covid-19, and non-Covid excess deaths had diminished to close to zero, or possibly become negative, in all age-sex groups. Interpretation: The death toll of Covid-19 pandemic, in middle and older ages, is substantially larger than the number of deaths reported as a result of confirmed infection, and was visible in vital statistics when the national lockdown was put in place. When all-cause mortality is considered, the mortality impact of the pandemic on men and women is more similar than when comparing deaths assigned to Covid-19 as underlying cause of death.

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

positive: On case-fatality rate: review and hypothesis. The relationship between log cumulative number of patients (X) and that of deaths (Y) in an epidemic follows the equation logY = klogX - klogN(0), where k is a constant determining the slope and N(0) is the value of X when Y = 1. Diseases with k = 1 are Ebola hemorrhagic fever, avian influenza H5N1, cholera, and hand, foot, and mouth disease; those with k > 1 are the influenza H1N1 2009 pandemic in countries other than Mexico and the SARS epidemic in some countries; and those with k < 1 include the influenza H1N1 2009 pandemic in Mexico. Epidemics with k > 1 can be simulated by postulating two subpopulations (normal population [NP] and vulnerable population [VP]), where the epidemic proceeds at higher speed and at higher mortality in VP than in NP. Epidemics with k < 1 can be simulated by postulating coexisting high virulence virus (HVV) and low virulence virus (LVV), with the former being propagated at slower speed and with a higher mortality rate than the latter. An epidemic with k > 1 was simulated using parameters that are fractions of subpopulations NP or VP from the total population (f) and NP- or VP-specific patient multiplication (M) and mortality (D) rates. An epidemic with k < 1 was simulated using parameters that are fractions of HVV- or LVV-infected human populations (f), and HVV- or LVV-specific M and D.

positive: Epidemic update of COVID-19 in Hubei Province compared with other regions in China Abstract Aims & Background The COVID-19 outbreak spread in China and is a threat to the world. The aims of this study to help health workers better understand the epidemic of the COVID-19 and provide different control strategies toward Hubei Province and other regions in China. Methods A comprehensive search of the Chinese Center for Disease Control and Prevention official websites and announcements was performed between 20 Jan 2019 and 29 Feb 2020. The relevant data of the distribution of the infection on each reported day were obtained. Results& findings Up to 29 Feb 2020, 79,824 confirmed cases with the COVID-19 including 66,907 in Hubei Province and 12,377 in other administrative regions were reported. The SARS-COV-2 showed faster epidemic trends compared with the 2003-SARS-CoV. A total of 2,870 deaths have been reported nationwide among 79,824 confirmed cases, with a mortality of 3.6%. The mortality of the COVID-19 was significantly higher in Hubei Province than that in other regions(4.1% versus 0.84%). Since 1 Feb 2020 the number of discharged cases exceeded the number of the dead. By 29 Feb 2020, the number of discharged patients was 41,625, which exceeded the number of hospitalized patients, and the trend has further increased. Conclusions The infection of the SARS-COV-2 is spreading and increasing nationwide, and Hubei Province is the main epidemic area, with higher mortality. The outbreak is now under initial control especially in other regions outside of Hubei Province. Due to the different epidemic characteristics between Hubei Province and other regions, we should focus on different prevention and control strategies.

positive: The lower COVID-19 related mortality and incidence rates in Eastern European countries are associated with delayed start of community circulation Background: The purpose of this analysis was to assess the variations in COVID-19 related mortality and incidence rates in relation to the time differences in the commencement of virus circulation and containment measures in different countries of the European Region. Methods: The data for the current analysis (N=50 countries) were retrieved from the John Hopkins University dataset on the 7th of May 2020, with countries as study units. A piecewise regression analysis was conducted with mortality and cumulative incidence rates introduced as dependent variables and time interval (days from the 22nd of January to the date when 100 first cases were reported) as the main predictor. The country average life expectancy at birth was statistically adjusted for in the regression model. Results: Mortality and incidence were strongly and inversely intercorrelated with days from January 22, respectively -0.83 (p<.0001) and -0.73 (p<.0001). Adjusting for average life expectancy, between days 33 to 50 from the 22th of the January, the average mortality rate decreased by 30.4/million per day (95% CI: 23.2, 37.1, p<0.0001). During interval 51 to 73 days, the change in mortality was no longer statistically significant but still showed a decreasing trend. A similar relationship with time interval was found in incidence. Life expectancy was not associated with mortality rate. Conclusion: Countries in Europe which observed the earliest COVID-19 circulation, suffered the worst consequences in terms of health outcomes, specifically mortality. The drastic social isolation measures, undertaken especially in Eastern European countries, where community circulation started after March 11th, may have been timely. This may explain their significantly lower COVID-related mortality compared with the Western European countries.

positive: Deaths in SARS-Cov-2 Positive Patients in Italy: The Influence of Underlying Health Conditions on Lethality This study aims to underline the clinical characteristics of patients who died after testing positive for SARS-CoV-2 infection in one region of Italian and to evaluate the influence of underlying health conditions on the fatal outcome. A matched case-control study was designed by analyzing the data regarding positive subjects observed up to April 21, 2020. The case fatality rate was 7.9%, with a higher proportion of deaths in men than women. The specific standardized mortality ratio was 0.15—0.13 for males and 0.2 for females, showing that mortality is much lower than expected. Cardiovascular diseases, chronic lung diseases and diabetes mellitus showed a significant association with the outcome. Although the case fatality rate in Sardinia in regard to age and gender patterns seems to be similar to that for Italy as a whole, its quantitative value was far lower than the national one and possible explanations might include the genetic characteristics of the Sardinian population or the immediate closure of its borders as soon as the epidemic started. Our results highlighted that lethality is strongly dependent on the presence of multiple concomitant serious diseases. It is important to have epidemiological strategies for effective guidance on public health actions in order to improve chances of survival.

positive: Morbidity and mortality in homeless individuals, prisoners, sex workers, and individuals with substance use disorders in high-income countries: a systematic review and meta-analysis. BACKGROUND Inclusion health focuses on people in extremely poor health due to poverty, marginalisation, and multimorbidity. We aimed to review morbidity and mortality data on four overlapping populations who experience considerable social exclusion: homeless populations, individuals with substance use disorders, sex workers, and imprisoned individuals. METHODS For this systematic review and meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library for studies published between Jan 1, 2005, and Oct 1, 2015. We included only systematic reviews, meta-analyses, interventional studies, and observational studies that had morbidity and mortality outcomes, were published in English, from high-income countries, and were done in populations with a history of homelessness, imprisonment, sex work, or substance use disorder (excluding cannabis and alcohol use). Studies with only perinatal outcomes and studies of individuals with a specific health condition or those recruited from intensive care or high dependency hospital units were excluded. We screened studies using systematic review software and extracted data from published reports. Primary outcomes were measures of morbidity (prevalence or incidence) and mortality (standardised mortality ratios [SMRs] and mortality rates). Summary estimates were calculated using a random effects model. FINDINGS Our search identified 7946 articles, of which 337 studies were included for analysis. All-cause standardised mortality ratios were significantly increased in 91 (99%) of 92 extracted datapoints and were 11·86 (95% CI 10·42-13·30; I2=94·1%) in female individuals and 7·88 (7·03-8·74; I2=99·1%) in men. Summary SMR estimates for the International Classification of Diseases disease categories with two or more included datapoints were highest for deaths due to injury, poisoning, and other external causes, in both men (7·89; 95% CI 6·40-9·37; I2=98·1%) and women (18·72; 13·73-23·71; I2=91·5%). Disease prevalence was consistently raised across the following categories: infections (eg, highest reported was 90% for hepatitis C, 67 [65%] of 103 individuals for hepatitis B, and 133 [51%] of 263 individuals for latent tuberculosis infection), mental health (eg, highest reported was 9 [4%] of 227 individuals for schizophrenia), cardiovascular conditions (eg, highest reported was 32 [13%] of 247 individuals for coronary heart disease), and respiratory conditions (eg, highest reported was 9 [26%] of 35 individuals for asthma). INTERPRETATION Our study shows that homeless populations, individuals with substance use disorders, sex workers, and imprisoned individuals experience extreme health inequities across a wide range of health conditions, with the relative effect of exclusion being greater in female individuals than male individuals. The high heterogeneity between studies should be explored further using improved data collection in population subgroups. The extreme health inequity identified demands intensive cross-sectoral policy and service action to prevent exclusion and improve health outcomes in individuals who are already marginalised. FUNDING Wellcome Trust, National Institute for Health Research, NHS England, NHS Research Scotland Scottish Senior Clinical Fellowship, Medical Research Council, Chief Scientist Office, and the Central and North West London NHS Trust.

positive: Cross-Country Comparison of Case Fatality Rates of COVID-19/SARS-COV-2 OBJECTIVES: Case fatality rates (CFR) and recovery rates are important readouts during epidemics and pandemics. In this article, an international analysis was performed on the ongoing coronavirus disease 2019 (COVID-19) pandemic. METHODS: Data were retrieved from accurate databases according to the user’s guide of data sources for patient registries, CFR and recovery rates were calculated for each country. A comparison of CFR between countries with total cases ≥ 1,000 was observed for 12(th) and 23(rd) March. RESULTS: Italy’s CFR was the highest of all countries studied for both time points (12(th) March, 6.22% versus 23(rd) March, 9.26%). The data showed that even though Italy was the only European country reported on 12(rd) March, Spain and France had the highest CFR of 6.16 and 4.21%, respectively, on 23(rd) March, which was strikingly higher than the overall CFR of 3.61%. CONCLUSION: Obtaining detailed and accurate medical history from COVID-19 patients, and analyzing CFR alongside the recovery rate, may enable the identification of the highest risk areas so that efficient medical care may be provided. This may lead to the development of point-of-care tools to help clinicians in stratifying patients based on possible requirements in the level of care, to increase the probabilities of survival from COVID-19 disease.

positive: Outcomes from intensive care in patients with COVID-19: a systematic review and meta-analysis of observational studies The emergence of coronavirus disease 2019 (COVID-19) has led to high demand for intensive care services worldwide. However, the mortality of patients admitted to the Intensive Care Unit (ICU) with COVID-19 is unclear. Here, we perform a systematic review and meta-analysis, in line with PRISMA guidelines, to assess the reported ICU mortality for patients with confirmed COVID-19. We searched MEDLINE, EMBASE, PubMed and Cochrane databases up to 31 May 2020 for studies reporting ICU mortality for adult patients admitted with COVID-19. The primary outcome measure was death in intensive care as a proportion of completed intensive care unit admissions, either through discharge from the ICU or death. The definition thus excluded patients still alive on ICU. Twenty-four observational studies including 10,150 patients were identified from centres across Asia, Europe, and North America. In-ICU mortality in reported studies ranged from 0-84.6%. Seven studies reported outcome data for all patients. In the remaining studies, the proportion of patients discharged from ICU at the point of reporting varied from 24.5-97.2%. In patients with completed ICU admissions with COVID-19 infection, combined ICU mortality was 41.6% (95%CI 34.0-49.7%, I2 = 93.2%). Subgroup analysis by continent showed that mortality is broadly consistent across the globe. As the pandemic has progressed the reported mortality rates have reduced from above 50% to close to 40%. The in-ICU mortality from COVID-19 is higher than usually seen in ICU admissions with other viral pneumonias. Importantly, the mortality from completed episodes of ICU differs considerably from the crude mortality rates in some early reports.

positive: Is case fatality rate an appropriate index to represent the status of case-finding process for COVID-19 in different countries?

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

positive: Case fatality rate of novel coronavirus disease 2019 in China Abstract Background: A pandemic of coronavirus disease 2019 (COVID-19) which have caused more than 80 thousand persons infected globally is still ongoing. This study aims to calculate its case fatality rate (CFR). Methods: The method, termed as converged CFR calculation, was based on the formula of dividing the number of known deaths by the number of confirmed cases T days before, where T was an average time period from case confirmation to death. It was found that supposing a T, if it was smaller (bigger) than the true T, calculated CFRs would gradually increase (decrease) to infinitely near the true T with time went on. According to the law, the true T value could be determined by trends of daily CFRs calculated with different assumed T values (left of true T is decreasing, right is increasing). Then the CFR could be calculated. Results: CFR of COVID-19 in China except Hubei Province was 0.8% to 0.9%. So far, the CFR had accurately predicted the death numbers more than 3 weeks. CFR in Hubei of China was 5.4% by which the calculated death number corresponded with the reported number for 2 weeks. Conclusion: The method could be used for CFR calculating while pandemics are still ongoing. Dynamic monitoring of the daily CFRs trends could help outbreak-controller to have a clear vision in the timeliness of the case confirmation.

positive: Clinical Characteristics, Associated Factors, and Predicting COVID-19 Mortality Risk: A Retrospective Study in Wuhan, China INTRODUCTION: COVID-19 has become a serious global pandemic. This study investigates the clinical characteristics and the risk factors for COVID-19 mortality and establishes a novel scoring system to predict mortality risk in patients with COVID-19. METHODS: A cohort of 1,663 hospitalized patients with COVID-19 in Wuhan, China, of whom 212 died and 1,252 recovered, were included in this study. Demographic, clinical, and laboratory data on admission were collected from electronic medical records between January 14, 2020 and February 28, 2020. Clinical outcomes were collected until March 26, 2020. Multivariable logistic regression was used to explore the association between potential risk factors and COVID-19 mortality. The receiver operating characteristic curve was used to predict COVID-19 mortality risk. All analyses were conducted in April 2020. RESULTS: Multivariable regression showed that increased odds of COVID-19 mortality was associated with older age (OR=2.15, 95% CI=1.35, 3.43), male sex (OR=1.97, 95% CI=1.29, 2.99), history of diabetes (OR=2.34, 95% CI=1.45, 3.76), lymphopenia (OR=1.59, 95% CI=1.03, 2.46), and increased procalcitonin (OR=3.91, 95% CI=2.22, 6.91, per SD increase) on admission. Spline regression analysis indicated that the correlation between procalcitonin levels and COVID-19 mortality was nonlinear (p=0.0004 for nonlinearity). The area under the receiver operating curve of the COVID-19 mortality risk was 0.765 (95% CI=0.725, 0.805). CONCLUSIONS: The independent risk factors for COVID-19 mortality included older age, male sex, history of diabetes, lymphopenia, and increased procalcitonin, which could help clinicians to identify patients with poor prognosis at an earlier stage. The COVID-19 mortality risk score model may assist clinicians in reducing COVID-19-related mortality by implementing better strategies for more effective use of limited medical resources.

positive: Evaluating the massive underreporting and undertesting of COVID-19 cases in multiple global epicenters BACKGROUND: With continuous global COVID-19 outbreak, differing case numbers and mortality rates are observed. While actual case numbers appear vague, mortality numbers related to COVID-19 seem more precise. In this study, we used the mortality rate as the main indicator to evaluate the extent of underreporting and underdetection of COVID-19 cases. METHODS: We have analyzed all available data provided by the World Health Organization on the development of international COVID-19 cases and mortality numbers on March 17th, 2020. A crude case-fatality risk (cCFR) and adjusted case-fatality risk (aCFR) was calculated for China, South Korea, Japan, Italy, France, Spain, Germany, Iran and the United States. Additionally, a fold-change (FC) was derived for each country. RESULTS: The highest aCFR and FC were detected for Spain. Based on their FC values, an extremely high number of undetected COVID-19 cases was displayed in France, the United States, Italy and Spain. For these countries, our findings indicate a detection rate of only 1-2% of total actual COVID-19 cases. CONCLUSIONS: Due to limited testing capacities, mortality numbers may serve as a better indicator for COVID-19 case spread in many countries. Our data indicate that countries like France, Italy, the United States, Iran and Spain have extremely high numbers of undetected and underreported cases. Differences in testing availability and capacity, containment as well as overall health care and medical infrastructure result in significantly different mortality rates and COVID-19 case numbers for each respective country.

positive: Basic Reproduction Rate and Case Fatality Rate of COVID-19: Application of Meta-analysis Abstract Background: The outbreak of novel coronavirus disease of 2019 (COVID-19) has a wider geographical spread than other previous viruses such as Ebola and H1N1. The onset of disease and its transmission and severity has become a global concern. The policymakers have a serious concern for containing the spread and minimising the risk of death. Aim: This study aims to provide the estimates of basic reproduction rate (R0) and case fatality rate (CFR) which applies to a generalised population. Methods: A systematic review was carried out to retrieve the published estimates of reproduction rate and case fatality rate in peer-reviewed articles from PubMed MEDLINE database with defined inclusion and exclusion criteria in the period 15 December 2019 to 3 May 2020. The systematic review led to the selection of 24 articles for R0 and 17 articles for CFR. These studies used data from China and its provinces, other Asian countries such as Japan, Korea, the Philippines, and countries from other parts of the world such as Nigeria, Iran, Italy, Europe as a whole, France, Latin America, Turkey, the United Kingdom (UK), and the United States of America (USA). These selected articles gave an output of 30 counts of R0 and 29 counts of CFR which were used in a meta-analysis. A meta-analysis, with the inverse variance method, fixed- and random-effects model and the Forest plot, was performed to estimate the mean effect size or mean value of basic reproduction rate and case fatality rate. The Funnel plot is used to comprehend the publication bias. Results: We estimated the robust estimate of R0 at 3.11 (2.49-3.71) persons and the robust estimate of CFR at 2.56 (2.06-3.05) per cent after accounting for heterogeneity among studies, using the random-effects model. The regional subgroup analysis in a meta-analysis was significant for R0 but was not significant for CFR. The R0 values varied from 1.90 (1.06-2.74) persons to 3.83 (2.44-5.22) persons across the regions. The Funnel plot confirms that the selected studies are significant at one per cent level of significance. Conclusion: We found that one person is likely to infect two to three persons in the absence of any control measures, and around three per cent of the population are at the risk of death within one-and-a-half months from the onset of disease COVID-19 in a generalised population. The emergence of SARS-CoV-2 varies across regions, but the risk of death remains the same. Contribution: The estimates of R0 and CFR are independent of data from a particular region or time or a homogeneous population. These estimates are applicable to a generalised population. Therefore, the estimates of R0 and CFR are unequivocally applicable to developing country like India and its states or districts, in ambivalence. The assessments of R0 and CFR values across the developed nations make all of us aware of consequences of COVID-19, and hence these estimates are of crucial importance for government authorities for the practical implementation of strategies and control measures to contain the disease. Keywords: Covid-19, SARS-CoV-2, Reproduction Rate, Case Fatality Rate, Systematic Review, Meta-analysis

positive: Associations between ambient air pollutants exposure and case fatality rate of COVID-19: a multi-city ecological study in China. Background: Environmental factors, including air pollution, can strongly impact on spatio-temporal patterns of infectious diseases outbreak. In this study, we aimed to investigate the association and correlation between ambient air pollutants and case fatality rate (CFR) of the novel coronavirus disease (COVID-19) in China.Methods: Publicly accessible data on COVID-19 average CFR were utilized in the data analysis.The ambient daily air pollution including fine particulate matter(PM2.5), inhalable particles(PM10)and nitrogen dioxide(NO2)during the period from December 25,2019 to March 5,2020 were obtained from National Air Quality Real-time Publishing System of China.Ecological analysis was performed to explore the association and correlation between the cumulative average exposure of ambient air pollutants at different lags(14 and 28 days)and average CFR in China outside Hubei and cities in Hubei provinces via model fitting.Results:The average case fatality rate was highest in Wuhan city(4.53%) and the cumulative average exposure of ambient PM2.5, PM10 and NO2 at lag 28 days was 55.8{+/-} 12.1g/m3,66.8{+/-}9.2g/m3, 20.7{+/-}4.4g/m3, respectively in Hubei province during the study period.Ecological analysis showed that ambient PM2.5, PM10 and NO2 exposure at both lag 14 and 28 days was positively correlated with average CFR in China outside Hubei(province-level).For city-level analysis in Hubei,significant associations were only found between cumulative ambient NO2 exposure and average CFR(r=0.693 for Lag0-14,r=0.697 for Lag0-28,respectively)during the same period.Conclusions: Our findings suggest ambient PM2.5, PM10 and NO2 exposure, especially at 28 lag days,positively associated with the case fatality rate of COVID-19 in China.These results could help provide guidance for identifying potential exposure windows and preventing and controlling the epidemic.

positive: Exercising caution in correlating COVID-19 incidence and mortality rates with BCG vaccination policies due to variable rates of SARS CoV-2 testing TThe Bacillus Calmette-Guerin (BCG) vaccine provides protection against tuberculosis (TB), and is proposed to provide protection to non-TB infectious diseases. The COVID-19 outbreak results from infection with the novel coronavirus SARS-CoV-2 (CoV-2) and was declared a pandemic on March 11th, 2020. We queried whether the BCG vaccine offers protection against CoV-2 infection. We observed that countries with a current universal BCG vaccination policy have a significantly lower COVID-19 incidence than countries which never had a universal BCG policy or had one in the past. However, population density, median age, TB incidence, urban population, and, most significantly, CoV-2 testing rate, were also connected with BCG policy and could potentially confound the analysis. By limiting the analysis to countries with high CoV-2 testing rates, defined as greater than 2,500 tests per million inhabitants, these parameters were no longer statistically associated with BCG policy. When analyzing only countries with high testing rates, there was no longer a significant association between the number of COVID-19 cases per million inhabitants and the BCG vaccination policy. Although preliminary, our analyses indicate that the BCG vaccination may not offer protection against CoV-2 infection. While reporting biases may confound our observations, our findings support exercising caution in determining potential correlation between BCG vaccination and COVID-19 incidence, in part due significantly lower rates of CoV-2 testing per million inhabitants in countries with current universal BCG vaccination policy.

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: Impacto de la COVID-19 en la mortalidad de la comunidad autónoma de Castilla y León./ [Impact of COVID-19 on mortality in the autonomous community of Castilla y León (Spain)] OBJECTIVE: To estimate the increase in mortality associated with the SARS-CoV-2 coronavirus pandemic in the autonomous community of Castilla y León (Spain). METHOD: Ecological study based on population and death data for the months of March 2016 to 2020 in Castilla y León. The general and provincial standardized rates, the relative risks of the year 2020 with respect to previous years and the risks adjusted by sex, periods and province, using Poisson regression, were calculated. Trend analysis was performed using joinpoint linear regression. RESULTS: An increase in mortality was observed in March 2020 with respect to previous years, with an increase of 39% for men (relative risk [RR]: 1.39; 95% confidence interval [95%CI]: 1.32-1.47) and 28% for women (RR: 1.28; 95%CI: 1.21-1.35). The model predicts excess mortality of 775 deaths. In the trend analysis there is a significant turning point in 2019 in men, globally and for almost all provinces. The increase in mortality is general, although heterogeneous by sex, age group and province. CONCLUSIONS: Although the observed increase in mortality cannot be totally attributed to the disease, it is the best estimate we have of the real impact on deaths directly or indirectly related to it. The number of declared deaths only reaches two thirds of the increase in mortality observed.

positive: Untangling factors associated with country-specific COVID-19 incidence, mortality and case fatality rates during the first quarter of 2020 At early stages of the COVID-19 pandemic which we are experiencing, the publicly reported incidence, mortality and case fatality rates (CFR) vary significantly between countries. Here we aim to untangle factors that are associated with the differences during the first quarter of the year 2020. Number of performed COVID-19 tests has a strong correlation with country-specific incidence (p <2×10-16) and mortality rate (p = 5.1×10-8). Using multivariate linear regression we show that incidence and mortality rates correlate significantly with GDP per capita (p = 2.6×10-15 and 7.0×10-4, respectively), country-specific duration of the outbreak (2.6×10-4 and 0.0019), fraction of citizens over 65 years old (p = 0.0049 and 3.8×10-4) and level of press freedom (p = 0.021 and 0.019) which cumulatively explain 80% of variability of incidence and more than 60% of variability of mortality of the disease during the period analyzed. Country hemisphere demonstrated significant correlation only with mortality (p = 0.17 and 0.036) whereas population density (p = 0.94 and p = 0.75) and latitude (p = 0.61 and 0.059) did not reach significance in our model. Case fatality rate is shown to rise as the outbreak progresses (p = 0.028). We rank countries by COVID-19 mortality corrected for incidence and the factors that were shown to affect it, and by CFR corrected for outbreak duration, yielding very similar results. Among the countries where the outbreak started after the 15th of February and with at least 1000 registered patients during the period analyzed, the lowest corrected CFR are seen in Israel, South Africa and Chile. The ranking results should be considered with caution as they do not consider all confounding factors or data reporting biases.

positive: Estimating the infection and case fatality ratio for COVID-19 using age-adjusted data from the outbreak on the Diamond Princess cruise ship Adjusting for delay from confirmation-to-death, we estimated case and infection fatality ratios (CFR, IFR) for COVID-19 on the Diamond Princess ship as 2.3% (0.75%-5.3%) and 1.2% (0.38-2.7%). Comparing deaths onboard with expected deaths based on naive CFR estimates using China data, we estimate IFR and CFR in China to be 0.5% (95% CI: 0.2-1.2%) and 1.1% (95% CI: 0.3-2.4%) respectively.

positive: Geo temporal distribution of 1,688 Chinese healthcare workers infected with COVID-19 in severe conditions, a secondary data analysis Introduction The COVID 19 outbreak is posing an unprecedented challenge to healthcare workers. This study analyzes the geo temporal effects on disease severity for the 1,688 Chinese healthcare workers infected with COVID 19. Method Using the descriptive results recently reported by the Chinese CDC, we compare the percentage of infected healthcare workers in severe conditions over time and across three areas in China, and the fatality rate of infected healthcare workers with all the infected individuals in China aged 22 to 59 years. Results Among the infected Chinese healthcare workers whose symptoms onset appeared during the same ten day period, the percentage of those in severe conditions decreased statistical significantly from 19.7% (Jan 11 to 20) to 14.4% (Jan 21 to 31) to 8.7% (Feb 1 to 11). Across the country, there was also a significant difference in the disease severity among patients symptoms onset during the same period, with Wuhan being the most severe (17%), followed by Hubei Province (10.4%), and the rest of China (7.0%). The case fatality rate for the 1,688 infected Chinese healthcare workers was significantly lower than that for the 29,798 infected patients aged 20 to 59 years 0.3% (5/1,688) vs. 0.65% (193/29,798), respectively. Conclusion The disease severity improved considerably over a short period of time in China. The more severe conditions in Wuhan compared to the rest of the country may be attributable to the draconian lockdown. The clinical outcomes of infected Chinese healthcare workers may represent a more accurate estimation of the severity of COVID 19 for those who have access to quality healthcare.

positive: COVID-19 in Colombia endpoints. Are we different, like Europe? The infection by the new coronavirus (SARS-CoV-2) has taken the dimension of a pandemic, affecting more than 160 countries in a few weeks. In Colombia, despite the implementation of the rules established by the national government, exists an elevate concern both for mortality and for the limited capacity of the health system to respond effectively to the needs of patients infected. For Colombia, assuming a case fatality rate among people infected with SARS-CoV-2 of 0.6% (average data from the information reported for Latin American countries for March 18) (Table 1), the number of deaths, in one or two weeks, could be 16 and 243, respectively. These estimates differ markedly from those documented in countries such as Spain and Italy, in which COVID-19 case fatality rates exceed 8% (case of Italy) and from the percentage of patients who have required intensive care, which has ranged from 9% to 11% of patients in Mediterranean European countries. These differences could be explained due to: a) the percentage of the population at risk (individuals older than 60 years); b) a higher epidemiological exposure to viral respiratory infections associated with more frequent exposure to them, due to geographic and climatic conditions; c) less spread of the virus by location in the tropical zone; and d) earlier preventive measures to contain the spread of SARS-CoV-2 infection. Therefore, it is possible to establish that the situation in this country will be different from in European Mediterranean and that Colombia could have different endpoints from Spain and Italy.

positive: Global between-countries variance in SARS-CoV-2 mortality is driven by reported prevalence, age distribution, and case detection rate Objective: To explain the global between-countries variance in number of deaths per million citizens (nDpm) and case fatality rate (CFR) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Design: Systematic analysis. Data sources: Worldometer, European Centre for Disease Prevention and Control, United Nations Main outcome measures: The explanators of nDpm and CFR were mathematically hypothesised and tested on publicly-available data from 88 countries with linear regression models on May 1st 2020. The derived explanators - age-adjusted infection fatality rate (IFRadj) and case detection rate (CDR) - were estimated for each country based on a SARS-CoV-2 model of China. The accuracy and agreement of the models with observed data was assessed with R2 and Bland-Altman plots, respectively. Sensitivity analyses involved removal of outliers and testing the models at five retrospective and two prospective time points. Results: Globally, IFRadj estimates varied between countries, ranging from below 0.2% in the youngest nations, to above 1.3% in Portugal, Greece, Italy, and Japan. The median estimated global CDR of SARS-CoV-2 infections on April 16th 2020 was 12.9%, suggesting that most of the countries have a much higher number of cases than reported. At least 93% and up to 99% of the variance in nDpm was explained by reported prevalence expressed as cases per million citizens (nCpm), IFRadj, and CDR. IFRadj and CDR accounted for up to 97% of the variance in CFR, but this model was less reliable than the nDpm model, being sensitive to outliers (R2 as low as 67.5%). Conclusions: The current differences in SARS-CoV-2 mortality between countries are driven mainly by reported prevalence of infections, age distribution, and CDR. The nDpm might be a more stable estimate than CFR in comparing mortality burden between countries.

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: Time-to-Death approach in revealing Chronicity and Severity of COVID-19 across the World BACKGROUND: The outbreak of coronavirus disease, 2019 (COVID-19), which started from Wuhan, China, in late 2019, have spread worldwide. A total of 5,91,971 cases and 2,70,90 deaths were registered till 28th March, 2020. We aimed to predict the impact of duration of exposure to COVID-19 on the mortality rates increment. METHODS: In the present study, data on COVID-19 infected top seven countries viz., Germany, China, France, United Kingdom, Iran, Italy and Spain, and World as a whole, were used for modeling. The analytical procedure of generalized linear model followed by Gompertz link function was used to predict the impact lethal duration of exposure on the mortality rates. FINDINGS: Of the selected countries and World as whole, the projection based on 21st March, 2020 cases, suggest that a total (95% Cl) of 76 (65-151) days of exposure in Germany, mortality rate will increase by 5 times to 1%. In countries like France and United Kingdom, our projection suggests that additional exposure of 48 days and 7 days, respectively, will raise the mortality rates to10%. Regarding Iran, Italy and Spain, mortality rate will rise to 10% with an additional 3-10 days of exposure. World's mortality rates will continue increase by 1% in every three weeks. The predicted interval of lethal duration corresponding to each country has found to be consistent with the mortality rates observed on 28th March, 2020. CONCLUSION: The prediction of lethal duration was found to have apparently effective in predicting mortality, and shows concordance with prevailing rates. In absence of any vaccine against COVID-19 infection, the present study adds information about the quantum of the severity and time elapsed to death will help the Government to take necessary and appropriate steps to control this pandemic.

positive: Association between ABO blood groups and clinical outcome of coronavirus disease 2019: Evidence from two cohorts Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the third most common coronavirus that causes large-scale infections worldwide. The correlations between pathogen susceptibility and blood type distribution have attracted attention decades ago. The current retrospective study aimed to examine the correlation between blood type distribution and SARS-CoV-2 infection, progression, and prognosis in patients with coronavirus disease 2019 (COVID-19). With 265 patients from multiple medical centers and two established cohorts, we found that the blood type A population was more sensitive to SARS-CoV-2. Moreover, the blood type distribution was not relevant to acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), and mortality in COVID-19 patients. These findings are indicative of coping with the great threat since it probed the relationship between blood types and ARDS, AKI, and mortality, in addition to susceptibility in COVID-19 patients.

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

positive: Racial disparity in Covid-19 mortality rates - A plausible explanation

positive: Factors associated with increased all-cause mortality during the COVID-19 pandemic in Italy Abstract Background The number of excess deaths in February-March 2020 in Italy, in comparison to the previous years, was considerably higher than recorded COVID19-related deaths. The present study is aimed at exploring the associations of excess mortality with some indices related to the epidemic and its management. Methods Data on all-cause mortality from February 20th to March 31st, in years from 2015 to 2020, and demographic, socioeconomic and healthcare organization data of each Italian region were obtained from Italian Institute of Statistics. Non-COVID19-Imputed Excess Mortality (NCIEM) was calculated as the difference between excess 2020 mortality and reported COVID19 mortality. The association of NCIEM with the rate of COVID-19 cases, COVID-19 mortality, and other potential moderators was assessed using linear regression models. Results The nationwide number of excess deaths, COVID-19 deaths was 26,701 and 13,710, respectively, with a difference of 12,991. NCIEM in different Regions showed a direct correlation with COVID-19 mortality (r2 = 0.61, p < 0.001) and total cases (r2 = 0.30, p = 0.012), and an inverse correlation with cases/total tests ratio (r2 = 0.49, p = 0.001). Direct correlations were also found with the proportion of institutionalized elderly, whereas inverse correlations were observed with prevalence of diabetes, cardiovascular mortality, and density of general practitioners. Conclusions The impact of the COVID19 epidemic on all-cause mortality is considerably greater than that indicated by official counts of victims. Limited testing capacity and causes of death other than COVID19 could contribute to the increase in overall mortality rates.

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: Worldwide differences in COVID-19-related mortality. Mortality statistics due to COVID-19 worldwide are compared, by adjusting for the size of the population and the stage of the pandemic. Data from the European Centre for Disease Control and Prevention, and Our World in Data websites were used. Analyses are based on number of deaths per one million inhabitants. In order to account for the stage of the pandemic, the baseline date was defined as the day in which the 10th death was reported. The analyses included 78 countries and territories which reported 10 or more deaths by April 9. On day 10, India had 0.06 deaths per million, Belgium had 30.46 and San Marino 618.78. On day 20, India had 0.27 deaths per million, China had 0.71 and Spain 139.62. On day 30, four Asian countries had the lowest mortality figures, whereas eight European countries had the highest ones. In Italy and Spain, mortality on day 40 was greater than 250 per million, whereas in China and South Korea, mortality was below 4 per million. Mortality on day 10 was moderately correlated with life expectancy, but not with population density. Asian countries presented much lower mortality figures as compared to European ones. Life expectancy was found to be correlated with mortality.

positive: 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.

positive: Association of Poor Housing Conditions with COVID-19 Incidence and Mortality Across US Counties Objective: Poor housing conditions have been linked with worse health outcomes and infectious spread in communities but its relationship with incidence and mortality of COVID19 is unknown. Therefore, we undertook this study to determine the association between poor housing condition and COVID19 incidence and mortality in US counties. Methods: We conducted cross sectional analysis of county level data from the US Centers for Disease Control, US Census Bureau and John Hopkins Coronavirus Resource Center for 3141 US counties. The exposure of interest was percentage of households with poor housing conditions (one or more of: overcrowding, high housing cost, incomplete kitchen facilities, or incomplete plumbing facilities). Outcomes were incidence rate ratios (IRR) and mortality rate ratios (MRR) of COVID19 across US counties through 4/21/2020. Multilevel generalized linear modeling was utilized with adjustment for population density and county characteristics including demographics, income, education, prevalence of medical comorbidities, access to healthcare insurance and emergency rooms, and state level COVID19 test density. Results: Across 3135 US counties, the mean percentage of households with poor housing conditions was 14.2% (range 2.7%, 60.2%). The mean (SD) incidence and mortality of COVID19 were 255.68 (2877.03) cases and 13.90 (272.22) deaths per county, respectively. In the fully adjusted models, with each 5% increase in percent households with poor housing conditions, there was a 50% higher risk of COVID19 incidence (IRR 1.50, 95% CI: 1.38,1.62) and a 42% higher risk of COVID19 mortality (MRR 1.42, 95% CI: 1.25,1.61). Results remained similar using earlier timepoints (3/31/2020 and 4/10/2020). Conclusions and Relevance: Counties with a higher percentage of households with poor housing had higher incidence of, and mortality associated with, COVID19. These findings suggest targeted health policies to support individuals living in poor housing conditions should be considered in further efforts to mitigate adverse outcomes associated with COVID19.

positive: World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19) Abstract An unprecedented outbreak of pneumonia of unknown aetiology in Wuhan City, Hubei province in China emerged in December 2019. A novel coronavirus was identified as the causative agent and was subsequently termed COVID-19 by the World Health Organization (WHO). Considered a relative of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), COVID-19 is caused by a betacoronavirus named SARS-CoV-2 that affects the lower respiratory tract and manifests as pneumonia in humans. Despite rigorous global containment and quarantine efforts, the incidence of COVID-19 continues to rise, with 90,870 laboratory-confirmed cases and over 3,000 deaths worldwide. In response to this global outbreak, we summarise the current state of knowledge surrounding COVID-19.

positive: Regional outcomes of severe acute respiratory syndrome coronavirus 2 infection in hospitalised patients with haematological malignancy OBJECTIVES: We sought to characterise the outcomes of patients with haematological malignancy and SARS‐CoV‐2 infection in hospital in our regional network of 7 hospitals. METHODS: Consecutive hospitalised patients with haematological malignancy and SARS‐CoV‐2 infection were identified from 01/03/2020 to 06/05/2020. Outcomes were categorised as death, resolved, or ongoing. The primary outcome was preliminary case fatality rate (pCFR), defined as the number of cases resulting in death as a proportion of all diagnosed cases. Analysis was primarily descriptive. RESULTS: 66 Patients were included, overall pCFR was 51.5%. Patients ≥ 70 years accounted for the majority of hospitalised cases (42, 63%) and fatalities (25, 74%). Mortality was similar between females (52%) and males (51%). Immunosuppressive or cytotoxic treatment within 3 months of the diagnosis of SARS‐CoV‐2 infection was associated with a significantly higher preliminary Case Fatality Rate (pCFR) of 70%, compared with 28% in those not on active treatment (P = 0.0013, 2 proportions z‐test). CONCLUSIONS: Mortality rates in patients with haematological malignancy and SARS‐CoV‐2 infection in hospital are high supporting measures to minimise the risk of infection in this population.

positive: 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.

positive: Clinical outcomes of 402 patients with COVID-2019 from a single center in Wuhan, China The outbreak of SARS-CoV-2 has become a pandemic with significant mortality. Published studies describing clinical characteristics of the disease contain small cohorts from individual centers or larger series consisting of mixed series from multiple different hospitals. We report here analyses of mortality and disease severity among 402 patients from a single hospital. The cohort includes 297 patients with confirmed and 105 with clinical diagnosis. The latter group consists of cases with inconclusive nucleic acid test but meeting the criteria for clinical diagnosis. Data are compared between genders and among different age groups. The overall case fatality is 5.2%. However, age at 70 years or older is associated with a significantly higher mortality (17.8%) and higher rate of severe and critical illness (57.5%). Case fatality is 8% in patients 50 years of age or older, and 1.2% in those younger than 50 years. In addition, case fatality is 7.6% in male patients, as opposed to 2.9% in females, demonstrating a clear gender difference. This article is protected by copyright. All rights reserved.

positive: Risk Factors for Mortality of COVID-19 Patients Background: Lethality rates of COVID-19 are so different between countries and continents. This lethality seems to be very low in Africa and Asia, but exceedingly high in western Europe and North America. Many factors could have a role in this disparity such as comorbidities. Advanced age, obesity, cardiovascular disease, diabetes and cancer were the most frequently cited in the reported COVID-19 data. The main objective was to analyse the association between the COVID-19 mortality and the mentioned factors in 164 countries. Methods: The Data of COVID-19 deaths, latitude degrees, population age distribution, cardiovascular diseases, obesity, diabetes and cancer were extracted from different online sources. For the statistical analysis, we used Spearman to measure the correlation coefficient between numbers of deaths and the mentioned factors until June 29, 2020. Results: The correlation between COVID-19 mortality and latitude, high age, obesity, CVD and number of cancer patients per 100,000 is significant at 0.01 level with r = 0.489, r=0.511, r=0.489, r=0.561 and r=0.536 respectively. The correlation between the number of deaths and diabetes is less strong than the previous ones, and the correlation coefficient is r= 0.154. Conclusion: The great lethality of COVID-19 in western Europe and North America can be explained in part by the highest of age, cancer and CVD percentage in these regions. It seems also plausible that the increased obesity in the USA and vitamin D deficiency in Europe may contribute to increasing the number of COVID-19 deaths.

positive: Risk Factors for Mortality in Patients with COVID-19 in New York City BACKGROUND: New York City emerged as an epicenter of the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVE: To describe the clinical characteristics and risk factors associated with mortality in a large patient population in the USA. DESIGN: Retrospective cohort study. PARTICIPANTS: 6493 patients who had laboratory-confirmed COVID-19 with clinical outcomes between March 13 and April 17, 2020, who were seen in one of the 8 hospitals and/or over 400 ambulatory practices in the New York City metropolitan area MAIN MEASURES: Clinical characteristics and risk factors associated with in-hospital mortality. KEY RESULTS: A total of 858 of 6493 (13.2%) patients in our total cohort died: 52/2785 (1.9%) ambulatory patients and 806/3708 (21.7%) hospitalized patients. Cox proportional hazard regression modeling showed an increased risk of in-hospital mortality associated with age older than 50 years (hazard ratio [HR] 2.34, CI 1.47–3.71), systolic blood pressure less than 90 mmHg (HR 1.38, CI 1.06–1.80), a respiratory rate greater than 24 per min (HR 1.43, CI 1.13–1.83), peripheral oxygen saturation less than 92% (HR 2.12, CI 1.56–2.88), estimated glomerular filtration rate less than 60 mL/min/1.73m(2) (HR 1.80, CI 1.60–2.02), IL-6 greater than 100 pg/mL (HR 1.50, CI 1.12–2.03), D-dimer greater than 2 mcg/mL (HR 1.19, CI 1.02–1.39), and troponin greater than 0.03 ng/mL (HR 1.40, CI 1.23–1.62). Decreased risk of in-hospital mortality was associated with female sex (HR 0.84, CI 0.77–0.90), African American race (HR 0.78 CI 0.65–0.95), and hydroxychloroquine use (HR 0.53, CI 0.41–0.67). CONCLUSIONS: Among patients with COVID-19, older age, male sex, hypotension, tachypnea, hypoxia, impaired renal function, elevated D-dimer, and elevated troponin were associated with increased in-hospital mortality and hydroxychloroquine use was associated with decreased in-hospital mortality. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11606-020-05983-z) contains supplementary material, which is available to authorized users.

positive: Estimating The Infection Fatality Rate Among Symptomatic COVID-19 Cases In The United States Knowing the infection fatality rate (IFR) of novel coronavirus (SARS-CoV-2) infections is essential for the fight against the coronavirus disease (COVID-19) pandemic. Using data through April 20, 2020, I fit a statistical model to COVID-19 case fatality rates over time at the US county level to estimate the COVID-19 IFR among symptomatic cases (IFR-S) as time goes to infinity. The IFR-S in the US was estimated to be 1.3 percent. County-specific rates varied from 0.5 percent to 3.6 percent. The overall IFR for COVID-19 should be lower when I account for cases where patients are asymptomatic and recover without symptoms. When used with other estimating approaches, my model and estimates can help disease and policy modelers obtain more accurate predictions for the epidemiology of the disease and the impact of various policy levers to contain the pandemic. The model could also be used with future pandemics to get an early sense of the magnitude of symptomatic infection at the population level before other direct estimates are available. Substantial variation across patient demographics likely exists and should be the focus of future studies.

positive: Wuhan and Hubei COVID-19 mortality analysis reveals the critical role of timely supply of medical resources • COVID-19 mortality rates in Wuhan and Hubei decay exponentially. • COVID-19 mortality rates outside Hubei and Wuhan are nearly constant. • COVID-19 recovery rates in Wuhan and Hubei grow exponentially. • Over 40,000 aided health workers help Hubei to effectively treat patients. • Newly supplied beds allow over 38,000 patients in Wuhan to be treated in hospitals.

positive: Covid-19 transmission, outcome and associated risk factors in cancer patients at the first month of the pandemic in a Spanish hospital in Madrid BACKGROUND: There are no large reported series determining the Covid-19 cancer patient’s characteristics. We determine whether differences exist in cumulative incidence and mortality of Covid-19 infection between cancer patients and general population in Madrid. MATERIAL AND METHODS: We reviewed 1069 medical records of all cancer patients admitted at Oncology department between Feb 1 and April 7, 2020. We described Covid-19 cumulative incidence, treatment outcome, mortality, and associated risk factors. RESULTS: We detected 45/1069 Covid-19 diagnoses in cancer patients vs 42,450/6,662,000 in total population (p < 0.00001). Mortality rate: 19/45 cancer patients vs 5586/42,450 (p = 0.0001). Mortality was associated with older median age, adjusted by staging and histology (74 vs 63.5 years old, OR 1.06, p = 0.03). Patients who combined hydroxychloroquine and azithromycin presented 3/18 deaths, regardless of age, staging, histology, cancer treatment and comorbidities (OR 0.02, p = 0.03). CONCLUSION: Cancer patients are vulnerable to Covid-19 with an increase in complications. Combined hydroxychloroquine and azithromycin is presented as a good treatment option.

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: Global COVID-19 fatality analysis reveals Hubei-like countries potentially with severe outbreaks 1. CFR in Iran in the early stage of the outbreak is the highest among all the countries 2. CFRs in the USA and Italy are similar to that in Hubei Province in the early stage of the outbreak. 3. CFRs in South Korea are similar to that outside Hubei (in China), indicating less severe outbreaks therein. 4. Our findings highlight the potential severity of outbreaks globally, particular in the USA.

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

positive: 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: Excess mortality and potential undercounting of COVID-19 deaths by demographic group in Ohio Background: There are significant gaps in our understanding of the mortality effects of COVID-19 due to evolving diagnosis criteria, shortages of testing supplies, and challenges faced by physicians in treating patients in crisis environments. Accurate information on the number of deaths caused by COVID-19, both population wide and for demographic subgroups, is vital for policy makers and health care providers. Methods: We performed a retrospective study of weekly data for Ohio, a large American state. To estimate expected mortality in 2020 we employed data from 2010 through 2019, adjusted for secular trends and seasonality. We estimated excess mortality as the number of observed deaths less the number of expected deaths. We conducted the analysis for the entire population and by gender, race, age, and county of residence. Findings: We estimated 1,485 (95% CI 680-2,345) excess all-cause deaths in Ohio from March 15, 2020 through May 23, 2020. When limited to deaths due to natural causes, the estimated excess number of deaths increased to 2,504 (95% CI 1,633-3,221), reflecting the countervailing effect of a decrease in deaths due to external causes. While the largest number excess of deaths was observed in the 80+ age group, excess deaths comprised 45.3% (95% CI 21.8-60.9) of observed deaths in the groups corresponding to ages between 20 and 49 years old. Our estimate of 729 (95% CI 355-966) excess deaths for this group substantially exceeds the reported number of COVID-19 deaths of 51. We found elevated excess deaths for older individuals, blacks, and males. Interpretation: Our methodology addressed some of the challenges of estimating the number of deaths caused by COVID-19. Our finding of high proportional levels of excess deaths among younger age groups suggests that increases in the infection rates for this cohort may have a greater mortality impact than expected. Funding: None.

positive: Age-Dependent Risks of Incidence and Mortality of COVID-19 in Hubei Province and Other Parts of China The new coronavirus SARS-CoV-2 pandemic of early 2020 poses an enormous challenge to global public health. Coronavirus Disease 2019 (COVID-19) caused by the virus has spread rapidly throughout the world, taking thousands of lives in just over 2 months. It is critical to refine the incidence and mortality risks of COVID-19 for the effective management of the general public and patients during the outbreak. In this report, we investigate the incidence and mortality risks of the infection by analyzing the age composition of 5,319 infected patients, 76 fatal cases, and 1,144,648 individuals of the general public in China. Our results show a relatively low incidence risk for young people but a very high mortality risk for seniors. Notably, mortality risk could be as high as 0.48 for people older than 80 years. Furthermore, our study suggests that a good medical service can effectively reduce the mortality rate of the viral infection to 1% or less.

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

positive: Coronavirus disease 2019 and gender-related mortality in European countries: A meta-analysis OBJECTIVE: To examine mortality rates related to coronavirus disease 2019 (COVID-19) by gender among European countries. METHODS: PubMed, preprint medRxiv and bioRxiv repositories, and Google were searched for the terms COVID-19, mortality rates, gender, and Europe. Only Google provided a website with appropriate information. COVID-19 cases and deaths from European countries were extracted by gender from the Global Health 50/50 repository up to May 23, 2020. Extracted data included country, the total number of COVID-19 cases and the number of related deaths by gender. Random effects models with the inverse variance method were used for meta-analyses. Results are reported as death risk ratios (RRs). RESULTS: We identified information from 23 European countries that reported separately by gender mortality rates related to COVID-19. The sample comprised 484,919 men and 605,229 women positive for COVID-19. The mortality rate was significantly higher in men than in women (risk ratio = 1.60, 95% confidence interval [CI] 1.53, 1.68). The trend was similar when countries reporting < 5,000, or < 10,000 cases were excluded from the analysis (RR = 1.60, 95% CI 1.52, 1.69 and RR = 1.68; CI 1.62, 1.76, respectively). CONCLUSION: In Europe, the new zoonotic coronavirus causes significantly more deaths in men than in women.

positive: Excess all-cause mortality during the COVID-19 pandemic in Europe – preliminary pooled estimates from the EuroMOMO network, March to April 2020 A remarkable excess mortality has coincided with the COVID-19 pandemic in Europe. We present preliminary pooled estimates of all-cause mortality for 24 European countries/federal states participating in the European monitoring of excess mortality for public health action (EuroMOMO) network, for the period March–April 2020. Excess mortality particularly affected ≥ 65 year olds (91% of all excess deaths), but also 45–64 (8%) and 15–44 year olds (1%). No excess mortality was observed in 0–14 year olds.

positive: Mortality Attributed to COVID-19 in High-Altitude Populations Background: Since partial oxygen pressure decreases as altitude increases, environmental hypoxia could worsen COVID-19 patient's hypoxemia. We compared COVID-19 mortality at different altitudes. Methods: Retrospective analysis of population-level data on COVID-19 deaths in the U.S. (1,016 counties) and Mexico (567 municipalities). Mixed-model Poisson regression analysis of the association between altitude and COVID-19 mortality using individual-level data from 40,168 Mexican subjects with COVID-19, adjusting for multiple covariates. Results: Between January 20 and April 13, 2020, mortality rates were higher in U.S. counties located at [≥]2,000 m elevation vs. those located below 1,500 m (12.3 vs. 3.2 per 100,000; P<0.001). In Mexico, between March 13 and May 13, 2020, mortality rates were higher in municipalities located at [≥]2,000 m vs. <1,500 m (5.3 vs. 3.9 per 100,000; P<0.001). Among Mexican subjects <65 years old, the risk of death was 36% higher in those living at [≥]2,000 m vs. <1,500 m (adjusted incidence rate ratio: 1.36; 95% CI, 1.05-1.78; P=0.022). Among men, the risk of death was 31% higher at [≥]2,000 m vs. <1,500 m (adjusted IRR: 1.31; 95% CI, 1.03-1.66; P=0.025). No association was found among women. Conclusion: Altitude is associated with COVID-19 mortality in men younger than 65 years.

positive: Assessing racial and ethnic disparities using a COVID-19 outcomes continuum for New York State PURPOSE: Heightened COVID-19 mortality among Black non-Hispanic and Hispanic communities (relative to white non-Hispanic) is well established. This study aims to estimate the relative contributions to fatality disparities in terms of differences in SARS-CoV-2 infections, diagnoses, and disease severity. METHODS: We constructed COVID-19 outcome continua (similar to the HIV care continuum) for white non-Hispanic, Black non-Hispanic, and Hispanic adults in New York State. For each stage in the COVID-19 outcome continua (population, infection experience, diagnosis, hospitalization, fatality), we synthesized the most recent publicly-available data. We described each continuum using overall percentages, fatality rates, and relative changes between stages, with comparisons between race and ethnicity using risk ratios. RESULTS: Estimated per-population COVID-19 fatality rates were 0.03%, 0.18%, and 0.12% for white non-Hispanic, Black non-Hispanic, and Hispanic adults. The 3.48-fold disparity for Hispanic, relative to white, communities was explained by differences in infection-experience, whereas the 5.38-fold disparity for non-Hispanic Black, relative to white, communities was primarily driven by differences in both infection-experience and in the need for hospitalization, given infection. CONCLUSIONS: These findings suggest the most impactful stages upon which to intervene with programs and policies to build COVID-19 health equity.

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: 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.

positive: Besides population age structure, health and other demographic factors can contribute to understanding the COVID-19 burden

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

positive: Relationship Between Blood Group and Risk of Infection and Death in COVID-19: a live Meta-Analysis Introduction: The relationship between ABO blood group and the incidence of COVID-19 infection and death has been investigated in several studies. The reported results were controversial, so the objective of the present study is to assess the relationship between different blood groups and the onset and mortality of COVID-19 infection using meta-analysis method. Methods: We searched the databases using appropriate MeSH terms. We screened articles on the basis of titles, abstracts, and full texts and the articles that met the inclusion criteria were selected. Quality assessment was done with the Newcastle-Ottawa Scale checklist. The estimated frequency of COVID-19 infection and death in terms of ABO blood group and the overall estimate of the odd ratio between blood group with COVID-19 infection and death was done with 95% confidence interval. Results: The pooled frequency of blood groups A, B, O, and AB among COVID-19 infected individuals was estimated as 36.22%, 24.99%, 29.67%, and 9.29% respectively. The frequency of blood groups A, B, O, and AB among the dead cases due to COVID-19 infection was estimated as 40%, 23%, 29%, and 8% respectively. The odd ratio of COVID-19 infection for blood group A versus the other blood groups was estimated 1.16 (CI 95%: 1.02-1.33). The corresponding figures for blood groups O and AB versus other blood groups were estimated as 0.73 (CI 95%: 0.60-0.88) and 1.25(CI 95%: 0.84-1.86) respectively. Conclusion: This meta-analysis showed that individuals with blood group A are at higher risk for COVID-19 infection while those with blood group O are at lower risk. Although the odds ratio of death for AB blood group was non-significant, it was considerable.

positive: Hypertension and its severity or mortality in Coronavirus Disease 2019 (COVID-19): a pooled analysis. INTRODUCTION As the coronavirus disease 2019 (COVID-19) outbreak, identification of clinical predictors of severe or fatal disease are necessary to enable risk stratification and optimize allocation of limited resources. Hypertension has been widely reported to be associated with increase disease severity, however, other studies have reported different findings. OBJECTIVES To evaluate the association of hypertension and severe and fatal COVID-19. PATIENTS AND METHODS Scopus, Medline, and Web of Science was performed to identify studies reporting the rate of hypertension in COVID-19 patients with severe or non-severe disease or among survivors and non-survivors. The obtained data was pooled into a meta-analysis to calculate odds ratio (OR) with 95% confidence intervals (95%CI). RESULTS Hypertension was associated with a nearly 2.5-fold significantly increased risk of severe COVID-19 disease (OR: 2.49 [95%CI: 1.98-3.12] I2=24%), as well as with a similarly significant higher risk of mortality (OR: 2.42 [95%CI: 1.51-3.90] I2=0%). In meta-regression, a significant correlation was observed with an increase in mean age of patients with severe COVID-19 associated with increased log odds of hypertension and severity (p=0.03). CONCLUSIONS The results of this pooled analysis of the current scientific literature would suggest that hypertension may be associated with an up to 2.5-fold higher risk of severe and fatal COVID-19, especially among older individuals.

positive: El SARS-CoV-2, una nueva zoonosis pandémica que amenaza al mundo On December 31, 2019, an outbreak of pneumonia of unknown etiology was detected in the city of Wuhan (China). A week later, a new coronavirus was isolated in these patients, initially designated as 2019-nCoV and subsequently SARS-CoV-2. This is a new virus that is much closer genetically to the coronavirus of bats than to human SARS. The new virus infects and replicates in the lung parenchyma pneumocytes and macrophages in which the ACE-2 cell receptor resides. He has now infected many more people than his predecessors (> 85,000). From the clinical point of view, those infected have an average age of 55 years; the main symptoms are fever, dry cough, lymphopenia, dyspnea, and pneumonia in its severe form. The overall lethality rate is 2-3% in China and 0.1% in cases detected outside of this country. The incubation period has been set at about 3 days (0-24 days). There are no specific antivirals or vaccines.

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

positive: Estimated inequities in COVID-19 infection fatality rates by ethnicity for Aotearoa New Zealand There is limited evidence as to how COVID-19 infection fatality rates (IFR) may vary by ethnicity. We combine demographic and health data for ethnic groupings in Aotearoa New Zealand with international data on IFR for different age groups to estimate inequities in IFR by ethnicity. We find that, if age is the dominant factor determining IFR, estimated IFR for Māori is around 50% higher than non-Māori. If underlying health conditions are more important than age per se, then estimated IFR for Māori is more than 2.5 times that of New Zealand European, and estimated IFR for Pasifika is almost double that of New Zealand European. IFRs for Māori and Pasifika are likely to be increased above these estimates by racism within the healthcare system and other inequities not reflected in official data. IFR does not account for differences among ethnicities in COVID-19 incidence, which could be higher in Māori and Pasifika as a result of crowded housing and higher inter-generational contact rates. These factors should be included in future disease incidence modelling. The communities at the highest risk will be those with elderly populations, and Māori and Pasifika communities, where the compounded effects of underlying health conditions, socioeconomic disadvantage, and structural racism result in imbricated risk of contracting COVID-19, becoming unwell, and death.

positive: Inequalities in COVID19 mortality related to ethnicity and socioeconomic deprivation Background: Initial reports suggest that ethnic minorities may be experiencing more severe clinical outcomes of coronavirus disease 2019 (COVID19) infections. We therefore assessed the association between ethnic composition, income deprivation and COVID19 mortality rates in England. Methods: We performed a cross-sectional ecological analysis across upper tier local authorities in England. We assessed the association between the proportion of the population from Black, Asian and Minority Ethnic (BAME) backgrounds, income deprivation and COVID19 mortality rates using negative binomial regression models, whilst adjusting for population density, proportion of the population aged 50-79 and 80+ years, and the duration of the epidemic in each area. Findings: Local authorities with a greater proportion of residents from ethnic minority backgrounds had statistically significantly higher COVID19 mortality rates, as did local authorities with a greater proportion of residents experiencing deprivation relating to low income. After adjusting for income deprivation and other covariates, each percentage point increase in the proportion of the population from BAME backgrounds was associated with a 1% increase in the COVID19 mortality rate [IRR=1.01, 95%CI 1.01 to 1.02]. Each percentage point increase in the proportion of the population experiencing income deprivation was associated with a 2% increase in the COVID19 mortality rate [IRR=1.02, 95%CI 1.01 to 1.04]. Interpretation: This study provides evidence that both income deprivation and ethnicity are associated with greater COVID19 mortality. To reduce these inequalities governments need to target effective control measures at these disadvantaged communities, ensuring investment of resources reflects their greater need and vulnerability to the pandemic. Funding: National Institute of Health Research; Medical Research Council

positive: [The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China]. Objective: An outbreak of 2019 novel coronavirus diseases (COVID-19) in Wuhan, China has spread quickly nationwide. Here, we report results of a descriptive, exploratory analysis of all cases diagnosed as of February 11, 2020. Methods: All COVID-19 cases reported through February 11, 2020 were extracted from China's Infectious Disease Information System. Analyses included: 1) summary of patient characteristics; 2) examination of age distributions and sex ratios; 3) calculation of case fatality and mortality rates; 4) geo-temporal analysis of viral spread; 5) epidemiological curve construction; and 6) subgroup analysis. Results: A total of 72 314 patient records-44 672 (61.8%) confirmed cases, 16 186 (22.4%) suspected cases, 10567 (14.6%) clinical diagnosed cases (Hubei only), and 889 asymptomatic cases (1.2%)-contributed data for the analysis. Among confirmed cases, most were aged 30-79 years (86.6%), diagnosed in Hubei (74.7%), and considered mild (80.9%). A total of 1 023 deaths occurred among confirmed cases for an overall case-fatality rate of 2.3%. The COVID-19 spread outward from Hubei sometime after December 2019 and by February 11, 2020, 1 386 counties across all 31 provinces were affected. The epidemic curve of onset of symptoms peaked in January 23-26, then began to decline leading up to February 11. A total of 1 716 health workers have become infected and 5 have died (0.3%). Conclusions: The COVID-19 epidemic has spread very quickly. It only took 30 days to expand from Hubei to the rest of Mainland China. With many people returning from a long holiday, China needs to prepare for the possible rebound of the epidemic.

positive: Association of Cardiovascular Disease with Coronavirus Disease 2019 (COVID-19) Severity: A Meta-Analysis Abstract Observational studies have reported an association between underlying cardiovascular diseases (CVD) and worse prognosis in COVID-19 patients, but this still remains unclear. We conducted a meta-analysis of recent studies that reported the association of CVD with worse prognosis and increased mortality in COVID-19 patients. Literature search through PubMed, the Cochrane Library, and Embase was completed by 2 reviewers from November 1, 2019 to April 20, 2020. Inclusion criteria were observational case-control or cohort studies on COVID-19 patients with a history of CVD included, which reported outcomes of COVID-19 infection severity, clearly outlined the definition of “severe disease” and with sample size >10. Data were abstracted independently by 2 authors. Studies were divided into two separate cohorts for analysis: severity (severe vs. non-severe) and mortality (non-survivors vs. survivors). Data was pooled into a meta-analysis to estimate pooled odds ratio (OR) with 95% confidence interval (95% CI) for each outcome. A total of 18 studies (n= 4,858 patients) were included. Sixteen studies were from China, while 2 were from the United States. Pre-existing CVD was associated with a significantly increased risk of a severe form of COVID-19 (OR= 3.14; 95% CI 2.32-4.24; I2=0%; Q= 8.68, p=0.73) and overall risk of COVID-19 all-cause mortality (OR= 11.08; 95% CI: 2.59-47.32; I2=55%; p=0.11). However, this study did not find a significant association between previous history of CVD and mortality in severe COVID-19 disease (OR=1.72; 95% CI: 0.97-3.06, I2=0%, p=0.46). Pre-existing CVD is associated with worse outcomes among patients with COVID-19. Clinicians and policymakers need to take account of these findings in implementing risk stratification models.

positive: The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality WHO declared SARS-CoV-2 a global pandemic. The present aim was to propose an hypothesis that there is a potential association between mean levels of vitamin D in various countries with cases and mortality caused by COVID-19. The mean levels of vitamin D for 20 European countries and morbidity and mortality caused by COVID-19 were acquired. Negative correlations between mean levels of vitamin D (average 56 mmol/L, STDEV 10.61) in each country and the number of COVID-19 cases/1 M (mean 295.95, STDEV 298.7, and mortality/1 M (mean 5.96, STDEV 15.13) were observed. Vitamin D levels are severely low in the aging population especially in Spain, Italy and Switzerland. This is also the most vulnerable group of the population in relation to COVID-19. It should be advisable to perform dedicated studies about vitamin D levels in COVID-19 patients with different degrees of disease severity.

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

positive: COVID-19 Fatalities, Latitude, Sunlight, and Vitamin D BACKGROUND: Since Vitamin D is known to be vital in regulating the immune system, and sunlight UV radiation exposure on the skin produces Vitamin D and UV intensity is highest nearest the equator, a study was done to examine the correlation between the latitude and COVID-19 fatality rates for countries. METHODS: Eighty-eight countries were selected based on their likelihood of providing reliable data. Using death rates/million for each country from the “worldometer” web site, a correlation analysis was done between death rates and a country's latitude. RESULTS: A highly significant, positive correlation was found between lower death rates and a country's proximity to the equator (Pearson r = .40 p<.0001, two-tailed t-test). The R squared of .16 means that 16% of the variation in death rates among nations is accounted for by the latitude of the country. Evidence is presented suggesting a direct correlation between sunlight exposure and reduced mortality. DISCUSSION: This study is the first to document a statistically significant correlation between a country's latitude and its COVID-19 mortality and is consistent with other research regarding latitude, Vitamin D deficiency, and COVID-19 fatalities. Limitations of this study are noted. CONCLUSION: Further research is needed to confirm the correlation between latitude and COVID-19 fatalities, and to determine the optimum amounts of safe sunlight exposure and/or vitamin D oral supplementation to reduce COVID-19 fatalities in populations that are at high risk for vitamin D deficiency.

positive: Fasting plasma glucose associated with mortality rate

positive: Association of Bacille Calmette-Guerin (BCG), Adult Pneumococcal and Adult Seasonal Influenza Vaccines with Covid-19 Adjusted Mortality Rates in Level 4 European countries Introduction Non-specific effects of vaccines have gained increasing interest during the Covid-19 pandemic. In particular, population use of BCG vaccine has been associated with improved outcomes. This study sought to determine the association of population use of BCG, adult pneumococcal and adult seasonal influenza vaccination with Covid-19 mortality when adjusted for a number of confounding variables. Methods: Using publicly available data, mortality adjusted for the timeframe of crisis, population size and population characteristics was calculated. The primary analysis was the relationship between each of the day 15 and day 30 standardised mortality rates and BCG, adult pneumococcal and influenza vaccination scores using unadjusted measures and with adjustment for population structure and case fatality rates. Secondary analyses were measures of case increases and mortality increases from day 15 to day 30 for each of the relative vaccination scores. Finally, we also analysed the peak Z score reflecting increases in total mortality from historical averages reported by EuroMOMO (Euromomo.eu), Results: Following adjustment for the effects of population size, median age, population density, the proportion of population living in an urban setting, life-expectancy, the elderly dependency ratio (or proportion over 65 years), net migration, days from day 1 to lockdown and case-fatality rate, only BCG vaccination score remained significantly associated with Covid-19 mortality at day 30. In the best fit model, BCG vaccination score was associated with a 64% reduction in log(10) mortality per 10 million population (OR 0.362 reduction [95% CI 0.188 to 0.698]), following adjustment for population size, median age, density, urbanization, elderly dependency ratio, days to lockdown, yearly migration and case fatality rate. Conclusion BCG vaccine was associated with reduced mortality rates in level 4 countries while adult pneumococcal and adult seasonal influenza vaccines were not when adjusted for a number of confounding variables. A number of trials are ongoing to determine if BCG is protective against severe Covid-19 infection.

positive: COVID-19 in Colombia endpoints. Are we different, like Europe? Abstract The infection by the new coronavirus (SARS-CoV-2) has taken the dimension of a pandemic, affecting more than 160 countries in a few weeks. In Colombia, despite the implementation of the rules established by the national government, exists an elevate concern both for mortality and for the limited capacity of the health system to respond effectively to the needs of patients infected. For Colombia, assuming a case fatality rate among people infected with SARS-CoV-2 of 0.6% (average data from the information reported for Latin American countries for March 18) (Table 1), the number of deaths, in one or two weeks, could be 16 and 243, respectively. These estimates differ markedly from those documented in countries such as Spain and Italy, in which COVID-19 case fatality rates exceed 8% (case of Italy) and from the percentage of patients who have required intensive care, which has ranged from 9% to 11% of patients in Mediterranean European countries. These differences could be explained due to: a) the percentage of the population at risk (individuals older than 60 years); b) a higher epidemiological exposure to viral respiratory infections associated with more frequent exposure to them, due to geographic and climatic conditions; c) less spread of the virus by location in the tropical zone; and d) earlier preventive measures to contain the spread of SARS-CoV-2 infection. Therefore, it is possible to establish that the situation in this country will be different from in European Mediterranean and that Colombia could have different endpoints from Spain and Italy.

positive: Population-Level Mortality Rates from Novel Coronavirus (COVID-19) in South Korea Background: South Korea was among the first countries to report a case of the novel coronavirus (COVID-19) outside of China. As of 22 March, 2020, South Korea reported 8897 confirmed cases of and 104 deaths from COVID-19. Methods: We collected the number of laboratory-confirmed cases and deaths in South Korea from the World Health Organization (as of 21 March, 2020) and case distribution and fatality rates by age from the Korean Center for Disease Control and Prevention (as of 22 March, 2020). We estimated population-level mortality rates by fitting a negative binomial regression model with the number of deaths as the outcome and population by age as an offset. We then calculated the age-standardized death rate (ASDR) based on the current COVID-19 figures and for alternative scenarios of increased prevalence. Findings: The COVID-19 population-level mortality rate (per 100,000 person-years) increased with age: from 0.1 deaths among 30-39 year olds to 9.5 deaths among ≥80 year olds. The ASDR (per 100,000 person-years) was 0.8 deaths. The ASDR would increase to 52.0 deaths at a 1% prevalence (becoming the third leading cause of death) and 155.9 deaths at 3% prevalence (becoming the leading cause of death). Interpretation: Currently, the population-level mortality burden of COVID-19 in South Korea, as measured by the ASDR, was relatively low compared to other causes of death partly due to the low prevalence of COVID-19. If the prevalence increases from another outbreak, the mortality burden could increase substantially and surpass other leading causes.

positive: Population age structure only partially explains the large number of COVID-19 deaths at the oldest ages To date any attention paid to the age shape of COVID-19 deaths has been mostly in relation to attempts to understand the differences in case fatality rates between countries. The aim of this paper is to explore differences in age distribution of deaths from COVID-19 among European countries which have old age structures. We do this by way of a cross-country comparison and put forward some reasons for potential differences.

positive: COVID-19 pandemic scenario in India compared to China and rest of the world: a data driven and model analysis The COVID-19 is a rapidly spreading respiratory illness caused with the infection of SARS-CoV-2. The COVID-19 data from India was compared with China and rest of the world. The average values of daily growth rate (DGR), case recovery rate (CRR), case fatality rate (CFR), serial interval (SI) of COVID-19 in India was 17%, 8.25%, and 1.87%, and 5.76 days respectively, as of April 9, 2020. The data driven estimates of basic reproduction number (R0), average reproduction number (R) and effective reproduction number (Re) were 1.03, 1.73, and 1.35, respectively. The results of exponential and SIR model showed higher estimates of R0, R and Re. The data driven as well as estimated COVID-19 cases reflect the growing nature of the epidemic in India and world excluding China, whereas the same in China reveal the involved population became infected with the disease and moved into the recovered stage. The epidemic size of India was estimated to be ~30,284 (as of April 15, 2020 with 12,370 infectious cases) with an estimated end of the epidemic on June 9, 2020. The Re values in India before and after lockdown were 1.62 and 1.37 respectively, with SI 5.52 days and 5.98 days, respectively, as of April 17, 2020, reflecting the effectiveness of lockdown strategies. Beyond April 17, 2020, our estimate of 24,431 COVID-19 infected cases with lockdown is 78% lower compared to the 112,042 case estimates in absence of lockdown, on April 27, 2020. To early end of the COVID-19 epidemic, strong social distancing is important.

positive: Rapid estimation of excess mortality in times of COVID-19 in Portugal - Beyond reported deaths Background: One month after the first COVID-19 infection was recorded, Portugal counted 18 051 cases and 599 deaths from COVID-19. To understand the overall impact on mortality of the pandemic of COVID-19, we estimated the excess mortality registered in Portugal during the first month of the epidemic, from March 16 until April 14 using two different methods. Methods: We compared the observed and expected daily deaths (historical average number from daily death registrations in the past 10 years) and used 2 standard deviations confidence limit for all-cause mortality by age and specific mortality cause, considering the last 6 years. An adapted ARIMA model was also tested to validate the estimated number of all-cause deaths during the study period. Results: Between March 16 and April 14, there was an excess of 1,255 all-cause deaths, 14% more than expected. The number of daily deaths often surpassed the 2 standard deviations confidence limit. The excess mortality occurred mostly in people aged 75+. Forty-nine percent (49%) of the estimated excess deaths were registered as due to COVID-19, The other 51% registered as other natural causes. Conclusion: Even though Portugal took early containment measures against COVID-19, and the population complied massively with those measures, there was significant excess mortality during the first month of the pandemic, mostly among people aged 75+. Only half of the excess mortality was registered as directly due do COVID-19.

positive: An international comparison of the second derivative of COVID-19 deaths after implementation of social distancing measures This work compares deaths for confirmed COVID-19 cases in China to eight other countries, Italy, Spain, France, USA, UK, Germany, Netherlands and South Korea. After implementing varying intensities and timing of social distancing measures, several appear to be converging onto the decline in the daily growth rate of deaths, or relative second derivative of total deaths, seen in China after the implementation an aggressive social distancing policy. By calculating future trajectories in these countries based on the observed Chinese fatality statistics, an estimate of the total deaths and maximum daily death rates over a defined period of time is made. Our lower bound estimate for the United Kingdom based on the real data approximates the lower bound estimate of the recent modelling study of Ferguson et al. [1]. These results suggest there may be a threshold of effective public health intervention. Our method of viewing the data may be helpful in monitoring the course of the epidemic, judging the effectiveness of implementation, and monitoring the relaxation of social distancing.

positive: Association of hypertension with the severity and fatality of SARS-CoV-2 infection: A meta-analysis Hypertension is a common comorbidity in COVID-19 patients. However, the association of hypertension with the severity and fatality of COVID-19 remain unclear. In the present meta-analysis, relevant studies reported the impacts of hypertension on SARS-CoV-2 infection were identified by searching PubMed, Elsevier Science Direct, Web of Science, Wiley Online Library, Embase and CNKI up to 20 March 2020. As the results shown, 12 publications with 2389 COVID-19 patients (674 severe cases) were included for the analysis of disease severity. The severity rate of COVID-19 in hypertensive patients was much higher than in non-hypertensive cases (37.58% vs 19.73%, pooled OR: 2.27, 95% CI: 1.80–2.86). Moreover, the pooled ORs of COVID-19 severity for hypertension vs. non-hypertension was 2.21 (95% CI: 1.58–3.10) and 2.32 (95% CI: 1.70–3.17) in age <50 years and ⩾50 years patients, respectively. Additionally, six studies with 151 deaths of 2116 COVID-19 cases were included for the analysis of disease fatality. The results showed that hypertensive patients carried a nearly 3.48-fold higher risk of dying from COVID-19 (95% CI: 1.72–7.08). Meanwhile, the pooled ORs of COVID-19 fatality for hypertension vs. non-hypertension was 6.43 (95% CI: 3.40–12.17) and 2.66 (95% CI: 1.27–5.57) in age <50 years and ⩾50 years patients, respectively. Neither considerable heterogeneity nor publication bias was observed in the present analysis. Therefore, our present results provided further evidence that hypertension could significantly increase the risks of severity and fatality of SARS-CoV-2 infection.

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

positive: Factors Associated With Surgical Mortality and Complications Among Patients With and Without Coronavirus Disease 2019 (COVID-19) in Italy Importance: There are limited data on mortality and complications rates in patients with coronavirus disease 2019 (COVID-19) who undergo surgery. Objective: To evaluate early surgical outcomes of patients with COVID-19 in different subspecialties. Design, Setting, and Participants: This matched cohort study conducted in the general, vascular and thoracic surgery, orthopedic, and neurosurgery units of Spedali Civili Hospital (Brescia, Italy) included patients who underwent surgical treatment from February 23 to April 1, 2020, and had positive test results for COVID-19 either before or within 1 week after surgery. Gynecological and minor surgical procedures were excluded. Patients with COVID-19 were matched with patients without COVID-19 with a 1:2 ratio for sex, age group, American Society of Anesthesiologists score, and comorbidities recorded in the surgical risk calculator of the American College of Surgeons National Surgical Quality Improvement Program. Patients older than 65 years were also matched for the Clinical Frailty Scale score. Exposures: Patients with positive results for COVID-19 and undergoing surgery vs matched surgical patients without infection. Screening for COVID-19 was performed with reverse transcriptase-polymerase chain reaction assay in nasopharyngeal swabs, chest radiography, and/or computed tomography. Diagnosis of COVID-19 was based on positivity of at least 1 of these investigations. Main Outcomes and Measures: The primary end point was early surgical mortality and complications in patients with COVID-19; secondary end points were the modeling of complications to determine the importance of COVID-19 compared with other surgical risk factors. Results: Of 41 patients (of 333 who underwent operation during the same period) who underwent mainly urgent surgery, 33 (80.5%) had positive results for COVID-19 preoperatively and 8 (19.5%) had positive results within 5 days from surgery. Of the 123 patients of the combined cohorts (78 women [63.4%]; mean [SD] age, 76.6 [14.4] years), 30-day mortality was significantly higher for those with COVID-19 compared with control patients without COVID-19 (odds ratio [OR], 9.5; 95% CI, 1.77-96.53). Complications were also significantly higher (OR, 4.98; 95% CI, 1.81-16.07); pulmonary complications were the most common (OR, 35.62; 95% CI, 9.34-205.55), but thrombotic complications were also significantly associated with COVID-19 (OR, 13.2; 95% CI, 1.48-∞). Different models (cumulative link model and classification tree) identified COVID-19 as the main variable associated with complications. Conclusions and Relevance: In this matched cohort study, surgical mortality and complications were higher in patients with COVID-19 compared with patients without COVID-19. These data suggest that, whenever possible, surgery should be postponed in patients with COVID-19.

positive: News from the front: Excess mortality and life expectancy in two major epicentres of the COVID-19 pandemic in Italy Existing studies commonly rely on national official reports to estimate the impact of COVID-19 on population health and human life. However, relying on national reports is problematic because classification and estimation of COVID-19 mortality are not consistent across countries. Likewise, delay coronavirus test results and shortage of testing kits can result in undercounting of coronavirus deaths. To overcome these problems, this study exploits all cause daily death registrations data provide by the Italian Statistical Office (ISTAT) from 1st January to 4th April 2020. This allows us to: 1) calculate excess mortality in 2020 compared to the years 2015 to 2019; and 2) estimate life expectancy on a seasonal and annual basis. We focus our analysis on Bergamo and Brescia, the two hardest hit provinces in Lombardy, northern Italy. Given the clustering nature of the epidemic, focusing on the areas with high concentration of severe illness and deaths allows us to capture the true impact of COVID-19 on mortality and life expectancy, which are likely to be underestimated in the national level data. We find that on the period 1 Jan to 4 April 2020, seasonal life expectancy in Bergamo reduced by around 8.1 and 6.5 years compared to 2019 for men and women respectively (4.5 and 3.4 years in Brescia). The drop in period life expectancy for 2020 may total up to 3 years in the case of men and 2 years in the case of women. Such a sharp decrease in life expectancy has not been experienced in modern history since the Second World War. This study shows that, in the absence of public health interventions to reduce the spread of the virus, COVID-19 has set life expectancy in Bergamo and Brescia back to the Italian life expectancy of 15 years ago.

positive: Risk Factors for Mortality among COVID-19 Patients Abstract Aims COVID-19 is a current globalpandemic. However, comprehensive global data analyses for its mortality risk factors are lacking. The current investigation aimed to assess the predictors of death among COVID-19 patients from worldwide open access data. Methods A total of 828 confirmed cases of COVID-19 with definite outcomes were retrospectively identified from open access individual-level worldwide data. Univariate followed by multivariable regression analysis were used to evaluate the association between potential risk factors and mortality. Results Majority of the patients were males 59.1% located in Asia 69.3%. Based on the data, older age (adjusted odds ratio (aOR), 1.079; 95% confidence intervals (95% CI), 1.064-1.095 per year increase), males (aOR, 1.607; 95% CI, 1.002-2.576), patients with hypertension (aOR, 3.576; 95% CI, 1.694-7.548), diabetes mellitus (aOR, 12.234; 95% CI, 4.126-36.272), and patients located in America (aOR, 7.441; 95% CI, 3.546-15.617) were identified as the risk factors of mortality among COVID-19 patients. Conclusions Males, advanced age, hypertension patients, diabetes mellitus patients, and patients located in America were the independent risk factors of death among COVID-19 patients. Extra attention is required to be given to these factors and additional studies on the underlying mechanisms of these effects.

positive: Meta-regression of COVID-19 prevalence/fatality on socioeconomic characteristics of data from top 50 U.S. large cities To screen potential risk and protective socioeconomic factors for Coronavirus disease 2019 (COVID-19) prevalence and fatality, meta-regression of data from top 50 U.S. large-population cities was performed. The population estimate (in 2019) of each country to which the city belongs was abstracted from the "County Population Totals: 2010-2019." From the "Johns Hopkins Coronavirus Resource Center," the cumulative number of confirmed cases and deaths of COVID-19 in each country was obtained on May 22, 2020. Socioeconomic characteristics of each country were extracted from the "2014-2018 American Community Survey (ACS) 5-Year Data Profile" and "Small Area Income and Poverty Estimates (SAIPE) Program (for 2018)." Radom-effects meta-regression was performed using OpenMetaAnalyst (http://www.cebm.brown.edu/openmeta/index.html). A coefficient (slope of the meta-regression line) for COVID-19 prevalence was significantly negative for male sex, education attainment, computer and Internet use, and private health insurance. Whereas, the coefficient was significantly positive for black race, never matrimony, unemployment, and poverty. In the multivariable model, the coefficient was significantly negative for male sex (P = 0.036) and computer use (P = 0.024), and significantly positive for never matrimony (P < 0.001). A coefficient for COVID-19 fatality was significantly negative for no health insurance, and significantly positive for elderly, unemployment, and public coverage. In the multivariable model, the coefficient was significantly positive for only elderly (P = 0.002). In conclusion, a number of socioeconomic factors, e.g. male sex (negatively for prevalence), elderly (positively for fatality), never matrimony (positively for prevalence), and computer use (negatively for prevalence) may be associated with COVID-19.

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

positive: Adjusted fatality rates of COVID19 pandemic: a comparison across countries Background: A key impact measure of COVID-19 pandemic is the case fatality rate (CFR), but estimating it during an epidemic is challenging as the true number of cases may remain elusive. Objective: To estimate the CFR applying a delay-adjusted method across countries, exploring differences to simple methods and potential correlation to country level variables. Methods: Secondary analysis of publicly available data from countries with [≥]500 cases by April 30th. We calculated CFR adjusting for delay time from diagnosis to death and using simple methods for comparison. We performed a random effects meta-analysis to pooling CFRs for all countries and for those with high testing coverage and low positivity rate. We explored correlation of adjusted CFR with age structure and health care resources at country level. Results: We included 107 countries and the Diamond Princess cruise-ship. The overall delay adjusted CFR was 2.8% (95%CI: 2.1 to 3.1) while naive CFR was 5.1% (95%CI: 4.1 to 6.2). In countries with high testing coverage/low positivity rate the pooled adjusted CFR was 2.1% (95%CI: 1.5 to 3.0), there was a correlation with age over 65 years ({beta} = 0.12; 95%CI: 0.06 to 0.18), but not with number of physician or critical care beds. Naive method underestimated the CFR of the CFR with a median of 1.3% across countries. Conclusion: Our best estimation of CFR across countries is 2% and varies according to the aged population size. Modelers and policy makers may consider these results to assess the impact of lockdowns or other mitigation policies.

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

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

positive: Is BCG vaccination causally related to reduced COVID-19 mortality? The ongoing severe acute respiratory sickness coronavirus 2 (SARS-CoV-2) pandemic has resulted in more than 3,600,000 detected cases of COVID-19 illness and nearly 260,000 deaths worldwide as of May 6, 2020. Recently, BCG vaccination was shown to correlate with reduced COVID-19 case fatality rates (preprint: Miller et al, 2020; preprint: Sala & Miyakawa, 2020; https://www.jsatonotes.com/2020/03/if-i-were-north-americaneuropeanaustral.html). The most recent data from publicly available resources also indicate that both COVID-19 incidence and total deaths are strongly associated with the presence or absence of national mandatory BCG vaccination programs. As seen in Table 1, seven of eight countries with very low numbers of total deaths (< 40 per 1 million population) adopted a mandatory BCG vaccination program using one of a set of 6 separate BCG strains (Table 1). In contrast, COVID-19 mortality was markedly higher in countries where BCG vaccination is not widely administered or is given only to high-risk groups. COVID-19 mortality was also higher in countries where widespread BCG vaccination was discontinued more than 20 years ago and in countries that used the BCG Denmark strain regularly or temporarily. This raises the question of whether BCG vaccination and reduced COVID-19 mortality are causally related. An additional question is why different BCG strains may be variably associated with mortality.

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: Estimating the early death toll of COVID-19 in the United States BACKGROUND: Efforts to track the severity and public health impact of the novel coronavirus, COVID-19, in the US have been hampered by testing issues, reporting lags, and inconsistency between states. Evaluating unexplained increases in deaths attributed to broad outcomes, such as pneumonia and influenza (P&I) or all causes, can provide a more complete and consistent picture of the burden caused by COVID-19. METHODS: We evaluated increases in the occurrence of deaths due to P&I above a seasonal baseline (adjusted for influenza activity) or due to any cause across the United States in February and March 2020. These estimates are compared with reported deaths due to COVID-19 and with testing data. RESULTS: There were notable increases in the rate of death due to P&I in February and March 2020. In a number of states, these deaths pre-dated increases in COVID-19 testing rates and were not counted in official records as related to COVID-19. There was substantial variability between states in the discrepancy between reported rates of death due to COVID-19 and the estimated burden of excess deaths due to P&I. The increase in all-cause deaths in New York and New Jersey is 1.5–3 times higher than the official tally of COVID-19 confirmed deaths or the estimated excess death due to P&I. CONCLUSIONS: Excess P&I deaths provide a conservative estimate of COVID-19 burden and indicate that COVID-19-related deaths are missed in locations with inadequate testing or intense pandemic activity.

positive: Biological and Epidemiological Trends in the Prevalence and Mortality due to Outbreaks of Novel Coronavirus COVID-19 Medical education during pandemics: a UK perspective The novel coronavirus (Covid-19) infection outbreak has posed a major threat to international health system and economy This study is aimed at investigating the biological and epidemiological trends in the prevalence and mortality due to outbreaks of novel coronavirus (COVID-19) infections The data on the global outbreak of COVID-19, were obtained from World Health Organization (WHO), Worldometer, Centers for Disease Control and Prevention (CDC), and research institutes The information was also recorded from research documents published in global scientific journals indexed in Pub Med and Institute of Scientific Information (ISI) Web of Science on the trends in the prevalence and mortality due to COVID-19 infection outbreaks The results show rising trends in the transmission, prevalence and mortality rate due to coronavirus COVID-19 During the period of December 29, 2019 through March 31, 2020, it has infected 750890 people worldwide, resulting in 36405 deaths with a mortality rate of 4 84% The infections were more frequent among male gender with above 60 years of age The mean growth rate index for total number of cases from January 23 to March 31, 2020 was 1 20 and growth rate index for mortality rate was 1 12 There was a positive association between the prevalence and mortality rate (R2=0 996) The novel coronavirus COVID-19 is highly contagious and has affected a large number of people worldwide It is still spreading with mutable prevalence and mortality outbreak trends The global health officials have taken priority measures to prevent the further outbreaks of this emerging pathogen across the globe However, the rising number of cases and mortality risk estimates are demonstrating that enhanced public health mediations, good hygienic conditions, social distancing and movement limitations may control the COVID-19 epidemics

positive: Age-dependent gender differences of COVID-19 in mainland China: comparative study BACKGROUND: The ongoing pandemic of novel coronavirus disease 2019 (COVID-19) is challenging global public health system. Sex-differences in infectious diseases are a common but neglected problem. METHODS: We used the national surveillance database of COVID-19 in mainland China to compared gender differences in attack rate (AR), proportion of severe and critical cases (PSCC) and case fatality rate (CFR) in relation to age, affected province, and onset-to-diagnosis interval. RESULTS: The overall AR was significantly higher in female population than in males (63.9 versus 60.5 per million persons; P ˂ .001). By contrast, PSCC and CFR were significantly lower among female patients (16.9% and 4.0%) than among males (19.5% and 7.2%), with ORs of 0.87 and 0.57, respectively (both P ˂ .001). The female-to-male differences were age-dependent, which were significant among people aged 50–69 years for AR, and in the patients of 30-years or older for both PSCC and CFR (all P ≤ .001). The AR, PSCC and CFR varied greatly from province to province. However, female-to-male differences in AR, PSCC and CFR were significant in the epicenter, Hubei province, where 82.2% confirmed cases and 97.4% deaths occurred. After adjusting for age, affected province and onset-to-diagnosis interval, the female-to-male difference in AR, PSCC and CFR remained significant in multivariate logistic regression analyses. CONCLUSIONS: We elucidate an age-dependent gender dimorphism for COVID-19, in which the females have higher susceptibility but lower severity and fatality. Further epidemiological and biological investigations are required to better understand the sex-specific differences for effective interventions.

positive: Analysis and forecast of COVID-19 spreading in China, Italy and France Abstract In this note we analyze the temporal dynamics of the coronavirus disease 2019 outbreak in China, Italy and France in the time window 22 / 01 − 15 / 03 / 2020 . A first analysis of simple day-lag maps points to some universality in the epidemic spreading, suggesting that simple mean-field models can be meaningfully used to gather a quantitative picture of the epidemic spreading, and notably the height and time of the peak of confirmed infected individuals. The analysis of the same data within a simple susceptible-infected-recovered-deaths model indicates that the kinetic parameter that describes the rate of recovery seems to be the same, irrespective of the country, while the infection and death rates appear to be more variable. The model places the peak in Italy around March 21st 2020, with a peak number of infected individuals of about 26000 (not including recovered and dead) and a number of deaths at the end of the epidemics of about 18,000. Since the confirmed cases are believed to be between 10 and 20% of the real number of individuals who eventually get infected, the apparent mortality rate of COVID-19 falls between 4% and 8% in Italy, while it appears substantially lower, between 1% and 3% in China. Based on our calculations, we estimate that 2500 ventilation units should represent a fair figure for the peak requirement to be considered by health authorities in Italy for their strategic planning. Finally, a simulation of the effects of drastic containment measures on the outbreak in Italy indicates that a reduction of the infection rate indeed causes a quench of the epidemic peak. However, it is also seen that the infection rate needs to be cut down drastically and quickly to observe an appreciable decrease of the epidemic peak and mortality rate. This appears only possible through a concerted and disciplined, albeit painful, effort of the population as a whole.

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

positive: 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: Comorbid Chronic Diseases and Acute Organ Injuries Are Strongly Correlated with Disease Severity and Mortality among COVID-19 Patients: A Systemic Review and Meta-Analysis The recent outbreak of COVID-19 has been rapidly spreading on a global scale. To date, there is no specific vaccine against the causative virus, SARS-CoV-2, nor is there an effective medicine for treating COVID-19, thus raising concerns with respect to the effect of risk factors such as clinical course and pathophysiological parameters on disease severity and outcome in patients with COVID-19. By extracting and analyzing all available published clinical data, we identified several major clinical characteristics associated with increased disease severity and mortality among patients with COVID-19. Specifically, preexisting chronic conditions such as hypertension, cardiovascular disease, chronic kidney disease, and diabetes are strongly associated with an increased risk of developing severe COVID-19; surprisingly, however, we found no correlation between chronic liver disease and increased disease severity. In addition, we found that both acute cardiac injury and acute kidney injury are highly correlated with an increased risk of COVID-19-related mortality. Given the high risk of comorbidity and the high mortality rate associated with tissue damage, organ function should be monitored closely in patients diagnosed with COVID-19, and this approach should be included when establishing new guidelines for managing these high-risk patients. Moreover, additional clinical data are needed in order to determine whether a supportive therapy can help mitigate the development of severe, potentially fatal complications, and further studies are needed to identify the pathophysiology and the mechanism underlying this novel coronavirus-associated infectious disease. Taken together, these findings provide new insights regarding clinical strategies for improving the management and outcome of patients with COVID-19.

positive: 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.

positive: Distinct clinical characteristics and risk factors for mortality in female COVID-19 inpatients: a sex-stratified large-scale cohort study in Wuhan, China BACKGROUND: As the coronavirus disease 2019 (COVID-19) outbreak accelerates worldwide, it is highly significant to evaluate sex-specific clinical characteristics and outcomes, that may affect public health policies. METHODS: COVID-19 patients admitted to Tongji Hospital between January 18and March 27, 2020 were evaluated. Clinical features, laboratory data, complications and outcomes were compared between females and males. Risk factors for mortality in the whole population, females and males were determined respectively. RESULTS: There were 1667 (50.38%) females among the3309 patients included in this study. The mortality rate was only 5.9% in females but 12.7% in males. Compared with males, more females had no initial symptoms (11.1% vs 8.3%, p=0.008). Complications including acute respiratory distress syndrome, acute kidney injury, septic shock, cardiac injury and coagulation disorder were less common in females; critical illness was also significant less common in females (31.1% vs 39.4%, p<0.0001). Significantly fewer female patients received antibiotics treatment (p=0.001), antiviral therapy (p=0.025) glucocorticoids treatment (p<0.0001), mechanical ventilation (p<0.0001) and had Intensive Care Unit admission (p<0.0001). A lower risk of death was found in females (odds ratio 0.44, 95% confidence interval 0.34-0.58) after adjusting for age and coexisting diseases. Among females, age, malignancy, chronic kidney disease and days from onset to admission were significant associated with mortality, while chronic kidney disease was not risk factor in males. CONCLUSIONS: Significantly more mild illness and fewer deaths were found in female COVID-19 inpatients and risk factors associated with mortality varied among male and female population.

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

positive: Estimating excess 1-year mortality associated with the COVID-19 pandemic according to underlying conditions and age: a population-based cohort study BACKGROUND: The medical, societal, and economic impact of the coronavirus disease 2019 (COVID-19) pandemic has unknown effects on overall population mortality. Previous models of population mortality are based on death over days among infected people, nearly all of whom thus far have underlying conditions. Models have not incorporated information on high-risk conditions or their longer-term baseline (pre-COVID-19) mortality. We estimated the excess number of deaths over 1 year under different COVID-19 incidence scenarios based on varying levels of transmission suppression and differing mortality impacts based on different relative risks for the disease. METHODS: In this population-based cohort study, we used linked primary and secondary care electronic health records from England (Health Data Research UK–CALIBER). We report prevalence of underlying conditions defined by Public Health England guidelines (from March 16, 2020) in individuals aged 30 years or older registered with a practice between 1997 and 2017, using validated, openly available phenotypes for each condition. We estimated 1-year mortality in each condition, developing simple models (and a tool for calculation) of excess COVID-19-related deaths, assuming relative impact (as relative risks [RRs]) of the COVID-19 pandemic (compared with background mortality) of 1·5, 2·0, and 3·0 at differing infection rate scenarios, including full suppression (0·001%), partial suppression (1%), mitigation (10%), and do nothing (80%). We also developed an online, public, prototype risk calculator for excess death estimation. FINDINGS: We included 3 862 012 individuals (1 957 935 [50·7%] women and 1 904 077 [49·3%] men). We estimated that more than 20% of the study population are in the high-risk category, of whom 13·7% were older than 70 years and 6·3% were aged 70 years or younger with at least one underlying condition. 1-year mortality in the high-risk population was estimated to be 4·46% (95% CI 4·41–4·51). Age and underlying conditions combined to influence background risk, varying markedly across conditions. In a full suppression scenario in the UK population, we estimated that there would be two excess deaths (vs baseline deaths) with an RR of 1·5, four with an RR of 2·0, and seven with an RR of 3·0. In a mitigation scenario, we estimated 18 374 excess deaths with an RR of 1·5, 36 749 with an RR of 2·0, and 73 498 with an RR of 3·0. In a do nothing scenario, we estimated 146 996 excess deaths with an RR of 1·5, 293 991 with an RR of 2·0, and 587 982 with an RR of 3·0. INTERPRETATION: We provide policy makers, researchers, and the public a simple model and an online tool for understanding excess mortality over 1 year from the COVID-19 pandemic, based on age, sex, and underlying condition-specific estimates. These results signal the need for sustained stringent suppression measures as well as sustained efforts to target those at highest risk because of underlying conditions with a range of preventive interventions. Countries should assess the overall (direct and indirect) effects of the pandemic on excess mortality. FUNDING: National Institute for Health Research University College London Hospitals Biomedical Research Centre, Health Data Research UK.

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

positive: Transmission and epidemiological characteristics of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infected Pneumonia (COVID-19): preliminary evidence obtained in comparison with 2003-SARS Objectives: Latest epidemic data of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infected Pneumonia (COVID-19) was collected and a detailed statistical analysis was carried out to make comparison with 2003-SARS in order to provide scientific reference for the prevention and control of COVID-19. Methods: The information of COVID-19 and 2003-SARS from websites of NHCPRC and the World Health Organization was collected, and then the transmission dynamics of the two kinds of infectious diseases were analyzed. The information of 853 confirmed COVID-19 patients obtained from the website of health committees of 18 provinces. A descriptive epidemiological analysis method was employed to carefully analyze the epidemic characteristics. Subsequently, the COVID-19 epidemic data in Wuhan and other inland regions of China was analyzed separately and compared. A multivariate function model was constructed based on the confirmed COVID-19 case data. Results: The growth rate of new cases and deaths of COVID-19 were significantly faster than those of 2003-SARS. The number of confirmed cases in Wuhan and other inland areas both showed increasing trends. 853 confirmed COVID-19 cases aged 1 months to 94 years and the average age was (45.05 ± 17.22) years. The gender ratio (M: F) was 1.12: 1. Conclusions: The fatality rate of COVID-19 is lower than that of 2003-SARS and the cure rate is higher. The age of COVID-19 patients is mainly concentrated in the 30-50 years old (60.61%). The harm of the first-generation COVID-19 patients is higher than that of secondary cases.

positive: Enhanced comparisons of COVID-19 mortality across populations Background The reported crude case fatality rate (CFR) for COVID-19 varies considerably across countries. Crude CFRs could by biased by larger proportions of older COVID-19 cases in population data, who are also at increased mortality risk. Such distorted age case structures are a common feature of selective COVID 19 testing strategies in many countries, and they potentially mask underlying differences arising from other important factors such as health system burden. Methods We used the method of direct case-age standardisation to evaluate the effects of age variations on CFRs. Data on cases and death by age from Italy, Spain, China, Australia and South Korea were analysed to derive standardised CFRs. Findings were compared across different case age distribution references as standards. Results Using the South Korean case age distribution as a standard, the fivefold higher crude CFR for Italy is reduced to less than two-fold after adjustment, while the crude CFR difference for Spain is virtually eliminated. The adjusted CFR for Australia is the lowest among all countries. Discussion Mortality differences based on crude CFRs are exaggerated by age structures, which are effectively controlled by case age standardization. Residual CFR differences could be attributed to health and health system factors. The South Korean case age distribution is an appropriate reference standard, given its robust case detection and contact tracing program. Till reliable population level indicators of incidence and mortality are available, the age-standardized CFR could be a viable option for international comparison of the impact of the COVID 19 epidemic.

positive: Age-Related Morbidity and Mortality among Patients with COVID-19 On March 11, 2020, the World Health Organization declared coronavirus disease (COVID-19), caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a pandemic. During the COVID-19 pandemic, an age-associated vulnerability in the burden of disease has been uncovered. Understanding the spectrum of illness and the pathogenic mechanism of the disease in a vulnerable population is critical, especially during the pandemic. Herein, we reviewed published COVID-19 epidemiology data from several countries to identify any consistent trends in the relationship between age and COVID-19-associated morbidity or mortality. We also reviewed the literature for studies explaining the difference in the host response to SARS-CoV-2 infection according to age. The insights from these data will be useful in determining the treatment policies and preventive measures of COVID-19.

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

positive: Estimating and forecasting COVID-19 attack rates and mortality {We describe a model for estimating past and current infections as well as future deaths due to the ongoing COVID-19 pandemic. The model does not use confirmed case numbers and is based instead on recorded numbers of deaths and on the age-specific population distribution. A regularized deconvolution technique is used to infer past infections from recorded deaths. Forecasting is based on a compartmental SIR-type model, combined with a probability distribution for the time from infection to death. The effect of non-pharmaceutical interventions (NPIs) is modelled empirically, based on recent trends in the death rate. The model can also be used to study counterfactual scenarios based on hypothetical NPI policies.

positive: Morbid Obesity as an Independent Risk Factor for COVID‐19 Mortality in Hospitalized Patients Younger than 50 OBJECTIVE: COVID‐19 continues to spread and younger patients are also being critically affected. This study analyzed obesity as an independent risk factor for mortality in hospitalized patients younger than fifty. METHODS: We retrospectively analyzed data of COVID‐19 patients hospitalized to a large academic hospital system in New York City between March 1st and May 17th, 2020. Data included demographics, comorbidities, BMI and smoking status. Obesity groups included: BMI 30–40 kg/m(2) and BMI ≥ 40 kg/m(2). Multivariable logistic regression models identified variables independently associated with mortality in patients younger and older than 50. RESULTS: Overall, 3,406 patients were included. 572 (17.0%) of the patients were younger than 50. In the younger age group, 60 (10.5%) patients died. In the older age group, 1,076 (38.0%) patients died. For the younger population, BMI above 40 kg/m(2) was independently associated with mortality (aOR 5.1, 95% CI 2.3–11.1). For the older population, BMI above 40 kg/m2 was also independently associated with mortality to a lesser extent (aOR 1.6, 95% CI 1.2 – 2.3). CONCLUSION: Our study demonstrates that hospitalized patients younger than 50 with morbid obesity are more likely to die from COVID‐19. This is particularly relevant in the western world where obesity rates are high.

positive: Ecologic correlation between underlying population level morbidities and COVID-19 case fatality rate among countries infected with SARS-CoV-2 Background: The ongoing Coronavirus disease 2019 (COVID-19) pandemic is unprecedented in scope. High income countries (HIC) seemingly account for the majority of the mortalities considering that these countries have screened more persons. Low middle income countries (LMIC) countries may experience far worse mortalities considering the existence of a weaker health care system and the several underlying population level morbidities. As a result, it becomes imperative to understand the ecological correlation between critical underlying population level morbidities and COVID-19 case fatality rates (CFR). Method: This is an ecological study using data on COVID-19 cases, prevalence of COPD, prevalence of tobacco use, adult HIV prevalence, quality of air and life expectancy. We plotted a histogram, performed the Shapiro-Wilk normality test and used spearman correlation to assess the degree of correlation between COVID-19 case fatality rate (CFR) and other covariates mentioned above. Result: As at the 31st of March 2020, there were a total of 846,281 cases of COVID-19 from 204 countries and a global case fatality rate of 5% (range 0% to 29%). Angola and Sudan both had the highest CFR of 29%, while Italy had the highest number of deaths (i.e. 12,428) as at 31st of March 2020. Adult HIV prevalence has a significant but weak negative correlation with CFR (correlation coefficient = - 0.24, p value =0.01) while all the other variables have positive correlation with CFR due to COVID-19 though not statistically significant. Of the 204 countries analyzed, only 11 countries (i.e. 5%) had complete datasets across all 5 population level morbidities (i.e. prevalence of COPD, prevalence of tobacco use, life expectancy, quality of air, and adult HIV prevalence variables). Correlations of CFR from these 11 countries were similar to that from the 204 countries except for the correlation with quality of air and prevalence of tobacco use. Conclusion: While we interpret our data with caution given the fact that this is an ecological study, our findings suggest that population level factors such as prevalence of COPD, prevalence of tobacco use, life expectancy and quality of air are positively correlated with CFR from COVID-19 but, adult HIV prevalence has a weak and negative correlation with COVID-19 CFR and would require extensive research.

positive: Association between consumption of fermented vegetables and COVID-19 mortality at a country level in Europe Background Many foods have an antioxidant activity and nutrition may mitigate COVID-19. Some of the countries with a low COVID-19 mortality are those with a relatively high consumption of traditional fermented foods. To test the potential role of fermented foods in COVID-19 mortality in Europe, we performed an ecological study. Methods The European Food Safety Authority (EFSA) Comprehensive European Food Consumption Database was used to study the country consumption of fermented vegetables, pickled/marinated vegetables, fermented milk, yoghurt and fermented sour milk. We obtained the COVID-19 mortality per number of inhabitants from the Johns Hopkins Coronavirus Resource Center. EuroStat data were used for data on potential confounders at the country level including Gross Domestic Product (GDP) (2019), population density (2018), percentage of people older than 64 years (2019), unemployment rate (2019) and percentage obesity (2014, to avoid missing values). Mortality counts were analyzed with quasi-Poisson regression models - with log of population as an offset - to model the death rate while accounting for over-dispersion. Results Of all the variables considered, including confounders, only fermented vegetables reached statistical significance with the COVID-19 death rate per country. For each g/day increase in the average national consumption of fermented vegetables, the mortality risk for COVID-19 decreased by 35.4% (95% CI: 11.4%, 35.5%). Adjustment did not change the point estimate and results were still significant. Discussion The negative ecological association between COVID-19 mortality and consumption of fermented vegetables supports the a priory hypothesis previously reported. The hypothesis needs to be tested in individual studies performed in countries where the consumption of fermented vegetables is common.

positive: Changing patterns of mortality during the COVID-19 pandemic: population-based modelling to understand palliative care implications Background COVID-19 has directly and indirectly caused high mortality worldwide. Aim To explore patterns of mortality during the COVID-19 pandemic and implications for palliative care provision, planning, and research. Design Descriptive analysis and population-based modelling of routine data. Participants and setting All deaths registered in England and Wales between 7th March and 15th May 2020. We described the following mortality categories by age, gender and place of death: 1) baseline deaths (deaths that would typically occur in a given period) 2) COVID-19 deaths 3) additional deaths not directly attributed to COVID-19. We estimated the proportion of COVID-19 deaths among people who would be in their last year of life in the absence of the pandemic, using simple modelling with explicit assumptions. Results During the first 10 weeks of the pandemic there were 101,615 baseline deaths, 41,105 COVID-19 deaths and 14,520 additional deaths. Deaths in care homes increased by 220% compared to home and hospital deaths which increased by 77% and 90%. Hospice deaths fell by 20%. Additional deaths were among older people (86% aged [≥]75 years), and most occurred in care homes (56%) and at home (43%). We estimate that 44% (38% to 50%) of COVID-19 deaths occurred among people who would have been in their last year of life in the absence of the pandemic. Conclusions Healthcare systems must ensure availability of palliative care to support people with severe COVID-19 in community and hospital settings. Integrated models of palliative care in care homes are urgently needed.

positive: Scrutinising the COVID-19 data on 590.000 cases. A retrospective, population-based descriptive study for data quality surveillance and a review at 4.540.000 cases. Reports on the detected positive patients with COVID-19 are as per today the best estimation of a country spread of the pandemic. In order to evaluate the early indicators for true lethality and recovery time, the data where the model is built must be quality checked. Each country sets different procedures and criteria for fatality count due to COVID-19 and the health system is stressed by having insufficient testing, untracked patients and premature discharge. In this paper the dynamics behind such data quality issues are discussed throughout the disease course to support better modeling and decision-making processes in a stressed healthcare system. From 593.291 cases in the sample, and its 7 representative groups, the recovery time and the local CFR are negatively correlated, having the highest fatality rates (21%, Spain) the countries with shorter recovery time (11 days, Spain). Also, CFR can be an indicator of Infection inconsistencies (i.e. South Korea, CFR 1%, Time to recovery 25 days). At the review part, focus is made on the inconsistencies detected in Germany and South Korea datasets as well as the potential misfits on China and Spain. Overall, the Time to Fatality ranges between 4 and 8 days, and the mean is of 6 days (South Korea, 7 days; Japan, 6days). Only Germany and France are detecting earlier than other countries and admit 10 days before fatality occurs. One simple explanation for the local CFR and Recovery time correlation is to define such rate as a measure of the healthcare system overload. Anomalous CFR indexes point to a stressed healthcare system. The higher the overload, the more focus on critical cases and hence the higher local CFR. The COVID-19 intrinsic CFR is unlikely to change by a factor of 10x from countries with similar lifestyle, GDP per capita and health services (i.e. the Mediterranean Basin, Northern Europe, etc.). Because of this fact, early CFR measured before Healthcare system overwhelming (COVID-19 free flow) are considered to be more accurate than the measured CFR while the outbreak is still ongoing, Finally, the synthetic Infection indexes may be a helpful indirect measure of the real population infection rate and also used for data quality audit. Any model built upon inconsistent data will be complex to explain and justify.

positive: 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

positive: Excess mortality in England and Wales during the first wave of the COVID-19 pandemic Background Deaths during the COVID-19 pandemic result directly from infection and exacerbation of other diseases and indirectly from deferment of care for other conditions, and are socially and geographically patterned. We quantified excess mortality in regions of England and Wales during the pandemic, for all causes and for non-COVID-19 associated deaths. Methods Weekly mortality data for 1 Jan 2010 to 1 May 2020 for England and Wales were obtained from the Office of National Statistics. Mean-dispersion negative binomial regressions were used to model death counts based on pre-pandemic trends and exponentiated linear predictions were subtracted from: i) all-cause deaths; and ii) all-cause deaths minus COVID-19 related deaths for the pandemic period (07-13 March to 25 April to 8 May). Findings Between 7 March and 8 May 2020, there were 47,243 (95%CI: 46,671 to 47,815) excess deaths in England and Wales, of which 9,948 (95%CI: 9,376 to 10,520) were not associated with COVID-19. Overall excess mortality rates varied from 49 per 100,000 (95%CI: 49 to 50) in the South West to 102 per 100,000 (95%CI: 102 to 103) in London. Non-COVID-19 associated excess mortality rates ranged from -1 per 100,000 (95%CI: -1 to 0) in Wales (i.e. mortality rates were no higher than expected) to 26 per 100,000 (95%CI: 25 to 26) in the West Midlands. Interpretation The COVID-19 pandemic has had markedly different impacts on the regions of England and Wales, both for deaths directly attributable to COVID-19 infection and for deaths resulting from the national public health response.

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

positive: Estimating the infection and case fatality ratio for coronavirus disease (COVID-19) using age-adjusted data from the outbreak on the Diamond Princess cruise ship, February 2020 Adjusting for delay from confirmation to death, we estimated case and infection fatality ratios (CFR, IFR) for coronavirus disease (COVID-19) on the Diamond Princess ship as 2.6% (95% confidence interval (CI): 0.89–6.7) and 1.3% (95% CI: 0.38–3.6), respectively. Comparing deaths on board with expected deaths based on naive CFR estimates from China, we estimated CFR and IFR in China to be 1.2% (95% CI: 0.3–2.7) and 0.6% (95% CI: 0.2–1.3), respectively.

positive: Longitudinal association between markers of liver injury and mortality in COVID‐19 in China Coronavirus disease 2019 (COVID‐19) is a new infectious disease. To reveal the hepatic injury related to this disease and its clinical significance, we conducted a multicenter retrospective cohort study that included 5,771 adult patients with COVID‐19 pneumonia in Hubei Province. We reported the distributional and temporal patterns of liver injury indicators in these patients and determined their associated factors and death risk. Longitudinal liver function tests were retrospectively analyzed and correlated with the risk factors and death. Liver injury dynamic patterns differed in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBIL). AST elevated first, followed by ALT, in severe patients. ALP modestly increased during hospitalization and largely remained in the normal range. The fluctuation in TBIL levels was mild in the non‐severe and the severe group. AST abnormality was associated with the highest mortality risk compared to other indicators of liver injury during hospitalization. Common factors associated with elevated liver injury indicators were lymphocyte count decrease, neutrophil count increase, and male gender. CONCLUSION: The dynamic patterns of liver injury indicators and their potential risk factors may provide an important explanation for the COVID‐19‐associated liver injury. Because elevated liver injury indicators, particularly AST, are strongly associated with the mortality risk, our study indicates that these parameters should be monitored during hospitalization.

positive: Are black and Hispanic persons disproportionately affected by COVID-19 because of higher obesity rates? BACKGROUND: On March 13, 2020, the World Health Organization declared COVID-19 a pandemic. Shortly after that, it was reported that mortality rates in New York City (NYC), the epicenter of the pandemic in the United States, were found to be significantly higher in black and Hispanic populations. OBJECTIVES: The aim of this article is to evaluate the mortality rates in NYC among the different ethnic groups and the different boroughs as they relate to the obesity rates to see whether this issue merits further evaluation. SETTING: NYC. METHODS: COVID-19 data were obtained from the official New York authorities in relation to total number of cases in the different boroughs of NYC. Age-adjusted COVID-19-related mortality rates of the different ethnic groups were also obtained. These data were cross-compared with historic community health data on obesity rates previously published and also obesity rates among the different ethnic groups in NYC. RESULTS: The 2 NYC boroughs that have the highest mortality rates are the Bronx (6%) and Brooklyn (5.4%). Both the Bronx and Brooklyn were also found to have the highest obesity rates at 32% and 27%, respectively. The 2 ethnic groups with the highest obesity rates (Hispanic and black) were also found to have the highest age-adjusted mortality rates per 100,000 compared with the other ethnic groups (22.8% and 19.8%, respectively). CONCLUSIONS: The Hispanic and black populations in NYC seem to be disproportionately affected by the COVID-19 pandemic because of the higher incidence of mortality rates. Obesity may have played a role in the high incidence of mortality in those ethnic groups.

positive: Using Early Data to Estimate the Actual Infection Fatality Ratio from COVID-19 in France The number of screening tests carried out in France and the methodology used to target the patients tested do not allow for a direct computation of the actual number of cases and the infection fatality ratio (IFR). The main objective of this work is to estimate the actual number of people infected with COVID-19 and to deduce the IFR during the observation window in France. We develop a ‘mechanistic-statistical’ approach coupling a SIR epidemiological model describing the unobserved epidemiological dynamics, a probabilistic model describing the data acquisition process and a statistical inference method. The actual number of infected cases in France is probably higher than the observations: we find here a factor ×8 (95%-CI: 5–12) which leads to an IFR in France of 0.5% (95%-CI: 0.3–0.8) based on hospital death counting data. Adjusting for the number of deaths in nursing homes, we obtain an IFR of 0.8% (95%-CI: 0.45–1.25). This IFR is consistent with previous findings in China (0.66%) and in the UK (0.9%) and lower than the value previously computed on the Diamond Princess cruse ship data (1.3%).

positive: Estimation of SARS-CoV-2 infection fatality rate by real-time antibody screening of blood donors Background: The pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has tremendous consequences for our societies. Knowledge of the seroprevalence of SARS-CoV-2 is needed to accurately monitor the spread of the epidemic and also to calculate the infection fatality rate (IFR). These measures may help the authorities to make informed decisions and adjust the current societal interventions. Blood donors comprise approximately 4.7% of the similarly aged population of Denmark and blood is donated in all areas of the country. The objective of this study was to perform real-time seroprevalence surveying among blood donors as a tool to estimate previous SARS-CoV-2 infections and the population based IFR. Methods: All Danish blood donors aged 17-69 years giving blood April 6 to 17 were tested for SARS-CoV-2 immunoglobulin M and G antibodies using a commercial lateral flow test. Antibody status was compared between areas and an estimate of the IFR was calculated. The seroprevalence was adjusted for assay sensitivity and specificity taking the uncertainties of the test validation into account when reporting the 95% confidence intervals (CI). Results: The first 9,496 blood donors were tested and a combined adjusted seroprevalence of 1.7% (CI: 0.9-2.3) was calculated. The seroprevalence differed across areas. Using available data on fatalities and population numbers a combined IFR in patients younger than 70 is estimated at 82 per 100,000 (CI: 59-154) infections. Conclusions: The IFR was estimated to be slightly lower than previously reported from other countries not using seroprevalence data. The IFR, including only individuals with no comorbidity, is likely several fold lower than the current estimate. This may have implications for risk mitigation. We have initiated real-time nationwide anti-SARS-CoV-2 seroprevalence surveying of blood donations as a tool in monitoring the epidemic.

positive: Cancer history is an independent risk factor for mortality in hospitalized COVID-19 patients: a propensity score-matched analysis BACKGROUND: Although research on the effects of comorbidities on coronavirus disease 2019 (COVID-19) patients is increasing, the risk of cancer history has not been evaluated for the mortality of patients with COVID-19. METHODS: In this retrospective study, we included 3232 patients with pathogen-confirmed COVID-19 who were hospitalized between January 18th and March 27th, 2020, at Tongji Hospital in Wuhan, China. Propensity score matching was used to minimize selection bias. RESULTS: In total, 2665 patients with complete clinical outcomes were analyzed. The impacts of age, sex, and comorbidities were evaluated separately using binary logistic regression analysis. The results showed that age, sex, and cancer history are independent risk factors for mortality in hospitalized COVID-19 patients. COVID-19 patients with cancer exhibited a significant increase in mortality rate (29.4% vs. 10.2%, P < 0.0001). Furthermore, the clinical outcomes of patients with hematological malignancies were worse, with a mortality rate twice that of patients with solid tumors (50% vs. 26.1%). Importantly, cancer patients with complications had a significantly higher risk of poor outcomes. One hundred nine cancer patients were matched to noncancer controls in a 1:3 ratio by propensity score matching. After propensity score matching, the cancer patients still had a higher risk of mortality than the matched noncancer patients (odds ratio (OR) 2.98, 95% confidence interval (95% CI) 1.76-5.06). Additionally, elevations in ferritin, high-sensitivity C-reactive protein, erythrocyte sedimentation rate, procalcitonin, prothrombin time, interleukin-2 (IL-2) receptor, and interleukin-6 (IL-6) were observed in cancer patients. CONCLUSIONS: We evaluated prognostic factors with epidemiological analysis and highlighted a higher risk of mortality for cancer patients with COVID-19. Importantly, cancer history was the only independent risk factor for COVID-19 among common comorbidities, while other comorbidities may act through other factors. Moreover, several laboratory parameters were significantly different between cancer patients and matched noncancer patients, which may indicate specific immune and inflammatory reactions in COVID-19 patients with cancer.

positive: Meta-analysis of Relation of Creatine kinase-MB to Risk of Mortality in Coronavirus Disease 2019 Patients Recently, several emerging papers have focused on the association of the creatine kinase-MB (CK-MB) levels with the risk of mortality in infected coronavirus disease 2019 (COVID-19) patients. However, the conclusions are inconsistent. In order to obtain a definitive conclusion on the association between the levels of CK-MB and the risk of mortality in COVID-19 patients, a quantitative meta-analysis was conducted on the basis of published data. Chinese National Knowledge Infrastructure, Web of Science and PubMed databases were extensively searched. Five studies performed in China were finally included in this meta-analysis. The overall results showed that higher levels of CK-MB were significantly associated with an increased risk of the mortality in COVID-19 infected patients (SMD 0.99; 95% CI 0.57 to 1.42; P < 0.001). In conclusion, the elevated CK-MB levels were a crucial characteristic of the mortality of COVID-19 patients.

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

positive: Acute Physiology and Chronic Health Evaluation II Score as a Predictor of Hospital Mortality in Patients of Coronavirus Disease 2019 OBJECTIVES: Coronavirus disease 2019 has emerged as a major global health threat with a great number of deaths in China. We aimed to assess the association between Acute Physiology and Chronic Health Evaluation II score and hospital mortality in patients with coronavirus disease 2019, and to compare the predictive ability of Acute Physiology and Chronic Health Evaluation II score, with Sequential Organ Failure Assessment score and Confusion, Urea, Respiratory rate, Blood pressure, Age 65 (CURB65) score. DESIGN: Retrospective observational cohort. SETTING: Tongji Hospital in Wuhan, China. SUBJECTS: Confirmed patients with coronavirus disease 2019 hospitalized in the ICU of Tongji hospital from January 10, 2020, to February 10, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 178 potentially eligible patients with symptoms of coronavirus disease 2019, 23 patients (12.92%) were diagnosed as suspected cases, and one patient (0.56%) suffered from cardiac arrest immediately after admission. Ultimately, 154 patients were enrolled in the analysis and 52 patients (33.77%) died. Mean Acute Physiology and Chronic Health Evaluation II score (23.23 ± 6.05) was much higher in deaths compared with the mean Acute Physiology and Chronic Health Evaluation II score of 10.87 ± 4.40 in survivors (p < 0.001). Acute Physiology and Chronic Health Evaluation II score was independently associated with hospital mortality (adjusted hazard ratio, 1.07; 95% CI, 1.01–1.13). In predicting hospital mortality, Acute Physiology and Chronic Health Evaluation II score demonstrated better discriminative ability (area under the curve, 0.966; 95% CI, 0.942–0.990) than Sequential Organ Failure Assessment score (area under the curve, 0.867; 95% CI, 0.808–0.926) and CURB65 score (area under the curve, 0.844; 95% CI, 0.784–0.905). Based on the cut-off value of 17, Acute Physiology and Chronic Health Evaluation II score could predict the death of patients with coronavirus disease 2019 with a sensitivity of 96.15% and a specificity of 86.27%. Kaplan-Meier analysis showed that the survivor probability of patients with coronavirus disease 2019 with Acute Physiology and Chronic Health Evaluation II score less than 17 was notably higher than that of patients with Acute Physiology and Chronic Health Evaluation II score greater than or equal to 17 (p < 0.001). CONCLUSIONS: Acute Physiology and Chronic Health Evaluation II score was an effective clinical tool to predict hospital mortality in patients with coronavirus disease 2019 compared with Sequential Organ Failure Assessment score and CURB65 score. Acute Physiology and Chronic Health Evaluation II score greater than or equal to 17 serves as an early warning indicator of death and may provide guidance to make further clinical decisions.

positive: History of coronary heart disease increases the mortality rate of COVID-19 patients: a nested case-control study Background: China has experienced an outbreak of a novel human coronavirus (SARS-CoV-2) since December 2019, which quickly became a worldwide pandemic in early 2020. There is limited evidence on the mortality risk effect of pre-existing comorbidities for coronavirus disease 2019 (COVID-19), which has important implications for early treatment. Objective: Evaluate the risk of pre-existing comorbidities on COVID-19 mortality, and provide clinical suggestions accordingly. Method: This study used a nested case-control design. A total of 94 publicly reported deaths in locations outside of Hubei Province, China, between December 18th, 2019 and March 8th, 2020 were included as cases. Each case was matched with up to three controls, based on gender and age (94 cases and 181 controls). The inverse-probability-weighted Cox proportional hazard model was performed. Results: History of comorbidities significantly increased the death risk of COVID-19: one additional pre-existing comorbidity led to an estimated 40% higher risk of death (p<0.001). The estimated mortality risk in patients with CHD was three times of those without CHD (p<0.001). The estimated 30-day survival probability for a profile patient with pre-existing CHD (65-year-old female with no other comorbidities) was 0.53 (95% CI [0.34-0.82]), while it was 0.85 (95% CI [0.79-0.91]) for those without CHD. Older age was also associated with increased death risk: every 5-year increase in age was associated with a 20% increased risk of mortality (p<0.001). Conclusion: Extra care and early medical intervention are needed for patients with pre-existing comorbidities, especially CHD.

positive: 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: Is BCG vaccination causally related to reduced COVID‐19 mortality? The ongoing severe acute respiratory sickness coronavirus 2 (SARS‐CoV‐2) pandemic has resulted in more than 3,600,000 detected cases of COVID‐19 illness and nearly 260,000 deaths worldwide as of May 6, 2020. Recently, BCG vaccination was shown to correlate with reduced COVID‐19 case fatality rates (preprint: Miller et al, 2020; preprint: Sala & Miyakawa, 2020; https://www.jsatonotes.com/2020/03/if-i-were-north-americaneuropeanaustral.html). The most recent data from publicly available resources also indicate that both COVID‐19 incidence and total deaths are strongly associated with the presence or absence of national mandatory BCG vaccination programs. As seen in Table 1, seven of eight countries with very low numbers of total deaths (< 40 per 1 million population) adopted a mandatory BCG vaccination program using one of a set of 6 separate BCG strains (Table 1). In contrast, COVID‐19 mortality was markedly higher in countries where BCG vaccination is not widely administered or is given only to high‐risk groups. COVID‐19 mortality was also higher in countries where widespread BCG vaccination was discontinued more than 20 years ago and in countries that used the BCG Denmark strain regularly or temporarily. This raises the question of whether BCG vaccination and reduced COVID‐19 mortality are causally related. An additional question is why different BCG strains may be variably associated with mortality.

positive: COVID-19 and diabetes mellitus: what we know, how our patients should be treated now, and what should happen next

positive: [Covid-19 - deaths and analysis]. Mortality from Covid-19 is monitored in detail and compared between countries with different strategies against the virus. There is, however, often a lack of understanding of what is required in terms of measures and interpretation to enable correct comparisons. The number of deaths from Covid-19 is affected by the testing strategy and many other things that differ between countries. Therefore, today, the most reliable source for monitoring and comparing mortality from Covid-19 is total mortality. In Sweden, there is good correspondence of Covid-19 deaths and total mortality, with a tendency to a higher total mortality indicating some under-reporting of Covid-19 mortality.

positive: Predicted COVID-19 fatality rates based on age, sex, comorbidities, and health system capacity Early reports suggest the fatality rate from COVID-19 varies greatly across countries, but non-random testing and incomplete vital registration systems render it impossible to directly estimate the infection fatality rate (IFR) in many low- and middle-income countries. To fill this gap, we estimate the adjustments required to extrapolate estimates of the IFR from high- to lower-income regions. Accounting for differences in the distribution of age, sex, and relevant comorbidities yields substantial differences in the predicted IFR across 21 world regions, ranging from 0.11% in Western Sub-Saharan Africa to 0.95% for High Income Asia Pacific. However, these predictions must be treated as lower bounds, as they are grounded in fatality rates from countries with advanced health systems. In order to adjust for health system capacity, we incorporate regional differences in the relative odds of infection fatality from childhood influenza. This adjustment greatly diminishes, but does not entirely erase, the demography-based advantage predicted in the lowest income settings, with regional estimates of the predicted COVID-19 IFR ranging from 0.43% in Western Sub-Saharan Africa to 1.74% for Eastern Europe.

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

positive: Estimating the cure rate and case fatality rate of the ongoing epidemic COVID-19 The epidemic caused by the novel coronavirus COVID-19 in Wuhan at the end of 2019 has become an urgent public event of worldwide concern. However, due to the changing data of the epidemic, there is no scientific estimate of the cure rate and case fatality rate of the epidemic. This study proposes a method to estimate the cure rate and case fatality rate of COVID-19. The ratio of cumulative discharges on a given day to the sum of cumulative discharges on a given day and cumulative deaths before j days is used to estimate the cure rate. Moreover, the case fatality ratio can also be estimated. After simulation calculations, j is statistically appropriate when it is 8-10, and it is also clinically appropriate. When j is 9, based on the available data, it is inferred that the cure rate of this epidemic is about 93% and the case fatality rate is about 7%. This method of estimating the cure rate can be used to evaluate the effectiveness of treatment in different medical schemes and different regions, and has great value and significance for decision-making in the epidemic.

positive: Gender differences in patients with COVID-19: Focus on severity and mortality Importance: The recent outbreak of Novel Coronavirus (SARS-CoV-2) Disease (COVID-19) has put the world on alert, that is reminiscent of the SARS outbreak seventeen years ago. Objective: We aim to compare the severity and mortality between male and female patients with both COVID-19 and SARS, to explore the most useful prognostic factors for individualized assessment. Design, Setting, and Participants: We extracted the data from a case series of 43 hospitalized patients we treated, a public data set of the first 37 cases died of COVID-19 in Wuhan city and 1019 survived patients from six cities in China. We also analyzed the data of 524 patients with SARS, including 139 deaths, from Beijing city in early 2003. Main Outcomes and Measures: Severity and mortality. Results: Older age and high number of comorbidities were associated with higher severity and mortality in patients with both COVID-19 and SARS. The percentages of older age (≥65 years) were much higher in the deceased group than in the survived group in patients with both COVID-19 (83.8 vs. 13.2, P<0.001) and SARS (37.4 vs. 4.9, P<0.001). In the case series, men tend to be more serious than women (P=0.035), although age was comparable between men and women. In the public data set, age was also comparable between men and women in the deceased group or the survived group in patients with COVID-19. Meanwhile, gender distribution was exactly symmetrical in the 1019 survivors of COVID-19. However, the percentage of male were higher in the deceased group than in the survived group (70.3 vs. 50.0, P=0.015). The gender role in mortality was also observed in SARS patients. Survival analysis showed that men (hazard ratio [95% CI] 1.47 [1.05-2.06, P= 0.025) had a significantly higher mortality rate than women in patients with SARS. Conclusions and Relevance: Older age and male gender are risk factors for worse outcome in patients with COVID. While men and women have the same susceptibility to both SARS-CoV-2 and SARS-CoV, men may be more prone to have higher severity and mortality independent of age and susceptibility.

positive: 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.

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

positive: Characteristics and outcomes of a cohort of SARS-CoV-2 patients in the Province of Reggio Emilia, Italy Objectives. To describe the age- and sex-specific prevalence of SARS-CoV-2 disease (COVID-19) and its prognostic factors. Design. Population-based prospective cohort study on archive data. Setting. Preventive services and hospital care in the province of Reggio Emilia, Northern Italy. Participants. All 2653 symptomatic patients who tested positive for SARS-CoV-2 from February 27 to April 2, 2020 in the province of Reggio Emilia. Main outcome measures. Hospitalization and death up to April 2, 2020. Results. Females had higher prevalence of infection than males below age 50 (2.61 vs. 1.84 per 1000), but lower in older ages (16.49 vs. 20.86 per 1000 over age 80). Case fatality rate reached 20.7% (22/106) in cases with more than 4 weeks follow up. After adjusting for age and comorbidities, men had a higher risk of hospitalization (hazard ratio (HR) 1.4 95% confidence interval (95% CI) 1.2 to 1.6) and of death (HR 1.6, 95% CI 1.2 to 2.1). Patients over age 80 compared to < age 50 had HR 7.1 (95% CI 5.4 to 9.3) and HR 27.8 (95% CI 12.5 to 61.7) for hospitalization and death, respectively. Immigrants had a higher risk of hospitalization (HR 1.3, 95% CI 0.99 to 1.81) than Italians and a similar risk of death. Risk of hospitalization and of death were higher in patients with heart failure (HR 1.6, 95% CI 1.2 to 2.1and HR 2.3, 95% CI 1.6 to 3.2, respectively), arrhythmia (HR 1.5, 95% CI 1.2 to 1.9 and HR 1.8, 95% CI 1.3 to 2.5, respectively), dementia (HR 1.2, 95% CI 0.9 to 1.8 and HR 1.8, 95% CI 1.1 to 2.8, respectively), ischemic heart disease (HR 1.3, 95% CI 1.0 to 1.7 and HR 1.7, 95% CI 1.2 to 2.5, respectively), diabetes (HR 1.5, 95% CI 1.3 to 1.9 and HR 1.6, 95% CI 1.1 to 2.2, respectively), and hypertensions(HR 1.4, 95% CI 1.2 to 2.6 and HR 1.6, 95% CI 1.2 to 2.1, respectively), while COPD increased the risk of hospitalization (HR 1.9, 95% CI 1.4 to 2.5) but not of death (HR 1.1, 95% CI 0.7 to 1.7). Previous use of ACE inhibitors has no effect on risk of death (HR 0.97, 95% CI 0.69 to 1.34) Conclusions. The mechanisms underlying these associations are mostly unknown. A deeper understanding of the causal chain from infection, disease onset, and immune response to outcomes may explain how these prognostic factors act.

positive: Addressing inequities in COVID-19 morbidity and mortality: research and policy recommendations The COVID-19 pandemic is the greatest global public health crisis since the 1918 influenza outbreak. As of early June, the novel coronavirus has infected more than 6.3 million people worldwide and more than 1.9 million in the United States (US). The total number of recorded deaths due to COVID-19 are growing at an alarming rate globally (³383,000) and nationally (³109,000) Evidence is mounting regarding the heavier burden of COVID-19 infection, morbidity, and mortality on the underserved populations in the US. This commentary focuses on this global health pandemic and how mitigation of the virus relies heavily on health behavior change to slow its spread, highlighting how the pandemic specifically affects the most socially and economically disadvantaged populations in the US. The commentary also offers short, intermediate and long-term research and policy focused recommendations. Both the research and policy recommendations included in this commentary emphasize equity-driven: (1) research practices, including applying a social determinants and health equity lens on monitoring, evaluation, and clinical trials activities on COVID-19; and (2) policy actions, such as dedicating resources to prioritize high-risk communities for testing, treatment, and prevention approaches and implementing organizational, institutional, and legislative policies that address the social and economic barriers to overall well-being that these populations face during a pandemic. It is our hope that these recommendations will generate momentum in delivering timely, effective, and lifesaving changes.

positive: The novel Coronavirus (SARS-CoV-2) is a one health issue

positive: Arterial hypertension and risk of death in patients with COVID-19 infection: systematic review and meta-analysis

positive: Estimating weekly excess mortality at subnational level in Italy during the COVID-19 pandemic Background Excess mortality from all-cause has been estimated at national level for different countries, to provide a picture of the total burden of the COVID-19 pandemic. Nevertheless, there have been no attempts at modelling it at high spatial resolution, needed to understand geographical differences in the mortality patterns, to evaluate temporal lags and to plan for future waves of the pandemic. Methods This is the first subnational study on excess mortality during the COVID-19 pandemic in Italy, the third most-hit country. We considered municipality level and estimated all-cause mortality weekly trends based on the first four months of 2016 -- 2019. We specified a Bayesian hierarchical model allowing for spatial heterogeneity as well as for non-linear smooth spatio-temporal terms. We predicted the weekly mortality rates at municipality level for 2020 based on the modelled spatio-temporal trends (i.e.~in the absence of the pandemic) and estimated the excess mortality and the uncertainty surrounding it. Results We found strong evidence of excess mortality for Northern Italy, with higher mortality rates than expected from the end of February in Lombardia, with total excess deaths of 23,946 (23,013 -- 24,786), and the beginning of March for North East and North West with total excess deaths of 8,033 (7,061 -- 9,044) and 1,588 (404 -- 2,700) respectively. We found marked geographical differences, with percent excess of up to 88.9% (81.9% -- 95.2%) at the peak of the pandemic, in the city of Bergamo (Lombardia).

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

positive: Association between platelet parameters and mortality in coronavirus disease 2019: Retrospective cohort study BACKGROUND: Thrombocytopenia has been implicated in patients infected with severe acute respiratory syndrome coronavirus 2, while the association of platelet count and changes with subsequent mortality remains unclear. METHODS: The clinical and laboratory data of 383 patients with the definite outcome by March 1, 2020 in the Central Hospital of Wuhan were reviewed. The association between platelet parameters and mortality risk was estimated by utilizing Cox proportional hazard regression models. RESULTS: Among the 383 patients, 334 (87.2%) were discharged and survived, and 49 (12.8%) died. Thrombocytopenia at admission was associated with mortality of almost three times as high as that for those without thrombocytopenia (P < 0.05). Cox regression analyses revealed that platelet count was an independent risk factor associated with in-hospital mortality in a dose-dependent manner. An increment of per 50 × 109/L in platelets was associated with a 40% decrease in mortality (hazard ratio: 0.60, 95%CI: 0.43, 0.84). Dynamic changes of platelets were also closely related to death during hospitalization. CONCLUSIONS: Baseline platelet levels and changes were associated with subsequent mortality. Monitoring platelets during hospitalization may be important in the prognosis of patients with coronavirus disease in 2019.

positive: Estimating the risk of COVID-19 death during the course of the outbreak in Korea, February-March, 2020 Background: In Korea, a total of 8,799 confirmed cases of COVID-19 including 102 deaths have been recorded as of Mar 21, 2020. The time-delay adjusted case fatality risk of COVID-19 in Korea is yet to be estimated. Methods: We obtained the daily series of confirmed cases and deaths in Korea reported prior to March 21,2020. Using statistical methods, we estimated the time-delay adjusted risk for death from COVID-19 in the city of Daegu, Gyeongsangbuk-do, other regions in Korea, as well as for the entire country. Results: Our model-based crude CFR fitted the observed data well throughout the course of the epidemic except for the very early stage in Gyeongsangbuk-do, partially due to the reporting delay. Our estimates of the risk for death in Gyeongsangbuk-do reached 2.4% (95% CrI: 1.6-3.4%), 1.3% (95% CrI: 1.0-1.6%) in Daegu and 0.7% (95% CrI: 0.3-1.4%) in other regions, whereas the national estimate of the risk for death was estimated at 1.4% (95% CrI: 1.2-1.7%) in Korea. Conclusions: The relatively low CFRs are associated with the early implementation of public health interventions including widespread testing, social distancing, and delayed school openings in Korea. Geographic differences in CFR are likely influenced by clusters of nosocomial transmission.

positive: Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study BACKGROUND: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. METHODS: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. FINDINGS: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 82·6% (219 of 265) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p<0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p<0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p<0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). INTERPRETATION: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. FUNDING: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research.

positive: Mental health and COVID-19: is the virus racist? COVID-19 has changed our lives and it appears to be especially harmful for some groups more than others. Black and Asian ethnic minorities are at particular risk and have reported greater mortality and intensive care needs. Mental illnesses are more common among Black and ethnic minorities, as are crisis care pathways including compulsory admission. This editorial sets out what might underlie these two phenomena, explaining how societal structures and disadvantage generate and can escalate inequalities in crises.

positive: Beyond Deaths per Capita: Three CoViD-19 Mortality Indicators for Temporal and International Comparisons CoViD-19 deaths to population size ratios fail to account for well-documented age and sex differences in CoViD-19 mortality. To assess trends across populations for which CoViD-19 deaths might not be available by age and sex, an indirect age-and-sex adjustment can still be performed. The corresponding Comparative CoViD-19 Mortality Ratio (CCMR) only requires population age and sex compositions. To compare CoViD-19 and overall mortality levels, the Crude Death Rate (CDR) and life expectancy at birth for recent calendar years are the most widely available overall mortality indicators. Readily comparable to an annual CDR, a Crude CoViD-19 Death Rate (CCDR) can be calculated for periods of any duration. CoViD-19-induced declines in projected life expectancy at birth for 2020 can also be calculated from existing life tables. We calculate the CCMR and CCDR for the period from their first CoViD-19 death to the present using US age and sex data and current estimates of CoViD-19 deaths in 166 Countries whose population composition is available from the UN, 28 Provinces in China, the 50 United States and DC. Across these 245 populations, 14 States and 11 Countries have CCMR values above 1—the US value by construction. Most affected to date, the period CCDR in New York exceeds its CDR for the most recent year available (7.83 per thousand in 2017). We also calculate CCMR and CCDR values corresponding to projections for the 50 States and DC, and for 49 countries, for which we can additionally calculate reductions in 2020 life expectancy at birth using UN life tables. This suggests life-expectancy reductions between .5 and 1 year for 7 European Countries, 3 South-American Countries and the US. The .55 reduction in the U.S. amounts to nearly twice the largest single-year decline induced by HIV/AIDS (−.3 between 1992 and 1993) or the total decline induced by opioid overdoses (also −.3 between 2014 and 2017), and would bring US life expectancy at birth down to its lowest level since 2008. As current CoViD-19 death counts likely underestimate the total increase in deaths and current projections do not account for possible new infection waves later this year, the impact on 2020 life expectancies at birth should be expected to exceed these figures.

positive: The overall mortality caused by COVID-19 in the European region is highly associated with demographic composition: A spatial regression-based approach The demographic factors have a substantial impact on the overall casualties caused by the COVID-19. In this study, the spatial association between the key demographic variables and COVID-19 cases and deaths were analyzed using the spatial regression models. Total 13 (for COVID-19 case factor) and 8 (for COVID-19 death factor) key variables were considered for the modelling. Total five spatial regression models such as Geographically weighted regression (GWR), Spatial Error Model (SEM), Spatial Lag Model (SLM), Spatial Error_Lag model (SEM_SLM), and Ordinary Least Square (OLS) were performed for the spatial modelling and mapping of model estimates. The local R2 values, which suggesting the influences of the selected demographic variables on overall casualties caused by COVID-19, was found highest in Italy and the UK. The moderate local R2 was observed for France, Belgium, Netherlands, Ireland, Denmark, Norway, Sweden, Poland, Slovakia, and Romania. The lowest local R2 value for COVID-19 cases was accounted for Latvia and Lithuania. Among the 13 variables, the highest local R2 was calculated for total population (R2 = 0.92), followed by death crude death rate (R2 = 0.9), long time illness (R2 = 0.84), population with age>80 (R2 = 0.59), employment (R2 = 0.46), life expectancy at 65 (R2 = 0.34), crude birth rate (R2 = 0.31), life expectancy (R2 = 0.31), Population with age 65-80 (R2 = 0.29), Population with age 15-24 (R2 = 0.27), Population with age 25-49 (R2 = 0.27), Population with age 0-14 (R2 = 0.23), and Population with age 50-65 (R2 = 0.23), respectively.

positive: Prevalence, Severity and Mortality associated with COPD and Smoking in patients with COVID-19: A Rapid Systematic Review and Meta-Analysis Background: Coronavirus disease 2019 (COVID-19) is an evolving infectious disease that dramatically spread all over the world in the early part of 2020. No studies have yet summarised the potential severity and mortality risks caused by COVID-19 in patients with chronic obstructive pulmonary disease (COPD), and we update information in smokers. Methods: We systematically searched electronic databases from inception to March 24, 2020. Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Study quality was assessed using a modified version of the Newcastle Ottawa Scale. We synthesised a narrative from eligible studies and conducted a meta-analysis using a random-effects model to calculate pooled prevalence rates and 95% confidence intervals (95%CI). Results: In total, 123 abstracts were screened and 61 full-text manuscripts were reviewed. A total of 15 studies met the inclusion criteria, which included a total of 2473 confirmed COVID-19 patients. All studies were included in the meta-analysis. The crude case fatality rate of COVID-19 was 6.4%. The pooled prevalence rates of COPD patients and smokers in COVID-19 cases were 2% (95% CI, 1%-3%) and 9% (95% CI, 4%-14%) respectively. COPD patients were at a higher risk of more severe disease (risk of severity = 63%, (22/35) compared to patients without COPD 33.4% (409/1224) [calculated RR, 1.88 (95% CI, 1.4-2.4)]. This was associated with higher mortality (60%). Our results showed that 22% (31/139) of current smokers and 46% (13/28) of ex-smokers had severe complications. The calculated RR showed that current smokers were 1.45 times more likely [95% CI: 1.03-2.04] to have severe complications compared to former and never smokers. Current smokers also had a higher mortality rate of 38.5%. Conclusion: Although COPD prevalence in COVID-19 cases was low in current reports, COVID-19 infection was associated with substantial severity and mortality rates in COPD. Compared to former and never smokers, current smokers were at greater risk of severe complications and higher mortality rate. Effective preventive measures are required to reduce COVID-19 risk in COPD patients and current smokers.

positive: Deaths from Covid-19: Who are the forgotten victims? Background: With the spreading global pandemic of coronavirus disease 2019 (Covid-19) there has been disruption to normal clinical activity in response to the increased demand on health services. There are reports of a reduction in non-Covid-19 emergency presentations. Consequentially, there are concerns that deaths from non-Covid-19 causes could increase. We examined recent reported population-based mortality rates, compared with expected rates, and compared any excess in deaths with the number of deaths attributed to Covid-19. Methods: National agency and death registration reports were searched for numbers of deaths attributed to Covid-19 and overall mortality that had been publicly reported by 16 April 2020. Data on the number of deaths attributed to Covid-19, the total number of deaths registered in the population and the historical average over at least 3 years were collected. Data were available for 3 Northern European countries (England & Wales, Scotland and the Netherlands) and New York State, United States of America. Results: There was an increase in observed, compared with expected, mortality in Scotland (+27%), England and Wales (+35%), the Netherlands (+60%) and New York state (+26%). Of these deaths, only 43% in Scotland and England and Wales, 49% in the Netherlands and 30% in New York state were attributed to Covid-19 leaving a number of excess deaths not attributed to Covid-19. Conclusions: A substantial proportion of excess deaths observed during the current COVID-19 pandemic are not attributed to COVID-19 and may represent an excess of deaths due to other causes.

positive: The infection fatality rate of COVID-19 inferred from seroprevalence data Objective To estimate the infection fatality rate of coronavirus disease 2019 (COVID-19) from data of seroprevalence studies. Methods Population studies with sample size of at least 500 and published as peer-reviewed papers or preprints as of May 12, 2020 were retrieved from PubMed, preprint servers, and communications with experts. Studies on blood donors were included, but studies on healthcare workers were excluded. The studies were assessed for design features and seroprevalence estimates. Infection fatality rate was estimated from each study dividing the number of COVID-19 deaths at a relevant time point by the number of estimated people infected in each relevant region. Correction was also attempted accounting for the types of antibodies assessed. Results Twelve studies were identified with usable data to enter into calculations. Seroprevalence estimates ranged from 0.113% to 25.9% and adjusted seroprevalence estimates ranged from 0.309% to 33%. Infection fatality rates ranged from 0.03% to 0.50% and corrected values ranged from 0.02% to 0.40%. Conclusions The infection fatality rate of COVID-19 can vary substantially across different locations and this may reflect differences in population age structure and case-mix of infected and deceased patients as well as multiple other factors. Estimates of infection fatality rates inferred from seroprevalence studies tend to be much lower than original speculations made in the early days of the pandemic.

positive: What Can We Estimate from Fatality and Infectious Case Data using the Susceptible-Infected-Removed (SIR) model? A case Study of Covid-19 Pandemic The rapidly spreading Covid-19 that affected almost all countries, was first reported at the end of 2019. As a consequence of its highly infectious nature, countries all over the world have imposed extremely strict measures to control its spread. Since the earliest stages of this major pandemic, academics have done a huge amount of research in order to understand the disease, develop medication, vaccines and tests, and model its spread. Among these studies, a great deal of effort has been invested in the estimation of epidemic parameters in the early stage, for the countries affected by Covid-19, hence to predict the course of the epidemic but the variability of the controls over the course of the epidemic complicated the modeling processes. In this article, the determination of the basic reproduction number, the mean duration of the infectious period, the estimation of the timing of the peak of the epidemic wave is discussed using early phase data. Daily case reports and daily fatalities for ten countries over the period January 22, 2020 - April 18, 2020 are evaluated using the Susceptible-Infected-Removed (SIR) model. For each country, the SIR models fitting cumulative infective case data within 5% error are analysed. It is observed that the basic reproduction number and the mean duration of the infectious period can be estimated only in cases where the spread of the epidemic is over (for China and South Korea in the present case). Nevertheless, it is shown that the timing of the maximum and timings of the inflection points of the proportion of infected individuals can be robustly estimated from the normalized data. The validation of the estimates by comparing the predictions with actual data has shown that the predictions were realised for all countries except USA, as long as lock-down measures were retained.

positive: Understanding the asymmetric spread and case fatality rate (CFR) for COVID-19 among countries The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are rising rapidly every day in the world, causing the disease COVID-19 with around 2 million people infected and more than 100,000 people died so far, in more than 200 countries. One of the baffling aspects of this pandemic is the asymmetric increase in cases and case fatality rate (CFR) among countries. We analyze the time series of the infection and fatality numbers and found two interesting aspects. Firstly, the rate of spread in a region is directly connected to the population density of the region where the virus is spreading. For example, the high rate of increase in cases in the United States of America (USA) is related to the high population density of New York City. This is shown by scaling the cumulative number of cases with a measure of the population density of the affected region in countries such as Italy, Spain, Germany, and the USA and we see that the curves are coinciding. Secondly, we analyzed the CFR number as a function of the number of days, since the first death, and we found that there are two clear categories among countries: one category with high CFR numbers (around 10%) and the other category with low CFR numbers (2% to 4%). When we analyzed the results, we see that countries with lower CFR numbers more or less tend to have implemented active control measures such as aggressive testing, tracking down possible infections, effective quarantine measures, etc. Moreover, we did not see any convincing correlation between mortality rates and the median age of the population.

positive: Performing risk stratification for COVID-19 when individual level data is not available, the experience of a large healthcare organization With the global coronavirus disease 2019 (COVID-19) pandemic, there is an urgent need for risk stratification tools to support prevention and treatment decisions. The Centers for Disease Control and Prevention (CDC) listed several criteria that define high-risk individuals, but multivariable prediction models may allow for a more accurate and granular risk evaluation. In the early days of the pandemic, when individual level data required for training prediction models was not available, a large healthcare organization developed a prediction model for supporting its COVID-19 policy using a hybrid strategy. The model was constructed on a baseline predictor to rank patients according to their risk for severe respiratory infection or sepsis (trained using over one-million patient records) and was then post-processed to calibrate the predictions to reported COVID-19 case fatality rates. Since its deployment in mid-March, this predictor was integrated into many decision-processes in the organization that involved allocating limited resources. With the accumulation of enough COVID-19 patients, the predictor was validated for its accuracy in predicting COVID-19 mortality among all COVID-19 cases in the organization (3,176, 3.1% death rate). The predictor was found to have good discrimination, with an area under the receiver-operating characteristics curve of 0.942. Calibration was also good, with a marked improvement compared to the calibration of the baseline model when evaluated for the COVID-19 mortality outcome. While the CDC criteria identify 41% of the population as high-risk with a resulting sensitivity of 97%, a 5% absolute risk cutoff by the model tags only 14% to be at high-risk while still achieving a sensitivity of 90%. To summarize, we found that even in the midst of a pandemic, shrouded in epidemiologic "fog of war" and with no individual level data, it was possible to provide a useful predictor with good discrimination and calibration.

positive: Potential association between COVID-19 mortality and health-care resource availability

positive: 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; I2=29%; unadjusted OR 3.67, 95% CI 2.31 to 5.83; I2=57%, respectively). Acute cardiac injury was also associated with a higher unadjusted odds of 21.15 (95% CI 10.19 to 43.94; I2=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.

positive: Reducing mortality and morbidity in patients with severe COVID-19 disease by advancing ongoing trials of Mesenchymal Stromal (stem) Cell (MSC) therapy - achieving global consensus and visibility for cellular host-directed therapies Abstract As of May 11th 2020, the coronavirus disease 2019 (COVID-19) pandemic, caused by the novel, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused 274,361 deaths out of 3,917,366 (7% case fatality rate). As with the two other novel coronavirus zoonotic diseases of humans, SARS and MERS, no specific treatments for reducing mortality or morbidity are yet available. Deaths from COVID-19 will continue to rise globally until effective and appropriate treatments and vaccines are found. With no specific treatments being available for treating COVID-19 patients, the global medical, scientific, pharma and funding communities have rapidly initiated over 500 COVID-19 clinical on a range of antiviral drug regimens, biologics, repurposed drugs in various combinations. We focus this editorial specifically on the background to, and the rationale for, the use and evaluation of mesenchymal stromal (Stem) cells (MSCs) in treatment trials of patients with severe COVID-19 disease. This is an area which has been eclipsed by the current emphasis the huge number of trials evaluating new anti-viral drugs, repurposed drugs and combinations thereof. MSCs should also be trialed for treatment of severe cases of MERS where mortality rates are upto 34% and MERS-CoV remains a WHO priority Blueprint pathogen. It’s about time funding agencies now invest more into development MSCs per se and other host-directed therapies in combination with other therapeutic interventions. MSC therapy could turn out to be an important contribution to bringing an end to the high COVID-19 and MERS death rates.

positive: Differential mortality in COVID-19 patients from India and western countries BACKGROUND AND AIMS: COVID-19 disease has been associated with disproportionate mortality amongst world population. We try to elucidate various reasons for lower mortality rate in the Indian subcontinent due to COVID-19 pandemic. METHOD: We carried out a comprehensive review of the literature using suitable keywords such as ‘COVID-19’, ‘Pandemics’, ‘disease outbreaks’ and ‘India’ on the search engines of PubMed, SCOPUS, Google Scholar and Research Gate in the month of May 2020 during the current COVID-19 pandemic and assessed mortality data. RESULTS: The mortality observed in Indian and south Asian subcontinent is lower than in the west. Multifactorial reasons indicated for this differential mortality due to COVID-19 have been described in the current literature. CONCLUSIONS: The effects of COVID-19 on the health of racial and ethnic minority groups are still emerging with disproportionate burden of illness and death amongst some black and ethnic minority groups. Overall the current COVID-19 related mortality appears to be lower in the health and resource challenged populous Indian subcontinent. Further scientific studies would be helpful to understand this disparity in mortality due to COVID-19 in the world population.

positive: Morbid Obesity as an Independent Risk Factor for COVID-19 Mortality in Hospitalized Patients Younger than 50 OBJECTIVE: COVID-19 continues to spread and younger patients are also being critically affected. This study analyzed obesity as an independent risk factor for mortality in hospitalized patients younger than fifty. METHODS: We retrospectively analyzed data of COVID-19 patients hospitalized to a large academic hospital system in New York City between March 1st and May 17th, 2020. Data included demographics, comorbidities, BMI and smoking status. Obesity groups included: BMI 30-40 kg/m2 and BMI ≥ 40 kg/m2 . Multivariable logistic regression models identified variables independently associated with mortality in patients younger and older than 50. RESULTS: Overall, 3,406 patients were included. 572 (17.0%) of the patients were younger than 50. In the younger age group, 60 (10.5%) patients died. In the older age group, 1,076 (38.0%) patients died. For the younger population, BMI above 40 kg/m2 was independently associated with mortality (aOR 5.1, 95% CI 2.3-11.1). For the older population, BMI above 40 kg/m2 was also independently associated with mortality to a lesser extent (aOR 1.6, 95% CI 1.2 - 2.3). CONCLUSION: Our study demonstrates that hospitalized patients younger than 50 with morbid obesity are more likely to die from COVID-19. This is particularly relevant in the western world where obesity rates are high.

positive: A scaling approach to estimate the COVID-19 infection fatality ratio from incomplete data SARS-CoV-2 has disrupted the life of billions of people around the world since the first outbreak was officially declared in China at the beginning of 2020. Yet, important questions such as how deadly it is or its degree of spread within different countries remain unanswered. In this work, we exploit the `universal' growth of the mortality rate with age observed in different countries since the beginning of their respective outbreaks, combined with the results of the antibody prevalence tests in the population of Spain, to unveil both unknowns. We validate these results with an analogous antibody rate survey in the canton of Geneva, Switzerland. We also argue that the official number of deaths over 70 years old is importantly underestimated in most of the countries, and we use the comparison between the official records with the number of deaths mentioning COVID-19 in the death certificates to quantify by how much. Using this information, we estimate the fatality infection ratio (IFR) for the different age segments and the fraction of the population infected in different countries assuming a uniform exposure to the virus in all age segments. We also give estimations for the non-uniform IFR using the sero-epidemiological results of Spain, showing a very similar growth of the fatality ratio with age. Only for Spain, we estimate the probability (if infected) of being identified as a case, being hospitalized or admitted in the intensive care units as function of age. In general, we observe a nearly exponential growth of the fatality ratio with age, which anticipates large differences in total IFR in countries with different demographic distributions, with numbers that range from 1.82\% in Italy, to 0.62\% in China or even 0.14\% in middle Africa.

positive: Interaction between malarial transmission and BCG vaccination with COVID-19 incidence in the world map: A changing landscape human immune system? Background: COVID-19 (Corona virus Disease-2019) is a new public health emergency and is a pandemic currently. Incidence and mortality of COVID-19 vary in different geographical areas. In this study we aimed to analyse the relationship between malaria transmission and BCG vaccination with COVID-19 incidence in the world map. Materials and methods: We collected malaria cases data (World Health Organisation (WHO), 2018), worldwide COVID-19 cases and mortality data (European Centre for Disease Prevention and Control) and data on BCG vaccination. COVID-19 incidence and mortality was compared. Findings: Data on 5316978938 persons from 166 countries were analysed. Malaria incidence rate was negatively correlated with COVID-19 incidence rate (correlation coefficient = -0.513, p<0.001). Malaria free countries had significantly higher number of COVID-19 cases compared to malaria endemic countries. In Europe and Americas, countries, which have higher BCG vaccination coverage, had significantly less mortality per thousand population compared to those with low BCG coverage (median 0.0002 (0-0.0005) vs 0.0029 (0.0002-0.0177), p=0.017). The case fatality ratio of COVID-19 was related nonlinearly to the malaria incidence. Conclusions: The results suggest the changing human immune system as we progress to eliminate parasitic diseases with time. Chloroquine exposure in malaria endemic zones might have a protective effect.

positive: High rates of 30-day mortality in patients with cirrhosis and COVID-19 BACKGROUND AND AIMS: Coronavirus disease (COVID-19) is a major worldwide threat for healthy individuals as well as for patients with comorbidities, but its impact on patients with cirrhosis is currently unknown. This study aimed at evaluating the impact of COVID-19 on the clinical outcome of these patients. METHODS: In this multicenter retrospective study, cirrhotic patients with confirmed Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection were enrolled between 1st and 31th March 2020. Clinical and biochemical data at COVID-19 and at the last outpatient visit were obtained through review of medical records. RESULTS: Fifty cirrhotic patients with confirmed SARS-CoV-2 infection were enrolled (age 67 years, 70% men, 38% virus-related, 52% previously compensated cirrhosis). At diagnosis, 64% of patients presented fever, 42% shortness of breath/polypnea, 22% encephalopathy, 96% needed hospitalization or prolonged an ongoing one. Respiratory-support was necessary in 71%, 52% received antivirals, 80% heparin. Serum albumin significantly decreased, while bilirubin, creatinine and prothrombin time significantly increased at COVID-19 diagnosis compared to last available data. The proportion of patients with MELD≥15 increased from 13% to 26% (p=0.037), acute-on-chronic liver failure and and de novo acute liver injury occurred in 14 (28%) and 10 patients, respectively. Seventeen patients died after a median of 10 (4-13) days from COVID-19 diagnosis, with a 30-day-mortality rate of 34%. Severity of lung and liver (according to CLIF-C, CLIF-OF and MELD scores) diseases independently predicted mortality. Mortality was significantly higher in hospitalized cirrhotics with COVID-19 than in those hospitalized for bacterial infections. CONCLUSION: COVID-19 is associated with liver function deterioration and elevated mortality in cirrhotic patients.

positive: Estimating excess 1-year mortality associated with the COVID-19 pandemic according to underlying conditions and age: a population-based cohort study BACKGROUND: The medical, societal, and economic impact of the coronavirus disease 2019 (COVID-19) pandemic has unknown effects on overall population mortality. Previous models of population mortality are based on death over days among infected people, nearly all of whom thus far have underlying conditions. Models have not incorporated information on high-risk conditions or their longer-term baseline (pre-COVID-19) mortality. We estimated the excess number of deaths over 1 year under different COVID-19 incidence scenarios based on varying levels of transmission suppression and differing mortality impacts based on different relative risks for the disease. METHODS: In this population-based cohort study, we used linked primary and secondary care electronic health records from England (Health Data Research UK-CALIBER). We report prevalence of underlying conditions defined by Public Health England guidelines (from March 16, 2020) in individuals aged 30 years or older registered with a practice between 1997 and 2017, using validated, openly available phenotypes for each condition. We estimated 1-year mortality in each condition, developing simple models (and a tool for calculation) of excess COVID-19-related deaths, assuming relative impact (as relative risks [RRs]) of the COVID-19 pandemic (compared with background mortality) of 1·5, 2·0, and 3·0 at differing infection rate scenarios, including full suppression (0·001%), partial suppression (1%), mitigation (10%), and do nothing (80%). We also developed an online, public, prototype risk calculator for excess death estimation. FINDINGS: We included 3â862â012 individuals (1â957â935 [50·7%] women and 1â904â077 [49·3%] men). We estimated that more than 20% of the study population are in the high-risk category, of whom 13·7% were older than 70 years and 6·3% were aged 70 years or younger with at least one underlying condition. 1-year mortality in the high-risk population was estimated to be 4·46% (95% CI 4·41-4·51). Age and underlying conditions combined to influence background risk, varying markedly across conditions. In a full suppression scenario in the UK population, we estimated that there would be two excess deaths (vs baseline deaths) with an RR of 1·5, four with an RR of 2·0, and seven with an RR of 3·0. In a mitigation scenario, we estimated 18â374 excess deaths with an RR of 1·5, 36â749 with an RR of 2·0, and 73â498 with an RR of 3·0. In a do nothing scenario, we estimated 146â996 excess deaths with an RR of 1·5, 293â991 with an RR of 2·0, and 587â982 with an RR of 3·0. INTERPRETATION: We provide policy makers, researchers, and the public a simple model and an online tool for understanding excess mortality over 1 year from the COVID-19 pandemic, based on age, sex, and underlying condition-specific estimates. These results signal the need for sustained stringent suppression measures as well as sustained efforts to target those at highest risk because of underlying conditions with a range of preventive interventions. Countries should assess the overall (direct and indirect) effects of the pandemic on excess mortality. FUNDING: National Institute for Health Research University College London Hospitals Biomedical Research Centre, Health Data Research UK.

positive: Mortality from COVID-19: A cross-country comparison of containment versus mitigation strategy

positive: Coronavirus Disease (Covid-19): What Are We Learning in a Country With High Mortality Rate?

positive: Magnitude and time-course of excess mortality during COVID-19 outbreak: population-based empirical evidence from highly impacted provinces in northern Italy Background: The real impact of SARS-CoV-2 on overall mortality remains uncertain and surveillance reports attributed to COVID-19 a limited amount of deaths during the outbreak. Aim of this study is to assess the excess mortality (EM) during COVID-19 outbreak in highly impacted areas of northern Italy. Methods: We analyzed data on deaths occurred in the first four months of 2020 in health protection agencies (HPA) of Bergamo and Brescia (Lombardy), building a time-series of daily number of deaths and predicting the daily standardized mortality ratio (SMR) and cumulative number of excess deaths (ED) through a Poisson generalized additive model of the observed counts in 2020, using 2019 data as a reference. Results: We estimated 5740 (95% Credible Set (CS): 5552-5936) ED in the HPA of Bergamo and 3703 (95% CS: 3535 - 3877) in Brescia, corresponding to 2.55 (95% CS: 2.50-2.61) and 1.93 (95% CS: 1.89-1.98) folds increase in the number of deaths. The ED wave started a few days later in Brescia, but the daily estimated SMR peaked at the end of March in both HPAs, roughly two weeks after the introduction of lock-down measures, with significantly higher estimates in Bergamo (9.4, 95% CI: 9.1-9.7). Conclusion: EM was significantly larger than that officially attributed to COVID-19, disclosing its hidden burden likely due to indirect effects on health system. Time-series analyses highlighted the impact of lockdown restrictions, with a lower EM in the HPA where there was a smaller delay between the epidemic outbreak and their enforcement.

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

positive: Belgian Covid-19 Mortality, Excess Deaths, Number of Deaths per Million, and Infection Fatality Rates (8 March - 9 May 2020) Objective. Scrutiny of COVID-19 mortality in Belgium over the period 8 March-9 May 2020 (Weeks 11-19), using number of deaths per million, infection fatality rates, and the relation between COVID-19 mortality and excess death rates. Data. Publicly available COVID-19 mortality (2020); overall mortality (2009-2020) data in Belgium and demographic data on the Belgian population; data on the nursing home population; results of repeated sero-prevalence surveys in March-April 2020. Statistical methods. Reweighing, missing-data handling, rate estimation, visualization. Results. Belgium has virtually no discrepancy between COVID-19 reported mortality (confirmed and possible cases) and excess mortality. There is a sharp excess death peak over the study period; the total number of excess deaths makes April 2020 the deadliest month of April since WWII, with excess deaths far larger than in early 2017 or 2018, even though influenza-induced January 1951 and February 1960 number of excess deaths were similar in magnitude. Using various sero-prevalence estimates, infection fatality rates (IFRs; fraction of deaths among infected cases) are estimated at 0.38-0.73% for males and 0.20-0.39% for females in the non-nursing home population (non-NHP), and at 0.79-1.52% for males and 0.88-1.31% for females in the entire population. Estimates for the NHP range from 38 to 73% for males and over 22 to 37% for females. The IFRs rise from nearly 0% under 45 years, to 4.3% and 13.2% for males in the non-NHP and the general population, respectively, and to 1.5% and 11.1% for females in the non-NHP and general population, respectively. The IFR and number of deaths per million is strongly influenced by extensive reporting and the fact that 66.0% of the deaths concerned NH residents. At 764 (our re-estimation of the figure 735, presented by "Our World in Data"), the number of COVID-19 deaths per million led the international ranking on May 9, 2020, but drops to 262 in the non-NHP. The NHP is very specific: age-related increased risk; highly prevalent comorbidities that, while non-fatal in themselves, exacerbate COVID-19; larger collective households that share inadvertent vectors such as caregivers and favor clustered outbreaks; initial lack of protective equipment, etc. High-quality health care countries have a relatively older but also more frail population [1], which is likely to contribute to this result.

positive: The Utility of rRT-PCR in Diagnosis and Assessment of Case-fatality rates of COVID-19 In the Iranian Population. Positive Test Results are a Marker for Illness Severity The utility of PCR-based testing in characterizing patients with COVID-19 and the severity of their disease remains unknown. We performed an observational study among patients presenting to hospitals in Iran who were tested for 2019-nCoV viral RNA by rRT-PCR between the fourth week of February 2020 to the fourth week of March 2020. Frequency of symptoms, comorbidities, intubation, and mortality rates were compared between COVID-19 positive vs. negative patients. 96103 patients were tested from 879 hospitals. 18754 (19.5%) tested positive for COVID-19. Positive testing was more frequent in those 50 years or older. The prevalence of cough (54.5% vs. 49.7%), fever (49.5% vs. 44.7%), and respiratory distress (43.0% vs. 39.0%) but not hypoxia (46.9% vs. 56.7%) was higher in COVID-19 positive vs. negative patients (p<0.001 for all). More patients had cardiovascular diseases (10.6% vs. 9.5%, p<0.001) and type 2 diabetes mellitus (10.8% vs. 8.7%, p<0.001) among COVID-19 positive vs. negative patients. There were fewer patients with cancer (1.1%, vs. 1.4%, p<0.001), asthma (1.9% vs. 2.5%, p<0.001), or pregnant (0.4% vs. 0.6%, =0.001) in COVID-19 positive vs. negative groups. COVID-19 positive vs. negative patients required more intubation (7.7% vs. 5.2%, p<0.001) and had higher mortality (14.6% vs. 6.3%, p<0.001). Odds ratios for death of positive vs negative patients range from 2.01 to 3.10 across all age groups. In conclusion, COVID-19 test-positive vs. test-negative patients had more severe symptoms and comorbidities, required higher intubation, and had higher mortality. rRT-PCR positive result provided diagnosis and a marker of disease severity in Iranians.

positive: Estimating clinical severity of COVID-19 from the transmission dynamics in Wuhan, China As of 29 February 2020 there were 79,394 confirmed cases and 2,838 deaths from COVID-19 in mainland China. Of these, 48,557 cases and 2,169 deaths occurred in the epicenter, Wuhan. A key public health priority during the emergence of a novel pathogen is estimating clinical severity, which requires properly adjusting for the case ascertainment rate and the delay between symptoms onset and death. Using public and published information, we estimate that the overall symptomatic case fatality risk (the probability of dying after developing symptoms) of COVID-19 in Wuhan was 1.4% (0.9-2.1%), which is substantially lower than both the corresponding crude or naïve confirmed case fatality risk (2,169/48,557 = 4.5%) and the approximator1 of deaths/deaths + recoveries (2,169/2,169 + 17,572 = 11%) as of 29 February 2020. Compared to those aged 30-59 years, those aged below 30 and above 59 years were 0.6 (0.3-1.1) and 5.1 (4.2-6.1) times more likely to die after developing symptoms. The risk of symptomatic infection increased with age (for example, at ~4% per year among adults aged 30-60 years).

positive: Why does COVID-19 case fatality rate vary among countries? Background While the epidemic of SARS-CoV-2 is spreading worldwide, there is much concern over the mortality rate that the infection induces. Available data suggest that COVID-19 case fatality rate varies temporally (as the epidemic progresses) and spatially (among countries). Here, we attempted to identify key factors possibly explaining the variability in case fatality rate across countries. Methods We used data on the temporal trajectory of case fatality rate provided by the European Center for Disease Prevention and Control, and country-specific data on different metrics describing the incidence of known comorbidity factors associated with an increased risk of COVID-19 mortality at the individual level (Institute for Health Metrics and Evaluation). We also compiled data on demography, economy and political regimes for each country. Findings We first showed that temporal trajectories of case fatality rate greatly vary among countries. We found no evidence for association between comorbidities and case fatality rate at the country level. Case fatality rate was negatively associated with number of hospital beds x1,000 inhabitants. We also report evidence suggesting an association between case fatality rate and the political regime, with democracies suffering from the highest mortality burden, compared to autocratic regimes. However, most of the among-country variance in case fatality rate remained unexplained. Interpretation Overall, these results emphasize the role of socio-economic and political factors as possible drivers of COVID-19 case fatality rate at the country level. Funding None.

positive: Mortality statistics in England and Wales: the SARS-CoV-2 paradox OBJECTIVE: To analyse mortality statistics in the United Kingdom during the initial phases of the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic and to understand the impact of the pandemic on national mortality. METHODS: Retrospective review of weekly national mortality statistics in the United Kingdom over the past 5 years, including subgroup analysis of respiratory mortality rates. RESULTS: During the early phases of the SARS-CoV-2 pandemic in the first months of 2020, there were consistently fewer deaths per week compared with the preceding 5 years. This pattern was not observed at any other time within the past 5 years. We have termed this phenomenon the “SARS-CoV-2 paradox.” We postulate potential explanations for this seeming paradox and explore the implications of these data. CONCLUSIONS: Paradoxically, but potentially importantly, lower rather than higher weekly mortality rates were observed during the early stages of the SARS-CoV-2 pandemic. This paradox may have implications for current and future healthcare utilisation. A rebound increase in non-SARS-CoV-2 mortality later this year might coincide with the peak of SARS-CoV-2 admissions and mortality.

positive: MantisCOVID: Rapid X-Ray Chest Radiograph and Mortality Rate Evaluation With Artificial Intelligence For COVID-19 The novel coronavirus pandemic has negative impacts over the health, economy and well-being of the global population. This negative effect is growing with the high spreading rate of the virus. The most critical step to prevent the spreading of the virus is pre-screening and early diagnosis of the individuals. This results in quaranteeing the patients not to effect the healthy population. COVID-19 is the name of the disease caused by the novel coronavirus. It has a high infection rate and it is urgent to diagnose many patients as we can to prevent the spread of the virus at the early stage. Rapid diagnostic tools development is urgent to save lives. MantisCOVID is a cloud-based pre-diagnosis tool to be accessed from the internet. This tool delivers a rapid screening test by analyzing the X-ray Chest Radiograph scans via Artificial Intelligence (AI) and it also evaluates the mortality rate of patients with the synthesis of the patient history with the machine learning methods. This study reveals the methods used over the platform and evaluation of the algorithms via open datasets.

positive: Mortality Analysis of COVID-19 Confirmed cases in Pakistan Introduction: COVID-19, a novel disease, appeared in December 2019 in China and rapidly spread across the world. Till the second week of April 2020, high incidence (2.9/100,000) and cases fatality rates (1.7%) were observed in Pakistan. This study was conducted to determine the temporal and spatial distribution of the first 100 deaths attributed to COVID-19 in Pakistan and their associated demographic factors. Method: We conducted a descriptive epidemiological analysis of the first 100 deaths reported among RT-PCR confirmed COVID-19 cases. Demographic, epidemiological, and risk factors information was obtained associated comorbidities and clinical signs and symptoms were recorded and frequencies were determined. Results: A total of 100 mortalities with overall Case Fatality Rate 1.67% (CFR) were analysed. Median age of patients was 64.5 years (IQR: 54-70) with 75% (n=75) Males. Among all deaths reported, 71 (71%) cases had one or more documented comorbidities at the time of diagnosis. Most frequently reported co-morbidities were; hypertension (67 %), followed by Diabetes Mellitus 945%) and Ischemic Heart Diseases (27%). First death was reported on 18 March 2020 and the most frequent presenting symptoms were shortness of breath (87%) and fever (79%). Median duration of illness was eight days (IQR: 4-11 days), the median delay reaching hospital to seek health care was three days (IQR: 0-6 days) while median duration of hospital stay was also three days (IQR: 1-7 days). Among all reported deaths, 62% were attributed to local transmission as these cases had no history of international travel. The most affected age group was 60-69 years while no death reported in age group below 20 years. Conclusion: High CFR among old age group and its association with co-morbidities (chronic disease) suggests targeted interventions such as social distancing and strict quarantine measure for elderly and morbid people. Comparative studies among deaths and recovered patients are recommended to explore further disease dynamics. Key words: COVID-19, Cases Fatality Rates, Co-morbidities, Epidemiology, Pakistan, Co-morbidities

positive: Association of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers with the Risk of Hospitalization and Death in Hypertensive Patients with Coronavirus Disease-19 BACKGROUND: Whether angiotensin-converting enzyme (ACE) Inhibitors and angiotensin receptor blockers (ARBs) mitigate or exacerbate SARS-CoV-2 infection remains uncertain. In a national study, we evaluated the association of ACE inhibitors and ARB with coronavirus disease-19 (COVID-19) hospitalization and mortality among individuals with hypertension. METHODS: Among Medicare Advantage and commercially insured individuals, we identified 2,263 people with hypertension, receiving ≥1 antihypertensive agents, and who had a positive outpatient SARS-CoV-2 test (outpatient cohort). In a propensity score-matched analysis, we determined the association of ACE inhibitors and ARBs with the risk of hospitalization for COVID-19. In a second study of 7,933 individuals with hypertension who were hospitalized with COVID-19 (inpatient cohort), we tested the association of these medications with in-hospital mortality. We stratified all our assessments by insurance groups. RESULTS: Among individuals in the outpatient and inpatient cohorts, 31.9% and 29.8%, respectively, used ACE inhibitors and 32.3% and 28.1% used ARBs. In the outpatient study, over a median 30.0 (19.0 - 40.0) days after testing positive, 12.7% were hospitalized for COVID-19. In propensity score-matched analyses, neither ACE inhibitors (HR, 0.77 [0.53, 1.13], P = 0.18), nor ARBs (HR, 0.88 [0.61, 1.26], P = 0.48), were significantly associated with risk of hospitalization. In analyses stratified by insurance group, ACE inhibitors, but not ARBs, were associated with a significant lower risk of hospitalization in the Medicare group (HR, 0.61 [0.41, 0.93], P = 0.02), but not the commercially insured group (HR: 2.14 [0.82, 5.60], P = 0.12; P-interaction 0.09). In the inpatient study, 14.2% died, 59.5% survived to discharge, and 26.3% had an ongoing hospitalization. In propensity score-matched analyses, neither use of ACE inhibitor (0.97 [0.81, 1.16]; P = 0.74) nor ARB (1.15 [0.95, 1.38]; P = 0.15) was associated with risk of in-hospital mortality, in total or in the stratified analyses. CONCLUSIONS: The use of ACE inhibitors and ARBs was not associated with the risk of hospitalization or mortality among those infected with SARS-CoV-2. However, there was a nearly 40% lower risk of hospitalization with the use of ACE inhibitors in the Medicare population. This finding merits a clinical trial to evaluate the potential role of ACE inhibitors in reducing the risk of hospitalization among older individuals, who are at an elevated risk of adverse outcomes with the infection.

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

positive: Risk of death by age and gender from CoVID-19 in Peru, March-May, 2020 Peru implemented strict social distancing measures during the early phase of the epidemic and is now experiencing one of the largest CoVID-19 epidemics in Latin America. Estimates of disease severity are an essential indicator to inform policy decisions about the intensity and duration of interventions needed to mitigate the outbreak. Here we derive delay-adjusted case fatality rates (aCFR) of CoVID-19 in a middle-income country in South America. We used government-reported time series of CoVID-19 cases and deaths stratified by age group and gender. Our estimates as of May 25, 2020, of the aCFR for men and women are 10.8% (95%CrI: 10.5-11.1%) and 6.5% (95%CrI: 6.2-6.8%), respectively, and an overall aCFR of 9.1% (95%CrI: 8.9-9.3%). Our results show that senior individuals are the most severely affected by CoVID-19, particularly men, with aCFR of almost 60% for those aged 80- years. We found that men have a significantly higher cumulative morbidity ratio than women across most age groups (proportion test, p-value< 0.001), with the exception of those aged 0-9 years. The COVID-19 epidemic is imposing a large mortality burden in Peru. Senior individuals, especially those who are older than 70 years of age, are being disproportionately affected by the COVID-19 pandemic.

positive: Epidemic Situation of Novel Coronavirus Pneumonia in China mainland [Objective] Analyze the occurrence of novel coronavirus pneumonia(NCP) in China mainland, explore the epidemiological rules, and evaluate the effect of prevention and control. [Methods] From December 1, 2019 to February 14, 2020, Analysis of 66,492 confirmed cases of NCP in China mainland. [Results] From December 1, 2019 to February 14, 2020, a total of 66,492 cases of NCP were confirmed in China mainland, a total of 54,406 cases were confirmed in Hubei Province, a total of 37,914 cases were confirmed in Wuhan city. On February 5, 2020, the number of suspected cases of NCP in China mainland reached a maximum of 5,328. Since then, the suspected cases have shown a significant downward trend. On February 4, 2020, the number of confirmed cases has gradually decreased in China mainland since then. On February 12, 2020, the number of confirmed cases of NCP in China mainland increased explosively to 15,152, and then began to decline. From February 3, 2020, except for Hubei Province, In China mainland, the number of newly confirmed cases of NCP has continued to decline; From December 1, 2019 to February 14, 2020, a total of 1,523 cases of NCP deaths in China mainland, a cumulative cure of 8096 cases, and mortality and cure rate were 2.29% (1523/66492) and 12.18% (8096/66492) respectively; Starting from January 27, 2020, The spread index of NCP gradually declined, and the extinction index of NCP rose little by little from January 29, 2020. [Conclusion] Starting from February 5, 2020, the number of suspected cases of the NCP is gradually decrease in China mainland. From February 3, 2020, the number of newly confirmed cases of NCP is continuous decline in China mainland except Hubei Province, This shows that the control of the transmission of NCP has achieved. Judged from the number of confirmed cases of NCP, controlling the outbreak in China mainland is to control the epidemic in Hubei province, and the key to controlling the outbreak in Hubei province is to control the epidemic in Wuhan city; Judging from the gradual increase in the number and cure rate of the NCP, and the gradual decline in the number of deaths and mortality, the trend of outbreak control and treatment is getting better; A decrease of the NCP spread index indicates a slowdown in the spread of the virus, but the cumulative confirmed cases is still increase, so the epidemic will continue for some time. However, the turning point of the epidemic in mainland China has not yet occurred. On February 12, 2020, the turning point of the epidemic in China mainland except Hubei province, has turned up.

positive: Age Pattern of Premature Mortality under varying scenarios of COVID-19 Infection in India Background India is vulnerable to community infection of COVID-19 due to crowded and poor living condition, high density, slums in urban areas and poor health care system. The number of COVID-19 infection has crossed 120,000 with over 3500 deaths despite a prolonged period of lockdown and restrictions in public spaces. Given the likely scale and magnitude of this pandemic, this is a modest attempt to assess its impact on the age pattern of mortality under the varying scenarios. Data and Methods Data from the Sample Registration System (SRS), covid19india.org and country-specific data from worldmeter are used in the analysis. Descriptive statistics, case fatality ratio, case fatality ratio with 14 days delay, abridged life table, years of potential life lost (YPLL), disability-adjusted life years (DALY) are used. Results The case fatality ratio (CFR) with 14 days delay for India is at least twice higher (8.0) than CFR of 3.4. Considering 8% mortality rate rate and varying scenarios of community infection by 0.5%, 1% and 2%, India's life expectancy will reduce by 0.8, 1.5 and 3.0 years and potential life lost by 12.1 million, 24.3 million and 48.6 million years respectively. A community infection of 0.5% may result in DALY by 6.2 per 1000 population. Major share of PYLL and DALY is accounted for the working ages. Conclusion COVID-19 has a visible impact on mortality with loss of productive life years in working ages. The sustained effort at containing the transmission at each administrative unit is recommended to arrest mortality owing by the working ages. Key Words: COVID-19, life expectancy, mortality, premature, DALY, India

positive: Modeling the COVID-19 outbreak in the United States The COVID-19 contagion has developed at an alarming rate in the US and as of April 24, 2020, tens of thousands of people have already died from the disease. In the event of an outbreak like such, forecasting the extent of the mortality that will occur is crucial to aid the implementation of effective interventions. Mortality depends on two factors: the case fatality rate and the case incidence. We combine a cohort-based model that determines case fatality rates along with a modified logistic model that evaluates the case incidence to determine the number of deaths in all the US states over time; the model is also able to include the impact of interventions. Both models yield exceptional goodness-of-fit. The model predicted a range of death outcomes (79k to 246k) all of which are considerably greater than the figures presented in mainstream media. This model can be used more effectively than current models to estimate the number of deaths during an outbreak, allowing for better planning.

positive: National Smoking Rates Correlate Inversely with COVID-19 Mortality ABSTRACT Introduction: Recent studies show cigarette smokers are markedly under-represented among patients hospitalized for COVID-19 in over a dozen countries. It is unclear if this may be related to confounding factors such as age distribution, access to care, and inaccurate records. We hypothesized that these concerns could be avoided by studying smoking prevalence in relation to COVID-19 mortality. Since climate has been identified as a factor in COVID-19, we studied groups of countries with relatively comparable temperatures. Methods: The 20 hottest and 20 coldest countries in the Johns Hopkins Mortality Analysis database with a minimum mortality rate of .3 deaths/100,000 were selected on the basis of the average temperatures of their largest city. Mortality rates were determined as of May 1, 2020 and correlated with national smoking rate adjusting for sex ratio, obesity, temperature, and elderly population. Results: A highly significant inverse correlation between current daily smoking prevalence and COVID-19 mortality rate was noted for the group of hot countries (R=-.718, p = .0002), cold countries (R=-.567, p=.0046), and the combined group (R=-.324, p=.0207). However, after adjustments only the regression for hot countries and the combined group remained significant. In hot countries, for each percentage point increase in smoking rate mortality decreased by .147 per 100,000 population (95% CI .102- 192, p=.0066). This resulted in mortality rates several-fold elevated in the countries with the lowest smoking rates relative to the highest smoking rates. In the combined group, mortality decreased by .257 per 100,000 population (95% CI .175-.339, p=.0034). Discussion: These findings add support to the finding of an inverse relationship between current smoking and seriously symptomatic COVID-19. However, we conclude that the difference in mortality between the highest and lowest smoking countries appears too large to be due primarily to the effects of smoking per se. A potentially beneficial effect of smoking is surprising, but compatible with a number of hypothetical mechanisms which deserve exploration: 1) Studies show smoking alters ACE2 expression which may affect COVID-19 infection or its progression to serious lung pathology. 2) Nicotine has anti-inflammatory activity and also appears to alter ACE2 expression. 3) Nitric oxide in cigarette smoke is known to be effective in treating pulmonary hypertension and has shown in vitro antiviral effects including against SARS-CoV-2. 4) Smoking has complicated effects on the immune system involving both up and down regulation, any of which might alone or in concert antagonize progression of COVID-19. 5) Smokers are exposed to hot vapors which may stimulate immunity in the respiratory tract by various heat-related mechanisms (e.g. heat shock proteins). Studies of steam and sauna treatments have shown efficacy in other viral respiratory conditions. At this time there is no clear evidence that smoking is protective against COVID-19, so the established recommendations to avoid smoking should be emphasized. The interaction of smoking and COVID-19 will only be reliably determined by carefully designed prospective study, and there is reason to believe that there are unknown confounds that may be spuriously suggesting a protective effect of smoking. However, the magnitude of the apparent inverse association of COVID-19 and smoking and its myriad clinical implications suggest the importance of further investigation.

positive: Spatiotemporal evolution of coronavirus disease 2019 mortality in Brazil in 2020

positive: Prevalence and Mortality due to Outbreak of Novel Coronavirus Disease (COVID‐19) in β‐Thalassemias: The Nationwide Iranian Experience In late December 2019, an ongoing outbreak of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection that was termed Coronavirus Disease 2019 (COVID‐19), was reported in Wuhan, China (Zhu, et al 2020).

positive: Covid-19: Deprived areas have the highest death rates in England and Wales.

positive: The predictors of 3- and 30-day mortality in 660 MERS-CoV patients BACKGROUND: The mortality rate of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) patients is a major challenge in all healthcare systems worldwide. Because the MERS-CoV risk-standardized mortality rates are currently unavailable in the literature, the author concentrated on developing a method to estimate the risk-standardized mortality rates using MERS-CoV 3- and 30-day mortality measures. METHODS: MERS-CoV data in Saudi Arabia is publicly reported and made available through the Saudi Ministry of Health (SMOH) website. The author studied 660 MERS-CoV patients who were reported by the SMOH between December 2, 2014 and November 12, 2016. The data gathered contained basic demographic information (age, gender, and nationality), healthcare worker, source of infection, pre-existing illness, symptomatic, severity of illness, and regions in Saudi Arabia. The status and date of mortality were also reported. Cox-proportional hazard (CPH) models were applied to estimate the hazard ratios for the predictors of 3- and 30-day mortality. RESULTS: 3-day, 30-day, and overall mortality were found to be 13.8%, 28.3%, and 29.8%, respectively. According to CPH, multivariate predictors of 3-day mortality were elderly, non-healthcare workers, illness severity, and hospital-acquired infections (adjusted hazard ratio (aHR) =1.7; 8.8; 6.5; and 2.8, respectively). Multivariate predictors of 30-day mortality were elderly, non-healthcare workers, pre-existing illness, severity of illness, and hospital-acquired infections (aHR =1.7; 19.2; 2.1; 3.7; and 2.9, respectively). CONCLUSIONS: Several factors were identified that could influence mortality outcomes at 3 days and 30 days, including age (elderly), non-healthcare workers, severity of illness, and hospital-acquired infections. The findings can serve as a guide for healthcare practitioners by appropriately identifying and managing potential patients at high risk of death.

positive: Comorbid Diabetes Mellitus was Associated with Poorer Prognosis in Patients with COVID-19: A Retrospective Cohort Study Background The 2019 novel coronavirus disease (COVID-19) emerged in Wuhan, Hubei province, China, and was characterized as pandemic by the World Health Organization. Diabetes mellitus is an established risk factor for poor clinical outcomes, but the association of diabetes with the prognosis of COVID-19 have not been reported yet. Methods In this cohort study, we retrospectively reviewed 258 consecutive hospitalized COVID-19 patients with or without diabetes at the West Court of Union Hospital of Huazhong University of Science and Technology in Wuhan, China, recruited from January 29 to February 12, 2020. The cases were confirmed by real-time PCR and the demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Prognosis was defined as hospitalization, discharged survivor and death, which was followed up until March 12, 2020. Results Of the 258 hospitalized patients (63 with diabetes) with COVID-19, the median age was 64 years (range 23-91), and 138 (53.5%) were male. No significant differences in age and sex were identified between patients with and without diabetes. Common symptoms included fever (82.2%), dry cough (67.1%), polypnea (48.1%), and fatigue (38%). Patients with diabetes had significantly higher leucocyte and neutrophil counts, and higher levels of fasting blood glucose, serum creatinine, urea nitrogen and creatine kinase isoenzyme MB at admission compared with those without diabetes. COVID-19 patients with diabetes were more likely to develop severe or critical disease condition with more complications at presentation, and had higher incidence rates of antibiotic therapy, non-invasive and invasive mechanical ventilation, and death (11.1% vs. 4.1%). Cox proportional hazard model showed that diabetes (adjusted hazard ratio [aHR]=3.64; 95% confidence interval [CI]: 1.09, 12.21) and fasting blood glucose (aHR=1.19; 95% CI: 1.08, 1.31) were associated with the fatality of COVID-19, adjusting for potential confounders. Conclusions Diabetes mellitus is associated with greater disease severity and a higher risk of mortality in patients with COVID-19. Primary and secondary prevention strategies are needed for COVID-19 patients with diabetes.

positive: COVID-19: unidades de terapia intensiva, ventiladores mecânicos e perfis latentes de mortalidade associados à letalidade no Brasil./ COVID-19: unidades de terapia intensiva, ventiladores mecânicos e perfis latentes de mortalidade associados à letalidade no Brasil./ COVID-19: intensive care units, mechanical ventilators, and latent mortality profiles associated with case-fatality in Brazil In response to the accelerated increase in the number of COVID-19 cases, countries must increase their supply of beds in intensive care units (ICUs). Respiratory diseases, neoplasms, cardiopathies and hypertension, and diabetes are associated with higher COVID-19 case-fatality. The study aimed to identify the regions of Brazil with higher specific mortality rates from these comorbidities and the regions with the greatest shortage of ICU beds and mechanical ventilators. A cross-sectional ecological study was performed in which the units of analysis were the country's Health Regions. Data were obtained from Brazilian Health Informatics Department - DATASUS (National Registry of Healthcare Establishments - 2019, Mortality Information Systems - 2017, and Population Projections - 2017). We calculated the disease group-specific mortality rates for hypertension, neoplasms, diabetes, cardiac diseases, respiratory diseases and the rates of total ICU beds, private ICU beds, ICU beds in the Brazilian Unified National Health System (SUS), and ventilators in the SUS, per 100,000 inhabitants. The mortality profile was determined by latent profiles analysis, and the cluster analysis of ICU beds and ventilators used the spatial scan method. Kernel maps were constructed for the data's visualization. Level of significance was set at 5%. Four latent mortality profiles were observed. The Health Regions with the highest mean mortality rates were located in regions with shortages of ICU beds and ventilators, especially in parts of the Northeast, Southeast, and South of Brazil. The spatial localization of regions with both the highest mortality and shortages of ICU beds/ventilators requires attention by policymakers and public planners to deal efficiently and fairly with the COVID-19 epidemic in Brazil.

positive: Case-Fatality Risk Estimates for COVID-19 Calculated by Using a Lag Time for Fatality We estimated the case-fatality risk for coronavirus disease cases in China (3.5%); China, excluding Hubei Province (0.8%); 82 countries, territories, and areas (4.2%); and on a cruise ship (0.6%). Lower estimates might be closest to the true value, but a broad range of 0.25%–3.0% probably should be considered.

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

positive: Correlating Covid-19 mortality and infection levels Covid-19 deaths and positive cases show a remarkable heterogeneity across countries which cannot be easily explained on the basis of similarities or differences in the quality of healthcare, access to healthcare, testing facilities, or preventive measures such as lockdowns. Here we show that there is a distinct correlation between the mortality level and the infection level across countries, which can explain the mortality levels for a wide spectrum of countries. This implies that the number of deaths per 100 infected individuals is approximately the same across diverse countries and can be estimated from the slope of the mortality level-infection level plot. The correlation presented here can potentially be combined with estimates of infection spread to forecast future mortality levels and therefore future needs in terms of healthcare and other resources. Tracking of an individual locations temporal path on this plot can potentially serve as a visual assessment of the nature of the epidemic. Methods presented here are not specific to the current epidemic. This is a preliminary report and uses data from a single source at a single time-point to demonstrate the capability of such an analysis.

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

positive: COVID 19 and Ethnicity: Spot light on the global rheumatology issues in developing and developed countries A key issue in the response to the coronavirus disease 2019 (COVID‐19) pandemic is the internationally recognised observation that COVID‐19 disproportionally affects the Black and Minority Ethnic Population (BAME) (1). We focus predominantly on the countries of the UK, USA, and India COVID‐19 rheumatology challenges and examples. This unprecedented public health crisis started in China in Dec 2019, following an infection caused by a novel coronavirus strain, named as SARS‐CoV2 (2). The World Health Organisation in March 2020 declared this public health emergency as a pandemic (2). COVID‐19 pandemic has moved from country to country peaking at different times despite implementation of strict preventive measures, including complete lock down periods with varied success. Case fatality and mortality rates have been highly variable across nations as well as different ethnic groups (3).

positive: Use of all cause mortality to quantify the consequences of covid-19 in Nembro, Lombardy: descriptive study OBJECTIVE: To quantify the impact of coronavirus disease 2019 (covid-19) on all cause mortality in Nembro, an Italian city severely affected by the covid-19 pandemic. DESIGN: Descriptive study. SETTING: Nembro, in the Bergamo province of Lombardy, northern Italy. POPULATION: Residents of Nembro. MAIN OUTCOME MEASURES: Monthly all cause mortality between January 2012 and April 2020 (data to 11 April), number of confirmed deaths from covid-19 to 11 April 2020, and weekly absolute number of deaths between 1 January and 4 April across recent years by age group and sex. RESULTS: Nembro had 11 505 residents as of 1 January 2020. Monthly all cause mortality between January 2012 and February 2020 fluctuated around 10 per 1000 person years, with a maximum of 21.5 per 1000 person years. In March 2020, monthly all cause mortality reached a peak of 154.4 per 1000 person years. For the first 11 days in April, this rate decreased to 23.0 per 1000 person years. The observed increase in mortality was driven by the number of deaths among older people (≥65 years), especially men. From the outbreak onset until 11 April 2020, only 85 confirmed deaths from covid-19 in Nembro were recorded, corresponding to about half of the 166 deaths from all causes observed in that period. CONCLUSIONS: The study findings show how covid-19 can have a considerable impact on the health of a small community. Furthermore, the results suggest that the full implications of the covid-19 pandemic can only be completely understood if, in addition to confirmed deaths related to covid-19, consideration is also given to all cause mortality in a given region and time frame.

positive: Worldwide differences in COVID-19-related mortality Mortality statistics due to COVID-19 worldwide are compared, by adjusting for the size of the population and the stage of the pandemic. Data from the European Centre for Disease Control and Prevention, and Our World in Data websites were used. Analyses are based on number of deaths per one million inhabitants. In order to account for the stage of the pandemic, the baseline date was defined as the day in which the 10th death was reported. The analyses included 78 countries and territories which reported 10 or more deaths by April 9. On day 10, India had 0.06 deaths per million, Belgium had 30.46 and San Marino 618.78. On day 20, India had 0.27 deaths per million, China had 0.71 and Spain 139.62. On day 30, four Asian countries had the lowest mortality figures, whereas eight European countries had the highest ones. In Italy and Spain, mortality on day 40 was greater than 250 per million, whereas in China and South Korea, mortality was below 4 per million. Mortality on day 10 was moderately correlated with life expectancy, but not with population density. Asian countries presented much lower mortality figures as compared to European ones. Life expectancy was found to be correlated with mortality.

positive: Importance of timely management of patients in reducing fatality rate of coronavirus disease 2019 Abstract The outbreak of coronavirus disease 2019 (COVID-19) characterized with pneumonia, firstly occurred in Wuhan city, China, in December 2019 has so far spread in over 200 countries and territories in the world. One of the important goals in facing outbreaks of COVID-19 is to reduce the case fatality rate. We reported here that the fatality rate of COVID-19 in other provinces of mainland China was 0.82% (121/14708), significantly lower than 6.62% (4512/68128) in Hubei province (p<0.0001). The main reason for the lower fatality rate was likely due to the timely management of the patients in other provinces, highlighting the importance of timely management of patients in reducing the fatality rate of COVID-19.

positive: How Large Was the Mortality Increase Directly and Indirectly Caused by the COVID-19 Epidemic? An Analysis on All-Causes Mortality Data in Italy Objective: Overall mortality is a relevant indicator of the population burden during an epidemic. It informs on both undiagnosed cases and on the effects of health system disruption. Methods: We aimed at evaluating the extent of the total death excess during the COVID-19 epidemic in Italy. Data from 4433 municipalities providing mortality reports until April 15th, 2020 were included for a total of 34.5 million residents from all Italian regions. Data were analyzed by region, sex and age, and compared to expected from 2015–2019. Results: In both genders, overall mortality was stable until February 2020 and abruptly increased from March 1st onwards. Within the municipalities studied, 77,339 deaths were observed in the period between March 1st to April 15th, 2020, in contrast to the 50,822.6 expected. The rate ratio was 1.11 before age 60 and 1.55 afterwards. Both sexes were affected. The excess was greater in the regions most affected by COVID-19 but always exceeded the deaths attributed to COVID-19. The extrapolation to the total Italian population suggests an excess of 45,033 deaths in the study period, while the number of COVID–19 deaths was 21,046. Conclusion: Our paper shows a large death excess during the COVID-19 epidemic in Italy; greater than the number attributed to it. Possible causes included both the undetected cases and the disruption of the Health Service organization. Timely monitoring of overall mortality based on unbiased nationwide data is an essential tool for epidemic control.

positive: Management of Patients on Dialysis and With Kidney Transplantation During the SARS-CoV-2 (COVID-19) Pandemic in Brescia, Italy The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as coronavirus disease (COVID-19), is a major pandemic challenging health care systems around the world. The optimal management of patients infected with COVID-19 is still unclear, although the consensus is moving toward the need of a biphasic approach. During the first phase of the disease (from onset of the symptoms up to 7–10 days) viral-induced effects are prominent, with the opportunity to institute antiviral therapy. In the second inflammatory phase of the disease, immunosuppressive strategies (for example with glucocorticoids or anticytokine drugs) may be considered. This latter stage is characterized by the development of progressive lung involvement with increasing oxygen requirements and occasionally signs of the hemophagocytic syndrome. The management of the disease in patients with kidney disease is even more challenging, especially in those who are immunosuppressed or with severe comorbidities. Here we present the therapeutic approach used in Brescia (Italy) for managing patients infected with COVID-19 who underwent kidney transplantation and are receiving hemodialysis. Furthermore, we provide some clinical and physiopathological background, as well as preliminary outcome data of our cohort, to better clarify the pathogenesis of the disease and clinical management.

positive: HIV and risk of COVID-19 death: a population cohort study from the Western Cape Province, South Africa BACKGROUND: The effect of HIV co-infection on COVID-19 outcomes in sub-Saharan Africa is unknown METHODS: We conducted a population cohort study using linked data from adults attending public sector health facilities in the Western Cape, South Africa We used Cox-proportional hazards models adjusted for age, sex, location and comorbidities to examine the association between HIV and COVID-19 death among (i) public sector 'active patients' (at least 1 health visit in the 3 years before March 2020), (ii) laboratory-diagnosed COVID-19 cases and (iii) hospitalized COVID-19 cases COVID-19 was diagnosed with SARS-CoV-2 PCR tests We calculated the standardized mortality ratio (SMR) for COVID-19 comparing HIV positive vs negative adults using modelled population estimates RESULTS: Among 3,460,932 public sector patients (16% HIV positive), 22,308 were diagnosed with COVID-19, of whom 625 died In adjusted analysis, HIV increased risk of COVID-19 mortality (adjusted hazard ratio [aHR]:2 14;95% confidence interval [CI]:1 70;2 70), with similar risks across strata of viral load and immunosuppression increased HIV-associated risk of COVID-19 death remained when restricting to COVID-19 cases (aHR:1 70;95%CI:132;2 18) or hospitalized cases (aHR:1 45;95%CI:1 14;1 84) Current and previous tuberculosis also increased COVID-19 mortality risk (aHR [95%CI]:2 70 [1 81;4 04] and 1 51 [1 18;1 93] respectively) The SMR for COVID-19 death associated with HIV was 2 39 (95% CI:1 96;2 86);population attributable fraction 8 5% (95%CI:6 1;11 1) CONCLUSION: HIV was associated with a doubling of COVID-19 mortality risk While our findings may over-estimate the HIV-associated risk COVID-19 death due to residual confounding, people with HIV should be considered a high-risk group for COVID-19 management

positive: Estimating Impact of Austerity policies in COVID-19 fatality rates:Examining the dynamics of economic policy and Case Fatality Rates (CFR) of COVID-19 in OCED countries The paper will attempt to estimate factors which determine the variability of case fatality rates of COVID-19 across OCED countries in recent time. The objective of the paper is to estimate the impact of government health policy on fatality rates (Case fatality rates) of COVID-19 in countries while controlling for other demographic and economic characteristics. The analysis is of done using non-parametric regression method, i.e. Quantile regression. The result from quartile regressions analysis shows that a policy of Austerity (health expenditure cuts) significantly increases the mortality rates of COVID-19 in OCED countries. The policy implication of the study is the need for a robust public-funded health system with wider accessibility to deals with a major public health crisis like a COVID-19 pandemic.

positive: COVID-19: intensive care units, mechanical ventilators, and latent mortality profiles associated with case-fatality in Brazil. In response to the accelerated increase in the number of COVID-19 cases, countries must increase their supply of beds in intensive care units (ICUs). Respiratory diseases, neoplasms, cardiopathies and hypertension, and diabetes are associated with higher COVID-19 case-fatality. The study aimed to identify the regions of Brazil with higher specific mortality rates from these comorbidities and the regions with the greatest shortage of ICU beds and mechanical ventilators. A cross-sectional ecological study was performed in which the units of analysis were the country's Health Regions. Data were obtained from Brazilian Health Informatics Department - DATASUS (National Registry of Healthcare Establishments - 2019, Mortality Information Systems - 2017, and Population Projections - 2017). We calculated the disease group-specific mortality rates for hypertension, neoplasms, diabetes, cardiac diseases, respiratory diseases and the rates of total ICU beds, private ICU beds, ICU beds in the Brazilian Unified National Health System (SUS), and ventilators in the SUS, per 100,000 inhabitants. The mortality profile was determined by latent profiles analysis, and the cluster analysis of ICU beds and ventilators used the spatial scan method. Kernel maps were constructed for the data's visualization. Level of significance was set at 5%. Four latent mortality profiles were observed. The Health Regions with the highest mean mortality rates were located in regions with shortages of ICU beds and ventilators, especially in parts of the Northeast, Southeast, and South of Brazil. The spatial localization of regions with both the highest mortality and shortages of ICU beds/ventilators requires attention by policymakers and public planners to deal efficiently and fairly with the COVID-19 epidemic in Brazil.

positive: Fatality risks for nosocomial outbreaks of Middle East respiratory syndrome coronavirus in the Middle East and South Korea Middle East respiratory syndrome coronavirus (MERS-CoV) was first isolated in 2012. The largest known outbreak outside the Middle East occurred in South Korea in 2015. As of 29 June 2016, 1769 laboratory-confirmed cases (630 deaths; 35.6 % case fatality rate [CFR]) had been reported from 26 countries, particularly in the Middle East. However, the CFR for hospital outbreaks was higher than that of family clusters in the Middle East and Korea. Here, we compared the mortality rates for 51 nosocomial outbreaks in the Middle East and one outbreak of MERS-CoV in South Korea. Our findings showed the CFR in the Middle East was much higher than that in South Korea (25.9 % [56/216] vs. 13.8 % [24/174], p = 0.003). Infected individuals who died were, on average, older than those who survived in both the Middle East (64 years [25–98] vs. 46 years [2–85], p = 0.000) and South Korea (68 years [49–82] vs. 53.5 years [16–87], p = 0.000). Similarly, the co-morbidity rates for the fatal cases were statistically higher than for the nonfatal cases in both the Middle East (64.3 % [36/56] vs. 28.1 % [45/160], p = 0.000) and South Korea (45.8 % [11/24] vs. 12.0 % [18/150], p = 0.000). The median number of days from onset to confirmation of infection in the fatal cases was longer than that for survivors from the Middle East (8 days [1–47] vs. 4 days [0–14], p = 0.009). Thus, older age, pre-existing concurrent diseases, and delayed confirmation increase the odds of a fatal outcome in nosocomial MERS-CoV outbreaks in the Middle East and South Korea. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-016-3062-x) contains supplementary material, which is available to authorized users.

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: Use of all cause mortality to quantify the consequences of covid-19 in Nembro, Lombardy: descriptive study OBJECTIVE: To quantify the impact of coronavirus disease 2019 (covid-19) on all cause mortality in Nembro, an Italian city severely affected by the covid-19 pandemic. DESIGN: Descriptive study. SETTING: Nembro, in the Bergamo province of Lombardy, northern Italy. POPULATION: Residents of Nembro. MAIN OUTCOME MEASURES: Monthly all cause mortality between January 2012 and April 2020 (data to 11 April), number of confirmed deaths from covid-19 to 11 April 2020, and weekly absolute number of deaths between 1 January and 4 April across recent years by age group and sex. RESULTS: Nembro had 11 505 residents as of 1 January 2020. Monthly all cause mortality between January 2012 and February 2020 fluctuated around 10 per 1000 person years, with a maximum of 21.5 per 1000 person years. In March 2020, monthly all cause mortality reached a peak of 154.4 per 1000 person years. For the first 11 days in April, this rate decreased to 23.0 per 1000 person years. The observed increase in mortality was driven by the number of deaths among older people (≥65 years), especially men. From the outbreak onset until 11 April 2020, only 85 confirmed deaths from covid-19 in Nembro were recorded, corresponding to about half of the 166 deaths from all causes observed in that period. CONCLUSIONS: The study findings show how covid-19 can have a considerable impact on the health of a small community. Furthermore, the results suggest that the full implications of the covid-19 pandemic can only be completely understood if, in addition to confirmed deaths related to covid-19, consideration is also given to all cause mortality in a given region and time frame.

positive: A demographic adjustment to improve measurement of COVID-19 severity at the developing stage of the pandemic The need for accurate statistics has never been felt so deeply as the novel COVID-19 pathogen spreads around the world and quantifying its severity is a primary clinical and public health issue. In Italy, the magnitude and increasing trend of the case-fatality risk (CFR) is fueling the already high levels of public alarm. In this paper, we highlight that the widely used crude CFR is an inaccurate measure of the disease severity since the pandemic is still unfolding. With the goal to improve its comparability over time and across countries at this stage, we then propose a demographic adjustment of the CFR that addresses the bias arising from differential case ascertainment by age. When applied to publicly released data for Italy, we show that until March 16 our adjusted CFR was similar to that of Wuhan, the most affected Chinese region, where COVID-19 has now been contained. This indicates that our adjusted CFR improves its comparability over time, making an important tool to chart the course of the COVID-19 pandemic across countries. Since March 16, the Italian COVID-19 outbreak has entered a new phase, with the northern and southern regions following different trajectories. As a result, our adjusted CFR has been increasing between March 16 and March 20. Data at the subnational level are needed to correctly assess the disease severity in the country at this stage.

positive: Understanding Epidemic Data and Statistics: A case study of COVID-19 The 2019-Novel-Coronavirus (COVID-19) has affected 181 countries and out of about 1197405 confirmed cases (By April 5). Understanding the transmission dynamics of the infection in each country which affected on a daily basis and evaluating the effectiveness of control policies is critical for our further actions. To date, the statistics of COVID-19 reported cases show more than 80 percent of infected had a mild case of disease, while around 14 percent of infected experienced a severe one and about 5 percent are categorized as critical disease victims. Today's report (2020-04-05; daily updates in the prepared website) shows the confirmed cases of COVID-19 in the US, Spain, Italy, and Germany are 308850, 126168, 124632, and 96092; respectively. Calculating the total Case Fatality Rate (CFR) of Italy (2020-04-04), about 13.3% of confirmed cases passed away. Compared to South Korea's rate of 1.8% (7 times lower than Italy) and China's 4% (69% lower than Italy), the CFR of Italy is too high. There are some effective policies that yield significant changes in the trend of cases. The lockdown policy in China, Italy, and Spain (the effect observed after some days), Shutdown of all non-essential companies in Hubei (the effect observed after 5 days), combined policy in South Korea, and reducing working hours in Iran.

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

positive: Assessing nitrogen dioxide (NO2) levels as a contributing factor to coronavirus (COVID-19) fatality Abstract Nitrogen dioxide (NO2) is an ambient trace-gas result of both natural and anthropogenic processes. Long-term exposure to NO2 may cause a wide spectrum of severe health problems such as hypertension, diabetes, heart and cardiovascular diseases and even death. The objective of this study is to examine the relationship between long-term exposure to NO2 and coronavirus fatality. The Sentinel-5P is used for mapping the tropospheric NO2 distribution and the NCEP/NCAR reanalysis for evaluating the atmospheric capability to disperse the pollution. The spatial analysis has been conducted on a regional scale and combined with the number of death cases taken from 66 administrative regions in Italy, Spain, France and Germany. Results show that out of the 4443 fatality cases, 3487 (78%) were in five regions located in north Italy and central Spain. Additionally, the same five regions show the highest NO2 concentrations combined with downwards airflow which prevent an efficient dispersion of air pollution. These results indicate that the long-term exposure to this pollutant may be one of the most important contributors to fatality caused by the COVID-19 virus in these regions and maybe across the whole world.

positive: Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia – A systematic review, meta-analysis, and meta-regression Abstract Background and aims Diabetes Mellitus (DM) is chronic conditions with devastating multi-systemic complication and may be associated with severe form of Coronavirus Disease 2019 (COVID-19). We conducted a systematic review and meta-analysis in order to investigate the association between DM and poor outcome in patients with COVID-19 pneumonia. Methods Systematic literature search was performed from several electronic databases on subjects that assess DM and outcome in COVID-19 pneumonia. The outcome of interest was composite poor outcome, including mortality, severe COVID-19, acute respiratory distress syndrome (ARDS), need for intensive care unit (ICU) care, and disease progression. Results There were a total of 6452 patients from 30 studies. Meta-analysis showed that DM was associated with composite poor outcome (RR 2.38 [1.88, 3.03], p < 0.001; I2: 62%) and its subgroup which comprised of mortality (RR 2.12 [1.44, 3.11], p < 0.001; I2: 72%), severe COVID-19 (RR 2.45 [1.79, 3.35], p < 0.001; I2: 45%), ARDS (RR 4.64 [1.86, 11.58], p = 0.001; I2: 9%), and disease progression (RR 3.31 [1.08, 10.14], p = 0.04; I2: 0%). Meta-regression showed that the association with composite poor outcome was influenced by age (p = 0.003) and hypertension (p < 0.001). Subgroup analysis showed that the association was weaker in studies with median age ≥55 years-old (RR 1.92) compared to <55 years-old (RR 3.48), and in prevalence of hypertension ≥25% (RR 1.93) compared to <25% (RR 3.06). Subgroup analysis on median age <55 years-old and prevalence of hypertension <25% showed strong association (RR 3.33) Conclusion DM was associated with mortality, severe COVID-19, ARDS, and disease progression in patients with COVID-19.

positive: Determinants of COVID-19 incidence and mortality: A cross-country analysis Objective: We undertook this study to explore the role of important determinants affecting global COVID-19 incidence and mortality taking multifactorial disease dynamics into consideration. Design: Secondary data as on March 28, 2020 were obtained for 97 countries. Association of COVID-19 cumulative incidence and mortality measures were assessed with ten indictors representing health system characteristics, climate, demography, promptness of international travel restriction and population movement using Generalized Linear Modelling. Main outcome measures: Country-specific COVID-19 cumulative incidence, cumulative cause-specific mortality and case fatality rate. Results: Significant inter-country variation in incidence and mortality rates were observed. Five variables were found to be associated with cumulative incidence: testing rate per 1000 population ({beta} = 0.119, p < 0.01), UHC index ({beta} = 0.043, p = 0.04), percentage elderly population ({beta} = 0.122, p < 0.01), percentage below-poverty line population ({beta} = -0.048, p < 0.01) and disability adjusted life years due to NCDs ({beta} = -0.013, p < 0.01). Case fatality rate was observed to be associated with testing rate per 1000 population ({beta} = -0.058, p = 0.03) and population density ({beta} = 0.002, p = 0.02), while the cumulative cause-specific mortality was associated with only percentage elderly population ({beta} = 0.096, p = 0.04) in the country. Conclusions: Health system response, population susceptibility and demography were the most important factors determining the progression. Policy response should focus towards increasing testing, primarily targeting high population density areas. Health system strengthening and reduction in population risk factors should be long term goals for a better response to such epidemics.

positive: Risk factors associated with mortality in hospitalized patients with SARS-CoV-2 infection. A prospective, longitudinal, unicenter study in Reus, Spain Spain is one of the countries that has suffered the most from the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the strain that causes coronavirus disease 2019 (COVID-19). However, there is a lack of information on the characteristics of this disease in the Spanish population. The objective of this study has been to characterize our patients from an epidemiological point of view and to identify the risk factors associated with mortality in our geographical area. We performed a prospective, longitudinal study on 188 hospitalized cases of SARS-Cov-2 infection in Hospital Universitari de Sant Joan, in Reus, Spain, admitted between 15th March 2020 and 30th April 2020. We recorded demographic data, signs and symptoms and comorbidities. We also calculated the Charlson and McCabe indices. A total of 43 deaths occurred during the study period. Deceased patients were older than the survivors (77.7 ± 13.1 vs. 62.8 ± 18.4 years; p < 0.001). Logistic regression analyses showed that fever, pneumonia, acute respiratory distress syndrome, diabetes mellitus and cancer were the variables that showed independent and statistically significant associations with mortality. The Charlson index was more efficient than the McCabe index in discriminating between deceased and survivors. This is one of the first studies to describe the factors associated with mortality in patients infected with SARS-CoV-2 in Spain, and one of the few in the Mediterranean area. We identified the main factors independently associated with mortality in our population. Further studies in are needed to complete and confirm our findings.

positive: 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.

positive: Survival of hospitalized COVID-19 patients in Northern Italy: a population-based cohort study by the ITA-COVID19 Network Background COVID19 case fatality rate in hospitalized patients varies across countries and studies, but reliable estimates specific for age, sex, and comorbidities are needed to design trials for COVID19 interventions. Aim of this study is to provide population-based survival curves of hospitalized COVID19 patients. Methods A cohort study was conducted in Lombardy, Veneto, and Reggio Emilia using COVID19 registries linked to hospital discharge databases containing patient clinical histories. All patients with positive SARS CoV 2 RTPCR test on oral/nasopharyngeal swabs hospitalized from 21st February to 21st April 2020 were identified. Kaplan Meier survival estimates were calculated at 14 and 30 days for death in any setting, stratifying by age, sex and Charlson Index. Findings Overall 42,926 hospitalized COVID19 patients were identified. Patients' median age was 69 years (IQR: 57; 79), 62.6% were males, 69.4% had a Charlson Index of 0. In total, 11,205 (26.1%) patients died over a median follow-up of 24 days (IQR: 10; 35). Survival curves showed that 22.0% of patients died within 14 days and 27.6% within 30 days of hospitalization. Survival was higher in younger patients and in females. Younger patients with comorbidities had a lower survival than older ones with comorbidities. Interpretation Over 27% of hospitalized COVID19 patients died within one month in three areas of Northern Italy that were heavily affected by SARS CoV 2 infection. Such a high fatality rate suggests that trials should focus on survival and have follow-up of at least one month.

positive: COVID-19 is an emergent disease of aging COVID-19 is an ongoing pandemic caused by the SARS-CoV-2 coronavirus that poses one of the greatest challenges to public health in recent years. SARS-CoV-2 is highly contagious and often leads to severe viral pneumonia with respiratory failure and death in the elderly and subjects with pre-existing conditions, but the reason for this age dependence is unclear. Here, we found that the case fatality rate for COVID-19 grows exponentially with age in Italy, Spain, South Korea, and China, with the doubling time approaching that of all-cause human mortality. In addition, men and those with multiple age-related diseases are characterized by increased mortality. Moreover, similar mortality patterns were found for all-cause pneumonia. We further report that the gene expression of ACE2, the SARS-CoV-2 receptor, grows in the lung with age, except for subjects on a ventilator. Together, our findings establish COVID-19 as an emergent disease of aging, and age and age-related diseases as its major risk factors. In turn, this suggests that COVID-19, and deadly respiratory diseases in general, may be targeted, in addition to therapeutic approaches that affect specific pathways, by approaches that target the aging process.

positive: Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis Abstract Background An epidemic of Coronavirus Disease 2019 (COVID-19) began in December 2019 and triggered a Public Health Emergency of International Concern (PHEIC). We aimed to find risk factors for the progression of COVID-19 to help reducing the risk of critical illness and death for clinical help. Methods The data of COVID-19 patients until March 20, 2020 were retrieved from four databases. We statistically analyzed the risk factors of critical/mortal and non-critical COVID-19 patients with meta-analysis. Results Thirteen studies were included in Meta-analysis, including a total number of 3027 patients with SARS-CoV-2 infection. Male, older than 65, and smoking were risk factors for disease progression in patients with COVID-19 (male: OR = 1.76, 95% CI (1.41, 2.18), P < 0.00001; age over 65 years old: OR =6.06, 95% CI(3.98, 9.22), P < 0.00001; current smoking: OR =2.51, 95% CI(1.39, 3.32), P = 0.0006). The proportion of underlying diseases such as hypertension, diabetes, cardiovascular disease, and respiratory disease were statistically significant higher in critical/mortal patients compared to the non-critical patients (diabetes: OR=3.68, 95% CI (2.68, 5.03), P < 0.00001; hypertension: OR = 2.72, 95% CI (1.60,4.64), P = 0.0002; cardiovascular disease: OR = 5.19, 95% CI(3.25, 8.29), P < 0.00001; respiratory disease: OR = 5.15, 95% CI(2.51, 10.57), P < 0.00001). Clinical manifestations such as fever, shortness of breath or dyspnea were associated with the progression of disease [fever: 0R = 0.56, 95% CI (0.38, 0.82), P = 0.003;shortness of breath or dyspnea: 0R=4.16, 95% CI (3.13, 5.53), P < 0.00001]. Laboratory examination such as aspartate amino transferase(AST) > 40U/L, creatinine(Cr) ≥ 133mol/L, hypersensitive cardiac troponin I(hs-cTnI) > 28pg/mL, procalcitonin(PCT) > 0.5ng/mL, lactatede hydrogenase(LDH) > 245U/L, and D-dimer > 0.5mg/L predicted the deterioration of disease while white blood cells(WBC)<4 × 109/L meant a better clinical status[AST > 40U/L:OR=4.00, 95% CI (2.46, 6.52), P < 0.00001; Cr ≥ 133μmol/L: OR = 5.30, 95% CI (2.19, 12.83), P = 0.0002; hs-cTnI > 28 pg/mL: OR = 43.24, 95% CI (9.92, 188.49), P < 0.00001; PCT > 0.5 ng/mL: OR = 43.24, 95% CI (9.92, 188.49), P < 0.00001;LDH > 245U/L: OR = 43.24, 95% CI (9.92, 188.49), P < 0.00001; D-dimer > 0.5mg/L: OR = 43.24, 95% CI (9.92, 188.49), P < 0.00001; WBC < 4 × 109/L: OR = 0.30, 95% CI (0.17, 0.51), P < 0.00001]. Conclusion Male, aged over 65, smoking patients might face a greater risk of developing into the critical or mortal condition and the comorbidities such as hypertension, diabetes, cardiovascular disease, and respiratory diseases could also greatly affect the prognosis of the COVID-19. Clinical manifestation such as fever, shortness of breath or dyspnea and laboratory examination such as WBC, AST, Cr, PCT, LDH, hs-cTnI and D-dimer could imply the progression of COVID-19.

positive: 2019 novel coronavirus of pneumonia in Wuhan, China: emerging attack and management strategies An ongoing outbreak of 2019-nCoV pneumonia was first identified in Wuhan, Hubei province, China at the end of 2019. With the spread of the new coronavirus accelerating, person-to-person transmission in family homes or hospitals, and intercity spread of 2019-nCoV occurred. At least 40,261 cases confirmed, 23,589 cases suspected, 909 cases death and 3444 cases cured in China and worldwide 24 countries confirmed 383 cases being diagnosed, 1 case death in February 10th, 2020. At present, the mortality of 2019-nCoV in China is 2.3%, compared with 9.6% of SARS and 34.4% of MERS reported by WHO. It seems the new virus is not as fatal as many people thought. Chinese authorities improved surveillance network, made the laboratory be able to recognize the outbreak within a few weeks and announced the virus genome that provide efficient epidemiological control. More comprehensive information is required to understand 2019-nCoV feature, the epidemiology of origin and spreading, and the clinical phenomina. According to the current status, blocking transmission, isolation, protection, and alternative medication are the urgent management strategies against 2019-nCoV.

positive: Impact of Cerebrovascular and Cardiovascular Diseases on Mortality and Severity of COVID-19 – Systematic Review, Meta-analysis, and Meta-regression Background We conducted this systematic review and meta-analysis to evaluate the latest evidence on the association between cerebrovascular, cardiovascular disease, and poor outcome in patients with Coronavirus Disease 2019 (COVID-19) pneumonia. Methods A comprehensive systematic literature search was performed using PubMed, SCOPUS, EuropePMC, and Cochrane Central Database. The outcome of interest was composite poor outcome that comprised of mortality and severe COVID-19. Results A total of 4448 patients were obtained from 16 studies. Cerebrovascular disease was associated with increased poor composite outcome (RR 2.04 [1.43, 2.91], p<0.001; I(2): 77%). Subgroup analysis revealed that cerebrovascular disease was associated with mortality (RR 2.38 [1.92, 2.96], p<0.001; I(2): 0%) and was borderline significant for severe COVID-19 (RR 1.88 [1.00, 3.51], p=0.05; I(2): 87%). Cardiovascular disease was associated with increased composite poor outcome (RR 2.23 [1.71, 2.91], p<0.001; I(2): 60%), and its mortality (RR 2.25 [1.53, 3.29], p<0.001; I(2): 33%) and severe COVID-19 (RR 2.25 [1.51, 3.36], p<0.001; I(2): 76%) subgroup. Meta-regression demonstrate that the association was not influenced by gender, age, hypertension, diabetes, and respiratory comorbidities. The association between cerebrovascular disease and poor outcome was not affected by cardiovascular diseases and vice versa. Conclusion Cerebrovascular and cardiovascular diseases were associated with increased risk for poor outcome in COVID-19.

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

positive: Relation of Dietary Factors with Infection and Mortality Rates of COVID-19 Across the World OBJECTIVE: Poor dietary habits are considered to be the second-leading risk factors for mortality and disability-adjusted life-years (DALYs) in the world. Dietary patterns are different based on cultural, environmental, technological, and economic factors. Nutritional deficiencies of energy, protein, and specific micronutrients have been shown to contribute to depressed immune function and increased susceptibility to infections. We aimed to explore the relation of dietary factors with global infection and mortality rates of COVID-19 in this study. DESIGN: In the current ecological study, the countries that had national dietary data from the Global Dietary Databases of the United Nations and Coronavirus disease statistics from the World Health Organization (WHO) were included. The countries that had Coronavirus disease statistics from the WHO were consecutively checked for the recent data of the dietary factors. SETTING: World. PARTICIPANTS: 158 countries across the world. MEASUREMENTS: infection and mortality rates of COVID-19; dietary factors. RESULTS: The median crude infection and mortality rates by COVID-19 were 87.78 (IQR: 468.03) and 0.0015 (IQR: 0.0059), respectively. The two highest percentage of the crude infection rate were between 0 and 500 (75.9%) and 500–1000 (8.9%) per one million persons. The regression analysis showed that the crude infection rate has been increased by raising consuming fruits (Beta: 0.237; P=0.006) and calcium (Beta: 0.286; P=0.007) and was decreased with rising consuming beans and legumes (Beta: −0.145; P=0.038). The analysis showed that the crude mortality rate was increased by raising consuming sugar-sweetened beverages (Beta: 0.340; P<0.001). Whereas, the crude mortality rate by COVID-19 has been decreased by increasing fruits consuming (Beta: −0.226; P=0.047) and beans and legumes (Beta: −0.176; P=0.046). CONCLUSION: The present study showed the higher intake of fruits and sugar-sweetened beverages had a positive effect on infection and mortally rates by COVID-19, respectively. In contrast, the higher intake of beans and legumes had a negative effect on both increasing infection and mortality rates.

positive: Trends of SARS-CoV-2 infection worldwide: Role of population density, age structure, and climate on transmission and case fatality Introduction The disease transmission pattern of COVID19 is highly heterogeneous, which suggests that the pandemic maybe driven by complex factors, which may include habitat suitability, region specific human mobility, and transmission related to susceptibility. The purpose of this study was to examine the effects of different spatial and demographic factors on COVID19 transmission and case fatality worldwide. Methods We assessed SARS CoV2 virus transmission and COVID19 related fatalities in 50 countries in all continents of the globe. Data from the COVID19 data repository of the Johns Hopkins Center for Systems Science and Engineering, the European center for disease control and prevention, and the World Health Organization were used to obtain the daily number of cases and organize the incidence data. Disease spread, was assessed using the reproduction number of the disease across the sampled countries. R0 package of R statistical software was used to estimate the reproduction number of the COVID19 using the exponential growth method. After computing the reproductive number of each country in the study, a multiple linear regression model was fitted by taking the R0 value as dependent variable, and latitude and population density as an independent variable. Disease severity was analyzed using the case fatality ratio of COVID19. The proportion of deaths to the total numbers of cases was meta analyzed using metaphor package of R statistical software using random effect inverse variance weighting to come up with the case fatality ratio. Results We found no statistically significant association between disease spread and latitude or population density. The regression model analysis that accounted for age, population density and latitude showed that age distribution remains an important driver shaping the current distribution of COVID19 cases. The relative frequency of people above 65 years old was positively correlated with the cumulative numbers of COVID19 cases as well as case fatality ratio in each country. The multiple linear regression model fitted between CFR and the three major covariates showed that, the demographic distribution of the sampled countries is strongly associated with the case fatality ratio. An increase in the elderly population proportion by 1 percent was associated with an increase in CFR by 0.32. Correlation with proportion of populations over 65 years old is concordant with the previous findings relationship between case fatality ratio and patient age. Conclusion This analysis provides important information that can inform the decisions of local and global health authorities. Particularly, as our study confirms that death and severity of COVID19 are associated with age, in countries with the biggest outbreaks, strategies must be employed to ensure that high risk groups, such as old people received adequate protection from COVID19.

positive: Differences by country-level income in COVID-19 cases, deaths, case-fatality rates, and rates per million population in the first five months of the pandemic Abstract Objective: To describe differences by country-level income in COVID-19 cases, deaths, case-fatality rates, incidence rates, and death rates per million population. Methods: Publicly available data on COVID-19 cases and deaths from December 31, 2019 to June 3, 2020 were analyzed. Kruskal-Wallis tests were used to examine associations of country-level income with COVID-19 cases, deaths, case-fatality rates, incidence rates, and death rates. Results: A total of 380,803 deaths out of 6,348,204 COVID-19 cases were reported from 210 countries and territories globally in the period under study, and the global case-fatality rate was 6.0%. Of the total globally reported cases and deaths, the percentages of cases and deaths were 59.9% and 75.0% for high-income countries, and 30.9% and 20.7% for upper-middle-income countries. Countries in higher-income categories had higher incidence rates and death rates. Between April and May, the incidence rates in higher-income groups of countries decreased, but in other groups, it increased. Conclusions In the first five months of the COVID-19 pandemic, most cases and deaths were reported from high-income and upper-middle-income countries, and those countries had higher incidence rates and death rates per million population than did lower-middle and low-income countries. Keywords: COVID-19, incidence rate, death rate, case fatality rate, income, and country

positive: A Chain Multinomial Model for Estimating the Real-Time Fatality Rate of a Disease, with an Application to Severe Acute Respiratory Syndrome It is well known that statistics using cumulative data are insensitive to changes. World Health Organization (WHO) estimates of fatality rates are of the above type, which may not be able to reflect the latest changes in fatality due to treatment or government policy in a timely fashion. Here, the authors propose an estimate of a real-time fatality rate based on a chain multinomial model with a kernel function. It is more accurate than the WHO estimate in describing fatality, especially earlier in the course of an epidemic. The estimator provides useful information for public health policy makers for understanding the severity of the disease or evaluating the effects of treatments or policies within a shorter time period, which is critical in disease control during an outbreak. Simulation results showed that the performance of the proposed estimator is superior to that of the WHO estimator in terms of its sensitivity to changes and its timeliness in reflecting the severity of the disease.

positive: Mortality Rate of Infection With COVID-19 in Korea From the Perspective of Underlying Disease On December 31, 2019 the China National Health Commission (NHC) reported that an unknown cause of pneumonia had been detected in Wuhan in Hubei province. On February 12, the disease caused by the novel coronavirus (2019-nCoV) was given a formal name, COVID-19. On January 20, 2020, the first case of COVID-19 was confirmed in Korea. The age-specific death rate was the highest among patients over 70 years of age, with underlying diseases in their circulatory system, such as myocardial infarction, cerebral infraction, arrythmia, and hypertension. Patients with underlying disease who are 70 years of age or older should recognize that there is a high possibility of developing a serious disease in case of viral infection and follow strict precautions.

positive: Case fatality rate in patients with COVID-19 infection and its relationship with length of follow up

positive: SARS-CoV-2 Viral Load Predicts COVID-19 Mortality The need for reliable and widely available SARS-CoV-2 testing is well recognized, but it will be equally necessary to develop quantitative methods that determine viral load in order to guide patient triage and medical decision making. We are the first to report that SARS-CoV-2 viral load at the time of presentation is an independent predictor of COVID-19 mortality in a large patient cohort (n=1,145). Viral loads should be used to identify higher-risk patients that may require more aggressive care and should be included as a key biomarker in the development of predictive algorithms.

positive: TRACKing Excess Deaths (TRACKED): an interactive online tool to monitor excess deaths associated with COVID-19 pandemic in the United Kingdom Aim: We aimed to describe trends of excess mortality in the United Kingdom (UK) stratified by nation and cause of death, and to develop an online tool for reporting the most up to date data on excess mortality. Methods: Population statistics agencies in the UK including the Office for National Statistics (ONS), National Records of Scotland (NRS), and Northern Ireland Statistics and Research Agency (NISRA) publish weekly data on deaths. We used mortality data up to 22nd May in the ONS and the NISRA and 24th May in the NRS. Crude mortality for non-COVID deaths (where there is no mention of COVID-19 on the death certificate) calculated. Excess mortality defined as difference between observed mortality and expected average of mortality from previous 5 years. Results: There were 56,961 excess deaths and 8,986 were non-COVID excess deaths. England had the highest number of excess deaths per 100,000 population (85) and Northern Ireland the lowest (34). Non-COVID mortality increased from 23rd March and returned to the 5-year average on 10th May. In Scotland, where underlying cause mortality data besides COVID-related deaths was available, the percentage excess over the 8-week period when COVID-related mortality peaked was: dementia 49%, other causes 21%, circulatory diseases 10%, and cancer 5%. We developed an online tool (TRACKing Excess Deaths - TRACKED) to allow dynamic exploration and visualisation of the latest mortality trends. Conclusions: Continuous monitoring of excess mortality trends and further integration of age- and gender-stratified and underlying cause of death data beyond COVID-19 will allow dynamic assessment of the impacts of indirect and direct mortality of the COVID-19 pandemic.

positive: Excess Mortality Estimation During the COVID-19 Pandemic: Preliminary Data from Portugal INTRODUCTION: Portugal is experiencing the effects of the COVID-19 pandemic since March 2020. All-causes mortality in Portugal increased during March and April 2020 compared to previous years, but this increase is not explained by COVID-19 reported deaths. The aim of this study was to analyze and consider other criteria for estimating excessive all-cause mortality during the early COVID-19 pandemic period. MATERIAL AND METHODS: Public data was used to estimate excess mortality by age and region between March 1 and April 22, proposing baselines adjusted for the lockdown period. RESULTS: An excess mortality of 2400 to 4000 deaths was observed. Excess mortality was associated with older age groups (over age 65) [corrected]. DISCUSSION: The data suggests a ternary explanation for early excess mortality: COVID-19, non-identified COVID-19 and decrease in access to healthcare. The estimates have implications in terms of communication of non-pharmaceutical actions, for research, and to healthcare professionals. CONCLUSION: Despite the inherent uncertainty, the excess mortality occurred between March 1 and April 22 could be 3.5- to 5-fold higher than what can be explained by the official COVID-19 deaths [corrected].

positive: The role of essential organ-based comorbidities in the prognosis of COVID-19 infection patients Objectives: To assess the role of essential organ-based comorbidities in the prognosis of COVID-19 patients.Methods: All consecutive patients diagnosed with COVID-19 admitted to the Zhongnan Hospital of Wuhan University from 11 January to 16 March 2020 were enrolled in this retrospective cohort study.Results: A total of 212 COVID-19 patients were included. COVID-19 patients with heart, liver and kidneycomorbidity, compared to patients without related comorbidities, were more likely to have cardiac injuries [9.1%(3/33) vs 2.2%(4/179), P = 0.043], liver injuries [13.0%(3/23) vs 3.2%(6/189), P = 0.027], kidney injury [54.5%(6/11) vs 2.0%(4/201), P < 0.001], and higher risk of mortality [Heart-comorbidity: 6.1%(2/33) vs 0.6%(1/179), P = 0.014; Liver-comorbidity: 8.7%(2/23) vs 0.5%(1/189), P = 0.002; Kidney-comorbidity: 27.3%(3/11) vs 1.0%(2/201), P < 0.001. Mortality was higher in patients with more severe Grade of organ injuries [Heart-injury: P = 0.044; Liver-injury: P = 0.020; Kidney-injury: P = 0.030].Conclusion: Male, older, co-existing of heart, liver, and kidney comorbidities, especially those with severe Grade organ injuries, had a poor prognosis after SARS-CoV-2 infection.

positive: Total COVID-19 Mortality in Italy: Excess Mortality and Age Dependence through Time-Series Analysis We perform a counterfactual time series analysis using two different Data Science methods applied to 2020 mortality data reported from towns in Italy, with data from the previous five years as control. We find an excess mortality that is correlated in time with the COVID-19 reported death rate time series. Our analysis shows good agreement with reported COVID-19 mortality for age<70 years, but an excess in total mortality increasing with age above 70 years, suggesting there is a large population of predominantly old people missing from the official fatality statistics. We estimate that the number of COVID-19 deaths in Italy is 52,000 ± 2000 as of April 18 2020, more than a factor of 2 higher than the official number. The Population Fatality Rate (PFR) has reached 0.22% in the most affected region of Lombardia and 0.57% in the most affected province of Bergamo,which constitutes a lower bound to the Infection Fatality Rate (IFR). We estimate PFR as a function of age, finding a steep age dependence: in Lombardia (Bergamo province) 0.6% (1.7%) of the total population in age group 70-79 died, 1.6% (4.6%) in age group 80-89, and 3.41% (10.2%) in the age group above 90. We combine this with the Test Positivity Rate to estimate the lower bound of 0.84% on the IFR for Lombardia. We observe IFR to trace the Yearly Mortality Rate (YMR) above 60 years, which can be used to estimate the IFR for other regions in the world. We predict an IFR lower bound of 0.5% for NYC and 26% of total COVID-19 mortality arising from the population below 65 years, in agreement with the existing data and several times higher than Lombardia. Combining PFR with the Princess Diamond cruise ship IFR for ages above 70 we estimate the infection rates(IR) of regions in Italy, which peak in Lombardia at 23% (12%-41%, 95% c.l.), and for provinces in Bergamo at 67% (33%-100%, 95% c.l.). This suggests that Bergamo may have reached herd immunity, and that the number of infected people greatly exceeds the number of positive tests, by a factor of 35 in Lombardia.

positive: Cancer history is an independent risk factor for mortality in hospitalized COVID-19 patients: a propensity score-matched analysis BACKGROUND: Although research on the effects of comorbidities on coronavirus disease 2019 (COVID-19) patients is increasing, the risk of cancer history has not been evaluated for the mortality of patients with COVID-19. METHODS: In this retrospective study, we included 3232 patients with pathogen-confirmed COVID-19 who were hospitalized between January 18th and March 27th, 2020, at Tongji Hospital in Wuhan, China. Propensity score matching was used to minimize selection bias. RESULTS: In total, 2665 patients with complete clinical outcomes were analyzed. The impacts of age, sex, and comorbidities were evaluated separately using binary logistic regression analysis. The results showed that age, sex, and cancer history are independent risk factors for mortality in hospitalized COVID-19 patients. COVID-19 patients with cancer exhibited a significant increase in mortality rate (29.4% vs. 10.2%, P < 0.0001). Furthermore, the clinical outcomes of patients with hematological malignancies were worse, with a mortality rate twice that of patients with solid tumors (50% vs. 26.1%). Importantly, cancer patients with complications had a significantly higher risk of poor outcomes. One hundred nine cancer patients were matched to noncancer controls in a 1:3 ratio by propensity score matching. After propensity score matching, the cancer patients still had a higher risk of mortality than the matched noncancer patients (odds ratio (OR) 2.98, 95% confidence interval (95% CI) 1.76–5.06). Additionally, elevations in ferritin, high-sensitivity C-reactive protein, erythrocyte sedimentation rate, procalcitonin, prothrombin time, interleukin-2 (IL-2) receptor, and interleukin-6 (IL-6) were observed in cancer patients. CONCLUSIONS: We evaluated prognostic factors with epidemiological analysis and highlighted a higher risk of mortality for cancer patients with COVID-19. Importantly, cancer history was the only independent risk factor for COVID-19 among common comorbidities, while other comorbidities may act through other factors. Moreover, several laboratory parameters were significantly different between cancer patients and matched noncancer patients, which may indicate specific immune and inflammatory reactions in COVID-19 patients with cancer.

positive: Age-dependence of mortality from novel coronavirus disease (COVID-19) in highly exposed populations: New York transit workers and residents and Diamond Princess passengers. Background. Populations heavily exposed to the novel coronavirus provide an opportunity to estimate the mortality from COVID-19 in different age groups. Methods. The mortality reported by May 13 from COVID-19 among Diamond Princess cruise ship passengers, and New York residents and Metropolitan Transit Authority (MTA) workers was estimated based on publicly available information. Results. The mortality among children (age 0 to 17 yrs) in New York City was 1 in 172,692. The mortality in New York state was 1 in 322,217 for ages 10-19 yrs., and 1 in 36,725 for ages 20-29 yrs. The mortality among New York transit workers was estimated to be 1 in 7,329 for ages 30-39 years; 1 in 1,075 for ages 40-49 yrs.; 1 in 343 for ages 50-59 yrs.; and 1 in 178 for ages 60-69 yrs. Among Diamond Princess passengers, the mortality was estimated to be 1 in 145 for ages 70-79, and 1 in 54 for ages 80-89. Conclusions: Mortality among populations exposed to the novel coronavirus increases with age, ranging from about 1 in 170,000 below the age of 18 years, to 1 in 54 above the age of 80 years.

positive: Multivariate Analysis of Factors Affecting COVID-19 Case and Death Rate in U.S. Counties: The Significant Effects of Black Race and Temperature Objectives: Coronavirus disease-19 (COVID-19) has spread rapidly around the world, and many risk factors including patient demographics, social determinants of health, environmental variables, underlying health conditions, and adherence to social distancing have been hypothesized to affect case and death rates. However, little has been done to account for the potential confounding effects of these factors. Using a large multivariate analysis, this study illuminates modulators of COVID-19 incidence and mortality in U.S. counties while controlling for risk factors across multiple domains. Methods: Data on COVID-19 and various risk factors in all U.S. counties was collected from publicly available data sources through April 14, 2020. Counties with at least 50 COVID-19 cases were included in case analyses and those with at least 10 deaths were included in mortality models. The 661 counties meeting inclusion criteria for number of cases were grouped into quartiles and comparisons of risk factors were made using t-tests between the highest and lowest quartiles. Similar comparisons for 217 counties were made for above average and below average deaths/100,000. Adjusted linear and logistic regression analyses were performed to evaluate the independent effects of factors that significantly impacted cases and deaths. Results: Univariate analyses demonstrated numerous significant differences between cohorts for both cases and deaths. Risk factors associated with increased cases and/or deaths per 100,000 included increased GDP per capita, decreased social distancing, increased age, increased percent Black, decreased percent Hispanic, decreased percent Asian, decreased health, increased poverty, increased diabetes, increased coronary heart disease, increased physical inactivity, increased alcohol consumption, increased tobacco use, and decreased access to primary care. Multivariate regression analyses demonstrated Black race is a risk factor for worse COVID-19 outcome independent of comorbidities, poverty, access to health care, and other mitigating factors. Lower daily temperatures was also an independent risk factor in case load but not deaths. Conclusions: U.S. counties with a higher proportion of Black residents are associated with increased COVID-19 cases and deaths. However, the various suggested mechanisms, such as socioeconomic and healthcare predispositions, did not appear to drive the effect of race in our model. Counties with higher average daily temperatures are also associated with decreased COVID-19 cases but not deaths. Several theories are posited to explain these findings, including prevalence of vitamin D deficiency. Additional studies are needed to further understand these effects.

positive: The Contribution of Age Structure to the Number of Deaths from Covid-19 in the UK by Geographical Units This study investigates the contribution of population age structure to mortality from Covid-19 in the UK by geographical units. We project death rates at various spatial scales by applying data on age-specific fatality rates to the area's population by age and sex. Our analysis shows a significant variation in the projected death rates between the constituent countries of the UK, between its regions and within regions. First, Scotland and Wales have higher projected fatality levels from Covid-19 than England, whereas Northern Ireland has lower rate. Second, the infection fatality rates are projected to be substantially higher in small towns and rural areas than those in large urban areas. Third, our analysis shows that within urban regions there are also 'pockets' of high projected death rates. Overall, the areas with high and low fatality rates tend to cluster because of the high residential separation of different population age-groups in the UK. Our analysis also reveals that the Welsh-, Gaelic- and Cornish-speaking communities with relatively old populations are likely to experience heavy population losses if the virus spreads widely across the UK.

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: Clinical characteristics of patients hospitalized with COVID-19 in Spain: results from the SEMI-COVID-19 Network. Background. Spain has been one of the countries most affected by the COVID-19 pandemic. Objective. To create a registry of patients with COVID-19 hospitalized in Spain in order to improve our knowledge of the clinical, diagnostic, therapeutic, and prognostic aspects of this disease. Methods. A multicentre retrospective cohort study, including consecutive patients hospitalized with confirmed COVID-19 throughout Spain. Epidemiological and clinical data, additional tests at admission and at seven days, treatments administered, and progress at 30 days of hospitalization were collected from electronic medical records. Results. Up to April 30th 2020, 6,424 patients from 109 hospitals were included. Their median age was 69.1 years (range: 18-102 years) and 56.9% were male. Prevalences of hypertension, dyslipidemia, and diabetes mellitus were 50.2%, 39.7%, and 18.7%, respectively. The most frequent symptoms were fever (86.2%) and cough (76.5%). High values of ferritin (72.4%), lactate dehydrogenase (70.2%), and D-dimer (61.5%), as well as lymphopenia (52.6%), were frequent. The most used antiviral drugs were hydroxychloroquine (85.7%) and lopinavir/ritonavir (62.4%). 31.5% developed respiratory distress. Overall mortality rate was 21.1%, with a marked increase with age (50-59 years: 4.2%, 60-69 years: 9.1%, 70-79 years: 21.4%, 80-89 years: 42.5%, [≥] 90 years: 51.1%). Conclusions. The SEMI-COVID-19 Network provides data on the clinical characteristics of patients with COVID-19 hospitalized in Spain. Patients with COVID-19 hospitalized in Spain are mostly severe cases, as one in three patients developed respiratory distress and one in five patients died. These findings confirm a close relationship between advanced age and mortality.

positive: Epidemiological and Clinical Aspects of COVID-19; a Narrative Review There are significant misconceptions and many obstacles in the way of illuminating the epidemiological and clinical aspects of COVID-19 as a new emerging epidemic. In addition, usefulness of some evidence published in the context of the recent epidemic for decision making in clinic as well as public health is questionable. However, misinterpreting or ignoring strong evidence in clinical practice and public health probably results in less effective and somehow more harmful decisions for individuals as well as subgroups in general populations of countries in the initial stages of this epidemic. Accordingly, our narrative review appraised epidemiological and clinical aspects of the disease including genetic diversity of coronavirus genus, mode of transmission, incubation period, infectivity, pathogenicity, virulence, immunogenicity, diagnosis, surveillance, clinical case management and also successful measures for preventing its spread in some communities.

positive: Risk factors for predicting mortality in elderly patients with COVID-19: a review of clinical data in China Abstract While elderly patients are at high risk of fatality, research concerning COVID-19 has largely been done on clarifying the clinical features. As such, the present work aims to identify risk factors for mortality in elderly patients with COVID-19. Given that single-centre studies are less likely informative as elderly remains a minority in the total Chinese population, the present study reviewed the clinical data of geriatric COVID-19 patients gathered from different sources in the public domain. Based on the data of 154 individuals from 26 provinces, age remained a key mortality risk factor among geriatric patients of different ages. While dyspnoea and chest pain/discomfort were more commonly seen in deceased patients as they represented severe pneumonia, fever was more prominent in surviving patients. This was likely due to the lower baseline body temperature observed in elderly which translated to a lower maximum temperature of fever. However, lowering the threshold temperature for fever is not recommended in surveillance. Instead, baseline body temperature measured on a regular basis should be used to define the threshold temperature for fever. Against mixed results, more research should be done on identifying comorbidities associated with mortality in geriatric patients.

positive: The potential effect of the African population age structure on COVID-19 mortality Currently (mid May 2020), most active cases of COVID-19 are found in Europe and North America while it is still in the initial phases in Africa. As COVID-19 mortality occurs mainly in elderly and as Africa has a comparably young population, the death rates should be lower than on other continents. We calculated standardised mortality ratios (SMR) using age-specific case fatality rates for COVID-19 and the age structure of the population of Africa and of other continents. Compared to a European or Northern American population, the standardised mortality ratio was only 0.22 and 0.25, respectively, corresponding to reduction of deaths rates to a quarter. Compared to the Asian and Latin American & Caribbean population, the SMR was 0.43 and 0.44, respectively, corresponding to half the death rate for Africa. It is useful to quantify the isolated effect of the African age-structure on potential COVID-19 mortality for illustrative and communication purposes, keeping in mind the importance of public health measures that have been shown to be effective in reducing cases and deaths. The different aspect of age pyramids of a European and an African population are striking and the potential implications for the pandemic are often discussed but rarely quantified.

positive: COVID-19 mortality rates in the European Union, Switzerland, and the UK: effect of timeliness, lockdown rigidity, and population density BACKGROUND: To date the European experience with COVID-19 mortality has been different to the observed in China and Asia. We aimed to forecast mortality trends in the 27 countries of the European Union (EU), plus Switzerland and the United Kingdom (UK), where lockdown dates and confinement interventions have been heterogeneous, and to explore its determinants. METHODS: We have adapted our predictive model of COVID-19-related mortality, which rested on the observed mortality within the first weeks of the outbreak and the date of the respective lockdown in each country. It was applied in a training set of three countries (Italy, Germany and Spain), and then applied to the EU plus the UK and Switzerland. In addition, we explored the effects of timeliness and rigidity of the lockdown (on a five-step scale) and population density in our forecasts. We report r2, and percent variation of expected versus observed deaths, all following TRIPOD guidance. RESULTS: We identified a homogeneous distribution of deaths, and found a median of 24 days after lockdown adoption to reach the maximum daily deaths. Strikingly, cumulative deaths up to April 25th, 2020 observed in Europe separated countries in three waves, according to the time lockdown measures were adopted following the onset of the outbreak: after a week, within a week, or even prior to the outbreak (r2=0.876). In contrast, no correlation neither with lockdown rigidity nor population density were observed. CONCLUSIONS: The European experience confirms that early, effective interventions of 86 lockdown are fundamental to minimizing the COVID-19 death toll.

positive: Simpson's paradox in Covid-19 case fatality rates: a mediation analysis of age-related causal effects We point out an instantiation of Simpson's paradox in Covid-19 case fatality rates (CFRs): comparing data of 44,672 cases from China with early reports from Italy (9th March), we find that CFRs are lower in Italy for every age group, but higher overall. This phenomenon is explained by a stark difference in case demographic between the two countries. Using this as a motivating example, we introduce basic concepts from mediation analysis and show how these can be used to quantify different direct and indirect effects when assuming a coarse-grained causal graph involving country, age, and mortality. As a case study, we then investigate total, direct, and indirect (age-mediated) causal effects between different countries and at different points in time. This allows us to separate age-related effects from others unrelated to age, and thus facilitates a more transparent comparison of CFRs across countries throughout the evolution of the Covid-19 pandemic.

positive: Biological and Epidemiological Trends in the Prevalence and Mortality due to Outbreaks of Novel Coronavirus COVID-19 The novel coronavirus (Covid-19) infection outbreak has posed a major threat to international health system and economy. This study is aimed at investigating the biological and epidemiological trends in the prevalence and mortality due to outbreaks of novel coronavirus (COVID-19) infections. The data on the global outbreak of COVID-19, were obtained from World Health Organization (WHO), Worldometer, Centers for Disease Control and Prevention (CDC), and research institutes. The information was also recorded from research documents published in global scientific journals indexed in Pub Med and Institute of Scientific Information (ISI) Web of Science on the trends in the prevalence and mortality due to COVID-19 infection outbreaks. The results show rising trends in the transmission, prevalence and mortality rate due to coronavirus COVID-19. During the period of December 29, 2019 through March 31, 2020, it has infected 750890 people worldwide, resulting in 36405 deaths with a mortality rate of 4.84%. The infections were more frequent among male gender with above 60 years of age. The mean growth rate index for total number of cases from January 23 to March 31, 2020 was 1.20 and growth rate index for mortality rate was 1.12. There was a positive association between the prevalence and mortality rate (R2=0.996). The novel coronavirus COVID-19 is highly contagious and has affected a large number of people worldwide. It is still spreading with mutable prevalence and mortality outbreak trends. The global health officials have taken priority measures to prevent the further outbreaks of this emerging pathogen across the globe. However, the rising number of cases and mortality risk estimates are demonstrating that enhanced public health mediations, good hygienic conditions, social distancing and movement limitations may control the COVID-19 epidemics.

positive: Covid-19: Projections of mortality in the US rise as states open up.

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

positive: Similarity in Case Fatality Rates (CFR) of COVID-19/SARS-COV-2 in Italy and China. As of 28 February 2020, Italy had 888 cases of SARS-CoV-2 infections, with most cases in Northern Italy in the Lombardia and Veneto regions. Travel-related cases were the main source of COVID-19 cases during the early stages of the current epidemic in Italy. The month of February, however, has been dominated by two large clusters of outbreaks in Northern Italy, south of Milan, with mainly local transmission the source of infections. Contact tracing has failed to identify patient zero in one of the outbreaks. As of 28 February 2020, twenty-one cases of COVID-19 have died. Comparison between case fatality rates in China and Italy are identical at 2.3. Additionally, deaths are similar in both countries with fatalities in mostly the elderly with known comorbidities. It will be important to develop point-of-care devices to aid clinicians in stratifying elderly patients as early as possible to determine the potential level of care they will require to improve their chances of survival from COVID-19 disease.

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

positive: Relative disease burdens of COVID-19 and seasonal influenza in New York City, February 1 - April 18, 2020. Comparisons between the mortality burdens of COVID-19 and seasonal influenza often fail to account for the fact that the United States Centers for Disease Control and Prevention (CDC) reports annual influenza mortality estimates which are calculated based upon a series of assumptions about the underreporting of flu deaths. COVID-19 deaths, in contrast, are being reported as raw counts. In this report, we compare COVID-19 death counts to seasonal influenza death counts in New York City during the interval from February 1 - April 18, 2020. Using this approach, COVID-19 appears to have caused 21.4 times the number of deaths as seasonal influenza during the same period. We also assessed excess mortality in order to verify this finding. New York City has had approximately 13,032 excess all-cause mortality deaths during this time period. We assume that most of these deaths are COVID-19 related. We therefore calculated the ratio of excess deaths (i.e. assumed COVID-19 deaths) to seasonal influenza deaths during the same time interval and found a similar ratio of 21.1 COVID-19 to seasonal influenza deaths. Our findings are consistent with conditions on the ground today. Comparing COVID-19 deaths with CDC estimates of yearly influenza-related deaths would suggest that, this year, seasonal influenza has killed approximately the same number of Americans as COVID-19 has. This does not comport with the realities of the pandemic we see today.

positive: 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.

positive: Explore the Possible Impact of BCG Vaccination Policy on the Morbidity, Mortality, and Recovery Rates due to COVID-19 Infection. BACKGROUND The Coronavirus Disease-19 (COVID-19) is the new form of an acute infectious respiratory disease and has quickly spread over most continents in the world. Recently, it has been shown that Bacille Calmette-Guerin (BCG) might protect against COVID-19. This study aims to investigate the possible correlation between BCG vaccination and morbidity/mortality/recovery rate associated with COVID-19 infection. METHODS Data of COVID-19 confirmed cases, deaths, recoveries, and population were obtained from https://www.worldometers.info/coronavirus/ (Accessed on 12 June, 2020). To have meaningful comparisons among countries' mortality and recovery rates, we only choose those countries with COVID-19 infected cases at least 200. The Poisson regression and logistic regression were used to explore the relationship between BCG vaccination and morbidity, mortality and recovery rates. RESULTS Among those 158 countries with at least 200 COVID-19 infected cases, there were 141 countries with BCG vaccination information available. The adjusted rates ratio of COVID-19 confirmed cases for Current BCG vaccination vs. non-Current BCG vaccination was 0.339 (with 95% CI= (0.338,0.340)). Moreover, the adjusted odds ratio (OR) of death and recovery after coronavirus infected for Current BCG vaccination vs. non-Current BCG vaccination were 0.258 (with 95% CI= (0.254,0.261)) and 2.151 (with 95% CI= (2.140,2.163)), respectively. CONCLUSIONS That data in this study show the BCG might provide the protection against COVID-19, with consequent less COVID-19 infection and deaths and more rapid recovery. BCG vaccine might bridge the gap before the disease-specific vaccine is developed, but this hypothesis needs to be further tested in rigorous randomized clinical trials.

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

positive: COVID-19 pandemic: is a gender-defined dosage effect responsible for the high mortality rate among males?

positive: Estimation of instant case fatality rate of COVID-19 in Wuhan and Hubei based on daily case notification data Background The outbreak of coronavirus disease 2019 (COVID-19) initially appeared and has most rapidly spread in Wuhan, China. The case fatality rate is the most direct indicator to assess the hazards of an infectious disease. We aimed to estimate the instant fatality rate and cure rate of COVID-19 in Wuhan City and its affiliated Hubei Province. Methods We collected the daily case notification data of COVID-19 from Dec 8, 2019 to Mar 10, 2020 in Wuhan City and Hubei Province officially announced by the Chinese authority. The numbers of daily confirmed/deaths/cured cases and the numbers of daily cumulative confirmed/deaths/cured cases were obtained. The death time and cure time of COVID-19 patients were calculated based on the dates of diagnosis, death and discharge of individual cases. Then the estimated diagnosis dates of deaths and cured cases were obtained on the basis of the median death or medium cure time, respectively. Finally, the instant fatality rate of COVID-19 was calculated according to the numbers of deaths and cured cases on the same estimated diagnosis dates. Results From Jan 1, 2020 to Feb 22, 2020 in Wuhan City, the instant case fatality rate of COVID-19 was 3.4%～19.5% and the instant cured rate was 80.0%～96.6%. The average fatality rate reached 11.4% while the average cure rate was 88.6%. During the same period in Hubei Province, the instant case fatality rate was 3.8%～16.6% and the instant cured rate was 83.4%～96.6%. The average fatality rate and the average cure rate were 9.2% and 91.8%, respectively. Conclusions The fatality rate and cure rate of COVID-19 in Wuhan City and Hubei Province were underestimated. Wuhan showed higher fatality rate and cure rate than the whole Hubei Province did.

positive: Estimation of COVID-19 case fatality ratio based on a bi-directional correction method The case fatality rate (CFR) can be used to predict the number of potential deaths in the epidemic and thus can reflect the appropriateness and quality of medical measures developed by public health. When a new disease breaks out, it is particularly important to accurately estimate the CFR. However, while the epidemic is still developing, the crude CFR is often lower than the true value and the hospital CFR is often higher than the true value due to differences in occurrence time, patient number, and treatment plans. Therefore, this study proposes a bi-directional correction method to estimate the CFR. COVID-19 data from China were used to evaluate this method. The results show that this method provides more accurate results than both the crude CFR and hospital CFR. Additionally, this method was used to estimate the CFR of COVID-19 in other countries, with an aim to provide a reference for prevention and control decisions for the COVID-19 epidemic and for the evaluation of medical efforts.

positive: Fasting blood glucose at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes: a multi-centre retrospective study AIMS/HYPOTHESIS: Hyperglycaemia is associated with an elevated risk of mortality in community-acquired pneumonia, stroke, acute myocardial infarction, trauma and surgery, among other conditions. In this study, we examined the relationship between fasting blood glucose (FBG) and 28-day mortality in coronavirus disease 2019 (COVID-19) patients not previously diagnosed as having diabetes. METHODS: We conducted a retrospective study involving all consecutive COVID-19 patients with a definitive 28-day outcome and FBG measurement at admission from 24 January 2020 to 10 February 2020 in two hospitals based in Wuhan, China. Demographic and clinical data, 28-day outcomes, in-hospital complications and CRB-65 scores of COVID-19 patients in the two hospitals were analysed. CRB-65 is an effective measure for assessing the severity of pneumonia and is based on four indicators, i.e. confusion, respiratory rate (>30/min), systolic blood pressure (≤90 mmHg) or diastolic blood pressure (≤60 mmHg), and age (≥65 years). RESULTS: Six hundred and five COVID-19 patients were enrolled, including 114 who died in hospital. Multivariable Cox regression analysis showed that age (HR 1.02 [95% CI 1.00, 1.04]), male sex (HR 1.75 [95% CI 1.17, 2.60]), CRB-65 score 1–2 (HR 2.68 [95% CI 1.56, 4.59]), CRB-65 score 3–4 (HR 5.25 [95% CI 2.05, 13.43]) and FBG ≥7.0 mmol/l (HR 2.30 [95% CI 1.49, 3.55]) were independent predictors for 28-day mortality. The OR for 28-day in-hospital complications in those with FBG ≥7.0 mmol/l and 6.1–6.9 mmol/l vs <6.1 mmol/l was 3.99 (95% CI 2.71, 5.88) or 2.61 (95% CI 1.64, 4.41), respectively. CONCLUSIONS/INTERPRETATION: FBG ≥7.0 mmol/l at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes. Glycaemic testing and control are important to all COVID-19 patients even where they have no pre-existing diabetes, as most COVID-19 patients are prone to glucose metabolic disorders. [Figure: see text]

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: Estimating the case fatality ratio of the COVID-19 epidemic in China Background: Corona Virus Disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan city and rapidly spread throughout China since late December 2019. Crude case fatality ratio (CFR) with dividing the number of known deaths by the number of confirmed cases does not represent the true CFR and might be off by orders of magnitude. We aim to provide a precise estimate of the CFR of COVID-19 using statistical models at the early stage of the epidemic. Methods: We extracted data from the daily released epidemic report published by the National Health Commission P. R. China from 20 Jan 2020, to 1 March 2020. Competing risk model was used to obtain the cumulative hazards for death, cure, and cure-death hazard ratio. Then the CFR was estimated based on the slope of the last piece in joinpoint regression model, which reflected the most recent trend of the epidemic. Results: As of 1 March 2020, totally 80,369 cases were diagnosed as COVID-19 in China. The CFR of COVID-19 were estimated to be 70.9% (95% CI: 66.8%-75.6%) during Jan 20-Feb 2, 20.2% (18.6%-22.1%) during Feb 3-14, 6.9% (6.4%-7.4%) during Feb 15-23, 1.5% (1.4%-1.6%) during Feb 24-March 1 in Hubei province, and 20.3% (17.0%-25.3%) during Jan 20-28, 1.9% (1.8%-2.1%) during Jan 29-Feb 12, 0.9% (0.8%-1.1%) during Feb 13-18, 0.4% (0.4%-0.5%) during Feb 19-March 1 in other areas of China, respectively. Conclusions: Based on analyses of public data, we found that the CFR in Hubei was much higher than that of other regions in China, over 3 times in all estimation. The CFR would follow a downwards trend based on our estimation from recently released data. Nevertheless, at early stage of outbreak, CFR estimates should be viewed cautiously because of limited data source on true onset and recovery time.

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

positive: Sociodemographic, clinical and laboratory factors on admission associated with COVID-19 mortality in hospitalized patients: A retrospective observational study BACKGROUND: To identify and quantify associations between baseline characteristics on hospital admission and mortality in patients with COVID-19 at a tertiary hospital in Spain. METHODS AND FINDINGS: This retrospective case series included 238 patients hospitalized for COVID-19 at Hospital Universitario Clínico San Cecilio (Granada, Spain) who were discharged or who died. Electronic medical records were reviewed to obtain information on sex, age, personal antecedents, clinical features, findings on physical examination, and laboratory results for each patient. Associations between mortality and baseline characteristics were estimated as hazard ratios (HR) calculated with Cox regression models. Series mortality was 25.6%. Among patients with dependence for basic activities of daily living, 78.7% died, and among patients residing in retirement homes, 80.8% died. The variables most clearly associated with a greater hazard of death were age (3% HR increase per 1-year increase in age; 95%CI 1–6), diabetes mellitus (HR 2.42, 95%CI 1.43–4.09), SatO(2)/FiO(2) ratio (43% HR reduction per 1-point increase; 95%CI 23–57), SOFA score (19% HR increase per 1-point increase, 95%CI 5–34) and CURB-65 score (76% HR increase per 1-point increase, 95%CI 23–143). CONCLUSIONS: The patients residing in retirement homes showed great vulnerability. The main baseline factors that were independently associated with mortality in patients hospitalized for COVID-19 were older age, diabetes mellitus, low SatO(2)/FiO(2) ratio, and high SOFA and CURB-65 scores.

positive: Predicting Mortality Risk in Patients with COVID-19 Using Artificial Intelligence to Help Medical Decision-Making In the wake of COVID-19 disease, caused by the SARS-CoV-2 virus, we designed and developed a predictive model based on Artificial Intelligence (AI) and Machine Learning algorithms to determine the health risk and predict the mortality risk of patients with COVID-19. In this study, we used documented data of 117,000 patients world-wide with laboratory-confirmed COVID-19. This study proposes an AI model to help hospitals and medical facilities decide who needs to get attention first, who has higher priority to be hospitalized, triage patients when the system is overwhelmed by overcrowding, and eliminate delays in providing the necessary care. The results demonstrate 93% overall accuracy in predicting the mortality rate. We used several machine learning algorithms including Support Vector Machine (SVM), Artificial Neural Networks, Random Forest, Decision Tree, Logistic Regression, and K-Nearest Neighbor (KNN) to predict the mortality rate in patients with COVID-19. In this study, the most alarming symptoms and features were also identified. Finally, we used a separate dataset of COVID-19 patients to evaluate our developed model accuracy, and used confusion matrix to make an in-depth analysis of our classifiers and calculate the sensitivity and specificity of our model.

positive: BCG VACCINES MAY NOT REDUCE COVID-19 MORTALITY RATES The reason for the observed country-wise variability in incidence and severity of the COVID-19 outcome remains unknown. Few recent studies have suggested a positive protective correlation of the BCG vaccination policy of the countries with the observed COVID-19 severity. The current study was undertaken to reassess the existing data as of 4th April 2020. The incidence rates (cases per million population), Case Fatality Rates (CFR) and inherently more robust Infection Fatality Rates (IFR) were calculated across countries accounting for about 99% COVID-19 deaths. The initial scrutiny suggested a weaker association with BCG vaccination policy or BCG coverage, so positivity to the Tuberculin Sensitivity Test (TST)/ Interferon Gamma Release Assay (IGRA) as a measure of the potential protective effect of the resident populations exposure to Mycobacterium spp. whether from BCG vaccination or as a result of exposure to environmental mycobacteria was analyzed. The incidence rates (the number of cases per million population) decreased with an increase in % LTBI (TST/IGRA positivity) for the analyzed countries with R2 =0.6343, suggesting an exponentially negative covariation. However, the covariation of CFR estimates that ranged from 0.29% to 12.25 % (average 5.39%) among countries, was tenuous. Interim estimates of IFR (i-IFR), a more dependable measure for such studies, for the best and worst-case scenarios, i.e., i-IFR-l and i-IFR-h, predict on an average 20.57% to 30.15 % COVID-19 fatality rates globally, but individual country estimates display huge variation. Among countries accounting for 92.14% deaths (11 countries; top 20% countries included in current study) the estimate for lowest IFRs (i-IFR-l=4.16 (China) & i-IFR-h=4.61 (China)) and highest IFRs (i-IFR-l=96.39% (UK); & i-IFR-h=96.54% (UK)) displayed huge difference (average for the group: CFR=6.8 ± 3.6%; i-IFR-l=34.97 ± 30.55%; & i-IFR-h=44.20 ± 29.08%). Currently, the worst affected countries Italy (CFR=12.25%; i-IFR-l=42.63%; i-IFR-h=48.69%) and Spain (CFR=9.39%; i-IFR-l=26.85%; i-IFR-h=36.60%) would seemingly cope with COVID-19 better than UK, Netherlands and USA while the countries Germany (CFR=1.40%; i-IFR-l=4.93%; i-IFR-h=17.49%) and Switzerland (CFR=3.01%; i-IFR-l=10.87%; i-IFR-h=16.23%) along with China could fare the best. The rest of the 80% countries (accounting for 6.74% deaths), seemed to have reduced mortality (CFR=2.45 ± 2.01; i-IFR-l= 30.62 ± 28.24%; i-IFR-h=40.99 ± 30.47%) with associated high % LTBI (17.28 ± 8.87) than top 20% countries. The inherent issues in the data set (e.g., heterogeneity, non-random sampling, different criteria of sampling and reporting, access to health care, genetic composition, underlying co-morbidities, etc) need to be taken into account for making informed decisions.

positive: Predict the next moves of COVID-19: reveal the temperate and tropical countries scenario The spread of COVID-19 engulfs almost all the countries and territories of the planet, and infections and fatality are increasing rapidly. The first epi-center of its' massive spread was in Wuhan, Hubei province, China having a temperate weather, but the spread has got an unprecedented momentum in European temperate countries mainly in Italy and Spain (as of March 30, 2020). However, Malaysia and Singapore and the neighboring tropical countries of China got relatively low spread and fatality that created a research interest on whether there are potential impacts of weather condition on COVID-19 spread. Adopting the SIR (Susceptible Infected Removed) deviated model to predict potential cases and death in the coming days from COVID-19 was done using the secondary and official sources of data. This study shows that COVID-19 spread and fatality tend to be high across the world but compared to tropical countries, it is going to be incredibly high in the temperate countries having lower temperature (7-16°C) and humidity (80-90%) in last March. However, some literature predicted that this might not to be true, rather irrespective of weather conditions there might be a continuous spread and death. Moreover, a large number of asymptotic COVID-19 carrier in both temperate and tropical countries may re-outbreak in the coming winter. Therefore, a comprehensive global program with the leadership of WHO for testing of entire population of the world is required, which will be very useful for the individual states to take proper political action, social movement and medical services.

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

positive: Clinical features and outcomes of 197 adult discharged patients with COVID-19 in Yichang, Hubei Purpose To investigate the epidemiology and clinical features of discharged adult patients with COVID-19 in Yichang. Method The retrospective study recruited 197 cases of COVID-19 discharged from Yichang Central People's Hospital and Yichang Third People's Hospital from Jan 17 to Feb 26, 2020. All cases were confirmed by real-time RT-PCR or chest computer tomography (CT).The survivors were followed up until March 4,2020. Clinical data, including demographic characteristic, presentation, exposure history, laboratory examination, radiology and prognosis were enrolled and analyzed by SPSS 19.0 software. Results There were 197 adult discharged patients with COVID-19 in this study. Statistical analysis indicated that the average age was 55.94 years, and female patients were 50.3%. Those patients mainly resided in urban with exposure history in 2 weeks. Fever, cough and weakness were the common symptoms. Leucocytes were mainly normal or decreased in 185 patents, both lymphocytes and eosinophils reduced, the ratios were 56.9% and 50.3%, respectively. On the contrary, lactate dehydrogenases raised in 65 patients. C-reactive protein elevated in the most of patients. The sensitivity of RT-PCR was 63.5%. Chest CT indicated that bilateral patchy shadows were the most common imaging manifestations.169 patients recovered and transferred to a designated hospital for observation, and the others turned worst and died of acute respiratory failure. Conclusion COIVD-19 infection have become a life-threaten public health problem, the sensitivity of RT-PCR was limited. Chest CT scan was recommended for the suspected patients. Moreover, lymphocytopenia and eosinophils declining without leukocytes increasing may be considered as a useful evidence for the diagnosis.

positive: Determining risk factors for mortality in liver transplant patients with COVID-19

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

positive: The male excess in case-fatality rates for COVID-19. A meta-analytic study of the age-related differences and consistency over six countries Background Early in the COVID-19 pandemic, it was noted that males seemed to be more affected than females. We examined the magnitude and consistency of the sex differences in age-specific case-fatality rates (CFRs) in six countries. Methods Data on the cases and deaths from COVID-19, by sex and age group, were extracted from the published reports from Denmark, England, Israel, Italy, Spain, and the United States . Age-specific CFRs were computed for males and females separately. The ratio of the male to female CFRs were computed and meta-analytic methods were used to obtained pooled estimates of the male to female ratio of the CFRs over the six countries, for seven age-groups. Findings The CFRs were consistently higher in males at all ages. The differences were greater in the younger age groups. The pooled M:F CFR ratios were 2.53, 2.92, 2.57, 1.83, 1.57, 1.58 and 1.48 for ages 0-39, 40-49, 50-59, 60-69, 70-79, 80-89 and 90+. There was remarkable consistency between countries in the magnitude of the M:F CFRs, in each age group. In meta-regression, age group explained almost all the heterogeneity in the CFR ratios. Conclusions The sex differences in the CFRs are intriguing and are compatible with the male dominance in the incidence rates of many infectious diseases. For COVID-19, factors such as sex differences in the prevalence of underlying diseases may play a part in the CFR differences. However, the greater severity of the disease in males, particularly at younger ages, may be part of the disease mechanism and should be explored further.

positive: The association of cardiovascular disease and other pre-existing comorbidities with COVID-19 mortality: A systematic review and meta-analysis Importance. Exploring the association of coronavirus-2019 disease (COVID-19) mortality with chronic pre-existing conditions may promote the importance of targeting these populations during this pandemic in order to optimize survival. Objective. To explore the association of pre-existing conditions with COVID-19 mortality. Data Sources. MEDLINE, the OVID databases, SCOPUS, and Cochrane Register of Controlled Trials were searched for the period October 1, 2019 to May 1, 2020. Snowballing was used to identify additional studies. Study Selection. Observational studies (n=19) reporting on 61,455 patients with relative risks (RR) or hazard ratios or odds ratios that reported the risk of mortality in patients with COVID-19 and comorbid conditions were included for the current study. Data Extraction and Synthesis. Two independent reviewers extracted data and assessed the risk of bias. All analyses were performed using random-effects models and heterogeneity was quantified. Main Outcomes and Measures The outcome of interest was the risk of COVID-19 mortality in patients with and without pre-existing conditions, reported as RR. Comorbidities explored were cardiovascular diseases (coronary artery disease, hypertension, cardiac arrhythmias, and congestive heart failure), chronic obstructive pulmonary disease, type 2 diabetes, cancer, chronic kidney disease, chronic liver disease, and stroke. Results. Ten chronic conditions from 19 studies were included in the meta-analysis (n=61,455 patients with COVID-19; mean age, 61 years; 57% male). Any cardiovascular disease, coronary heart disease, hypertension, congestive heart failure, and cancer significantly increased the risk of mortality from COVID-19. Cardiovascular disease was associated with a 135% higher risk of COVID-19 mortality (RR=2.35, 95%CI 1.44-3.84 n=9). The risk of mortality from COVID-19 in patients with coronary heart disease was 2.4 times as high as those without coronary heart disease (RR= 2.40, 95%CI=1.71-3.37, n=5) and twice as high in patients with hypertension as high as that compared to those without hypertension (RR=1.89, 95%CI= 1.58-2.27, n=9). Patients with cancer also were at twice the risk of mortality from COVID-19 compared to those without cancer (RR=1.93 95%CI 1.15-3.24, n=4), and those with congestive heart failure were at 2.5 times the risk of mortality compared to those without congestive heart failure (RR=2.66, 95%CI 1.58-4.48, n=3). Conclusions and Relevance COVID-19 patients with all any cardiovascular disease, coronary heart disease, hypertension, congestive heart failure, and cancer have an increased risk of mortality. Tailored infection prevention and treatment strategies targeting this high-risk population are warranted to optimize survival.

positive: COVID-19 in long-term liver transplant patients: preliminary experience from an Italian transplant centre in Lombardy

positive: Prevalence and Mortality due to Outbreak of Novel Coronavirus Disease (COVID-19) in ß-Thalassemias: The Nationwide Iranian Experience In late December 2019, an ongoing outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that was termed Coronavirus Disease 2019 (COVID-19), was reported in Wuhan, China (Zhu, et al 2020).

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

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

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

positive: 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: Spatial Disparities in Coronavirus Incidence and Mortality in the United States: An Ecological Analysis as of May 2020 PURPOSE: This ecological analysis investigates the spatial patterns of the COVID-19 epidemic in the United States in relation to socioeconomic variables that characterize US counties. METHODS: Data on confirmed cases and deaths from COVID-19 for 2,814 US counties were obtained from Johns Hopkins University. We used Geographic Information Systems (GIS) to map the spatial aspects of this pandemic and investigate the disparities between metropolitan and nonmetropolitan communities. Multiple regression models were used to explore the contextual risk factors of infections and death across US counties. We included population density, percent of population aged 65+, percent population in poverty, percent minority population, and percent of the uninsured as independent variables. A state-level measure of the percent of the population that has been tested for COVID-19 was used to control for the impact of testing. FINDINGS: The impact of COVID-19 in the United States has been extremely uneven. Although densely populated large cities and their surrounding metropolitan areas are hotspots of the pandemic, it is counterintuitive that incidence and mortality rates in some small cities and nonmetropolitan counties approximate those in epicenters such as New York City. Regression analyses support the hypotheses of positive correlations between COVID-19 incidence and mortality rates and socioeconomic factors including population density, proportions of elderly residents, poverty, and percent population tested. CONCLUSIONS: Knowledge about the spatial aspects of the COVID-19 epidemic and its socioeconomic correlates can inform first responders and government efforts. Directives for social distancing and to "shelter-in-place" should continue to stem the spread of COVID-19.

positive: Robust Estimation of Infection Fatality Rates during the Early Phase of a Pandemic During a pandemic, robust estimation of case fatality rates (CFRs) is essential to plan and control suppression and mitigation strategies. At present, estimates for the CFR of COVID-19 caused by SARS-CoV-2 infection vary considerably. Expert consensus of 0.1-1% covers in practical terms a range from normal seasonable Influenza to Spanish Influenza. In the following, I deduce a formula for an adjusted Infection Fatality Rate (IFR) to assess mortality in a period following a positive test adjusted for selection bias. Official datasets on cases and deaths were combined with data sets on number of tests. After data curation and quality control, a total of IFR (n=819) was calculated for 21 countries for periods of up to 26 days between registration of a case and death. Estimates for IRFs increased with length of period, but levelled off at >9days with a median for all 21 countries of 0.11 (95%-CI: 0.073-0.15). An epidemiologically derived IFR of 0.040 % (95%-CI: 0.029%-0.055%) was determined for Iceland and was very close to the calculated IFR of 0.057% (95%-CI: 0.042-0.078), but 2.7-6-fold lower than CFRs. IFRs, but not CFRs, were positively associated with increased proportions of elderly in age-cohorts (n=21, spearman's ρ =.73, p =.02). Real-time data on molecular and serological testing may further displace classical diagnosis of disease and its related death. I will critically discuss, why, how and under which conditions the IFR, provides a more solid early estimate of the global burden of a pandemic than the CFR.

positive: Effects of temperature on COVID-19 transmission Coronavirus disease 2019 (COVID19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV2), it was first identified in 2019 in Wuhan, China and has resulted in the 2019-20 coronavirus pandemic. As of March 1, 2020, 79,968 patients in China and 7169 outside of China had tested positive for COVID19 and a mortality rate of 3.6% has been observed amongst Chinese patients. Its primary mode of transmission is via respiratory droplets from coughs and sneezes. The virus can remain viable for up to three days on plastic and stainless steel or in aerosols for upto 3 hours and is relatively more stable than the known human coronaviruses. It is stable in faeces at room temperature for at least 1-2 days and can be stable in infected patients for up to 4 days. Heat at 56 degree Celsius kills the SARS coronavirus at around 10000 units per 15 minutes. Thus, temperature is an important factor in survival of COVID19 virus and this article focuses on understanding the relationship between temperature and COVID19 transmission from the data available between January-March 2020.

positive: Virus emergentes y reemergentes: un nuevo reto para la salud mundial del milenio

positive: Estimation of the true infection rate and infection fatality rate of COVID-19 in the whole population of each country The true infection rate of COVID-19 and the infection fatality rate in the whole population have been estimated for each country. The estimate well coincided with local surveys. The fact that several tens of times, or more, of identified cases are already infected might require reconsideration of the strategy.

positive: Identifying novel factors associated with COVID-19 transmission and fatality using the machine learning approach The COVID-19 virus has infected millions of people and resulted in hundreds of thousands of deaths worldwide. By using the logistic regression model, we identified novel critical factors associated with COVID19 cases, death, and case fatality rates in 154 countries and in the 50 U.S. states. Among numerous factors associated with COVID-19 risk, we found that the unitary state system was counter-intuitively positively associated with increased COVID-19 cases and deaths. Blood type B was a protective factor for COVID-19 risk, while blood type A was a risk factor. The prevalence of HIV, influenza and pneumonia, and chronic lower respiratory diseases was associated with reduced COVID-19 risk. Obesity and the condition of unimproved water sources were associated with increased COVID-19 risk. Other factors included temperature, humidity, social distancing, smoking, and vitamin D intake. Our comprehensive identification of the factors affecting COVID-19 transmission and fatality may provide new insights into the COVID-19 pandemic and advise effective strategies for preventing and migrating COVID-19 spread.

positive: [Democracy and Covid-19 mortality in Europe.] OBJECTIVE In Europe there is a great variability in mortality by Covid-19 among different countries. While some countries, such as Greece, Belarus or Ukraine, have a mortality rate of less than 5 cases/100,000 inhabitants, other countries such as Belgium, Spain or the United Kingdom have a mortality rate of well over 50 cases/100,000 inhabitants. It is generally considered that the reason for this variability is multifactorial (including political reasons), but there are few studies that associate factors related to this variability. The objective of this work was to analyse political risk factors/markers that could explain the variability in mortality due to Covid-19 among different European countries. METHODS This is a retrospective, multinational, ecological study based on the exploitation of the database provided by the European Centre for Disease Prevention and Control which collects daily information worldwide on new cases and deaths. The accumulated mortality of Covid-19 in European countries (with more than 100 deaths on 01/05/2020) was calculated up to 29/05/2020. Political variables were compiled from different sources in the countries included in the study. The variables analysed were: the democracy index and the different factors included in it, the country's political system and the country's corruption index. On the other hand, specific political measures implemented in the different countries were collected, such as the number of days elapsed from the notification of the first infected person to 100 infected persons, to lockdown, to the closure of schools or the cancelation of meetings. The number of people infected up to the date of lockdown was also registered. For the statistical analysis of the association between the dependent variable (mortality) and the factors studied, correlation index were calculated, and the association was studied through univariate and multivariate linear regression models. RESULTS At May 1 2020, 27 European countries had at least 100 deaths. The mean mortality was 19.83 cases/100,000 inhabitants (SD 22.4) and a median of 7.95. Mortality varied from a minimum of 1.49 cases/100,000 population in Ukraine to 82.19 cases/100,000 population in Belgium. About factors analyzed both the democracy index (as well as the factors included in it), the political system (full democracy vs. no) and the corruption index were statistically associated with mortality. Also, the time until the implementation of the political measures was associated with mortality. CONCLUSIONS In Europe, there is a west to east (from highest to lowest) gradient in the mortality of Covid-19. Some of the observed mortality variability can be explained by political factors.

positive: Estimating instant case fatality rate of COVID-19 in China Abstract Objective The outbreak of coronavirus disease 2019 (COVID-19) in China has been basically controlled. However, the global epidemic of COVID-19 is worsening. We established a method to estimate instant case fatality rate and cure rate of COVID-19 in China. Methods We collected 82735 confirmed cases released officially by Chinese authorities from Dec 8, 2019 to April 18, 2020. The estimated diagnosis dates of deaths and cured cases were calculated based on median cure time or median death time of individual cases. Afterward, instant fatality rate was calculated according to the number of deaths and cured cases on the same estimated diagnosis date. Results In China, the instant case fatality rate of COVID-19 was 3.8-14.6% from Jan 1 to Jan 17, and then gradually declined and stabilized at 5.7% in April. The average case fatality rate in China was 6.1%±2.9%. While, the case fatality rate was 1.0±0.4% in China except Hubei. The cure rates of COVID-19 were 93.9%±2.9% in China, and stabilized at 94.3%, while it was 99.0%±0.4% in China except Hubei. Conclusion The instant case fatality rate of COVID-19 in China was much higher than that in China except Hubei. The case fatality rate of COVID-19 in China was underestimated.

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: Social determinants of COVID-19 mortality at the county level The United States is currently the global epicenter of the COVID-19 pandemic. Emerging data suggests that social determinants of health may be key drivers of the epidemic, and that minorities, migrants, and essential workers may bear a disproportionate degree of risk. We used publicly accessible datasets to build a series of spatial autoregressive models assessing county level associations between COVID-19 mortality and (1) Percentage of Non-English speaking households, (2) percentage of individuals engaged in hired farm work, (3) percentage of uninsured individuals under the age of 65, and (3) percentage of individuals living at or below the poverty line. Across all counties (n=2940), counties with more farmworkers, more residents living in poverty, higher density, and more residents over the age of 65 had significantly higher levels of mortality. In urban counties (n=114), only county density was significantly associated with mortality. In non-urban counties (n=2826), counties with more non-English speaking households and more farm workers had significantly higher levels of mortality, as did counties with higher levels of poverty and more residents over the age of 65. More uninsured residents was significantly associated with decreased reported COVID-19 mortality. Individuals who do not speak English, individuals engaged in farm work, and individuals living in poverty may be at heightened risk for COVID-19 mortality in non-urban counties. Mortality among the uninsured may be being systematically undercounted in county and national level surveillance.

positive: Influenza Vaccination and COVID19 Mortality in the USA COVID-19 mortality rate is higher in the elderly and in those with preexisting chronic medical conditions. The elderly also suffer from increased morbidity and mortality from seasonal influenza infection, and thus annual influenza vaccination is recommended for them. In this study, we explore a possible area-level association between influenza vaccination coverage in people aged 65 years and older and the number of deaths from COVID-19. To this end, we used COVID-19 data until June 10, 2020 together with population health data for the United States at the county level. We fit quasi-Poisson regression models using influenza vaccination coverage in the elderly population as the independent variable and the number of deaths from COVID-19 as the outcome variable. We adjusted for a wide array of potential confounding variables using both county-level generalized propensity scores for influenza vaccination rates, as well as direct adjustment. Our results suggest that influenza vaccination coverage in the elderly population is negatively associated with mortality from COVID-19. This finding is robust to using different analysis periods, different thresholds for inclusion of counties, and a variety of methodologies for confounding adjustment. In conclusion, our results suggest a potential protective effect of the influenza vaccine on COVID-19 mortality in the elderly population. The significant public health implications of this possibility point to an urgent need for studying the relationship between influenza vaccination and COVID-19 mortality at the individual level, to investigate both the epidemiology and any underlying biological mechanism.

positive: Interim Analysis of Pandemic Coronavirus Disease 2019 (COVID-19) and the SARS-CoV-2 virus in Latin America and the Caribbean: Morbidity, Mortality and Molecular Testing Trends in the Region Background: The relentless advance of the SARS-CoV-2 virus pandemic has resulted in a significant burden on countries, regardless of their socio-economic conditions. The virus has infected more than 2.5 million people worldwide, causing to date more than 150,000 deaths in over 210 countries. Objective: The aim of this study was to describe the trends in cases, tests and deaths related to novel coronavirus disease (COVID-19) in Latin American and Caribbean (LAC) countries. Methodology: Data were retrieved from the WHO-Coronavirus Disease (COVID-2019) situation reports and the Center for Systems Science and Engineering (CSSE) databases from Johns Hopkins University. Descriptive statistics including death rates, cumulative mortality and incidence rates, as well as testing rates per population at risk were performed. A comparison analysis among countries with [≥]50 confirmed cases was performed from February 26th, 2020 to April 8th, 2020. Results: Brazil had the greatest number of cases and deaths in the region. Panama experienced a rapid increase in the number of confirmed cases with Trinidad and Tobago, Bolivia and Honduras having the highest case fatality rates. Panama and Chile conducted more tests per million inhabitants and more tests per day per million inhabitants, followed by Uruguay and El Salvador. Dominican Republic, Bolivia, Ecuador and Brazil had the highest positive test rates. Conclusions: The COVID-19 disease pandemic caused by the SARS-CoV-2 virus has progressed rapidly in LAC countries. Some countries have been affected more severely than others, with some adopting similar disease control methods to help slow down the spread of the virus. With limited testing and other resources, social distancing is needed to help alleviate the strain on already stretched health systems.

positive: Are we equal in adversity? Does Covid-19 affect women and men differently? BACKGROUND & OBJECTIVES: This article examines whether women are less prone than men to Covid-19 infections and their complications. DATA SOURCES: We reviewed available databases and searched systematically for publications. To be taken into account, data had to be broken down by gender. There was no study evaluation nor quantification synthesis, due to the large heterogeneity of the studies. Nineteen databases were selected. 73 publications were considered and 33 were selected, to which 12 more were added. RESULTS: Globally, the proportion of men and women who tested positive is comparable. However, men are about 60% more likely to be severely ill or to die from the complications of Covid-19 than are women. LIMITATIONS: The study was hampered by a large heterogeneity in testing and reporting of the data. CONCLUSIONS: Although in the pandemic men die more frequently than women from Covid-19, it is not clear whether this is due to biological differences between men and women, differences in behavioral habits, or differences in the rates of co-morbidities. IMPLICATIONS OF KEY FINDINGS: Countries and studies should report their data by age, gender and co-morbidities. This may have implications in terms of vaccination strategies, the choice of treatments and future consequences for long-term health issues concerning gender equality.

positive: Time-to-Death approach in revealing Chronicity and Severity of COVID-19 across the World BACKGROUND: The outbreak of coronavirus disease, 2019 (COVID-19), which started from Wuhan, China, in late 2019, have spread worldwide. A total of 5,91,971 cases and 2,70,90 deaths were registered till 28(th) March, 2020. We aimed to predict the impact of duration of exposure to COVID-19 on the mortality rates increment. METHODS: In the present study, data on COVID-19 infected top seven countries viz., Germany, China, France, United Kingdom, Iran, Italy and Spain, and World as a whole, were used for modeling. The analytical procedure of generalized linear model followed by Gompertz link function was used to predict the impact lethal duration of exposure on the mortality rates. FINDINGS: Of the selected countries and World as whole, the projection based on 21st March, 2020 cases, suggest that a total (95% Cl) of 76 (65–151) days of exposure in Germany, mortality rate will increase by 5 times to 1%. In countries like France and United Kingdom, our projection suggests that additional exposure of 48 days and 7 days, respectively, will raise the mortality rates to10%. Regarding Iran, Italy and Spain, mortality rate will rise to 10% with an additional 3–10 days of exposure. World’s mortality rates will continue increase by 1% in every three weeks. The predicted interval of lethal duration corresponding to each country has found to be consistent with the mortality rates observed on 28th March, 2020. CONCLUSION: The prediction of lethal duration was found to have apparently effective in predicting mortality, and shows concordance with prevailing rates. In absence of any vaccine against COVID-19 infection, the present study adds information about the quantum of the severity and time elapsed to death will help the Government to take necessary and appropriate steps to control this pandemic.

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

positive: Excess mortality during COVID-19 in five European countries and a critique of mortality analysis data INTRODUCTION The COVID-19 pandemic is an ongoing event disrupting lives, health systems, and economies worldwide. Clear data about the pandemic's impact is lacking, namely regarding mortality. This work aims to study the impact of COVID-19 through the analysis of all-cause mortality data made available by different European countries, and to critique their mortality surveillance data. METHODS European countries that had publicly available data about the number of deaths per day/week were selected (England and Wales, France, Italy, Netherlands and Portugal). Two different methods were selected to estimate the excess mortality due to COVID19: (DEV) deviation from the expected value from homologue periods, and (RSTS) remainder after seasonal time series decomposition. We estimate total, age- and gender-specific excess mortality. Furthermore, we compare different policy responses to COVID-19. RESULTS Excess mortality was found in all 5 countries, ranging from 10.6% in Portugal (DEV) to 98.5% in Italy (DEV). Furthermore, excess mortality is higher than COVID-attributed deaths in all 5 countries. DISCUSSION The impact of COVID-19 on mortality appears to be larger than officially attributed deaths, in varying degrees in different countries. Comparisons between countries would be useful, but large disparities in mortality surveillance data could not be overcome. Unreliable data, and even a lack of cause-specific mortality data undermine the understanding of the impact of policy choices on both direct and indirect deaths during COVID-19. European countries should invest more on mortality surveillance systems to improve the publicly available data.

positive: Effect of social distancing on COVID-19 incidence and mortality in the US Social distancing policies were implemented in most US states as a containment strategy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The effectiveness of these policy interventions on morbidity and mortality remains unknown. Our analysis examined the associations between statewide policies and objective measures of social distancing, and objective social distancing and COVID-19 incidence and mortality. We used nationwide, de-identified smartphone GPS data to estimate county-level social distancing. COVID-19 incidence and mortality data were from the Johns Hopkins Coronavirus Resource Center. Generalized linear mixed models were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for the association between objective social distancing and COVID-19 incidence and mortality. Stay-at-home orders were associated with a 35% increase in social distancing. Higher social distancing was associated with a 29% reduction in COVID-19 incidence (adjusted IRR 0.71; 95% CI 0.57–0.87) and a 35% reduction in COVID-19 mortality (adjusted IRR 0.65; 95% CI 0.55–0.76). These findings provide evidence to inform ongoing national discussions on the effectiveness of these public health measures and the potential implications of returning to normal social activity.

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: 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: Estimation of fatality rate in Africa through the behavior of COVID-19 in Italy relevance to age profiles The emergence and pandemic of COVID-19 has rapidly become a global concern. In Italy, on 27 March 2020, there were 8165 deaths and 80539 confirmed cases of COVID-19. Demographic situations, like age profiles is reported to be the cause of high case fatality rate (CFR) in Italy. In Africa, the COVID-19 pandemic has not yet grasped epic proportion, but the estimation of CFR is still needed. We compared the CFR observed in Italy with the age profiles in 46 Africa countries and 2 territories which are already confirmed COVID-19 case. The estimation of the CFR in Africa ranges between (1.0%-5.4%) while in Italy is 10.1%. The five highest CFR countries and territories in Africa are Reunion (5.4%), Mauritius (5.1 %), Tunisia (3.9%), Seychelles (3.8%) and Morocco (3.3%). The last three countries with low CFR are Uganda (1.0%), Zambia (1.1%) and Angola (1.1%). The observed difference is related to the age profiles.

positive: Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19 RATIONALE: Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension. OBJECTIVE: To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19. METHODS AND RESULTS: This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55–68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57–69]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19–0.92]; P=0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15–0.89]; P=0.03). Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12–0.70]; P=0.01) in patients with COVID-19 and coexisting hypertension. CONCLUSIONS: Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.

positive: Cardiac Injury and COVID-19: A Systematic Review and Meta-Analysis BACKGROUND: During the current coronavirus disease 2019 (COVID-19) pandemic, a link between acute cardiac injury and COVID-19 infection has been observed. There is currently no consensus on the incidence of cardiac injury, its relationship to prognosis, or its possible cause. This article provides a comprehensive review and meta-analysis of the incidence, comorbidities, outcomes and possible mechanisms of acute cardiac injury in COVID-19 patients. METHODS: We searched PubMed and Embase for studies that evaluated cardiac injury in hospitalized COVID-19 patients. Demographic information, co-morbidities, and relevant laboratory values were extracted and a meta-analysis was performed. RESULTS: Sixteen studies from China, Italy and the US with 2224 patients were included in this meta-analysis. The incidence of cardiac injury was 24.4% (542/2224 patients) in hospitalized COVID-19 patients. The all-cause mortality in patients with cardiac injury was 72.6% (OR=17.32, 95% CI 9.21-32.57) compared to those without cardiac injury (14.5%). In subgroup analyses, factors associated with increased risk of developing cardiac injury were older age and history of hypertension (HTN), and chronic obstructive respiratory disease (COPD). CONCLUSION: Cardiac injury is common in hospitalized COVID-19 patients and is significantly associated with mortality. Patients who were older with HTN and COPD were prone to develop cardiac injury. Early screening, triage and cardiac monitoring are recommended for these patients.

positive: Does vitamin D status impact mortality from SARS-CoV-2 infection?

positive: Covid-19 health care demand and mortality in Sweden in response to non-pharmaceutical (NPIs) mitigation and suppression scenarios While the outbreak in China is now contained, since mid March 2020, the epicentre of the COVID-19 pandemic is in Europe, with Italy reporting more deaths than China. Various European countries have seen an exponential growth in daily new cases, and unless strong reductions in transmission, the wave is expected to hit all of Europe by the end of March 2020. There is an urgent need to reduce transmission and thus reduce the growth rate of this epidemic, reduce the height of the epidemic peak and the peak demand on healthcare services, as well as reduce the total number of infected persons. Here we estimate the impact of COVID-19 on the Swedish population at the municipality level, considering demography and human mobility under scenarios of mitigation and suppression. We estimate the timelines of incidence, hospitalization rates, the intensive care (ICU) need, and the mortality in relation to the current Swedish ICU capacity, and costs of care. We further investigate the sensitivity to various degrees of potential underreporting on the estimates.

positive: Analysis of Austrian COVID-19 deaths by age and sex We analyze the age and sex distribution of the reported COVID-19 deaths in Austria. In accordance with international studies, the Austrian data also suggests that the risk of death increases substantially with age. The observed age dependency of the proportions of registered COVID-19 deaths in relation to the population sizes in the age groups is approximately exponential, similar to the age dependency of the general age specific mortality rate. Furthermore, we compare the general age specific mortality rate in Austria with the estimates of the SARS-CoV2 infection fatality rate by Ferguson et al. (2020). The parallels to the general age specific mortality rates do not imply that COVID-19 does not pose an additional risk. On the contrary, it follows from the structure and magnitude of the infection fatality rate that it is substantial, especially for higher age groups. However, since in many cases persons with severe pre-existing conditions are affected, it is not yet possible to estimate what effects COVID-19 will have on life expectancy.

positive: A Review of Coronavirus Disease-2019 (COVID-19) There is a new public health crises threatening the world with the emergence and spread of 2019 novel coronavirus (2019-nCoV) or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus originated in bats and was transmitted to humans through yet unknown intermediary animals in Wuhan, Hubei province, China in December 2019. There have been around 96,000 reported cases of coronavirus disease 2019 (COVID-2019) and 3300 reported deaths to date (05/03/2020). The disease is transmitted by inhalation or contact with infected droplets and the incubation period ranges from 2 to 14 d. The symptoms are usually fever, cough, sore throat, breathlessness, fatigue, malaise among others. The disease is mild in most people; in some (usually the elderly and those with comorbidities), it may progress to pneumonia, acute respiratory distress syndrome (ARDS) and multi organ dysfunction. Many people are asymptomatic. The case fatality rate is estimated to range from 2 to 3%. Diagnosis is by demonstration of the virus in respiratory secretions by special molecular tests. Common laboratory findings include normal/ low white cell counts with elevated C-reactive protein (CRP). The computerized tomographic chest scan is usually abnormal even in those with no symptoms or mild disease. Treatment is essentially supportive; role of antiviral agents is yet to be established. Prevention entails home isolation of suspected cases and those with mild illnesses and strict infection control measures at hospitals that include contact and droplet precautions. The virus spreads faster than its two ancestors the SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), but has lower fatality. The global impact of this new epidemic is yet uncertain.

positive: COVID-19 in Italy: momentous decisions and many uncertainties

positive: Risk Factors for Mortality and Respiratory Support in Elderly Patients Hospitalized with COVID-19 in Korea BACKGROUND: The mortality risk of coronavirus disease 2019 (COVID-19) is higher in patients with older age, and many elderly patients are reported to require advanced respiratory support. METHODS: We reviewed medical records of 98 patients aged ≥ 65 years who were hospitalized with COVID-19 during a regional outbreak in Daegu/Gyeongsangbuk-do province of Korea. The outcome measures were in-hospital mortality and the treatment with mechanical ventilation (MV) or high-flow nasal cannula (HFNC). RESULTS: The median age of the patients was 72 years; 55.1% were female. Most (74.5%) had at least one underlying condition. Overall case fatality rate (CFR) was 20.4%, and median time to death after admission was 8 days. The CFR was 6.1% among patients aged 65-69 years, 22.7% among those aged 70-79 years, and 38.1% among those aged ≥ 80 years. The CFR among patients who required MV was 43.8%, and the proportion of patients received MV/HFNC was 28.6%. Nosocomial acquisition, diabetes, chronic lung diseases, and chronic neurologic diseases were significant risk factors for both death and MV/HFNC. Hypotension, hypoxia, and altered mental status on admission were also associated with poor outcome. CRP > 8.0 mg/dL was strongly associated with MV/HFNC (odds ratio, 26.31; 95% confidence interval, 7.78-88.92; P < 0.001), and showed better diagnostic characteristics compared to commonly used clinical scores. CONCLUSION: Patients aged ≥ 80 years had a high risk of requiring MV/HFNC, and mortality among those severe patients was very high. Severe initial presentation and laboratory abnormalities, especially high CRP, were identified as risk factors for mortality and severe hospital course.

negative: Association between climate variables and global transmission oF SARS-CoV-2 Abstract In this study, we aimed at analyzing the associations between transmission of and deaths caused by SARS-CoV-2 and meteorological variables, such as average temperature, minimum temperature, maximum temperature, and precipitation. Two outcome measures were considered, with the first aiming to study SARS-CoV-2 infections and the second aiming to study COVID-19 mortality. Daily data as well as data on SARS-CoV-2 infections and COVID-19 mortality obtained between December 1, 2019 and March 28, 2020 were collected from weather stations around the world. The country's population density and time of exposure to the disease were used as control variables. Finally, a month dummy variable was added. Daily data by country were analyzed using the panel data model. An increase in the average daily temperature by one degree Fahrenheit reduced the number of cases by approximately 6.4 cases/day. There was a negative correlation between the average temperature per country and the number of cases of SARS-CoV-2 infections. This association remained strong even with the incorporation of additional variables and controls (maximum temperature, average temperature, minimum temperature, and precipitation) and fixed country effects. There was a positive correlation between precipitation and SARS-CoV-2 transmission. Countries with higher rainfall measurements showed an increase in disease transmission. For each average inch/day, there was an increase of 56.01 cases/day. COVID-19 mortality showed no significant association with temperature.

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: Battling COVID‐19: critical care and peri‐operative healthcare resource management strategies in a tertiary academic medical centre in Singapore In December 2019, a cluster of atypical pneumonia cases were reported in Wuhan, China, and a novel coronavirus elucidated as the aetiologic agent. Although most initial cases occurred in China, the disease, termed coronavirus disease 2019, has become a pandemic and continues to spread rapidly with human‐to‐human transmission in many countries. This is the third novel coronavirus outbreak in the last two decades and presents an ensuing healthcare resource burden that threatens to overwhelm available healthcare resources. A study of the initial Chinese response has shown that there is a significant positive association between coronavirus disease 2019 mortality and healthcare resource burden. Based on the Chinese experience, some 19% of coronavirus disease 2019 cases develop severe or critical disease. This results in a need for adequate preparation and mobilisation of critical care resources to anticipate and adapt to a surge in coronavirus disease 2019 case‐load in order to mitigate morbidity and mortality. In this article, we discuss some of the peri‐operative and critical care resource planning considerations and management strategies employed in a tertiary academic medical centre in Singapore in response to the coronavirus disease 2019 outbreak.

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

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

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: Trends in childhood cancer mortality--United States, 1990-2004. Cancer is the fourth most common cause of death (after unintentional injury, homicide, and suicide) among persons aged 1-19 years in the United States. Because recent childhood cancer mortality has not been well characterized in terms of temporal, demographic, and geographic trends, CDC analyzed cancer death rates among children (defined as aged 0-14 years) and adolescents (defined as aged 15-19 years) for the period 1990-2004 by sex, age group, race, ethnicity, U.S. Census region, and primary cancer site/leading diagnosis, using the most recent data available from the National Vital Statistics System (NVSS). This report describes the results of that analysis, which indicated that, overall, age-adjusted childhood cancer death rates decreased significantly during 1990-2004 among both sexes, both age groups, all races (except American Indians/Alaska Natives [AI/ANs]), Hispanics, non-Hispanics, and all U.S. Census regions. However, decreases in death rates varied among U.S. Census regions and between Hispanics and non-Hispanics. Eliminating racial/ethnic health disparities is one of the overarching goals of Healthy People 2010. Further research is needed to understand geographic and ethnic disparities in childhood cancer death rates. Moreover, cancer prevention and intervention measures should be designed to reach populations that are underserved and at high risk.

negative: Molecular advances in the cell biology of SARS-CoV and current disease prevention strategies In the aftermath of the SARS epidemic, there has been significant progress in understanding the molecular and cell biology of SARS-CoV. Some of the milestones are the availability of viral genome sequence, identification of the viral receptor, development of an infectious cDNA clone, and the identification of viral antigens that elicit neutralizing antibodies. However, there is still a large gap in our understanding of how SARS-CoV interacts with the host cell and the rapidly changing viral genome adds another variable to this equation. Now the SARS-CoV story has entered a new phase, a search for preventive strategies and a cure for the disease. This review highlights the progress made in identifying molecular aspects of SARS-CoV biology that is relevant in developing disease prevention strategies. Authors conclude that development of successful SARS-CoV vaccines and antivirals depends on the progress we make in these areas in the immediate future.

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

negative: Impact of virus testing on COVID-19 case fatality rate: estimate using a fixed-effects model Background In response to the SARS-CoV2 pandemic, governments have adopted a variety of public health measures. There are variations in how much testing has been done across countries. South Korea, Germany, and Iceland take the bet of massive testing of their population. Whereas tests were not performed widely in southern European countries. As the former undergo a lower case-fatality rate due to the COVID-19 than the latter, the impact of the testing strategy must be investigated. In this study, we aimed to evaluate the impact of testing on the case fatality rate. Methods We use data on inpatients across French geographic areas and propose a novel methodology that exploits policy discontinuities at region borders to estimate the effect of COVID-19 tests on the case-fatality rate. In France, testing policies are determined locally. We compare all contiguous department pairs located on the opposite sides of a region border. The heterogeneity in testing rate between department pairs together with the similarities in other dimensions allow us to mimic the existence of treatment and control groups and to identify the impact of testing on mortality. Results The increase of one percentage point in the test rate is associated with a decrease of 0.001 percentage point in the death rate. In other words, for each additional 1000 tests, one person would have remained alive. Conclusion Massive population testing could have a significant effect on mortality in different ways. Mass testing may help decision-makers to implement healthcare measures to limit the spread of the disease.

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

negative: Potential of age distribution profiles for the prediction of COVID-19 infection origin in a patient group The COVID-19 pandemic is a serious and global public health concern. It is now well known that COVID-19 cases may result in mild symptoms leading to patient recovery. However, severity of infection, fatality rates, and treatment responses across different countries, age groups, and demographic groups suggest that the nature of infection is diverse, and a timely investigation of the same is needed for evolving sound treatment and preventive strategies. This paper reports an the analysis of age distribution patterns in six groups of Indian COVID-19 patient populations based on their likely geographical origin of infection viz. the United Kingdom, North America, the European Union, the Middle East, and Asian countries. It was observed that patient groups stratified in this way had a distinct age profile and that some of these groups e.g. patient groups from Asia, the European Union, and the United Kingdom formed a different cluster than those from North America, the Middle East, and other regions. Patient age profiles of a population were found to be highly predictive of the group they belong to, and there are indications of their distinct recovery and fatality rates across gender. Altogether this study provides a scalable framework to estimate the source of infection in a new population of COVID-19 patients with unknown origin. It is also concluded that greater public availability of age and other demographic profile details of patients may be helpful in gaining robust insights into COVID-19 infection origins. Datasets and scripts used in this work are shared at http://covid.sciwhylab.org.

negative: Scientific Opinion on the welfare of cattle kept for beef production and the welfare in intensive calf farming systems Information given in previous Opinions “Welfare of cattle kept for beef production” (SCAHAW, 2001) and “The risks of poor welfare in intensive calf farming systems” (EFSA, 2006) is updated and recent scientific evidence on the topics reviewed. Risks of poor welfare are identified using a structured analysis, and issues not identified in the SCAHAW (2001) beef Opinion, especially effects of housing and management on enteric and respiratory diseases are reviewed. The Opinion covers all systems of beef production, although the welfare of suckler cows or breeding bulls is not considered. The Chapter on beef cattle presents new evidence and recommendations in relation to heat and cold stress, mutilations and pain management, digestive disorders linked to high concentrate feeds and respiratory disorders linked to overstocking, inadequate ventilation, mixing of animals and failure of early diagnosis and treatment. Major welfare problems in cattle kept for beef production, as identified by risk assessment, were respiratory diseases linked to overstocking, inadequate ventilation, mixing of animals and failure of early diagnosis and treatment, digestive disorders linked to intensive concentrate feeding, lack of physically effective fibre in the diet, and behavioural disorders linked to inadequate floor space, and co‐mingling in the feedlot. Major hazards for white veal calves were considered to be iron‐deficiency anaemia, a direct consequence of dietary iron restriction, enteric diseases linked to high intakes of liquid feed and inadequate intake of physically effective fibre, discomfort and behavioural disorders linked to inadequate floors and floor space.

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

negative: Diseases of the Liver and Hepatobiliary System

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

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

negative: Work-related Covid-19 transmission Importance: Our study helps fill the knowledge gap related to work-related transmission in the emerging coronaviral pandemic. Objective: To demonstrate high-risk occupations for early coronavirus disease 2019 (Covid-19) local transmission. Methods: In this observational study, we extracted confirmed Covid-19 cases from governmental investigation reports in Hong Kong, Japan, Singapore, Taiwan, Thailand, and Vietnam. We followed each country/area for 40 days after its first locally transmitted case, and excluded all imported cases. We defined a possible work-related case as a worker with evidence of close contact with another confirmed case due to work, or an unknown contact history but likely to be infected in the working environment (e.g. an airport taxi driver). We calculated the case number for each occupation, and illustrated the temporal distribution of all possible work-related cases and healthcare worker (HCW) cases. The temporal distribution was further defined as early outbreak (the earliest 10 days of the following period) and late outbreak (11th to 40th days of the following period). Results: We identified 103 possible work-related cases (14.9%) among a total of 690 local transmissions. The five occupation groups with the most cases were healthcare workers (HCWs) (22%), drivers and transport workers (18%), services and sales workers (18%), cleaning and domestic workers (9%) and public safety workers (7%). Possible work-related transmission played a substantial role in early outbreak (47.7% of early cases). Occupations at risk varied from early outbreak (predominantly services and sales workers, drivers, construction laborers, and religious professionals) to late outbreak (predominantly HCWs, drivers, cleaning and domestic workers, police officers, and religious professionals). Conclusions: Work-related transmission is considerable in early Covid-19 outbreaks, and the elevated risk of infection was not limited to HCW. Implementing preventive/surveillance strategies for high-risk working populations is warranted.

negative: Antiviral Activity of Benzavir-2 against Emerging Flaviviruses Most flaviviruses are arthropod-borne viruses, transmitted by either ticks or mosquitoes, and cause morbidity and mortality worldwide. They are endemic in many countries and have recently emerged in new regions, such as the Zika virus (ZIKV) in South-and Central America, the West Nile virus (WNV) in North America, and the Yellow fever virus (YFV) in Brazil and many African countries, highlighting the need for preparedness. Currently, there are no antiviral drugs available to treat flavivirus infections. We have previously discovered a broad-spectrum antiviral compound, benzavir-2, with potent antiviral activity against both DNA- and RNA-viruses. Our purpose was to investigate the inhibitory activity of benzavir-2 against flaviviruses. We used a ZIKV ZsGreen-expressing vector, two lineages of wild-type ZIKV, and other medically important flaviviruses. Benzavir-2 inhibited ZIKV derived reporter gene expression with an EC(50) value of 0.8 ± 0.1 µM. Furthermore, ZIKV plaque formation, progeny virus production, and viral RNA expression were strongly inhibited. In addition, 2.5 µM of benzavir-2 reduced infection in vitro in three to five orders of magnitude for five other flaviviruses: WNV, YFV, the tick-borne encephalitis virus, Japanese encephalitis virus, and dengue virus. In conclusion, benzavir-2 was a potent inhibitor of flavivirus infection, which supported the broad-spectrum antiviral activity of benzavir-2.

negative: Burden of Middle East respiratory syndrome coronavirus infection in Saudi Arabia Abstract MERS-coronavirus infection is currently responsible for considerable morbidity and mortality in Saudi Arabia. Understanding its burden, as an emerging infectious disease, is vital for devising appropriate control strategies. In this study, the burden of MERS-CoV was estimated over 31months period from June 6, 2012 to January 5, 2015. The total number of patients was 835; 528 (63.2%) patients were male, 771 (92.3%) patients were ≥25 years of age, and 210 (25.1%) patients were healthcare workers. A total of 751 (89.9%) patients required hospitalization. The median duration between onset of illness and hospitalization was 2 days (interquartile range, 0–5). The median length of hospital stay was 14 days (IQR, 6–27). The overall case fatality rate was 43.1%. Basic reproductive number was 0.9. Being Saudi, non-healthcare workers, and age ≥65 years were significantly associated with higher mortality. In conclusion, MERS-CoV infection caused a substantial health burden in Saudi Arabia.

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

negative: Climate Change and Human Health Impacts in the United States: An Update on the Results of the U.S. National Assessment The health sector component of the first U.S. National Assessment, published in 2000, synthesized the anticipated health impacts of climate variability and change for five categories of health outcomes: impacts attributable to temperature, extreme weather events (e.g., storms and floods), air pollution, water- and food-borne diseases, and vector- and rodent-borne diseases. The Health Sector Assessment (HSA) concluded that climate variability and change are likely to increase morbidity and mortality risks for several climate-sensitive health outcomes, with the net impact uncertain. The objective of this study was to update the first HSA based on recent publications that address the potential impacts of climate variability and change in the United States for the five health outcome categories. The literature published since the first HSA supports the initial conclusions, with new data refining quantitative exposure–response relationships for several health end points, particularly for extreme heat events and air pollution. The United States continues to have a very high capacity to plan for and respond to climate change, although relatively little progress has been noted in the literature on implementing adaptive strategies and measures. Large knowledge gaps remain, resulting in a substantial need for additional research to improve our understanding of how weather and climate, both directly and indirectly, can influence human health. Filling these knowledge gaps will help better define the potential health impacts of climate change and identify specific public health adaptations to increase resilience.

negative: Pathological consequences of the unfolded protein response and downstream protein disulphide isomerases in pulmonary viral infection and disease Protein folding within the endoplasmic reticulum (ER) exists in a delicate balance; perturbations of this balance can overload the folding capacity of the ER and disruptions of ER homoeostasis is implicated in numerous diseases. The unfolded protein response (UPR), a complex adaptive stress response, attempts to restore normal proteostasis, in part, through the up-regulation of various foldases and chaperone proteins including redox-active protein disulphide isomerases (PDIs). There are currently over 20 members of the PDI family each consisting of varying numbers of thioredoxin-like domains which, generally, assist in oxidative folding and disulphide bond rearrangement of peptides. While there is a large amount of redundancy in client proteins of the various PDIs, the size of the family would indicate more nuanced roles for the individual PDIs. However, the role of individual PDIs in disease pathogenesis remains uncertain. The following review briefly discusses recent findings of ER stress, the UPR and the role of individual PDIs in various respiratory disease states.

negative: Severe acute respiratory syndrome (SARS): chest radiographic features in children BACKGROUND: Severe acute respiratory syndrome (SARS) is a recently recognized condition of viral origin associated with substantial morbidity and mortality rates in adults. Little information is available on its radiologic manifestations in children. OBJECTIVE: The goal of this study was to characterize the radiographic presentation of children with SARS. MATERIALS AND METHODS: We abstracted data (n=62) on the radiologic appearance and course of SARS in pediatric patients with suspect (n=25) or probable (n=37) SARS, diagnosed in five hospital sites located in three cities: Toronto, Singapore, and Hong Kong. Available chest radiographs and thoracic CTs were reviewed for the presence of the following radiographic findings: airspace disease, air bronchograms, airways inflammation and peribronchial thickening, interstitial disease, pleural effusion, and hilar adenopathy. RESULTS: A total of 62 patients (suspect=25, probable=37) were evaluated for SARS. Patient ages ranged from 5.5 months to 17 years and 11.5 months (average, 6 years and 10 months) with a female-to-male ratio of 32:30. Forty-one patients (66.1%) were in close contact with other probable, suspect, or quarantined cases; 10 patients (16.1%) had recently traveled to WHO-designated affected areas within 10 days; and 7 patients (11.2%) were transferred from other hospitals that had SARS patients. Three patients, who did not have close/hospital contact or travel history to affected areas, were classified as SARS cases based on their clinical signs and symptoms and on the fact that they were living in an endemic area. The most prominent clinical presentations were fever, with a temperature over 38 °C (100%), cough (62.9%), rhinorrhea (22.6%), myalgia (17.7%), chills (14.5%), and headache (11.3%). Other findings included sore throat (9.7%), gastrointestinal symptoms (9.7%), rigor (8.1%), and lethargy (6.5%). In general, fever and cough were the most common clinical presentations amongst younger pediatric SARS cases (age<10 years), whereas, in addition to these symptoms, headache, myalgia, sore throat, chills, and/or rigor were common in older patients (age≥10 years). The chest radiographs of 35.5% of patients were normal. The most prominent radiological findings that were observed in the remaining patients were areas of consolidation (45.2%), often peripheral with multifocal lesions in 22.6%. Peribronchial thickening was noted on chest radiographs of 14.5% of patients. Pleural effusion was observed only in one patient (age 17 years and 11.5 months), whereas interstitial disease was not observed in any patient. CONCLUSION: In pediatric cases, SARS manifests with nonspecific radiographic features making radiological differentiation difficult, especially from other commonly encountered childhood respiratory viral illnesses causing airspace disease. The radiographic presentation of suspected SARS cases ranged from normal to mild perihilar peribronchial thickening. The radiographic presentations, as expected, were relatively more pronounced in the SARS probable cases.

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

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

negative: COVID-19: The Concept of Herd Immunity – Is It A Strategy for South Africa?

negative: Epidemiologic approaches used in a herd health practice to investigate neonatal calf mortality Epidemiologic methods were applied in an investigation into causes of neonatal mortality on a 1400-cow dairy in the southern San Joaquin Valley of California. A format for collation of information on birthdate and date of death was assembled into a matrix which improved conceptualization of the data and which simplified procedures for estimation of mortality rates. Contemporary and birth cohort life table methods, mortality density estimations and relative risk assessment were used to ascertain if there were high-risk groups of calves that could be identified by age, day-of-the-week born, day-of-the-week died and sex. During the outbreak of neonatal diarrhea on this dairy, female calves were found to have experienced an atypically higher rate of mortality (10.7%) than did males (5.3%). Calves of both sexes died between the ages of 9 and 19 days. In addition, the risk of dying was 11 times greater for calves born on Wednesdays than for those born on Saturdays. These findings formed the basis for recommended changes in management of neonatal calves on the dairy.

negative: Report of the Federal Panel on Formaldehyde. The Federal Panel on Formaldehyde concluded that definitive experiments exist which demonstrate the mutagenicity and carcinogenicity of formaldehyde under laboratory conditions. Formaldehyde induces both gene mutations and chromosomal aberrations in a variety of test systems. Inhalation of formaldehyde causes cancer of the nose in rats. The concentrations of formaldehyde in inhaled air that caused nasal cancer in Fisher 344 rats are within the same order of magnitude as those to which humans may be exposed. The data presently available do not permit a direct assessment of the carcinogenicity of formaldehyde to man. Epidemiologic studies on exposed human populations are in progress and may further clarify the situation. Other experimental and human studies on toxic effects such as teratogenicity and reproductive disorders are as yet inadequate for a health risk assessment. The CIIT 24 month study on animal carcinogenicity has not yet been completely evaluated. Additional data are expected on the effects of prolonged exposure to lower doses of formaldehyde and on the possible carcinogenicity of formaldehyde in the mouse. The panel recommends that, for a comprehensive health risk assessment, further experiments be conducted on the effects of other modes of exposure (ingestion and skin penetration), the effects in humans, and on the pharmacokinetics of formaldehyde in man and animals and the possible role for formaldehyde in reproductive and chronic respiratory disorders. It is the conclusion of the panel that formaldehyde should be presumed to pose a carcinogenic risk to humans.

negative: Shifting trends in pathogen dynamics on a changing planet In this perspective we offer views on how microbial activities may change in response to the impact of human activities and an increasing human population. New knowledge is forthcoming in microbiology and immunology on the biology of emerging pathogens. With the exposure of human populations to changing environments, through climate change and human encroachment into previously unpopulated areas, there is likely to be increased incidences of diseases caused by existing, emerging and previously unrecognised pathogens.

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

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

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

negative: Dairy calf management, morbidity and mortality in Ontario Holstein herds. IV. Association of management with mortality Associations between heifer calf management and mortality were studied on 104 randomly selected Holstein dairy farms in southwestern Ontario between October 1980 and July 1983. At the farm level, data were stratified by season, with two six-month seasons (winter and summer) per year. The odds of farms with particular management strategies having above-median morbidity were calculated. At the individual calf level, the odds of a calf being treated, controlling for farm of origin and month of birth, were calculated for different management practices. Larger farms had significantly greater odds of experiencing mortality than smaller farms in both winter and summer. Farms which had policies of attending calvings and ensuring that calves received their first colostrum had significantly lower odds of experiencing winter mortality than farms which did not have these policies. Farms which housed calves in hutches had significantly lower odds, and those which housed calves in group pens had significantly higher odds, of experiencing summer mortality, than farms which used individual indoor calf-pens. A policy of teat removal between four weeks of age and weaning was associated with increased odds of summer mortality. At the individual calf level, calving ease, sire, navel treatment, assistance at first colostrum feeding, administration of vitamins A, D and E and anti-scour vaccines to the pregnant dam, and place of calving, were all associated with significantly altered odds of dying. However, several interactions entered the statistical models, and the effects of those management practices were not all straightforward.

negative: An expanded One Health model: Integrating social science and One Health to inform study of the human-animal interface Abstract Zoonotic disease emergence is not a purely biological process mediated only by ecologic factors; opportunities for transmission of zoonoses from animals to humans also depend on how people interact with animals. While exposure is conditioned by the type of animal and the location in which interactions occur, these in turn are influenced by human activity. The activities people engage in are determined by social as well as contextual factors including gender, age, socio-economic status, occupation, social norms, settlement patterns and livelihood systems, family and community dynamics, as well as national and global influences. This paper proposes an expanded “One Health” conceptual model for human-animal exposure that accounts for social as well as epidemiologic factors. The expanded model informed a new study approach to document the extent of human exposure to animals and explore the interplay of social and environmental factors that influence risk of transmission at the individual and community level. The approach includes a formative phase using qualitative and participatory methods, and a representative, random sample survey to quantify exposure to animals in a variety of settings. The paper discusses the different factors that were considered in developing the approach, including the range of animals asked about and the parameters of exposure that are included, as well as factors to be considered in local adaptation of the generic instruments. Illustrative results from research using this approach in Lao PDR are presented to demonstrate the effect of social factors on how people interact with animals. We believe that the expanded model can be similarly operationalized to explore the interactions of other social and policy-level determinants that may influence transmission of zoonoses.

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

negative: Calibrating Gompertz in reverse: What is your longevity-risk-adjusted global age?() This paper develops a computational framework for inverting Gompertz–Makeham mortality hazard rates, consistent with compensation laws of mortality for heterogeneous populations, to define a longevity-risk-adjusted global (L-RaG) age. To illustrate its salience and possible applications, the paper calibrates and presents L-RaG values using country data from the Human Mortality Database (HMD). Among other things, the author demonstrates that when properly benchmarked, the longevity-risk-adjusted global age of a 55-year-old Swedish male is 48, whereas a 55-year-old Russian male is closer in age to 67. The paper also discusses the connection between the proposed L-RaG age and the related concept of Biological age, from the medical and gerontology literature. Practically speaking, in a world of growing mortality heterogeneity, the L-RaG age could be used for pension and retirement policy. In the language of behavioral finance and economics, a salient metric that adjusts chronological age for longevity risk might help capture the public’s attention, educate them about lifetime uncertainty and induce many of them to take action — such as working longer and/or retiring later.

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: Early Safety Indicators of COVID-19 ConvalescentPlasma in 5,000 Patients Background: Convalescent plasma is the only antibody based therapy currently available for COVID-19 patients. It has robust historical precedence and sound biological plausibility. Although promising, convalescent plasma has not yet been shown to be safe as a treatment for COVID-19. Methods: Thus, we analyzed key safety metrics after transfusion of ABO-compatible human COVID-19 convalescent plasma in 5,000 hospitalized adults with severe or life threatening COVID-19, with 66% in the intensive care unit, as part of the US FDA Expanded Access Program for COVID-19 convalescent plasma. Results: The incidence of all serious adverse events (SAEs) in the first four hours after transfusion was <1%, including mortality rate (0.3%). Of the 36 reported SAEs, there were 25 reported incidences of related SAEs, including mortality (n=4), transfusion-associated circulatory overload (TACO; n=7), transfusion-related acute lung injury (TRALI; n=11), and severe allergic transfusion reactions (n=3). However, only 2 (of 36) SAEs were judged as definitely related to the convalescent plasma transfusion by the treating physician. The seven-day mortality rate was 14.9%. Conclusion: Given the deadly nature of COVID-19 and the large population of critically-ill patients included in these analyses, the mortality rate does not appear excessive. These early indicators suggest that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19.

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

negative: Focus on Middle East respiratory syndrome coronavirus (MERS-CoV) Abstract Since the first case of human infection by the Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia in June 2012, more than 2260 cases of confirmed MERS-CoV infection and 803 related deaths have been reported since the 16th of October 2018. The vast majority of these cases (71%) were reported in Saudi Arabia but the epidemic has now spread to 27 countries and has not ceased 6 years later, unlike SARS-CoV that disappeared a little less than 2 years after emerging. Due to the high fatality rate observed in MERS-CoV infected patients (36%), much effort has been put into understanding the origin and pathophysiology of this novel coronavirus to prevent it from becoming endemic in humans. This review focuses in particular on the origin, epidemiology and clinical manifestations of MERS-CoV, as well as the diagnosis and treatment of infected patients. The experience gained over recent years on how to manage the different risks related to this kind of epidemic will be key to being prepared for future outbreaks of communicable disease.

negative: Respiratory viral pathogens associated with lower respiratory tract disease among young children in the highlands of Papua New Guinea BACKGROUND: Acute lower respiratory tract infections (ALRI) commonly result in fatal outcomes in the young children of Papua New Guinea (PNG). However, comprehensive studies of the viral aetiology of ALRI have not been conducted in PNG for almost 30 years. OBJECTIVES: To determine the viruses associated with ALRI among children living in the PNG highlands using sensitive molecular detection techniques. STUDY DESIGN: Pernasal swabs were collected routinely between 1 week and 18 months of age and also during episodes of ALRI, as part of a neonatal pneumococcal conjugate vaccine trial. A tandem multiplex real-time PCR assay was used to test for a comprehensive range of respiratory viruses in samples collected from 221 young children. Picornavirus typing was supported by DNA sequence analysis. RESULTS: Recognized pathogenic respiratory viruses were detected in 198/273 (73%) samples collected from children with no evidence of ALRI and 69/80 (86%) samples collected during ALRI episodes. Human rhinoviruses (HRV) species A, B and C were detected in 152 (56%) samples from non-ALRI children and 50 (63%) samples collected during ALRI episodes. Partial structural region sequences for two new species C rhinoviruses were added to the GenBank database. ALRI was associated with detection of adenovirus species B (p < 0.01) or C (p < 0.05), influenza A (p < 0.0001) or respiratory syncytial virus (p < 0.0001). Multiple viruses were detected more often during ALRI episodes (49%) than when children displayed no symptoms of ALRI (18%) (p < 0.0001). CONCLUSIONS: The burden of infection with respiratory viruses remains significant in young children living in the PNG highlands.

negative: Epidemiology of Necrotizing Enterocolitis The descriptive epidemiology of necrotizing enterocolitis (NEC) is presented. Areas addressed include incidence, race, sex, age of onset, mortality rates, and endemic versus epidemic disease. Both descriptive and case control studies are reviewed to uncover clues relevant to the causes, pathogenesis, and prevention of NEC.

negative: Global rheumatology in the time of COVID-19

negative: A Unique Clade of SARS-CoV-2 Viruses is Associated with Lower Viral Loads in Patient Upper Airways The rapid spread of SARS-CoV-2, the causative agent of Coronavirus disease 2019 (COVID-19), has been accompanied by the emergence of distinct viral clades, though their clinical significance remains unclear. Here, we examined the genome sequences of 88 SARS-CoV-2 viruses from COVID-19 patients in Chicago, USA and identified three distinct phylogenetic clades. Clade 1 was most closely related to clades centered in New York, and showed evidence of rapid expansion across the USA, while Clade 3 was most closely related to those in Washington. Clade 2 was localized primarily to the Chicago area with limited evidence of expansion elsewhere. Average viral loads in the airways of patients infected with the rapidly spreading Clade 1 viruses were significantly higher than those of the poorly spreading Clade 2. These results show that multiple variants of SARS-CoV-2 are circulating in the USA that differ in their relative airway viral loads and potential for expansion.

negative: Mitigation Approaches to Combat the Flu Pandemic Management of flu pandemic is a perpetual challenge for the medical fraternity since time immemorial. Animal to human transmission has been observed thrice in the last century within an average range of 11-39 years of antigenic recycling. The recent outbreak of influenza A (H1N1, also termed as swine flu), first reported in Mexico on April 26, 2009, occurred in the forty first year since last reported flu pandemic (July 1968). Within less than 50 days, it has assumed pandemic proportions (phase VI) affecting over 76 countries with 163 deaths/35,928 cases (as on 15(th) June 2009). It indicated the re-emergence of genetically reassorted virus having strains endemic to humans, swine and avian (H5N1). The World Health Organisation (WHO) member states have already pulled up their socks and geared up to combat such criticalities. Earlier outbreaks of avian flu (H5N1) in different countries led WHO to develop pandemic preparedness strategies with national/regional plans on pandemic preparedness. Numerous factors related to climatic conditions, socio-economic strata, governance and sharing of information/logistics at all levels have been considered critical indicators in monitoring the dynamics of escalation towards a pandemic situation. The National Disaster Management Authority (NDMA), Government of India, with the active cooperation of UN agencies and other stakeholders/experts has formulated a concept paper on role of nonhealth service providers during pandemics in April 2008 and released national guidelines - management of biological disasters in July 2008. These guidelines enumerate that the success of medical management endeavors like pharmaceutical (anti-viral Oseltamivir and Zanamivir therapies), nonpharmaceutical interventions and vaccination development etc., largely depends on level of resistance offered by mutagenic viral strain and rationale use of pharmaco therapeutic interventions. This article describes the mitigation approach to combat flu pandemic with its effective implementation at national, state and local levels.

negative: Cryo-EM structures of HKU2 and SADS-CoV spike glycoproteins and insights into coronavirus evolution A new porcine coronavirus SADS-CoV was recently identified from suckling piglets with severe diarrhea in southern China and its genome sequence is most identical (~95% identity) to that of bat α-coronavirus HKU2. It again indicates bats are the natural reservoir of many coronaviruses that have great potential for cross-species transmission to animals and humans by recombination and/or mutation. Here we report the cryo-EM structures of HKU2 and SADS-CoV spike glycoprotein trimers at 2.38 Å and 2.83 Å resolution, respectively. HKU2 and SADS-CoV spikes exhibit very high structural similarity, with subtle differences mainly distributed in the NTD and CTD of the S1 subunit responsible for cell attachment and receptor binding. We systematically analyzed and compared the NTD, CTD, SD1 and SD2 domains of the S1 subunit and the S2 subunit of HKU2 spike with those of α-, β-, γ-, and δ-coronavirus spikes. The results show that the NTD and CTD of HKU2/SADS-CoV are probably the most ancestral in the evolution of spike. Although the S2 subunit mediating membrane fusion is highly conserved, the connecting region after fusion peptide in HKU2/SADS-CoV S2 subunit also adopts a conformation distinct from other coronaviruses. These results structurally demonstrate a close evolutionary relationship between HKU2 /SADS-CoV and β-coronavirus spikes and provide new insights into the evolution and cross-species transmission of coronaviruses.

negative: Changing health in China: re-evaluating the epidemiological transition model This paper reviews the changing health situation in China, which has shown remarkable improvement in the 50 years since the founding of the People’s Republic of China (PRC) in 1949. At first sight this improving health situation follows the classical epidemiological transition model. Just three decades ago health in China was characterised by high rates of infectious disease and early mortality (diseases of poverty) in a mainly peasant society. More recently infectious disease rates have decreased, with corresponding and extended morbidity and mortality associated with an aging population in a rapidly urbanising society. This process has given rise to new health problems, including chronic and degenerative diseases (diseases of affluence). Nonetheless, while there is some validity in the application of the epidemiological transition concept, further analysis demonstrates that China faces a new epidemiological phase, characterised by increasing life expectancy and diseases of affluence coupled with the emergence and re-emergence of infectious diseases. We demonstrate that China’s state policy plays a major role in defining the parameters of health in a Chinese context. We conclude that, today, China is faced with a new set of health issues, including the impact of smoking, hypertension, the health effects of environmental pollution and the rise of HIV/AIDS; however, state policy remains vital to the health of China’s vast population. The challenge for policy is to maintain health reform whilst tackling the problems associated with rapid urbanisation, widening social and spatial inequalities and the emergence of HIV/AIDS and other infectious diseases.

negative: Drug adherence and the incidence of coronary heart disease- and stroke-specific mortality among 218,047 patients newly prescribed an antihypertensive medication: A five-year cohort study Abstract Background Randomized trials have shown that optimal adherence to antihypertensive agents could protect against cardiovascular diseases, but whether adherence reduces cardiovascular deaths in community settings has not been explored so fully. This study evaluates the association between antihypertensive adherence and cardiovascular (coronary heart disease and stroke) mortality in the primary care settings. Methods From a territory-wide database in Hong Kong, we included all patients who were prescribed their first-ever antihypertensive agents in the years between 2001 and 2005 from the public healthcare sector. All patients were followed up for five years, and assigned as having poor (Proportion of Days Covered [PDC]<40%), intermediate (40–79%), and high (≥80%) adherence to antihypertensive agents. The association between antihypertensive adherence and cardiovascular mortality was evaluated by using the Cox proportional hazard models. Results From a total of 218,047 eligible patients, 3825 patients (1.75%) died of cardiovascular disease within five years after having received their first-ever antihypertensive agents. The proportions of patients having poor, intermediate, and high medication adherence were 32.9%, 12.1%, and 55.0%, respectively. Higher adherence levels at PDC 40%–79% (HR=0.46, 95% C.I. 0.41–0.52, p<0.001) and ≥80% (HR=0.91, 95% C.I. 0.85–0.98, p=0.012) were significantly less likely to be associated with mortality than the poor adherence (PDC0.040) group. Conclusions Better antihypertensive adherence was associated with lower cardiovascular mortality. This highlights the need to promote adherence through strategies which have been proved to be effective in clinical settings.

negative: Reducing the Impact of the Next Influenza Pandemic Using Household-Based Public Health Interventions BACKGROUND: The outbreak of highly pathogenic H5N1 influenza in domestic poultry and wild birds has caused global concern over the possible evolution of a novel human strain [1]. If such a strain emerges, and is not controlled at source [2,3], a pandemic is likely to result. Health policy in most countries will then be focused on reducing morbidity and mortality. METHODS AND FINDINGS: We estimate the expected reduction in primary attack rates for different household-based interventions using a mathematical model of influenza transmission within and between households. We show that, for lower transmissibility strains [2,4], the combination of household-based quarantine, isolation of cases outside the household, and targeted prophylactic use of anti-virals will be highly effective and likely feasible across a range of plausible transmission scenarios. For example, for a basic reproductive number (the average number of people infected by a typically infectious individual in an otherwise susceptible population) of 1.8, assuming only 50% compliance, this combination could reduce the infection (symptomatic) attack rate from 74% (49%) to 40% (27%), requiring peak quarantine and isolation levels of 6.2% and 0.8% of the population, respectively, and an overall anti-viral stockpile of 3.9 doses per member of the population. Although contact tracing may be additionally effective, the resources required make it impractical in most scenarios. CONCLUSIONS: National influenza pandemic preparedness plans currently focus on reducing the impact associated with a constant attack rate, rather than on reducing transmission. Our findings suggest that the additional benefits and resource requirements of household-based interventions in reducing average levels of transmission should also be considered, even when expected levels of compliance are only moderate.

negative: Host and Viral Proteins Modulating Ebola and Marburg Virus Egress The filoviruses Ebolavirus and Marburgvirus are among the deadliest viral pathogens known to infect humans, causing emerging diseases with fatality rates of up to 90% during some outbreaks. The replication cycles of these viruses are comprised of numerous complex molecular processes and interactions with their human host, with one key feature being the means by which nascent virions exit host cells to spread to new cells and ultimately to a new host. This review focuses on our current knowledge of filovirus egress and the viral and host factors and processes that are involved. Within the virus, these factors consist of the major matrix protein, viral protein 40 (VP40), which is necessary and sufficient for viral particle release, and nucleocapsid and glycoprotein that interact with VP40 to promote egress. In the host cell, some proteins are hijacked by filoviruses in order to enhance virion budding capacity that include members of the family of E3 ubiquitin ligase and the endosomal sorting complexes required for transport (ESCRT) pathway, while others such as tetherin inhibit viral egress. An understanding of these molecular interactions that modulate viral particle egress provides an important opportunity to identify new targets for the development of antivirals to prevent and treat filovirus infections.

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

negative: Alcohol and Cancer Epidemiology In a comprehensive worldwide assessment of cancer risk related to food and nutrition, the American Institute for Cancer Research (AICR 2007) identified alcohol consumption as a “convincing” or “probable” risk factor for esophageal, mouth, and laryngeal cancers, for liver cancer, for breast cancer in women, and for colorectal cancer especially in men. The World Health Organization’s Global Burden of Disease Project concluded that “A total of 390,000 cases of cancer are attributable to alcohol drinking worldwide, representing 3.6% of all cancers (5.2% in men, 1.7% in women)” each year, with a corresponding annual mortality rate of 233,000, representing 3.5% of all cancer deaths (Boffetta et al. 2006). For the USA, the Alcohol-Related Disease Impact (ARDI) report indicates an annual rate of 2,464 deaths in six different alcohol-related cancer categories for the period 2001–2006 (CDC 2010).

negative: COVID-19 and ethnicity: Spotlight on the global rheumatology issues in developing and developed countries

negative: Some remarks on protein attribute prediction and pseudo amino acid composition Abstract With the accomplishment of human genome sequencing, the number of sequence-known proteins has increased explosively. In contrast, the pace is much slower in determining their biological attributes. As a consequence, the gap between sequence-known proteins and attribute-known proteins has become increasingly large. The unbalanced situation, which has critically limited our ability to timely utilize the newly discovered proteins for basic research and drug development, has called for developing computational methods or high-throughput automated tools for fast and reliably identifying various attributes of uncharacterized proteins based on their sequence information alone. Actually, during the last two decades or so, many methods in this regard have been established in hope to bridge such a gap. In the course of developing these methods, the following things were often needed to consider: (1) benchmark dataset construction, (2) protein sample formulation, (3) operating algorithm (or engine), (4) anticipated accuracy, and (5) web-server establishment. In this review, we are to discuss each of the five procedures, with a special focus on the introduction of pseudo amino acid composition (PseAAC), its different modes and applications as well as its recent development, particularly in how to use the general formulation of PseAAC to reflect the core and essential features that are deeply hidden in complicated protein sequences.

negative: Epidemiological and clinical features of COVID-19 patients with and without pneumonia in Beijing, China Background:SARS-CoV-2-caused coronavirus disease (COVID-19) is posinga large casualty. The features of COVID-19patients withand without pneumonia,SARS-CoV-2 transmissibility in asymptomatic carriers, and factors predicting disease progression remain unknown. Methods: We collected information on clinical characteristics, exposure history, andlaboratory examinations of all laboratory-confirmed COVID-19 patients admitted to PLA General Hospital. Cox regression analysis was applied to identify prognostic factors. The last follow-up was February 18, 2020. Results:We characterized 55 consecutive COVID-19 patients. The mean incubation was 8.42(95% confidence interval [CI], 6.55-10.29) days. The mean SARS-CoV-2-positive duration from first positive test to clearance was 9.71(95%CI, 8.21-11.22) days. COVID-19 course was approximately 2 weeks. Asymptomatic carriers might transmit SARS-CoV-2. Compared with patients without pneumonia, those with pneumonia were 15 years older and had a higher rate of hypertension, higher frequencies of having a fever and cough, and higher levels of interleukin-6 (14.61 vs. 8.06pg/mL, P=0.040), B lymphocyte proportion (13.0% vs.10.0%, P=0.024), low account (<190/μL) of CD8+ T cells (33.3% vs. 0, P=0.019). Multivariate Cox regression analysis indicated that circulating interleukin-6 andlactate independently predicted COVID-19 progression, with a hazard ratio (95%CI) of 1.052 (1.000-1.107) and 1.082 (1.013-1.155), respectively. During disease course,T lymphocytes were generally lower,neutrophils higher, in pneumonia patients than in pneumonia-free patients. CD8+ lymphocytes did not increase at the 20th days after illness onset. Conclusion: The epidemiological features areimportant for COVID-19 prophylaxis. Circulating interleukin-6 and lactateare independent prognostic factors. CD8+ T cell exhaustion might be critical in the development of COVID-19.

negative: Case report: A kidney transplant patient with mild COVID-19 Coronavirus Disease 2019 (COVID-19) is currently a pandemic with a mortality rate of 1%-6% in the general population. However, the mortality rate seems to be significantly higher in elderly patients, especially those hospitalized with comorbidities, such as hypertension, diabetes, or coronary artery diseases. Because viral diseases may have atypical presentations in immunosuppressed patients, the course of the disease in the transplant patient population is unknown. Hence, the management of these patients with COVID-19 is an area of interest, and a unique approach is warranted. Here, we report the clinical features and our treatment approach for a kidney transplant patient with a diagnosis of COVID-19. We believe that screening protocols for SARS-Cov-2 should be re-evaluated in patients with solid-organ transplants.

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

negative: 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: Predicting the epidemic curve of the coronavirus (SARS-CoV-2) disease (COVID-19) using artificial intelligence Objectives: The current form of severe acute respiratory syndrome called coronavirus disease 2019 (COVID19) caused by a coronavirus (SARSCoV2) is a major global health problem. The aim of our study was to use the official data and predict the possible outcomes of the COVID 19 pandemic using artificial intelligence (AI) based RNNs (Recurrent Neural Networks), then compare and validate the predicted and observed data. Materials and Methods: We used the publicly available datasets of World Health Organization and Johns Hopkins University to create the training dataset, then have used recurrent neural networks (RNNs) with gated recurring units (Long Short Term Memory: LSTM units) to create 2 Prediction Models. Information collected in the first t time steps were aggregated with a fully connected (dense) neural network layer and a consequent regression output layer to determine the next predicted value. We used root mean squared logarithmic errors (RMSLE) to compare the predicted and observed data, then recalculated the predictions again. Results: The result of our study underscores that the COVID19 pandemic is probably a propagated source epidemic, therefore repeated peaks on the epidemic curve (rise of the daily number of the newly diagnosed infections) are to be anticipated. The errors between the predicted and validated data and trends seems to be low. Conclusions: The influence of this pandemic is great worldwide, impact our everyday lifes. Especially decision makers must be aware, that even if strict public health measures are executed and sustained, future peaks of infections are possible. The AI based predictions might be useful tools for predictions and the models can be recalculated according to the new observed data, to get more precise forecast of the pandemic.

negative: Age-Specific Excess Mortality Patterns During the 1918–1920 Influenza Pandemic in Madrid, Spain Although much progress has been made to uncover age-specific mortality patterns of the 1918 influenza pandemic in populations around the world, more studies in different populations are needed to make sense of the heterogeneous death impact of this pandemic. We assessed the absolute and relative magnitudes of 3 pandemic waves in the city of Madrid, Spain, between 1918 and 1920, on the basis of age-specific all-cause and respiratory excess death rates. Excess death rates were estimated using a Serfling model with a parametric bootstrapping approach to calibrate baseline death levels with quantified uncertainty. Excess all-cause and pneumonia and influenza mortality rates were estimated for different pandemic waves and age groups. The youngest and oldest persons experienced the highest excess mortality rates, and young adults faced the highest standardized mortality risk. Waves differed in strength; the peak standardized mortality risk occurred during the herald wave in spring 1918, but the highest excess rates occurred during the fall and winter of 1918/1919. Little evidence was found to support a “W”-shaped, age-specific excess mortality curve. Acquired immunity may have tempered a protracted fall wave, but recrudescent waves following the initial 2 outbreaks heightened the total pandemic mortality impact.

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

negative: Viruses: Definition, Structure, Classification Viruses are infectious units with diameters of about 16 nm (circoviruses) to over 300 nm (poxviruses; Table 2.1). Their small size makes them ultrafilterable, i.e. they are not retained by bacteria-proof filters. Viruses have evolved over millions of years, and have adapted to specific organisms or their cells. The infectious virus particles, or virions, are composed of proteins and are surrounded in some species of viruses by a lipid membrane, which is referred to as an envelope; the particles contain only one kind of nucleic acid, either DNA or RNA. Viruses do not reproduce by division, such as bacteria, yeasts or other cells, but they replicate in the living cells that they infect. In them, they develop their genomic activity and produce the components from which they are made. They encode neither their own protein synthesis machinery (ribosomes) nor energy-generating metabolic pathways. Therefore, viruses are intracellular parasites. They are able to re-route and modify the course of cellular processes for the optimal execution of their own reproduction. Besides the genetic information encoding their structural components, they additionally possess genes that code for several regulatory active proteins (such as transactivators) and enzymes (e.g. proteases and polymerases).

negative: What is the Role of Respiratory Viruses in Community Acquired Pneumonia; What is the Best Therapy for Influenza and Other Viral Causes of CAP? Respiratory viruses including influenza have long been appreciated as a cause of community acquired pneumonia (CAP), particularly among children, people with serious medical co-morbidities and military recruits. They are increasingly recognized as a cause of CAP among adults, particularly older adults. Polymerase chain reaction-based testing has allowed detection of newer agents (e.g. human metapneumovirus, coronavirus HKU1 and NL63) as well as improved the ability to detect “old” viral infections such as influenza virus and rhinovirus. When PCR is used, viruses have been detected in 45–75% of children and 15–54% of adults with CAP. Co-infection with viruses and bacteria is common and it remains challenging to determine which patients have only viral infection as the cause of CAP. Treatment for influenza with neuraminidase inhibitors should be started promptly for patients with CAP when influenza is suspected or documented, regardless of evidence of bacterial co-infection. Better ways to diagnose viral CAP and to integrate detection into management are urgently needed, as well as better treatment options for non-influenza respiratory viral infections.

negative: Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV Middle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease associated with more than 2468 human infections and over 851 deaths in 27 countries since 2012. There are no approved treatments for MERS-CoV infection although a combination of lopinavir, ritonavir and interferon beta (LPV/RTV-IFNb) is currently being evaluated in humans in the Kingdom of Saudi Arabia. Here, we show that remdesivir (RDV) and IFNb have superior antiviral activity to LPV and RTV in vitro. In mice, both prophylactic and therapeutic RDV improve pulmonary function and reduce lung viral loads and severe lung pathology. In contrast, prophylactic LPV/RTV-IFNb slightly reduces viral loads without impacting other disease parameters. Therapeutic LPV/RTV-IFNb improves pulmonary function but does not reduce virus replication or severe lung pathology. Thus, we provide in vivo evidence of the potential for RDV to treat MERS-CoV infections.

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

negative: Assessing COVID-19 Risk, Vulnerability and Infection Prevalence in Communities Background: The spread of coronavirus in the United States with nearly one million confirmed cases and over 53,000 deaths has strained public health and health care systems. While many have focused on clinical outcomes, less attention has been paid to vulnerability and risk of infection. In this study, we developed a planning tool that examines factors that affect vulnerability to COVID-19. Methods: Across 46 variables, we defined five broad categories: 1) access to medical, 2) underlying health conditions, 3) environmental exposures, 4) vulnerability to natural disasters, and 5) sociodemographic, behavioral, and lifestyle factors. We also used reported rates for morbidity, hospitalization, and mortality in other regions to estimate risk at the county (Harris County) and census tract levels. Analysis: A principal component analysis was undertaken to reduce the dimensions. Then, to identify vulnerable census tracts, we conducted rank-based exceedance and K-means cluster analyses. Results: Our study showed a total of 722,357 (~17% of the County population) people, including 171,403 between the ages of 45-65 (~4% of County population), and 76,719 seniors (~2% of County population), are at a higher risk based on the aforementioned categories. The exceedance and K-means cluster analysis demonstrated that census tracts in the northeastern, eastern, southeastern and northwestern regions of the County are at highest risk. The results of age-based estimations of hospitalization rates showed the western part of the County might be in greater need of hospital beds. However, cross-referencing the vulnerability model with the estimation of potential hospitalized patients showed that part of the County has the least access to medical facilities. Conclusion: Policy makers can use this planning tool to identify neighborhoods at high risk for becoming hot spots; efficiently match community resources with needs, and ensure that the most vulnerable have access to equipment, personnel, and medical interventions.

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

negative: Vertebrates as Hosts and Reservoirs of Zoonotic Microbial Agents This chapter presents a survey of zoonotic microorganisms that have been isolated from vertebrates (Vertebrata), and are potentially transmissible to humans. It is intended as an aid for microbiologists, zoologists and epidemiologists, making possible better orientation among hosts (and reservoirs) of zoonoses. A great number of sources have been used in this compilation, e.g. Davis et al. (1970), Kucheruk (1979, 1989), Karabatsos (1985–1995), Hubálek (1994), etc.

negative: Association of COVID-19 Infections in San Francisco in Early March 2020 with Travel to New York and Europe Real-time dissemination of epidemiological survey data from positive COVID-19 cases is critical to support efforts to contain or reduce spread of viral infection in the community. Here we detected a significant association between domestic travel or travel to Europe and the identification of new cases in San Francisco, California, USA. These findings suggest that domestic and European travelers may need to be prioritized for evaluation of acute infection from COVID-19 in the setting of limited testing capacity.

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: The Effect of Population Size for Pathogen Transmission on Prediction of COVID-19 Pandemic Spread Extreme public health interventions play a critical role in mitigating the local and global prevalence and pandemic potential of COVID-19. Here, we use population size for pathogen transmission to measure the intensity of public health interventions, which is a key characteristic variable for nowcasting and forecasting of the epidemic. By formulating a hidden Markov dynamic system and using nonlinear filtering theory, we have developed a stochastic epidemic dynamic model under public health interventions. The model parameters and states are estimated in time from internationally available public data by combining an unscented filter and an interacting multiple model filter. Moreover, we consider the computability of the population size and provide its selection criterion. We estimate the mean of the basic reproductive number of China and the rest of the globe except China (GEC) to be 2.46 (95% CI: 2.41-2.51) and 3.64 (95% CI: (3.55-3.72), respectively. We infer that the number of latent infections of GEC is about 7.47*10^5 (95% CI: 7.32*10^5-7.62*10^5) as of April 2, 2020. We predict that the peak of infections in hospitals of GEC may reach 3.00*10^6 on the present trajectory, i.e., if the population size for pathogen transmission and epidemic parameters remains unchanged. If the control intensity is strengthened, e.g., 50% reduction or 75% reduction of the population size for pathogen transmission, the peak would decline to 1.84*10^6, 1.27*10^6, respectively.

negative: Demographic, clinical, and outcomes of confirmed cases of Middle East Respiratory Syndrome coronavirus (MERS-CoV) in Najran, Kingdom of Saudi Arabia (KSA); A retrospective record based study Abstract Introduction MERS is caused by a viral infection, which was first identified in KSA, 2012. MERS-CoV infection consequences with either hospitalization or death. Methods All positive MERS-CoV cases that diagnosed in and reported to a referral hospital in Najran, KSA from March/2014 to December/2018 were revised retrospectively. We identified patients from infection control department and medical records. Demographic, clinical, and outcome data were collected. Results Of the 54 positive MERS-CoV cases, 3 cases were excluded because no available data. Therefore, the final number of the included cases in the study was 51 cases (94.4). Most of the patients were Saudi 36 (70.6%), and majority of cases were reported in the winter 18 (35.3) season. Fever 47 (92.2%), cough 44 (86.3%), and shortness of breath 37 (72.5%) were reported as most common symptoms. Most patients had DM and hypertension. Overall mortality rate was 37.3%, and interestingly the mortality rate dropped sharply over 5 years. In logistic regression analysis, Season and Chronic Kidney disease patients were the only two variables statistically significantly associated with death. The odds of death the patients infected by MERS-CoV during Autumn and Winter season were 4.09 times higher than those patients who infected during Spring and Summer season (OR = 4.09, CI 1.18-14.15, P < 0.026). Compared with MERS-CoV patients who had Non-Chronic kidney diseases, the odds of death the MERS-CoV patients who had chronic kidney diseases were 18.08 times higher (OR = 18.08, CI -2.01-162.99, P < 0.01). Conclusion The mortality rate of MERS-CoV infection was high. Further studies with large sample sizes are needed to explore the reasons behind the decrease in the mortality rate over the time period.

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

negative: Implementation of an algorithm for selection of antimicrobial therapy for diarrhoeic calves: Impact on antimicrobial treatment rates, health and faecal microbiota Abstract This study evaluated the impact of an algorithm targeting antimicrobial therapy of diarrhoeic calves on the incidence of diarrhoea, antimicrobial treatment rates, overall mortality, mortality of diarrhoeic calves and changes in the faecal microbiota. The algorithm was designed to target antimicrobial therapy in systemically ill calves from on two dairy farms. Retrospective (farm 1: 529 calves; farm 2: 639 calves) and prospective (farm 1: 639 calves; farm 2: 842 calves) cohorts were examined for 12 months before and after implementation of the algorithm. The Mantel–Haenszel test and Kaplan–Meier survival curves were used to assess the cumulative incidence risk (CIR) and time to development of each outcome before and after implementation of the algorithm. The CIR of antimicrobial treatment rates was 80% lower after implementation of the algorithm on both farms (CIR 0.19, 95% confidence interval 0.17–0.21). There was no difference in the CIR of overall mortality, but the CRI for mortality of diarrhoeic calves was lower in the period after implementation of the algorithm on one farm. The faecal microbiota of 15 healthy calves from both farms at each time period were characterised using a sequencing platform targeting the V4 region of the 16S rRNA gene. On both farms, there were significant differences in community membership and structure (parsimony P< 0.001). Use of the algorithm for treatment of diarrhoeic calves reduced antimicrobial treatment rates without a negative impact on the health of calves. However, the experimental design did not take into account the potential confounding effects of dietary changes between the study periods.

negative: Invasive pulmonary aspergillosis: high incidence of disseminated intravascular coagulation in fatal cases. BACKGROUND AND PURPOSE Disseminated intravascular coagulation (DIC) is a rarely described finding in invasive pulmonary aspergillosis (IPA) with unclear impact on mortality. METHODS This study included patients with positive cultures of Aspergillus spp. from respiratory specimens, serological evidence of aspergillosis, or lung biopsy findings supporting aspergillosis treated at National Taiwan University Hospital from January 1999 to June 2005. IPA was defined based on the consensus of the European Organization for Research and Treatment of Cancer, and the Mycosis Study Group of the National Institute of Allergy and Infectious Diseases. Univariate logistic regression analysis was used to evaluate the factors associated with mortality. RESULTS Proven or probable IPA was diagnosed in 26 patients. Hematological malignancy was found in 11 patients (42%) and immunosuppressive agents had been administered to 17 patients (65%). Among 20 culture-proven infections (77%), the most frequently encountered fungi were Aspergillus fumigatus (46%) and Aspergillus flavus (23%). The overall mortality rate was 62%. Univariate and multivariate analyses revealed that DIC was the only factor that was significantly associated with death attributable to IPA (p<0.01). CONCLUSIONS IPA is associated with a high mortality rate, particularly for patients with DIC.

negative: Severe influenza cases in paediatric intensive care units in Germany during the pre-pandemic seasons 2005 to 2008 BACKGROUND: Data on complications in children with seasonal influenza virus infection are limited. We initiated a nation-wide three-year surveillance of children who were admitted to a paediatric intensive care unit (PICU) with severe seasonal influenza. METHODS: From October 2005 to July 2008, active surveillance was performed using an established reporting system for rare diseases (ESPED) including all paediatric hospitals in Germany. Cases to be reported were hospitalized children < 17 years of age with laboratory-confirmed influenza treated in a PICU or dying in hospital. RESULTS: Twenty severe influenza-associated cases were reported from 14 PICUs during three pre-pandemic influenza seasons (2005-2008). The median age of the patients (12 males/8 females) was 7.5 years (range 0.1-15 years). None had received vaccination against influenza. In 14 (70%) patients, the infection had been caused by influenza A and in five (25%) by influenza B; in one child (5%) the influenza type was not reported. Patients spent a median of 19 (IQR 12-38) days in the hospital and a median of 11 days (IQR 6-18 days) in the PICU; 10 (50%) needed mechanical ventilation. Most frequent diagnoses were influenza-associated pneumonia (60%), bronchitis/bronchiolitis (30%), encephalitis/encephalopathy (25%), secondary bacterial pneumonia (25%), and ARDS (25%). Eleven (55%) children had chronic underlying medical conditions, including 8 (40%) with chronic pulmonary diseases. Two influenza A- associated deaths were reported: i) an 8-year old boy with pneumococcal encephalopathy following influenza infection died from cerebral edema, ii) a 14-year-old boy with asthma bronchiale, cardiac malformation and Addison's disease died from cardiac and respiratory failure. For nine (45%) patients, possibly permanent sequelae were reported (3 neurological, 3 pulmonary, 3 other sequelae). CONCLUSIONS: Influenza-associated pneumonia and secondary bacterial infections are relevant complications of seasonal influenza in Germany. The incidence of severe influenza cases in PICUs was relatively low. This may be either due to the weak to moderate seasonal influenza activity during the years 2005 to 2008 or due to under-diagnosis of influenza by physicians. Fifty% of the observed severe cases might have been prevented by following the recommendations for vaccination of risk groups in Germany.

negative: 2015 ACVIM Forum Research Abstract Program

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

negative: 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: Ethnic and socioeconomic differences in SARS-CoV2 infection in the UK Biobank cohort study Background Understanding of the role of ethnicity and socioeconomic position in the risk of developing SARS-CoV-2 infection is limited. We investigated this in the UK Biobank study. Methods The UK Biobank study recruited 40-70 year olds in 2006-2010 from the general population, collecting information about self-defined ethnicity and socioeconomic variables (including Townsend deprivation index and educational attainment). SARS-CoV-2 test results from Public Health England were linked to baseline UK Biobank data. Poisson regression with robust standard errors was used to assess risk ratios (RRs) between the exposures and dichotomous variables for: being tested, having a positive test and testing positive in hospital. We also investigated whether ethnicity and socioeconomic position were associated with having a positive test amongst those tested. We adjusted for covariates including age, sex, social variables (including healthcare work and household size), behavioural risk factors and baseline health. Findings Among 428,225 participants, 1,474 had been tested and 669 had tested positive between 16 March and 13 April 2020. Black, south Asian and white Irish people were more likely to have confirmed infection (RR 4.01 (95%CI 2.92-5.12); RR 2.11 (95%CI 1.43-3.10); and RR 1.60 (95% CI 1.08-2.38) respectively) and were more likely to be hospitalised compared to White British. While they were more likely to be tested, they were also more likely to test positive. Adjustment for baseline health and behavioural risk factors led to little change, with only modest attenuation when accounting for socioeconomic variables. Area socioeconomic deprivation and having no qualifications were consistently associated with a higher risk of confirmed infection (RR 1.91 (95%CI 1.53-2.38); and RR 2.26 (95%CI 1.76-2.90) respectively). Interpretation Some minority ethnic groups have a higher risk of confirmed SARS-CoV-2 infection in the UK Biobank study which was not accounted for by differences in socioeconomic conditions, measured baseline health or behavioural risk factors. An urgent response to addressing these elevated risks is required. Funding Medical Research Council, Chief Scientist Office.

negative: Analysis of epidemiological characteristics of coronavirus 2019 infection and preventive measures in Shenzhen China: a heavy population city Coronavirus 2019 infection (COVID-19) outbroke in Wuhan, Hubei and spread to all provinces in China and other countries. Shenzhen ranked the top cities outside Wuhan with reported 416 confirmed cases by February 20, 2020. Here, we analyzed the epidemiological characteristics of COVID-19 in Shenzhen and potential link to the preventive strategies for the whole city and inside hospitals. Based on the daily new cases, the epidemic of COVID-19 in Shenzhen can be classified into three phases: the slow increase phase from January 19 to January 28, the rapid increase and plateau phase from January 29 to February 5 and the decline phase since February 6. In the three phases, the number of patients from Hubei decreased, and the number of familial clustering cases increased. The newly diagnosed COVID-19 cases reached its peak around January 31, which was 7 days after the peak date of cases arrival at Shenzhen. A series of early preventive strategies were implemented since January 19, which included detection of body temperature at all entrances of main traffic and buildings, outpatients service specially for patients with fever in all main hospitals in Shenzhen. All the patients with fever were screened with nasal or throat swab PCR detection of coronavirus 2019, Chest CT and blood lymphocyte counting in order to find out early case of COVID-19. Observation wards were established in every main hospital and a designated hospital was responsible for admission and medical care of all confirmed cases. Protection procedure was established for all medical staff involved in the screening and care of suspected and confirmed cases. 14 days isolated observation of all subjects arrived at Shenzhen from Hubei was implemented in February 2. After the implementation of all these strategies and measures, the COVID-19 cases started to decline since February 6. There were almost no community transmission and nosocomial infection occurred in Shenzhen. In conclusion, in situation of major outbreak of respiratory infectious disease, such as COVID-19, in nearby province of Hubei, Shenzhen, a high population density, high proportion of external population and high mobility city, has to face the imported cases and risk of spreading the outbreak into Shenzhen city. The implementation of early preventive strategies and measures in Shenzhen were successful in early identification of COVID-19 cases and prevented major outbreak occurred in Shenzhen. Early identification of imported cases, prevention of family clustering transmission, preventive measures in the public area and very strict infection control procedure in hospital setting are crucial for the successful control of outbreak in Shenzhen.

negative: The 45th Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians – Poster Session

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

negative: The Impact of Viral Infections in Children with Community-Acquired Pneumonia For many years viral causes of community-acquired pneumonia were often been given limited attention. The number of published studies on influenza alone increased fivefold from 2001 to 2010. Specifically several studies have underlined that the involvement of viruses in community-acquired pneumonia has been underestimated, and this underestimation has been attributed to a lack of appropriate diagnostic methods. Now, with the advent of modern molecular assays, it is well recognized that viruses account for the largest proportion of community-acquired pneumonia in preschool children in both developed and developing countries. Respiratory syncytial virus, influenza virus, adenovirus, and parainfluenza virus are the major pathogens involved, but the relative importance of additional viruses (rhinoviruses, bocavirus, human metapneumovirus) is increasing and will be better defined by future research.

negative: Essential Role of Patient Blood Management in a Pandemic: A Call for Action The World Health Organization (WHO) has declared Coronavirus Disease 2019 (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a pandemic. Global health care now faces unprecedented challenges with widespread and rapid human-to-human transmission of SARS-CoV-2 and high morbidity and mortality with COVID-19 worldwide. Across the world, medical care is hampered by a critical shortage of not only hand sanitizers, personal protective equipment, ventilators, and hospital beds, but also impediments to the blood supply. Blood donation centers in many areas around the globe have mostly closed. Donors, practicing social distancing, some either with illness or undergoing self-quarantine, are quickly diminishing. Drastic public health initiatives have focused on containment and “flattening the curve” while invaluable resources are being depleted. In some countries, the point has been reached at which the demand for such resources, including donor blood, outstrips the supply. Questions as to the safety of blood persist. Although it does not appear very likely that the virus can be transmitted through allogeneic blood transfusion, this still remains to be fully determined. As options dwindle, we must enact regional and national shortage plans worldwide and more vitally disseminate the knowledge of and immediately implement patient blood management (PBM). PBM is an evidence-based bundle of care to optimize medical and surgical patient outcomes by clinically managing and preserving a patient’s own blood. This multinational and diverse group of authors issue this “Call to Action” underscoring “The Essential Role of Patient Blood Management in the Management of Pandemics” and urging all stakeholders and providers to implement the practical and commonsense principles of PBM and its multiprofessional and multimodality approaches.

negative: Mandated Bacillus Calmette-Guérin (BCG) vaccination predicts flattened curves for the spread of COVID-19 Prior work suggests that BCG vaccination reduces the risk of different infectious diseases. BCG vaccination may thus serve as a protective factor against COVID-19. Here, we drew on day-by-day reports of both confirmed cases and deaths and analyzed growth curves in countries that mandate BCG policies versus countries that do not. Linear mixed models revealed that the presence of mandated BCG policies was associated with a significant flattening of the exponential increase in both confirmed cases and deaths during the first 30-day period of country-wise outbreaks. This effect held after controlling for median age, gross domestic product per capita, population density, population size, net migration rate, and various cultural dimensions (e.g., individualism and the tightness vs. looseness of social norms). Our analysis suggests that mandated BCG vaccination can be effective in the fight against COVID-19.

negative: Trend analysis of mortality rates and causes of death in children under 5 years old in Beijing, China from 1992 to 2015 and forecast of mortality into the future: an entire population-based epidemiological study OBJECTIVES: To analyse trends in mortality and causes of death among children aged under 5 years in Beijing, China between 1992 and 2015 and to forecast under-5 mortality rates (U5MRs) for the period 2016–2020. METHODS: An entire population-based epidemiological study was conducted. Data collection was based on the Child Death Reporting Card of the Beijing Under-5 Mortality Rate Surveillance Network. Trends in mortality and leading causes of death were analysed using the χ(2) test and SPSS 19.0 software. An autoregressive integrated moving average (ARIMA) model was fitted to forecast U5MRs between 2016 and 2020 using the EViews 8.0 software. RESULTS: Mortality in neonates, infants and children aged under 5 years decreased by 84.06%, 80.04% and 80.17% from 1992 to 2015, respectively. However, the U5MR increased by 7.20% from 2013 to 2015. Birth asphyxia, congenital heart disease, preterm/low birth weight and other congenital abnormalities comprised the top five causes of death. The greatest, most rapid reduction was that of pneumonia by 92.26%, with an annual average rate of reduction of 10.53%. The distribution of causes of death differed among children of different ages. Accidental asphyxia and sepsis were among the top five causes of death in children aged 28 days to 1 year and accident was among the top five causes in children aged 1–4 years. The U5MRs in Beijing are projected to be 2.88‰, 2.87‰, 2.90‰, 2.97‰ and 3.09‰ for the period 2016–2020, based on the predictive model. CONCLUSION: Beijing has made considerable progress in reducing U5MRs from 1992 to 2015. However, U5MRs could show a slight upward trend from 2016 to 2020. Future considerations for child healthcare include the management of birth asphyxia, congenital heart disease, preterm/low birth weight and other congenital abnormalities. Specific preventative measures should be implemented for children of various age groups.

negative: 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.

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

negative: Aerosol Generation by Modern Flush Toilets. A microbe-contaminated toilet will produce bioaerosols when flushed. We assessed toilet plume aerosol from high efficiency (HET), pressure-assisted high efficiency (PAT), and flushometer (FOM) toilets with similar bowl water and flush volumes. Total and droplet nuclei "bioaerosols" were assessed. Monodisperse 0.25-1.9- μ m fluorescent microspheres served as microbe surrogates in separate trials in a mockup 5 m3 water closet (WC). Bowl water seeding was approximately 1012 particles/mL. Droplet nuclei were sampled onto 0.2- μ m pore size mixed cellulose ester filters beginning 15 min after the flush using open-face cassettes mounted on the WC walls. Pre- and postflush bowl water concentrations were measured. Filter particle counts were analyzed via fluorescent microscopy. Bowl headspace droplet count size distributions were bimodal and similar for all toilet types and flush conditions, with 95% of droplets <2μm diameter and>99%<5μ m. Up to 145,000 droplets were produced per flush, with the high-energy flushometer producing over three times as many as the lower energy PAT and over 12 times as many as the lowest energy HET despite similar flush volumes. The mean numbers of fluorescent droplet nuclei particles aerosolized and remaining airborne also increased with flush energy. Fluorescent droplet nuclei per flush decreased with increasing particle size. These findings suggest two concurrent aerosolization mechanisms-splashing for large droplets and bubble bursting for the fine droplets that form droplet nuclei.

negative: Dairy calf management, morbidity and mortality in Ontario Holstein herds. III. Association of management with morbidity Associations between heifer calf management and morbidity, particularly scours and pneumonia, were studied on 104 randomly selected Holstein dairy farms in southwestern Ontario between October 1980 and July 1983. At the farm level, data were stratified by season, with two six-month seasons (winter and summer) per year. The odds of farms with particular management strategies having above median morbidity were calculated. At the individual calf level, the odds of a calf being treated, controlling for farm of origin and month of birth, were calculated for different management practices. Farm size, and policies related to anti-scour vaccination, offering free-choice water and minerals to calves, methods of feeding, and the use of medicated feeds significantly altered the odds of a farm experiencing above-median pneumonia rates. Farm policies with regard to anti-scour vaccination, offering free-choice salt to calves, age at teat removal, type of calf housing, and use of preventive antimicrobials significantly altered the odds of a farm experiencing above-median scours rates. Scours and pneumonia were significantly associated with each other at both the farm and the calf level. No significant associations were found between individual calf management practices and the odds of being treated for scours. Sire used, method of first colostrum feeding, navel treatment, use of anti-scour vaccine in the dam, and the administration of preventive antimicrobials significantly altered the odds of a calf being treated for pneumonia.

negative: Assessing the impact of a symptom-based mass screening and testing intervention during a novel infectious disease outbreak: The case of COVID-19 A symptom-based mass screening and testing intervention (MSTI) can identify a large fraction of infected individuals during an infectious disease outbreak. China is currently using this strategy for the COVID-19 outbreak. However, MSTI might lead to increased transmission if not properly implemented. We investigate under which conditions MSTI is beneficial.

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

negative: Pneumonia in the tropics: Report from the Task Force on tropical diseases by the World Federation of Societies of Intensive and Critical Care Medicine Abstract The aetiology of community acquired pneumonia varies according to the region in which it is acquired. This review discusses those causes of CAP that occur in the tropics and might not be readily recognizable when transplanted to other sites. Various forms of pneumonia including the viral causes such as influenza (seasonal and avian varieties), the coronaviruses and the Hantavirus as well as bacterial causes, specifically the pneumonic form of Yersinia pestis and melioidosis are discussed.

negative: Testing for COVID-19 in lung cancer patients

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

negative: An Inverse Relationship between Hyperuricemia and Mortality in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis Background: The results have been inconsistent with regards to the impact of uric acid (UA) on clinical outcomes both in the general population and in patients with chronic kidney disease. The aim of this study was to study the influence of serum UA levels on mortality in patients undergoing continuous ambulatory peritoneal dialysis. Methods: Data on 492 patients from a single peritoneal dialysis unit were retrospectively analyzed. The mean age of the patients was 53.5 ± 15.3 years, with 52% being female (n = 255). The concomitant comorbidities at the start of continuous ambulatory peritoneal dialysis (CAPD) encompassed diabetes mellitus (n = 179, 34.6%), hypertension (n = 419, 85.2%), and cardiovascular disease (n = 186, 37.9%). The study cohort was divided into sex-specific tertiles according to baseline UA level. A Cox proportional hazard model was used to calculate hazard ratios (HRs) of all-cause, cardiovascular, and infection-associated mortality with adjustments for demographic and laboratory data, medications, and comorbidities. Results: Multivariate Cox regression analysis showed that, using UA tertile 1 as the reference, the adjusted HR of all-cause, cardiovascular, and infection-associated mortality for tertile 3 was 0.4 (95% confidence interval (CI) 0.24–0.68, p = 0.001), 0.4 (95% CI 0.2–0.81, p = 0.01), and 0.47 (95% CI 0.19–1.08, p = 0.1). In the fully adjusted model, the adjusted HRs of all-cause, cardiovascular, and infection-associated mortality for each 1-mg/dL increase in UA level were 0.84 (95% CI, 0.69–0.9, p = 0.07), 0.79 (95% CI, 0.61–1.01, p = 0.06), and 0.79 (95% CI, 0.48–1.21, p = 0.32) for men and 0.57 (95% CI, 0.44–0.73, p < 0.001), 0.6 (95% CI, 0.41–0.87, p = 0.006), and 0.41 (95% CI, 0.26–0.6, p < 0.001) for women, respectively. Conclusions: Higher UA levels are associated with lower risks of all-cause, cardiovascular and infection-associated mortality in women treated with continuous ambulatory peritoneal dialysis.

negative: MERS-CoV as an emerging respiratory illness: A review of prevention methods Abstract Introduction Middle East Respiratory Coronavirus Virus (MERS-CoV) first emerged from Saudi Arabia in 2012 and has since been recognized as a significant human respiratory pathogen on a global level. Methods In this narrative review, we focus on the prevention of MERS-CoV. We searched PubMed, Embase, Cochrane, Scopus, and Google Scholar, using the following terms: ‘MERS’, ‘MERS-CoV’, ‘Middle East respiratory syndrome’ in combination with ‘prevention’ or ‘infection control’. We also reviewed the references of each article to further include other studies or reports not identified by the search. Results As of Nov 2019, a total of 2468 laboratory-confirmed cases of MERS-CoV were diagnosed mostly from Middle Eastern regions with a mortality rate of at least 35%. A major outbreak that occurred outside the Middle East (in South Korea) and infections reported from 27 countries. MERS-CoV has gained recognition as a pathogen of global significance. Prevention of MERS-CoV infection is a global public health priority. Healthcare facility transmission and by extension community transmission, the main amplifier of persistent outbreaks, can be prevented through early identification and isolation of infected humans. While MERS-CoV vaccine studies were initially hindered by multiple challenges, recent vaccine development for MERS-CoV is showing promise. Conclusions The main factors leading to sustainability of MERS-CoV infection in high risk courtiers is healthcare facility transmission. MERS-CoV transmission in healthcare facility mainly results from laps in infection control measures and late isolation of suspected cases. Preventive measures for MERS-CoV include disease control in camels, prevention of camel to human transmission.

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

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

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

negative: Forecasting the Worldwide Spread of COVID-19 based on Logistic Model and SEIR Model Background: With the outbreak of coronavirus disease 2019 (COVID-19), a sudden case increase in late February 2020 led to deep concern globally. Italy, South Korea, Iran, France, Germany, Spain, the US and Japan are probably the countries with the most severe outbreaks. Collecting epidemiological data and predicting epidemic trends are important for the development and measurement of public intervention strategies. Epidemic prediction results yielded by different mathematical models are inconsistent; therefore, we sought to compare different models and their prediction results to generate objective conclusions. Methods: We used the number of cases reported from January 23 to March 20, 2020, to estimate the possible spread size and peak time of COVID-19, especially in 8 high-risk countries. The logistic growth model, basic SEIR model and adjusted SEIR model were adopted for prediction. Given that different model inputs may infer different model outputs, we implemented three model predictions with three scenarios of epidemic development. Results: When comparing all 8 countries short-term prediction results and peak predictions, the differences among the models were relatively large. The logistic growth model estimated a smaller epidemic size than the basic SERI model did; however, once we added parameters that considered the effects of public health interventions and control measures, the adjusted SERI model results demonstrated a considerably rapid deceleration of epidemic development. Our results demonstrated that contact rate, quarantine scale, and the initial quarantine time and length are important factors in controlling epidemic size and length. Conclusions: We demonstrated a comparative assessment of the predictions of the COVID-19 outbreak in eight high-risk countries using multiple methods. By forecasting epidemic size and peak time as well as simulating the effects of public health interventions, the intent of this paper is to help clarify the transmission dynamics of COVID-19 and recommend operation suggestions to slow down the epidemic. It is suggested that the quick detection of cases, sufficient implementation of quarantine and public self-protection behaviors are critical to slow down the epidemic.

negative: From plan to market in the health sector? China’s experience Abstract Countries worldwide confront the challenge of defining and achieving appropriate roles for government and market forces in the health sector. China—as both a developing and a transitional economy—represents an important case. This paper uses an international comparative perspective to examine how the health of China’s population and other aspects of health system performance changed during the reform era. We draw on standard public finance and health economics theory, as well as the more recent incomplete-contracting theory of property rights, to summarize the comparative advantages of government and market for financing and delivery of health services, particularly in developing and transitional economies. We then describe and analyze against this theoretical background the transformation of China’s health sector and recent commitment of government funds to move toward universal coverage.

negative: Epidemic spreading on activity-driven networks with attractiveness We study SIS epidemic spreading processes unfolding on a recent generalization of the activity-driven modeling framework. In this model of time-varying networks, each node is described by two variables: activity and attractiveness. The first describes the propensity to form connections, while the second defines the propensity to attract them. We derive analytically the epidemic threshold considering the time scale driving the evolution of contacts and the contagion as comparable. The solutions are general and hold for any joint distribution of activity and attractiveness. The theoretical picture is confirmed via large-scale numerical simulations performed considering heterogeneous distributions and different correlations between the two variables. We find that heterogeneous distributions of attractiveness alter the contagion process. In particular, in the case of uncorrelated and positive correlations between the two variables, heterogeneous attractiveness facilitates the spreading. On the contrary, negative correlations between activity and attractiveness hamper the spreading. The results presented contribute to the understanding of the dynamical properties of time-varying networks and their effects on contagion phenomena unfolding on their fabric.

negative: Acute Respiratory Distress Syndrome The acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in critically ill patients and is defined by the acute onset of noncardiogenic pulmonary edema, hypoxemia, and the need for mechanical ventilation. ARDS occurs most often in the setting of pneumonia, sepsis, aspiration of gastric contents or severe trauma, and is present in ~10% of all intensive care unit patients worldwide. Despite some improvements over the past decades, mortality remains high at 30–40% in most studies. Pathologic specimens from patients with ARDS most frequently reveal diffuse alveolar damage, and laboratory studies have demonstrated both alveolar epithelial and lung endothelial injury, resulting in accumulation of protein-rich inflammatory edema fluid in the alveolar space. Diagnosis is based on consensus syndromic criteria, with recent proposed modifications for under-resourced settings and for pediatric patients. Patient management focuses on implementing a lung-protective ventilation strategy; no specific pharmacotherapies have been identified. Long-term outcomes of patients with ARDS are increasingly recognized as important research targets, as many patients survive ARDS only to suffer ongoing functional and/or psychologic sequelae. Future directions include efforts to facilitate earlier recognition of ARDS, prognostic and/or predictive enrichment in clinical studies to identify responsive subsets, and ongoing efforts to understand fundamental mechanisms of lung injury that may respond to specific treatments.

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

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

negative: Temporal rise in the proportion of both younger adults and older adolescents among COVID-19 cases in Germany: evidence of lesser adherence to social distancing practices? BACKGROUND: There is uncertainty about the role of different age groups in propagating the SARS-CoV-2 epidemics in different countries, particularly under current social distancing practices. METHODS: We used the Robert Koch Institute data on weekly COVID-19 cases in different age groups in Germany. To minimize the effect of changes in healthcare seeking behavior (e.g. for older adults) and testing practices, we included the following eight 5-year age groups in the analyses: 10–14y through 45–49y. For each age group g, we considered the proportion PL(g) of individuals in age group g among all detected cases aged 10–49y during weeks 13–14, 2020 (later period), as well as corresponding proportion PE(g) for weeks 10–11, 2020 (early period), and defined the relative risk RR(g) for the age group g to be the ratio RR(g) = PL(g)/PE(g). For each pair of age groups g1, g2, a higher value of RR(g1) compared to RR(g2), or, alternatively, a value above 1 for the odds ratio OR(g1, g2) = RR(g1)/RR(g2) for a COVID-19 case to be in group g1 vs. g2 for the later vs. early periods is interpreted as the relative increase in the population incidence of SARS-Cov-2 in the age group g1 compared to g2 for the later vs. early period. RESULTS: The relative risk RR(g) was highest for individuals aged 20–24y (RR=1.4(95% CI (1.27,1.55))), followed by individuals aged 15–19y (RR=1.14(0.99,1.32)), aged 30–34y (RR=1.07(0.99,1.16)), aged 25–29y (RR= 1.06(0.98,1.15)), aged 35–39y (RR=0.95(0.87,1.03)), aged 40–44y (RR=0.9(0.83,0.98)), aged 45–49y (RR=0.83(0.77,0.89)) and aged 10–14y (RR=0.78(0.64,0.95)). For the age group 20–24y, the odds ratio relative to any other age group for a case to be during the later vs. early period was significantly above 1. For the age group 15–19y, the odds ratio relative to any other age group either above 35y or 10–14y for a case to be during the later vs. early period was significantly above 1. CONCLUSIONS: The observed relative increase with time in the prevalence of individuals aged 15–34y (particularly those aged 20–24y) among detected COVID-19 cases in Germany is unlikely to be explained by increases in the likelihood of seeking medical care or the likelihood of being tested for individuals in those age groups compared to individuals aged 35–49y or 10–14y, and should be indicative of the actual increase in the prevalence of individuals aged 15–34y among SARS-CoV-2 infections in the German population. That increase likely reflects elevated mixing among individuals aged 15–34y (particularly those aged 20–24y) compared to other age groups, possibly due to lesser adherence to social distancing practices.

negative: Using research to prepare for outbreaks of severe acute respiratory infection Severe acute respiratory infections (SARI) remain one of the leading causes of mortality around the world in all age groups. There is large global variation in epidemiology, clinical management and outcomes, including mortality. We performed a short period observational data collection in critical care units distributed globally during regional peak SARI seasons from 1 January 2016 until 31 August 2017, using standardised data collection tools. Data were collected for 1 week on all admitted patients who met the inclusion criteria for SARI, with follow-up to hospital discharge. Proportions of patients across regions were compared for microbiology, management strategies and outcomes. Regions were divided geographically and economically according to World Bank definitions. Data were collected for 682 patients from 95 hospitals and 23 countries. The overall mortality was 9.5%. Of the patients, 21.7% were children, with case fatality proportions of 1% for those less than 5 years. The highest mortality was in those above 60 years, at 18.6%. Case fatality varied by region: East Asia and Pacific 10.2% (21 of 206), Sub-Saharan Africa 4.3% (8 of 188), South Asia 0% (0 of 35), North America 13.6% (25 of 184), and Europe and Central Asia 14.3% (9 of 63). Mortality in low-income and low-middle-income countries combined was 4% as compared with 14% in high-income countries. Organ dysfunction scores calculated on presentation in 560 patients where full data were available revealed Sequential Organ Failure Assessment (SOFA) scores on presentation were significantly associated with mortality and hospital length of stay. Patients in East Asia and Pacific (48%) and North America (24%) had the highest SOFA scores of >12. Multivariable analysis demonstrated that initial SOFA score and age were independent predictors of hospital survival. There was variability across regions and income groupings for the critical care management and outcomes of SARI. Intensive care unit-specific factors, geography and management features were less reliable than baseline severity for predicting ultimate outcome. These findings may help in planning future outbreak severity assessments, but more globally representative data are required.

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

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

negative: 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: Pyogranulomatous panophthalmitis in a ferret

negative: An Invited Commentary on “World Health Organization declares global emergency: A review of the 2019 novel Coronavirus (COVID-19)": Emergency or new reality?

negative: In vitro mitogen responses and lymphocyte subpopulations in cheetahs Abstract Lack of genetic variability and apparent susceptibility of cheetahs (Acinonyx jubatus) to coronavirus infection has lead to speculation that this species may have immune system deficits. To establish a foundation for evaluation of the immune function, cheetah peripheral blood mononuclear cells (PBM) were stimulated by a panel of six mitogens, and responses compared with those of domestic cat PBM. Individual responses in both species were variable, but evenly distributed throughout the range of stimulation for each mitogen. Proliferation by PBM from domestic cats occured within the same range as that of the cheetahs. However, a significantly lower response to peanut agglutinin (PNA) was observed with domestic cat PBM. Although responses varied between animals, certain individual cheetahs were consistent responders. The decreased values could not be explained by lack of IL-2 responsiveness since exogenous IL-2 significantly enhanced mitogen-stimulated proliferation in 11 of 12 cheetahs tested. The phenotypic distribution of domestic cat and cheetah lymphocyte subpopulations was similar as assessed by immunofluorescence staining for surface immunoglobulin (sIg) and cytotoxic T (Tc) cells (using a specific monoclonal antibody, FT2). Values for B cells (31.2% sIg+) and Tc (28.7% FT2 +) were slightly higher in domestic cats as compared with cheetah PBM (13.3% sIg+; 19.0% FT2+). Even though no species-specific deficits were detected, a significant negative correlation between PHA-stimulated proliferation and percent FT2+ (Tc) cheetah cells was observed. This indicates that proliferation can be used indirectly to assess relative numbers of functional T helper cells in cheetahs. Our studies suggest that these aspects of the cheetah's immune system are comparable with the domestic cat, and establish a basis for in vitro assays evaluating antigen-specific responses.

negative: Severe acute respiratory syndrome coronavirus 19 and human pregnancy

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: 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: Gender difference in knowledge of tuberculosis and associated health-care seeking behaviors: a cross-sectional study in a rural area of China BACKGROUND: Tuberculosis (TB) detection under the national TB control program in China follows passive case-finding guidelines, which could be influenced by the accessibility of health service and patient's health-care seeking behaviors. One intriguing topic is the correlation between men and women's knowledge on TB and their health-care seeking behaviors. METHODS: Two cross-sectional studies were separately carried out in Yangzhong County, a rural area of China. One study, by using systematic sampling method, including 1,200 subjects, was conducted to investigate the TB knowledge among general population. Another study in the same source population screened 33,549 people aged 15 years or over among 20 stratified cluster-sampled villages for identifying prolonged cough patients at households and individual interviews were then carried out. Gender difference in the knowledge of TB and health-care seeking behaviors was analyzed particularly. RESULTS: Among general population, only 16.0% (men 17.1% vs. women 15.0%) knew the prolonged cough with the duration of 3 weeks or longer was a symptom for suspicious TB. Fewer women than men knew the local appointed health facility for TB diagnosis and treatment as well as the current free TB service policy. Moreover, women were less likely to learn information about TB and share it with others on their own initiatives. On the contrary, after the onset of the prolonged cough, women (79.2%) were more likely to seek health-care than men (58.6%) did. However, a large part of women preferred to visit the lower level non-hospital health facilities at first such as village clinics and drugstores. CONCLUSION: TB and DOTS program were not well known by rural Chinese. Gender issues should be considered to reduce diagnostic delay of TB and improve both men and women's access to qualified health facility for TB care. Strengthening awareness of TB and improving the accessibility of health-care service is essential in TB control strategy, especially under the current vertical TB control system.

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

negative: Octogenarians with blunt splenic injury: not all geriatrics are the same Geriatric trauma patients (GTP) (age ≥ 65 years) with blunt splenic injury (BSI) have up to a 6% failure rate of non-operative management (NOM). GTPs failing NOM have a similar mortality rate compared to GTPs managed successfully with NOM. However, it is unclear if this remains true in octogenarians (aged 80–89 years). We hypothesized that the failure rate for NOM in octogenarians would be similar to their younger geriatric cohort, patients aged 65–79 years; however risk of mortality in octogenarians who fail NOM would be higher than that of octogenarians managed successfully with NOM. The Trauma Quality Improvement Program (2010–2016) was queried for patients with BSI. Those undergoing splenectomy within 6 h were excluded to select for patients undergoing NOM. Patients aged 65–79 years (young GTPs) were compared to octogenarians. A multivariable logistic regression model was used to determine the risk for failed NOM and mortality. From 43,041 BSI patients undergoing NOM, 3660 (8.5%) were aged 65–79 years and 1236 (2.9%) were octogenarians. Both groups had a similar median Injury Severity Score (ISS) (p = 0.10) and failure rate of NOM (6.6% young GTPs vs. 6.8% octogenarians p = 0.82). From those failing NOM, octogenarians had similar units of blood products transfused (p > 0.05) and a higher mortality rate (40.5% vs. 18.2%, p < 0.001), compared to young GTPs. Independent risk factors for failing NOM in octogenarians included ≥ 1 unit of packed red blood cells (PRBC) (p = 0.039) within 24 h of admission. Octogenarians who failed NOM had a higher mortality rate compared to octogenarians managed successfully with NOM (40.5% vs 23.6% p = 0.001), which persisted in a multivariable logistic regression analysis (OR 2.25, CI 1.37–3.70, p < 0.001). Late failure of NOM ≥ 24 h (vs. early failure) was not associated with increased risk of mortality (p = 0.88), but ≥ 1 unit of PRBC transfused had higher risk (OR 1.88, CI 1.20–2.95, p = 0.006). Compared to young GTPs with BSI, octogenarians have a similar rate of failed NOM. Octogenarians with BSI who fail NOM have over a twofold higher risk of mortality compared to those managed successfully with NOM. PRBC transfusion increases risk for mortality. Therefore, clinicians should consider failure of NOM earlier in the octogenarian population to mitigate the risk of increased mortality.

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

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

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

negative: New Epidemiological and Clinical Signatures of 18 Pathogens from Respiratory Tract Infections Based on a 5-Year Study BACKGROUND: Respiratory tract infections (RTIs) are a heavy burden on society. However, due to the complex etiology of RTIs, the clinical diagnosis, treatment, and prevention of these infections remain challenging, especially in developing countries. METHODS: To determine the epidemiological and clinical characteristics of 18 respiratory pathogens, we analyzed 12,502 patients with acute respiratory infections (ARIs) by performing polymerase chain reaction (PCR) on patient pharyngeal swabs. RESULTS: Samples positive for at least 1 pathogen were obtained from 48.42% of the total patients. Of these pathogen-positive patients, 17.99% were infected with more than 1 pathogen. Of the 18 pathogens analyzed, four were detected with a positive detection rate (PDR) > 5%: influenza A virus (IAV) > respiratory syncytial virus (RSV) >Mycoplasma pneumoniae (MP) > human coronavirus (HCoV). The pathogens with the 4 highest co-infection rates (CIRs) were as follows: HCoV > human bocavirus (HBoV) > enterovirus (EV) > parainfluenza virus (PIV). The overall positive detection rate (PDR) varied significantly according to patient age, the season and year of detection, and the disease subgroup, but not according to patient sex. The individual PDRs of the pathogens followed 3 types of distributions for patient sex, 4 types of distributions for patient age, 4 types of seasonal distributions, 2 types of seasonal epidemic trends, 4 types of yearly epidemic trends, and different susceptibility distributions in the disease subgroups. Additionally, the overall CIR showed significantly different distributions according to patient sex, patient age, and the disease subgroup, whereas the CIRs of individual pathogens suggested significant preference characteristics. CONCLUSION: IAV remains the most common pathogen among the pathogens analyzed. More effort should be directed toward the prevention and control of pathogens that show a trend of increasing incidence such as HCoV, human adenovirus (ADV), and RSV. Although clinically distinguishing specific pathogens responsible for RTIs is difficult, the epidemiological and clinical characteristics of the various RTI-causing agents could provide clues for clinicians, thereby informing decisions regarding prevention and medication and guiding appropriate public health strategies.

negative: Application and optimization of RT-PCR in diagnosis of SARS-CoV-2 infection Background: Coronavirus Disease 2019 (COVID-19) caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global threat to public health. Aiming to construct an efficient screening pattern, we comprehensively evaluated the performances of RT-PCR and chest CT in diagnosing COVID-19. Methods: The records including demographics, RT-PCR, and CT from 87 confirmed COVID-19 cases and 481 exclusion cases were collected. The diagnostic accuracy of the pharyngeal swab RT-PCR, CT, combination with the second pharyngeal swab RT-PCR or with CT were evaluated individually. Besides, all the stool RT-PCR results were plotted by time to explore the value of stool RT-PCR. Findings: Combination of RT-PCR and CT has the higher sensitivity (91.9%,79/86) than RT-PCR alone (78.2%，68/87) or CT alone (66.7%, 54 of 81) or combination of two RT-PCR tests (86.2%,75/87). There was good agreement between RT-PCR and CT (kappa-value, 0.430). In 34 COVID-19 cases with inconsistent results, 94.1% (n=32) are mild infection, 62.5% of which (20/32) showed positive RT-PCR. 46.7% (35/75) COVID-19 patients had at least one positive stool during the course. Two cases had positive stool earlier than the pharyngeal swabs. Importantly, one patient had consecutive positive stool but negative pharyngeal swabs. Interpretation: Combination of RT-PCR and CT with the highest sensitivity is an optimal pattern to screen COVID-19. RT-PCR is superior to CT in diagnosing mild infections. Stool RT-PCR should be considered as an item for improving discovery rate and hospital discharge. This study shed light for optimizing scheme of screening and monitoring of SARS-CoV-2 infection.

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

negative: Hydroxychloroquine as antiviral prophylaxis for exposed caregivers to Covid-19: An urgent appraisal is needed BACKGROUND: Since the onset of the new coronavirus pandemic, the world is facing a public health emergency. Repositioning hydroxychloroquine (HQ) seems to be a promising option. Many emerging evidences have converged on the effectiveness of HQ in the treatment of Covid-19 infection. In a recent paper, Gautret et al. suggested that further works are needed to determine if HQ antiviral prophylaxis is useful, especially for healthcare workers. METHODS: The purpose of this paper is to assess the Covid-19 exposure and risks level among caregivers. For this, we performed research on internet and PubMed by crossing the following keywords: healthcare givers, healthcare workers, doctors, nurses, coronavirus, Covid-19, mortality, infection rate, chloroquine, hydroxychloroquine. RESULTS: Data on healthcare worker's infection and mortality by Covid-19 are partial and are not systematically published. However, it seems that the infection rate varies between 3.8% and 9% depending on the country. Moreover, the mean age of this population is relatively old, especially in the OECD area. CONCLUSIONS: Anti-Covid-19 HQ prophylaxis should be urgently accessed, especially for healthcare workers. It is to be hoped that HQ prophylaxis reduces the morbidity and mortality from Covid-19 infection among this population which is particularly exposed and relatively old.

negative: Recognition of Functional Sites in Protein Structures Abstract Recognition of regions on the surface of one protein, that are similar to a binding site of another is crucial for the prediction of molecular interactions and for functional classifications. We first describe a novel method, SiteEngine, that assumes no sequence or fold similarities and is able to recognize proteins that have similar binding sites and may perform similar functions. We achieve high efficiency and speed by introducing a low-resolution surface representation via chemically important surface points, by hashing triangles of physico-chemical properties and by application of hierarchical scoring schemes for a thorough exploration of global and local similarities. We proceed to rigorously apply this method to functional site recognition in three possible ways: first, we search a given functional site on a large set of complete protein structures. Second, a potential functional site on a protein of interest is compared with known binding sites, to recognize similar features. Third, a complete protein structure is searched for the presence of an a priori unknown functional site, similar to known sites. Our method is robust and efficient enough to allow computationally demanding applications such as the first and the third. From the biological standpoint, the first application may identify secondary binding sites of drugs that may lead to side-effects. The third application finds new potential sites on the protein that may provide targets for drug design. Each of the three applications may aid in assigning a function and in classification of binding patterns. We highlight the advantages and disadvantages of each type of search, provide examples of large-scale searches of the entire Protein Data Base and make functional predictions.

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: Global Economic Cost of Deaths Attributable to Ambient Air Pollution: Disproportionate Burden on the Ageing Population Summary Background The health impacts of ambient air pollution impose large costs on society. While all people are exposed to air pollution, older individuals tend to be disproportionally affected. As a result, there is growing concern about the public health impacts of air pollution as many countries undergo rapid population ageing. We investigated the spatial and temporal variation in the health economic cost of deaths attributable to ambient air pollution, and its interaction with population ageing from 2000 to 2016 at global and regional levels. Methods We developed an age-adjusted measure of the value of a statistical life year (VSLY) to estimate the health economic cost attributable to ambient PM2.5 pollution using the Global Burden of Disease 2017 data and country-level socioeconomic information. First, we estimated the global age- and cause-specific mortality and years of life lost (YLL) attributable to PM2.5 pollution using the global exposure mortality model (GEMM) and global estimates of exposure derived from ground monitoring, satellite retrievals and chemical transport model simulations at 0.1 by 0.1 degree (~11 km at the equator) resolution. Second, for each year between 2000 and 2016, we translated the YLL within each age-group into a health-related economic cost using a country-specific, age-adjusted measure of VSLY. Third, we decomposed the major driving factors that contributed to the temporal change in health costs related to PM2.5. Finally, we conducted a sensitivity test to analyze the variability of the estimated health costs to four alternative valuation measures. We identified the uncertainty intervals (UIs) from 1000 draws of the parameters and exposure-response functions by age, cause, country and year. All economic values are reported in 2011 purchasing-power-parity-adjusted US dollars. Findings Globally, 8.42 million (95% UI: 6.50, 10.52) deaths and 163.68 million (116.03, 219.44) YLL were attributable to ambient PM2.5 in 2016. The average attributable mortality for the older population was 12 times higher than for those younger than 60 years old. In 2016, the global health economic cost of ambient PM2.5 pollution for the older population was US$2.40 trillion (1.89, 2.93) accounting for 59% of the cost for the total population. The health cost for the older population alone was equivalent to 2.1% (1.7%, 2.6%) of global gross domestic product (GDP) in 2016. While the economic cost per capita for the older population was US$2739 (2160, 3345) in 2016, the cost per capita for the younger population was only US$268 (205, 335). From 2000 to 2016, the annual global health economic cost for the total population increased from US$2.37 trillion (1.88, 2.87) to US$4.09 trillion (3.19, 5.05). Decomposing the factors that contributed to the rise in health economic costs, we found that increases in GDP per capita, population ageing, population growth, age-specific mortality reduction, and PM2.5 exposure changed the total health economic cost by 77%, 21.2%, 15.6%, -41.1% and -0.2%, respectively. Compared to using an age-invariant VSLY or an age-invariant value of a statistical life (VSL), the estimates of the older population share of the total health economic cost using an age-adjusted VSLY was 2 and 18 percentage points lower, respectively. Interpretation The health economic cost borne by the older population almost doubled between 2000 and 2016, driven primarily by GDP growth, population ageing and population growth. Compared to younger individuals, air pollution leads to disproportionately higher health costs amongst the older population, even after accounting for their relatively shorter remaining life expectancy and increased disability. The age-specific estimates of health economic cost inform the optimal design of air pollution reduction strategies and allocation of healthcare resources. The positive relationship between age and economic costs suggests that countries with severe air pollution and rapid aging rates would particularly benefit from improving their air quality. In addition, strategies aimed at enhancing healthcare services, especially for the older population, may be beneficial for reducing the costs of ambient air pollution.

negative: HIV/SARS-CoV-2 co-infected patients in Istanbul, Turkey. In December 2019, the causative agent of Coronavirus disease 2019 (COVID-19) was identified and named as SARS-CoV-2. Since then it has been spreading and severe form of the illness predominantly occurs in adults with advanced age or underlying comorbidities. The European AIDS Clinical Society states the lack of evidence for a higher COVID-19 infection rate among people living with HIV (PLHIV) and there is a few published literature on the course of COVID-19 co-infection in PLHIV. We described four HIV/SARS-CoV-2 co-infected patients with different characteristics. The impression is that comorbidities is an important factor in mortality in HIV/SARS-CoV-2 co-infected cases. This article is protected by copyright. All rights reserved.

negative: The prevalence of antibodies to SARS-CoV-2 among blood donors in China Objectives The prevalence of antibodies to SARS-CoV-2 among blood donors in China remains unknown. To reveal the missing information, we investigated the seroprevalence of SARS-CoV-2 antibodies among blood donors in the cities of Wuhan, Shenzhen, and Shijiazhuang of China. Design Cross-sectional study Setting Three blood centers, located in the central, south and north China, respectively, recruiting from January to April 2020. Participants 38,144 healthy blood donors donated in Wuhan, Shenzhen and Shijiazhuang were enrolled, who were all met the criteria for blood donation during the COVID-19 pandemic in China. Main outcome measures Specific antibodies against SARS-CoV-2 including total antibody (TAb), IgG antibody against receptor-binding domain of spike protein (IgG-RBD) and nucleoprotein (IgG-N), and IgM. Pseudotype lentivirus-based neutralization test was performed on all TAb-positive samples. In addition, anonymous personal demographic information, including gender, age, ethnicity, occupation and educational level, and blood type were collected. Results A total of 519 samples from 410 donors were confirmed by neutralization tests. The SARS-CoV-2 seroprevalence among blood donors was 2.29% (407/17,794, 95%CI: 2.08% to 2.52%) in Wuhan, 0.029% (2/6,810, 95%CI: 0.0081% to 0.11%) in Shenzhen, and 0.0074% (1/13,540, 95%CI: 0.0013% to 0.042%) in Shijiazhuang, respectively. The earliest emergence of SARS-CoV-2 seropositivity in blood donors was identified on January 20, 2020 in Wuhan. The weekly prevalence of SARS-CoV-2 antibodies in Wuhan's blood donors changed dynamically and were 0.08% (95%CI: 0.02% to 0.28%) during January 15 to 22 (before city lockdown), 3.08% (95%CI: 2.67% to 3.55%) during January 23 to April 7 (city quarantine period) and 2.33% (95%CI: 2.06% to 2.63%) during April 8 to 30 (after lockdown easing). Female and older-age were identified to be independent risk factors for SARS-CoV-2 seropositivity among donors in Wuhan. Conclusions The prevalence of antibodies to SARS-CoV-2 among blood donors in China was low, even in Wuhan city. According to our data, the earliest emergence of SARS-CoV-2 in Wuhan's donors should not earlier than January, 2020. As most of the population of China remained uninfected during the early wave of COVID-19 pandemic, effective public health measures are still certainly required to block viral spread before a vaccine is widely available.

negative: Generation of Recombinant Coronaviruses Using Vaccinia Virus as the Cloning Vector and Stable Cell Lines Containing Coronaviral Replicon RNAs Coronavirus reverse genetic systems have become valuable tools for studying the molecular biology of coronavirus infections. They have been applied to the generation of recombinant coronaviruses, selectable replicon RNAs, and coronavirus-based vectors for heterologous gene expression. Here we provide a collection of protocols for the generation, cloning, and modification of full-length coronavirus cDNA using vaccinia virus as a cloning vector. Based on cloned coronaviral cDNA, we describe the generation of recombinant coronaviruses and stable cell lines containing coronaviral replicon RNAs. Initially, the vaccinia virus-based reverse genetic system was established for the generation of recombinant human coronavirus 229E. However, it is also applicable to the generation of other coronaviruses, such as the avian infectious bronchitis virus, mouse hepatitis virus, and SARS coronavirus.

negative: Extracorporeal Membrane Oxygenation as Treatment of Severe COVID-19 Infection: A Case Report Novel coronavirus 2019 (COVID-19) is a severe respiratory infection leading to acute respiratory distress syndrome (ARDS) accounting for thousands of cases and deaths across the world. Several alternatives in treatment options have been assessed and used in this patient population. However, when mechanical ventilation and prone positioning are unsuccessful, venovenous extracorporeal membrane oxygenation (VV-ECMO) may be used. We present a case of a 41-year-old female, with no significant medical history and no recent history of exposure to sick contacts, presented to the emergency department (ED) with fever, severe shortness of breath, and flu-like symptoms with a positive COVID-19 test. Ultimately, she worsened on mechanical ventilation and prone positioning and required VV-ECMO. The use of VV-ECMO in COVID-19 infected patients is still controversial. While some studies have shown a high mortality rate despite aggressive treatment, such as in our case, the lack of large sample size studies and treatment alternatives places healthcare providers against a wall without options in patients with severe refractory ARDS due to COVID-19.

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

negative: Middle East respiratory syndrome coronavirus in Al-Madinah City, Saudi Arabia: Demographic, clinical and survival data Abstract Background Middle East respiratory syndrome coronavirus (MERS-CoV), is an emerging virus respiratory infection. It has a high mortality rate and a wide spectrum of clinical features. This study describes the clinical characteristics and outcome of MERS infected patients. Methods A retrospective study was conducted of all confirmed MERS-CoV infections from March 2014 to May 2014 at two tertiary care hospitals in Al-Madinah region (Saudi Arabia). We gathered data about demographic, clinical presentation, and factors associated with severity and mortality. Results A total of 29 cases were identified; 20 males (69%) and nine females (31%), age 45±12years. The death rate was higher for men (52%) than for women (23%). Initial presentation was fever in 22 (75%) cases, cough in 20 (69%) cases, and shortness of breath in 20 (69%) cases. Associated comorbidities were diabetes mellitus in nine (31%) patients and chronic kidney disease (CKD) in eight (27%) patients. Duration of symptoms before hospitalization ranged from 2.9days to 5days. Elevated liver enzymes were present in 14 (50%) patients and impaired renal profile present in eight (27%) patients. We also describe in this study radiological patterns and factors associated with mortality. Conclusion MERS-CoV infection transmission continues to occur as clusters in healthcare facilities. The frequency of cases and deaths is higher among men than women and among patients with comorbidities.

negative: Evaluations of serological test in the diagnosis of 2019 novel coronavirus (SARS-CoV-2) infections during the COVID-19 outbreak The ongoing SARS-CoV-2 outbreak has killed over twenty-one thousand and sickened over four hundred thousand people worldwide, posing a great challenge to global public health. A sensitive and accurate diagnosis method will substantially help to control disease expansion. Here, we developed a chemiluminescence-immunoassay method based on the recombinant nucleocapsid antigen and the magnetic beads for diagnosis of SARS-CoV-2 infections and surveillance of antibody changing pattern. Serums from 29 healthy individuals, 51 tuberculosis patients, and 79 SARS-CoV-2 confirmed patients were employed to evaluate the performance of this approach. Compared to the IgM testing, the IgG testing was more reliable in which it identified 65 SARS-CoV-2 infections from the 79 confirmed patients and only two false-positive cases from the 80 control group with a sensitivity and specificity reaching 82.28% and 97.5%, respectively. However, only a slight difference (not statistically significant) in the detected cases of SARS-CoV-2 infections was observed between the IgM and IgG testing manner in patients at a different time of onset of disease. A performance comparison between an ELISA kit using the same nucleocapsid antigen and our chemiluminescence method was undertaken. The same false-positive cases were seen in both methods from the paired control group, while ELISA kit can only detect half of the SARS-CoV-2 infections from paired SARS-CoV-2 confirmed patients group than that of the chemiluminescence method, indicating a higher performance for the chemiluminescence-immunoassay approach. Together, our studies provide a useful and valuable serological testing tool for the diagnosis of SARS-CoV-2 infections in the community.

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

negative: siRNA for Influenza Therapy Influenza virus is one of the most prevalent and ancient infections in humans. About a fifth of world’s population is infected by influenza virus annually, leading to high morbidity and mortality, particularly in infants, the elderly and the immunocompromised. In the US alone, influenza outbreaks lead to roughly 30,000 deaths each year. Current vaccines and anti-influenza drugs are of limited use due to high mutation rate of the virus and side effects. In recent years, RNA interference, triggered by synthetic short interfering RNA (siRNA), has rapidly evolved as a potent antiviral regimen. Properly designed siRNAs have been shown to function as potent inhibitors of influenza virus replication. The siRNAs outperform traditional small molecule antivirals in a number of areas, such as ease of design, modest cost, and fast turnaround. Although specificity and tissue delivery remain major bottlenecks in the clinical applications of RNAi in general, intranasal application of siRNA against respiratory viruses including, but not limited to influenza virus, has experienced significant success and optimism, which is reviewed here.

negative: Respiratory Viral Infections in Solid Organ and Hematopoietic Stem Cell Transplantation Respiratory viruses are common in solid organ and hematopoietic stem cell transplant recipients and a recognized cause of significant morbidity and mortality. Epidemiology, risk factors, and attributable mortality in both populations are reviewed. In addition, virus-specific prevention and treatment options, including emerging investigational therapies, are discussed for respiratory syncytial virus, influenza, adenovirus, parainfluenza, and other respiratory viruses.

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

negative: Risk stratification protocol to reduce consumption of personal protective equipment for emergency surgeries during COVID-19 pandemic.

negative: Epidemiology of Sarcoidosis Sarcoidosis is a multisystemic disease in which lung involvement is common. Its incidence and prevalence have been extensively studied, but with contradictory results because of the lack of standard diagnostic criteria, variations in the methods for detecting cases, and the low sensitivity and specificity of diagnostic tests. Prognosis is generally favorable. Many of those affected remain asymptomatic and remission often occurs spontaneously, although between 10% and 30% of the patients have chronic disease and permanent deterioration in lung function. Sarcoidosis is caused by an external agent that triggers a characteristic immune response in genetically susceptible individuals. Environmental, occupational, and genetic factors have all been implicated, but research is still in the early stages. Case-control studies, as well as advances in molecular biology, will help to identify genetic susceptibility factors and to understand the different phenotypes of sarcoidosis.

negative: 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.

negative: The effect of public health measures on the 1918 influenza pandemic in U.S. cities. During the 1918 influenza pandemic, the U.S., unlike Europe, put considerable effort into public health interventions. There was also more geographic variation in the autumn wave of the pandemic in the U.S. compared with Europe, with some cities seeing only a single large peak in mortality and others seeing double-peaked epidemics. Here we examine whether differences in the public health measures adopted by different cities can explain the variation in epidemic patterns and overall mortality observed. We show that city-specific per-capita excess mortality in 1918 was significantly correlated with 1917 per-capita mortality, indicating some intrinsic variation in overall mortality, perhaps related to sociodemographic factors. In the subset of 23 cities for which we had partial data on the timing of interventions, an even stronger correlation was found between excess mortality and how early in the epidemic interventions were introduced. We then fitted an epidemic model to weekly mortality in 16 cities with nearly complete intervention-timing data and estimated the impact of interventions. The model reproduced the observed epidemic patterns well. In line with theoretical arguments, we found the time-limited interventions used reduced total mortality only moderately (perhaps 10-30%), and that the impact was often very limited because of interventions being introduced too late and lifted too early. San Francisco, St. Louis, Milwaukee, and Kansas City had the most effective interventions, reducing transmission rates by up to 30-50%. Our analysis also suggests that individuals reactively reduced their contact rates in response to high levels of mortality during the pandemic.

negative: SARS-CoV-2 epidemiology and control, different scenarios for Turkey BACKGROUND/AIM: Coronavirus Infectious Disease 2019 (COVID-19) is now a pandemic spreading in most countries including Turkey. MATERIALS AND METHODS: The current knowledge of COVID-19 and the virus causing it, SARS-CoV-2, was reviewed. The epidemiology and control in different countries was compared and the differences discussed. RESULTS: The population attack rates and case fatality rates vary from country to country with Lombardy in northern Italy reporting an attack rate in the general population of 0.37% compared to 0.004% in Hong Kong. The differences are caused by different testing strategies and reporting systems. CONCLUSION: Turkey is early in the outbreak. Different control strategies are available with South Korea, Hong Kong and Singapore being models to follow.

negative: Mathematical Models for Describing and Predicting the COVID-19 Pandemic Crisis The present article studies the extension of two deterministic models for describing the novel coronavirus pandemic crisis, the SIR model and the SEIR model. The models were studied and compared to real data in order to support the validity of each description and extract important information regarding the pandemic, such as the basic reproductive number R0, which might provide useful information concerning the rate of increase of the pandemic predicted by each model. We next proceed to making predictions and comparing more complex models derived from the SEIR model with the SIRD model, in order to find the most suitable one for describing and predicting the pandemic crisis. Aiming to answer the question if the simple SIRD model is able to make reliable predictions and deliver suitable information compared to more complex models.

negative: Dairy Calf Pneumonia The Disease and Its Impact The author discusses the syndrome of respiratory disease in dairy calves, reviewing the disease and the causative agents. Attention is given to the epidemiology of the disease with discussion of morbidity, mortality, proportionate mortality and risk factors associated with dairy calf pneumonia. The economic impact of dairy calf pneumonia is discussed in detail and management options for calf rearing are suggested.

negative: Targeting Coronaviral Replication and Cellular JAK2 Mediated Dominant NF-κB Activation for Comprehensive and Ultimate Inhibition of Coronaviral Activity Tylophorine-based compounds exert broad spectral, potent inhibition of coronaviruses. NF-κB activation is a common pro-inflammatory response of host cells to viral infection. The aims of this study were to (i) find an effective combination treatment for coronaviral infections through targeting of the virus per se and cellular NF-κB activity; and (ii) to study the underling mechanisms. We found that tylophorine-based compounds target the TGEV viral RNA and effectively inhibit TGEV replication. NF-κB inhibition also leads to anti-TGEV replication. NF-κB activation induced by TGEV infection was found to be associated with two convergent pathways, IKK-2_IκBα/p65 and JAK2 mediated p65 phosphorylation, in swine testicular cells. JAK2 inhibition either by CYT387 (a JAK family inhibitor) or by silencing JAK2-expression revealed a dominant JAK2 mediated p65 phosphorylation pathway for NF-κB activation and resulted in NF-κB inhibition, which overrode the IκBα regulation via the IKK-2. Finally, tylophorine-based compounds work cooperatively with CYT387 to impart comprehensive anti-TGEV activities. The combination treatment, wherein a tylophorine compound targets TGEV and a JAK2 inhibitor blocks the alternative dominant NF-κB activation mediated by JAK2, is more effective and comprehensive than either one alone and constitutes a feasible approach for the treatment of SARS-CoV or MERS-CoV.

negative: The Impact of Matching Vaccine Strains and Post-SARS Public Health Efforts on Reducing Influenza-Associated Mortality among the Elderly Public health administrators do not have effective models to predict excess influenza-associated mortality and monitor viral changes associated with it. This study evaluated the effect of matching/mismatching vaccine strains, type/subtype pattern changes in Taiwan's influenza viruses, and the impact of post-SARS (severe acute respiratory syndrome) public health efforts on excess influenza-associated mortalities among the elderly. A negative binomial model was developed to estimate Taiwan's monthly influenza-associated mortality among the elderly. We calculated three winter and annual excess influenza-associated mortalities [pneumonia and influenza (P&I), respiratory and circulatory, and all-cause] from the 1999–2000 through the 2006–2007 influenza seasons. Obtaining influenza virus sequences from the months/years in which death from P&I was excessive, we investigated molecular variation in vaccine-mismatched influenza viruses by comparing hemagglutinin 1 (HA1) of the circulating and vaccine strains. We found that the higher the isolation rate of A (H3N2) and vaccine-mismatched influenza viruses, the greater the monthly P&I mortality. However, this significant positive association became negative for higher matching of A (H3N2) and public health efforts with post-SARS effect. Mean excess P&I mortality for winters was significantly higher before 2003 than after that year [mean ± S.D.: 1.44±1.35 vs. 0.35±1.13, p = 0.04]. Further analysis revealed that vaccine-matched circulating influenza A viruses were significantly associated with lower excess P&I mortality during post-SARS winters (i.e., 2005–2007) than during pre-SARS winters [0.03±0.06 vs. 1.57±1.27, p = 0.01]. Stratification of these vaccine-matching and post-SARS effect showed substantial trends toward lower elderly excess P&I mortalities in winters with either mismatching vaccines during the post-SARS period or matching vaccines during the pre-SARS period. Importantly, all three excess mortalities were at their highest in May, 2003, when inter-hospital nosocomial infections were peaking. Furthermore, vaccine-mismatched H3N2 viruses circulating in the years with high excess P&I mortality exhibited both a lower amino acid identity percentage of HA1 between vaccine and circulating strains and a higher numbers of variations at epitope B. Our model can help future decision makers to estimate excess P&I mortality effectively, select and test virus strains for antigenic variation, and evaluate public health strategy effectiveness.

negative: Ecosystem approaches to the risk for schizophrenia

negative: Case report: A kidney transplant patient with mild COVID‐19 Coronavirus Disease 2019 (COVID‐19) is currently a pandemic with a mortality rate of 1%‐6% in the general population. However, the mortality rate seems to be significantly higher in elderly patients, especially those hospitalized with comorbidities, such as hypertension, diabetes, or coronary artery diseases. Because viral diseases may have atypical presentations in immunosuppressed patients, the course of the disease in the transplant patient population is unknown. Hence, the management of these patients with COVID‐19 is an area of interest, and a unique approach is warranted. Here, we report the clinical features and our treatment approach for a kidney transplant patient with a diagnosis of COVID‐19. We believe that screening protocols for SARS‐Cov‐2 should be re‐evaluated in patients with solid‐organ transplants.

negative: Recommendations on management of the SARS-CoV-2 coronavirus pandemic (Covid-19) in kidney transplant patients Abstract The SARS-CoV-2 (Covid-19) coronavirus pandemic is evolving very quickly and means a special risk for both immunosuppressed and comorbid patients. Knowledge about this growing infection is also increasing although many uncertainties remain, especially in the kidney transplant population. This manuscript presents a proposal for action with general and specific recommendations to protect and prevent infection in this vulnerable population such as kidney transplant recipients.

negative: Explaining the Neolithic Demographic Transition Three main questions are raised in this chapter. 1. The part of the signal of the NDT which is demographically identifiable, based on the proportion of the immature skeletons in cemeteries, shows that a baby-boom occurred and, beyond that, with the onset of the change in the economic system, a fertility transition towards high values also occurred. What was the biodemographic cause of this fertility explosion, beyond the proxy variable represented by sedentarism? The cause is a major shift in the maternal energetics of farming communities relative to mobile foragers. In the energy balance there was (i) on the intake side, an underlying trend towards a reduction in low-calorie food from hunting and fishing, and a correlative increase in high-calorie food from agriculture, (ii) on the expenditure side, a reduction in the physical energy devoted to mobility and the maternal stress of child transportation. 2. The NDT is detectable from a signal representing a fertility transition, but the transition relating to mortality is missing and must be inferred. If, during the fertility transition, mortality had remained the same as in the preceding forager period, then the population would have grown infinitely. The assumption of unchanged mortality during the entire fertility transition is therefore not realistic. Mortality, in its turn, must have begun to rise well before the end of the fertility transition. But when? Why? One of the answers consists of a model where, except at the start of the process, birth and mortality rates rise more or less simultaneously, bringing about a typical rate of increase for pre-industrial populations of slightly above zero. 3. According to the level and speed of the population growth, what should we expect in terms of population structure? What are the expected effects of this growth, not only on the population in numbers but also on age distribution, the distribution and structure of families, the distribution of households and on family systems?

negative: HIV protease inhibitor nelfinavir inhibits replication of SARS-associated coronavirus Abstract A novel coronavirus has been identified as an etiological agent of severe acute respiratory syndrome (SARS). To rapidly identify anti-SARS drugs available for clinical use, we screened a set of compounds that included antiviral drugs already in wide use. Here we report that the HIV-1 protease inhibitor, nelfinavir, strongly inhibited replication of the SARS coronavirus (SARS-CoV). Nelfinavir inhibited the cytopathic effect induced by SARS-CoV infection. Expression of viral antigens was much lower in infected cells treated with nelfinavir than in untreated infected cells. Quantitative RT-PCR analysis showed that nelfinavir could decrease the production of virions from Vero cells. Experiments with various timings of drug addition revealed that nelfinavir exerted its effect not at the entry step, but at the post-entry step of SARS-CoV infection. Our results suggest that nelfinavir should be examined clinically for the treatment of SARS and has potential as a good lead compound for designing anti-SARS drugs.

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: COVID-19 Policies can Perpetuate Violence Against Transgender Communities: Insights from Peru

negative: Cardiovascular disease and COVID-19: les liaisons dangereuses Patients with cardiovascular risk factors or established cardiovascular disease have an increased risk of developing coronavirus disease 19 and have a worse outcome when infected, but translating this notion into effective action is challenging. At present it is unclear whether cardiovascular therapies may reduce the likelihood of infection, or improve the survival of infected patients. Given the crucial importance of this issue for clinical cardiologists and all specialists dealing with coronavirus disease 19, we tried to recapitulate the current evidence and provide some practical recommendations.

negative: Seroprevalence of COVID-19 virus infection in Guilan province, Iran Background: The extent of infection by coronavirus disease 2019 has not been well documented. In this study we aimed to determine seropositivity of COVID-19 virus infection in population of a highly affected area in north of Iran. Methods: In a population-based cluster random sampling design through phone call invitation, a total of 196 household including 552 subjects agreed to participate in this study. Each participant were taken 50ml blood sample at health care center. Rapid test kits were used to detect antibody against COVID-19. Crude, population-weight adjusted and test performance adjusted prevalence of antibody seropositivity to SARS-CoV-2 were reported. Results: The prevalence of antibody seropositivity was 0.22 (95%CI: 0.19-0.26). The population weight adjusted estimate was 0.21 (95%CI: 0.14-0.29) and test performance adjusted prevalence was 0.33 (95%CI: 0.28-0.39). Based on these estimates the range of infected people in this province would be between 518000 and 777000. Conclusion: The population seropositivity prevalence of COVID-19 virus infection indicated that the asymptomatic infection is much higher than the number of confirmed cases of COVID-19. This estimate can be used to better detect infection fatality rate and decide for public policy guidelines.

negative: Chapter 8 Virus Evolution and Genetics Abstract Viruses are very diverse and they infect organisms from all domains of life and across all ecosystems, but related viruses often infect very different types of organisms, pointing to their very ancient origins. Three commonly proposed mechanisms for the origins of viruses are: Viruses descended from primitive precellular life forms; viruses are escaped cellular genetic elements; viruses devolved from more complex intracellular parasites. None of these theories easily explains the origins of all viruses and it is widely accepted that all viruses did not share a single common ancestor. Instead, distinct lineages of viruses probably evolved by different mechanism. There is also good evidence that viruses have shaped the evolution of their hosts, for at least hundreds of millions of years. While some virologists consider the ancient origins of viruses, others examine the forces that drive virus evolution today. Examples of ongoing virus evolution include: Cross-species jumps; decreased or increased virulence; emergence of drug resistance; escape from immune responses at the level of individuals and populations. Virus evolution is the outcome of two independent events. The first is genome mutation and the second is selection. Viruses with RNA genomes tend to have high mutation rates, but some appear to be evolutionarily stable nonetheless. Viruses have distinct phenotypes. For examples, some influenza viruses are highly virulent but others are much less so; influenza viruses also differ tremendously in their ability to be transmitted. Modern studies of virus genetics seek to correlate diverse phenotypes with specific genes and sequences. The ability to do reverse genetics is key to understanding viral genes. Reverse genetics involves cloning viral genomes, designing specific mutation, and introducing the mutated genomes back into cells to produce infectious particles whose phenotypes can then be measured.

negative: On Answering the Call to Action for COVID-19: Continuing a Bold Legacy of Health Advocacy The disproportionately high burden of death and disability observed for racial and ethnic minorities under the Coronavirus pandemic necessitates sustained advocacy by the medical and public health communities around critical determinants of population health. Prompting our advocacy should be the understanding that our collective ability to rebound from such crises may ultimately hinge on protecting and equipping our most vulnerable racial-ethnic minority groups and any susceptible individuals within those populations. If proven effective, recent historic firsts by the U.S. Department of Health and Human Services (HHS), through the Health Resources and Services Administration (HRSA), the Office of Minority Health (OMH) and the Centers for Disease Control and Prevention (CDC) in response to COVID-19 should be championed for permanency within policy, practice and funding. In addition, given the complex history of Black Americans in this country and persistent and substantial Black-white disparities on health and economic measures across the board, some kind of reparations for this group may serve as a logical starting point for further advocacy. Nevertheless, we remain supportive allies of all organizations concerned with communities who suffer the weight of this pandemic and any future world health disasters. Let us as human clinicians and public health professionals capture this moment of challenge and engage in thoughtful unification of effort and commit to measurable progress for as long as the need exists and certainly for the foreseeable future.

negative: New Respiratory Viruses and the Elderly The diagnostics of respiratory viral infections has improved markedly during the last 15 years with the development of PCR techniques. Since 1997, several new respiratory viruses and their subgroups have been discovered: influenza A viruses H5N1 and H1N1, human metapneumovirus, coronaviruses SARS, NL63 and HKU1, human bocavirus, human rhinoviruses C and D and potential respiratory pathogens, the KI and WU polyomaviruses and the torque teno virus. The detection of previously known viruses has also improved. Currently, a viral cause of respiratory illness is almost exclusively identifiable in children, but in the elderly, the detection rates of a viral etiology are below 40%, and this holds also true for exacerbations of chronic respiratory illnesses. The new viruses cause respiratory symptoms like the common cold, cough, bronchitis, bronchiolitis, exacerbations of asthma and chronic obstructive pulmonary disease and pneumonia. Acute respiratory failure may occur. These viruses are distributed throughout the globe and affect people of all ages. Data regarding these viruses and the elderly are scarce. This review introduces these new viruses and reviews their clinical significance, especially with regard to the elderly population.

negative: Therapeutic Options for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) – possible lessons from a systematic review of SARS-CoV therapy Abstract The Middle East Respiratory Syndrome coronavirus (MERS-CoV) has been detected in a number of countries in the Middle East and Europe with an apparently high mortality rate. It is phylogenetically related to the SARS coronavirus and has also been associated with severe respiratory illness as well as nosocomial transmission in healthcare settings. Current international recommendations do not support any specific therapies; however, there are a number of agents, which were used during the SARS epidemic of 2003. It is possible that these might be active against the related MERS coronavirus. We have reviewed the literature on the safety and efficacy of therapies used in patients with SARS with a view to their potential use in patients with MERS-CoV infections.

negative: The Diagnosis and Treatment of Elderly Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease and Chronic Bronchitis The syndrome of chronic obstructive pulmonary disease (COPD) consists of chronic bronchitis (CB), bronchiectasis, emphysema, and reversible airway disease that combine uniquely in an individual patient. Older patients are at risk for COPD and its components—emphysema, CB, and bronchiectasis. Bacterial and viral infections play a role in acute exacerbations of COPD (AECOPD) and in acute exacerbations of CB (AECB) without features of COPD. Older patients are at risk for resistant bacterial organisms during their episodes of AECOPD and AECB. Organisms include the more‐common bacteria implicated in AECOPD/AECB such as Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. Less‐common nonenteric, gram‐negative organisms including Pseudomonas aeruginosa, gram‐positive organisms including Staphylococcus aureus, and strains of nontuberculosis Mycobacteria are more often seen in AECOPD/AECB episodes involving elderly patients with frequent episodes of CB or those with bronchiectasis. Risk‐stratified antibiotic treatment guidelines appear useful for purulent episodes of AECOPD and episodes of AECB. These guidelines have not been prospectively validated for the general population and especially not for the elderly population. Using a risk‐stratification approach for elderly patients, first‐line antibiotics (e.g., amoxicillin, ampicillin, pivampicillin, trimethoprim/sulfamethoxazole, and doxycycline), with a more‐limited spectrum of antibacterial coverage, are used in patients who are likely to have a low probability of resistant organisms during AECOPD/AECB. Second‐line antibiotics (e.g., amoxicillin/clavulanic acid, second‐ or third‐generation cephalosporins, and respiratory fluoroquinolones) with a broader spectrum of coverage are reserved for patients with significant risk factors for resistant organisms and those who have failed initial antibiotic treatment.

negative: Dupilumab and COVID‐19: What should we expect? Coronavirus disease 2019 (COVID‐19) is a pandemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) with high morbidity and mortality. There are very limited data on the interference of immunomodulating drugs on the risk of infection and on the course of the disease. In particular, there are no current clinical data about the interference exerted by dupilumab, a biologic drugs blocking IL‐4 and IL‐13, used for adult atopic dermatitis. The pathogenesis of COVID‐19 is complex, characterized by an immune response mainly Th1/Th17. The hyper‐activation of these cells may cause the release of pro‐inflammatory cytokines that may result in lung impairment. IL‐4 and IL‐13 are Th2 cytokines, thus being part of a pathway not considered implicated in host defense mechanism against viral infections. Indeed, viral infections, including respiratory infections, have not been reported as a significant adverse event in clinical trials. Furthermore, dupilumab has been proved to be efficacious also in exacerbations of asthma, and it is known that viral infections can worsen asthma. Therefore, the current data seem to suggest that treatment with dupilumab should not be stopped during COVID‐19 pandemic. Obviously, a careful assessment is mandatory for each individual patient and further studies are necessary to characterize the immunologic responses in COVID‐19.

negative: Infections Acquired in the Nursery: Epidemiology and Control

negative: The association between Ostertagia ostertagi antibodies in bulk tank milk samples and parameters linked to cattle reproduction and mortality Abstract In Western Europe, gastrointestinal nematodes are widespread in dairy cattle. This study was carried out to evaluate the relationship between optical density ratio (ODR) measured on bulk tank milk with an indirect Ostertagia ostertagi ELISA and reproduction/mortality parameters. Data were collected between 2008 and 2010 from monitoring carried out on 1643 dairy herds (Normandy, Western France). ODR values of 3 samples from each farm taken from November 2008 to 2010 were averaged and then transformed into a categorical variable. Reproductive and mortality data were obtained from 1444 herds using cow records from government databases. Statistical analysis was carried out using ordinary logistic regression (OLR). The outcome variables were the case–control status of a herd for reproductive factors, age at first calving and inter-calving intervals, and mortality ratios of various age classes. The effect of the categorical ODR variable was studied and several potential confounder herd factors were used to improve the model fit. A significant relationship was found between high Ostertagia ODR levels and a late age at the first calving (>34.5 months) (odds ratio (OR)=1.94, p <0.001). No significant relationship was observed with OLR for inter-calving intervals although bivariate analysis showed that herds with high ODR levels had longer inter-calving intervals than herds with low ODR level (first inter-calving interval in herds with low vs. high ODR levels=412 days vs. 422 days, p <0.001; other inter-calving intervals=408 days vs. 413 days, p <0.01). A high ODR level was also associated with high mortality of calves between 0 and 30 days of life (mortality ratio>6%) (OR=1.43, p <0.05) and between 91 and 365 days (ratio>3%) (OR=1.72, p <0.01). No significant relationship was observed with multivariate approach for mortalities in other classes by age, but bivariate analysis showed that herds with high ODR level had higher mortalities than herds with low ODR levels (mortality between 31 and 90 days in herds with low vs. high ODR levels=1.89% vs. 2.91%, p <0.001; mortality after 365 days=1.67% vs. 2.93%, p <0.001). In conclusion, our results confirm the usefulness of ELISA as an indicator for production losses in dairy herds. This inexpensive tool could be advantageous, used to aid farmers and veterinarians to carry out appropriate control measures.

negative: Las estadísticas sanitarias y la invisibilidad por sexo y de género durante la epidemia de COVID-19 ABSTRACT Reports on COVID-19 from the Spanish Health Ministry are valuable, but incomplete, with the perverse effect that the susceptibility to COVID-19 by sex is unclear. Prevalence of COVID-19 by sexes differs between countries. The trend in Spain shows an unequal pattern, initially more frequent in men, but women outnumbered them from March 31, after two weeks lockdown. Infections are more frequent in women than in men in close contact with probable/confirmed COVID-19 cases. Consistent with deaths in men, they are hospitalized more frequently than women: Significant gender differences in signs/symptoms can drive this pattern, already observed in other pathologies. In late April, excess mortality is the same in women (67%) than in men (66%). But, lack of exhaustive information on deaths from COVID-19 in non-hospitalized patients may contribute to lower notification of deaths in women. Invisibility of data by sex and gender is probably affecting negatively women with COVID -19 more than men.

negative: Estimating the number of SARS-CoV-2 infections in the United States We apply a model developed by The COVID-19 Response Team [S. Flaxman, S. Mishra, A. Gandy, et al., ''Estimating the number of infections and the impact of non- pharmaceutical interventions on COVID-19 in 11 European countries,'' tech. rep., Imperial College London, 2020.] to estimate the total number of SARS-CoV-2 infections in the United States. Across the United States we estimate as of April 18, 2020 the fraction of the population infected was 4.6% [3.6%, 5.8%], 21 times the portion of the population with a positive test result. Excluding New York state, which we estimate accounts for over half of infections in the United States, we estimate an infection rate of 2.3% [2.1%, 2.8%]. We include the timing of each state's implementation of interventions including encouraging social distancing, closing schools, banning public events, and a lockdown / stay-at-home order. We assume fatalities are reported correctly and infer the number and timing of infections based on the infection fatality rate measured in populations that were tested universally for SARS-CoV-2. Underreporting of deaths would drive our estimates to be too low. Reporting of deaths on the wrong day could drive errors in either direction. This model does not include effects of herd immunity; in states where the estimated infection rate is very high - namely, New York - our estimates may be too high.

negative: Characterizing key attributes of the epidemiology of COVID-19 in China: Model-based estimations Background: A novel coronavirus strain, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China in late 2019. The resulting disease, Coronavirus Disease 2019 (COVID-2019), soon became a pandemic. This study aims to characterize key attributes of the epidemiology of this infection in China. Methods: An age-stratified mathematical model was constructed to describe the transmission dynamics and estimate the age-specific differences in the biological susceptibility to the infection, age-assortativeness in transmission mixing, case fatality rate (CFR), and transition in rate of infectious contacts (and reproduction number R0) following introduction of mass interventions. Results: The model estimated the infectious contact rate in early epidemic at 0.59 contacts per day (95% uncertainty interval (UI)=0.48-0.71). Relative to those 60-69 years of age, susceptibility to the infection was only 0.06 in those ≤19 years, 0.34 in 20-29 years, 0.57 in 30-39 years, 0.69 in 40-49 years, 0.79 in 50-59 years, 0.94 in 70-79 years, and 0.88 in ≥80 years. The assortativeness in transmission mixing by age was very limited at 0.004 (95% UI=0.002-0.008). Final CFR was 5.1% (95% UI=4.8-5.4%). R0 rapidly declined from 2.1 (95% UI=1.8-2.4) to 0.06 (95% UI=0.05-0.07) following onset of interventions. Conclusion: Age appears to be a principal factor in explaining the patterns of COVID-19 transmission dynamics in China. The biological susceptibility to the infection seems limited among children, intermediate among young to mid-age adults, but high among those >50 years of age. There was no evidence for differential contact mixing by age, consistent with most transmission occurring in households rather than in schools or workplaces.

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

negative: Early Epidemiological Assessment of the Virulence of Emerging Infectious Diseases: A Case Study of an Influenza Pandemic BACKGROUND: The case fatality ratio (CFR), the ratio of deaths from an infectious disease to the number of cases, provides an assessment of virulence. Calculation of the ratio of the cumulative number of deaths to cases during the course of an epidemic tends to result in a biased CFR. The present study develops a simple method to obtain an unbiased estimate of confirmed CFR (cCFR), using only the confirmed cases as the denominator, at an early stage of epidemic, even when there have been only a few deaths. METHODOLOGY/PRINCIPAL FINDINGS: Our method adjusts the biased cCFR by a factor of underestimation which is informed by the time from symptom onset to death. We first examine the approach by analyzing an outbreak of severe acute respiratory syndrome in Hong Kong (2003) with known unbiased cCFR estimate, and then investigate published epidemiological datasets of novel swine-origin influenza A (H1N1) virus infection in the USA and Canada (2009). Because observation of a few deaths alone does not permit estimating the distribution of the time from onset to death, the uncertainty is addressed by means of sensitivity analysis. The maximum likelihood estimate of the unbiased cCFR for influenza may lie in the range of 0.16–4.48% within the assumed parameter space for a factor of underestimation. The estimates for influenza suggest that the virulence is comparable to the early estimate in Mexico. Even when there have been no deaths, our model permits estimating a conservative upper bound of the cCFR. CONCLUSIONS: Although one has to keep in mind that the cCFR for an entire population is vulnerable to its variations among sub-populations and underdiagnosis, our method is useful for assessing virulence at the early stage of an epidemic and for informing policy makers and the public.

negative: Clinical predictors of mortality of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection: A cohort study Abstract Background Since the emergence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in 2012, the virus had caused a high case fatality rate. The clinical presentation of MERS varied from asymptomatic to severe bilateral pneumonia, depending on the case definition and surveillance strategies. There are few studies examining the mortality predictors in this disease. In this study, we examined clinical predictors of mortality of Middle East Respiratory Syndrome (MERS) infection. Methods This is a retrospective analysis of symptomatic admitted patients to a large tertiary MERS-CoV center in Saudi Arabia over the period from April 2014 to March 2018. Clinical and laboratory data were collected and analysis was done using a binary regression model. Results A total of 314 symptomatic MERS-CoV patients were included in the analysis, with a mean age of 48 (±17.3) years. Of these cases, 78 (24.8%) died. The following parameters were associated with increased mortality, age, WBC, neutrophil count, serum albumin level, use of a continuous renal replacement therapy (CRRT) and corticosteroid use. The odd ratio for mortality was highest for CRRT and corticosteroid use (4.95 and 3.85, respectively). The use of interferon-ribavirin was not associated with mortality in this cohort. Conclusion Several factors contributed to increased mortality in this cohort of MERS-CoV patients. Of these factors, the use of corticosteroid and CRRT were the most significant. Further studies are needed to evaluate whether these factors were a mark of severe disease or actual contributors to higher mortality.

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

negative: Remdesivir use in patients with coronavirus COVID-19 disease: a systematic review and meta-analysis Background Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2, has led to significant global mortality and morbidity. Until now, no treatment has proven to be effective in COVID-19. To explore whether the use of remdesivir, initially an experimental broad-spectrum antiviral, is effective in the treatment of hospitalized patients with COVID-19, we conducted a systematic review and meta-analysis of randomized, placebo-controlled trials investigating its use. Methods A rapid search of the MEDLINE and EMBASE medical databases was conducted for randomized controlled trials. A systematic approach was used to screen, abstract, and critically appraise the studies. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method was applied to rate the certainty and quality of the evidence reported per study. Results Two RCTs studies were identified (n=1,299). A fixed-effects meta-analysis revealed reductions in mortality (RR=0.69, 0.49 to 0.99), time to clinical improvement (3.95 less days, from 3.86 days less to 4.05 less days ), serious adverse events (RR=0.77, 0.63 to 0.94) and all adverse events (RR=0.87, 0.79 to 0.96). Conclusion In this rapid systematic review, we present pooled evidence from the 2 included RCT studies that reveal that remdesivir has a modest yet significant reduction in mortality and significantly improves the time to recovery, as well as significantly reduced risk in adverse events and serious adverse events. It is more than likely that as an antiviral, remdesivir is not sufficient on its own and may be suitable in combination with other antivirals or treatments such as convalescent plasma. Research is ongoing to clarify and contextual these promising findings.

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

negative: Phylogenetic and epidemic modeling of rapidly evolving infectious diseases Abstract Epidemic modeling of infectious diseases has a long history in both theoretical and empirical research. However the recent explosion of genetic data has revealed the rapid rate of evolution that many populations of infectious agents undergo and has underscored the need to consider both evolutionary and ecological processes on the same time scale. Mathematical epidemiology has applied dynamical models to study infectious epidemics, but these models have tended not to exploit – or take into account – evolutionary changes and their effect on the ecological processes and population dynamics of the infectious agent. On the other hand, statistical phylogenetics has increasingly been applied to the study of infectious agents. This approach is based on phylogenetics, molecular clocks, genealogy-based population genetics and phylogeography. Bayesian Markov chain Monte Carlo and related computational tools have been the primary source of advances in these statistical phylogenetic approaches. Recently the first tentative steps have been taken to reconcile these two theoretical approaches. We survey the Bayesian phylogenetic approach to epidemic modeling of infection diseases and describe the contrasts it provides to mathematical epidemiology as well as emphasize the significance of the future unification of these two fields.

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

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

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

negative: Evaluating epidemiological scenarios of isolation and further releases considering protection actions to control transmission of CoViD-19 in Sao Paulo State, Brazil. A mathematical model was formulated based on nonlinear ordinary differential equations considering young (below 60 years old) and elder (above 60 years) subpopulations, aiming to describe the introduction, dissemination and control of new coronavirus in Sao Paulo State, Brazil. In Sao Paulo State, the first case of CoViD-19 was confirmed on 26 February, the first death due to CoViD-19 was registered on 16 March, on 24 March the Sao Paulo State authorities implemented the isolation of persons in non-essential activities, which is programmed to end on June 1. The deterministic model used the data collected in Sao Paulo State to estimate the model parameters to describe the current epidemiological status in the State under isolation. We concluded that the proportion in isolation influenced the number of new cases in around 9 days ahead. We evaluate the suitability of lockdown in Sao Paulo State and concluded that this extreme measure should be efficient if lower transmission is occurring among isolated persons. Nevertheless, the isolated persons must be released one day. Based on this model, we studied the potential epidemiological scenarios of release by varying the release proportions of young and elder persons. We evaluated three releases divided in equal proportions elapsed 14 days between releases, and three strategies: the first release occurring on June 1, 15 and 23. We concluded that these three strategies are equivalent (little difference) in reducing the number of hospitalization due to severe CoViD-19 and deaths, due to presenting the effective reproduction number near one. However, if protection actions as using face mask and hygiene (washing hands, for instance) could be massively disseminated in the population, we concluded there health care system may not collapse.

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: 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.

negative: Community responses during the early phase of the COVID-19 epidemic in Hong Kong: risk perception, information exposure and preventive measures Background: Community responses are important for outbreak management during the early phase when non-pharmaceutical interventions are the major preventive options. Therefore, this study aims to examine the psychological and behavioral responses of the community during the early phase of the COVID-19 epidemic in Hong Kong. Method: A cross-sectional online survey was launched within 36 hours after confirmed COVID-19 cases were first reported. Councilors of all 452 district council constituency areas were approached for survey dissemination. Respondent demographics, anxiety level, risk perception, sources to retrieve COVID-19 information, actual adoption and perceived efficacy of precautionary measures were collected. Result: Analysis from 1715 complete responses indicated high perceived susceptibility (89%) and high perceived severity (97%). Most respondents were worried about COVID-19 (97%), and had their daily routines disrupted (slightly/greatly: 98%). The anxiety level, measured by the Hospital Anxiety and Depression Scale, was borderline abnormal (9.01). Nearly all respondents were alert to the disease progression (99.5%). The most trusted information sources were doctors (84%), followed by broadcast (57%) and newspaper (54%), but they were not common information sources (doctor: 5%; broadcast: 34%; newspaper: 40%). Only 16% respondents found official websites reliable. Enhanced personal hygiene practices and travel avoidance to China were frequently adopted (>77%) and considered effective (>90%). The adoption of social-distancing measures was lower (39%-88%), and their drivers for greater adoption include: being female (adjusted odds ratio [aOR]:1.27), living in the New Territories (aOR:1.32-1.55), perceived as having good understanding of COVID-19 (aOR:1.84) and being more anxious (aOR:1.07). Discussion: Risk perception towards COVID-19 in the community was high. Most respondents are alert to the disease progression, and adopt self-protective measures. This study contributes by examining the psycho-behavioral responses of hosts, in addition to the largely studied mechanistic aspects, during the early phase of the current COVID-19 epidemic. The timely psychological and behavioral assessment of the community is useful to inform subsequent interventions and risk communication strategies as the epidemic progresses.

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: Prediction of COVID-19 Outbreak in China and Optimal Return Date for University Students Based on Propagation Dynamics On 12 December 2019, a novel coronavirus disease, named COVID-19, began to spread around the world from Wuhan, China. It is useful and urgent to consider the future trend of this outbreak. We establish the 4+1 penta-group model to predict the development of the COVID-19 outbreak. In this model, we use the collected data to calibrate the parameters, and let the recovery rate and mortality change according to the actual situation. Furthermore, we propose the BAT model, which is composed of three parts: simulation of the return rush (Back), analytic hierarchy process (AHP) method, and technique for order preference by similarity to an ideal solution (TOPSIS) method, to figure out the best return date for university students. We also discuss the impacts of some factors that may occur in the future, such as secondary infection, emergence of effective drugs, and population flow from Korea to China.

negative: Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study Abstract An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its caused coronavirus disease 2019 (COVID-19) has been reported in China since December 2019. More than 16% of patients developed acute respiratory distress syndrome, and the fatality ratio was about 1%–2%. No specific treatment has been reported. Herein, we examine the effects of Favipiravir (FPV) versus Lopinavir (LPV)/ritonavir (RTV) for the treatment of COVID-19. Patients with laboratory-confirmed COVID-19 who received oral FPV (Day 1: 1600 mg twice daily; Days 2–14: 600 mg twice daily) plus interferon (IFN)-α by aerosol inhalation (5 million U twice daily) were included in the FPV arm of this study, whereas patients who were treated with LPV/RTV (Days 1–14: 400 mg/100 mg twice daily) plus IFN-α by aerosol inhalation (5 million U twice daily) were included in the control arm. Changes in chest computed tomography (CT), viral clearance, and drug safety were compared between the two groups. For the 35 patients enrolled in the FPV arm and the 45 patients in the control arm, all baseline characteristics were comparable between the two arms. A shorter viral clearance time was found for the FPV arm versus the control arm (median (interquartile range, IQR), 4 (2.5–9) d versus 11 (8–13) d, P < 0.001). The FPV arm also showed significant improvement in chest imaging compared with the control arm, with an improvement rate of 91.43% versus 62.22% (P = 0.004). After adjustment for potential confounders, the FPV arm also showed a significantly higher improvement rate in chest imaging. Multivariable Cox regression showed that FPV was independently associated with faster viral clearance. In addition, fewer adverse reactions were found in the FPV arm than in the control arm. In this open-label nonrandomized control study, FPV showed significantly better treatment effects on COVID-19 in terms of disease progression and viral clearance; if causal, these results should be important information for establishing standard treatment guidelines to combat the SARS-CoV-2 infection.

negative: TH17 responses in cytokine storm of COVID-19: An emerging target of JAK2 inhibitor Fedratinib Abstract COVID-19 emerges as a pandemic disease with high mortality. Development of effective prevention and treatment is an urgent need. We reviewed TH17 responses in patients with SARS-CoV-2 and proposed an FDA approved JAK2 inhibitor Fedratinib for reducing mortality of patients with TH17 type immune profiles.

negative: Age-dependent effects in the transmission and control of COVID-19 epidemics The COVID-19 pandemic has shown a markedly low proportion of cases among children. Age disparities in observed cases could be explained by children having lower susceptibility to infection, lower propensity to show clinical symptoms, or both. We evaluate these possibilities by fitting an age-structured mathematical model to epidemic data from six countries. We estimate that clinical symptoms occur in 25% (95% CrI: 19-32%) of infections in 10-19-year-olds, rising to 76% (68-82%) in over-70s, and that susceptibility to infection in under-20s is approximately half that of older adults. Accordingly, we find that interventions aimed at children may have a relatively small impact on total cases, particularly if the transmissibility of subclinical infections is low. The age-specific clinical fraction and susceptibility we have estimated has implications for the expected global burden of COVID-19 because of demographic differences across settings: in younger populations, the expected clinical attack rate would be lower, although it is likely that comorbidities in low-income countries will affect disease severity. Without effective control measures, regions with older populations may see disproportionally more clinical cases, particularly in the later stages of the pandemic.

negative: Age- and Sex-Specific Risk Profiles and In-Hospital Mortality in 13,932 Spanish Stroke Patients. BACKGROUND In-hospital stroke death rate is an important sanitary issue. Despite advances in the acute phase management of stroke patients, mortality and disability rates remain high. In aging populations and with different mortality between the sexes in general, the study of sex- and age-related differences becomes increasingly relevant for optimization of post-acute clinical care of stroke patients. METHODS We designed a cohort follow-up study with 13,932 consecutive ischemic stroke (IS) patients from 19 Spanish hospitals. Data was obtained from the Spanish Stroke Registry; transient ischemic attacks and ages <18 years were excluded. Patients were organised by age group and sex. We compared female and male patient cohorts within and across age groups univariately and used multivariable logistic regression to adjust for confounders in differential in-hospital mortality. RESULTS The median (percentiles 2.5 and 97.5%) age was 78 (41-92) years old for women and 71 (41-92) for men. IS women were more likely to be older, to exhibit cardio-embolic aetiology, and less likely to have been admitted to a stroke unit or to have had a stroke code activated. Both pre-stroke modified Rankin Scale and National Institute of Health Stroke Scale (NIHSS) scores at admission increased significantly with age and were higher in women than those in men. Differences in distributions of common risk factors for IS and of in-hospital outcomes between women and men actually changed with patient's age. It is to be noted here that although there were no statistically significant differences (p > 0.05) between the sexes within any age group, in-hospital mortality appeared significantly higher in women than that in men when analysed overall, due to confounding. Death was more closely related to stroke in women than in men and occurred earlier. Although there were some age-specific sex differences between the predictors for in-hospital mortality, stroke severity measured by NIHSS was the main predictor of in-hospital mortality for both sexes. Topographic classifications - partial anterior circulatory infarct and total anterior circulatory infarct - were significant prognostic factors for men aged <60 years and for those in the 60-69 years range respectively. CONCLUSION Although most of our findings were consistent with previous studies, it is important to take into account and highlight differences in in-hospital mortality between the sex and age group. Not to account for age-related differences between the sexes can give false results that may mislead management decisions. As most deaths in women were related to stroke, it is important to improve their early management, stroke code activation, access to stroke units and/or revascularisation therapies, especially in the older age groups.

negative: Chapter 25 Public Health Policies in European Union: An Innovation Strategy—Horizon 2020 Abstract Health planning and policy seek to create a group of mutually interacting bodies to produce goods and services to meet the health needs of a population. Recent developments in the health status of the population are characterized by continuous improvement in life expectancy, chronic diseases which absorb 90% of total health care expenditure, differences in the causes of mortality (more than 70% mortality from cancer, heart and brain, and external causes). The new trends in health indicators define the current health policies and lead to the necessity of adapting the health system so as to meet the changing health needs of the population. Especially in the context of the changes in the epidemiological spectrum and the variability in the indices of morbidity and mortality, the focus is not only to further prolong life expectancy but also to improve life expectancy without chronic diseases and without disabilities and to reduce the avoidable mortality, the potential years of life lost before the age of 65years. According to this approach, the main strategic priorities of health policy in the European Union for the period 2014–2020 are: (1) Prevention and health promotion (to combat diseases associated with the modern way of life), (2) Protection from cross-border threats (to address the external impact from cross-border relations, combating epidemics, pandemics), (3) Viability (to address the lack of resources by adopting innovation), (4) Accessibility (to assure the access to medical expertise).Therefore, the key priorities are the prevention of disease and the improvement of life in good health, the patient safety and quality of health services, and the readiness to manage crises and health risks.

negative: Investigating spatial variability in COVID-19 pandemic severity across 19 geographic areas, Spain, 2020 Background: Spain has been disproportionately affected by the COVID-19 pandemic with the second highest death toll in the world after Italy. Here we analyzed estimates of pandemic severity and investigated how different factors shaped the severity of the COVID-19 pandemic. Methods: We retrieved the daily cumulative numbers of laboratory-confirmed COVID-19 cases and deaths in Spain from February 20, 2020 to April 2, 2020. We used statistical methods to estimate the time-delay adjusted case fatality ratio (CFR) for 17 autonomous areas and 2 autonomous cities of Spain. We then assessed how transmission and sociodemographic variables were associated with the CFR across areas in Spain using multivariate regression analysis. Results: We estimated the highest time-delay-adjusted CFR for Madrid (38.4%) and the average adjusted CFR in Spain at 23.9%. Our multivariate regression analysis revealed a statistically significant three predictor variables: infant mortality rate, poverty risk rate and the cumulative morbidity rate. Conclusions: Our estimates of the time-delay adjusted CFR for 12 autonomous areas/cities in Spain are significantly higher than those previously estimated for other geographic regions including China and Korea. Our results call for urgent public health interventions focusing on low socioeconomic groups to ameliorate the burden of the COVID-19 pandemic in Spain.

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

negative: Surveillance on secular trends of incidence and mortality for device–associated infection in the intensive care unit setting at a tertiary medical center in Taiwan, 2000–2008: A retrospective observational study BACKGROUND: Device–associated infection (DAI) plays an important part in nosocomial infection. Active surveillance and infection control are needed to disclose the specific situation in each hospital and to cope with this problem effectively. We examined the rates of DAI by antimicrobial-resistant pathogens, and 30–day and in–hospital mortality in the intensive care unit (ICU). METHODS: Prospective surveillance was conducted in a mixed medical and surgical ICU at a major teaching hospital from 2000 through 2008. Trend analysis was performed and logistic regression was used to assess prognostic factors of mortality. RESULTS: The overall rate of DAIs was 3.03 episodes per 1000 device–days. The most common DAI type was catheter–associated urinary tract infection (3.76 per 1000 urinary catheter–days). There was a decrease in DAI rates in 2005 and rates of ventilator–associated pneumonia (VAP, 3.18 per 1000 ventilator–days) have remained low since then (p < 0.001). The crude rates of 30–day (33.6%) and in–hospital (52.3%) mortality, as well as infection by antibiotic-resistant VAP pathogens also decreased. The most common antimicrobial-resistant pathogens were methicillin–resistant Staphylococcus aureus (94.9%) and imipenem–resistant Acinetobacter baumannii (p < 0.001), which also increased at the most rapid rate. The rate of antimicrobial resistance among Enterobacteriaceae also increased significantly (p < 0.05). After controlling for potentially confounding factors, the DAI was an independent prognostic factor for both 30–day mortality (OR 2.51, 95% confidence interval [CI] 1.99–3.17, p = 0.001) and in–hospital mortality (OR 3.61, 95% CI 2.10–3.25, p < 0.001). CONCLUSIONS: The decrease in the rate of DAI and infection by resistant bacteria on the impact of severe acute respiratory syndrome can be attributed to active infection control and improved adherence after 2003.

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

negative: Cost-effectiveness Analysis of Antiepidemic Policies and Global Situation Assessment of COVID-19 With a two-layer contact-dispersion model and data in China, we analyze the cost-effectiveness of three types of antiepidemic measures for COVID-19: regular epidemiological control, local social interaction control, and inter-city travel restriction. We find that: 1) intercity travel restriction has minimal or even negative effect compared to the other two at the national level; 2) the time of reaching turning point is independent of the current number of cases, and only related to the enforcement stringency of epidemiological control and social interaction control measures; 3) strong enforcement at the early stage is the only opportunity to maximize both antiepidemic effectiveness and cost-effectiveness; 4) mediocre stringency of social interaction measures is the worst choice. Subsequently, we cluster countries/regions into four groups based on their control measures and provide situation assessment and policy suggestions for each group.

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: DIALYSIS. EPIDEMIOLOGY, OUTCOME RESEARCH, HEALTH SERVICES 1

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

negative: Achievements and highlights for Infection, Disease and Health

negative: Preweaned heifer management on US dairy operations: Part V. Factors associated with morbidity and mortality in preweaned dairy heifer calves ABSTRACT The objective of this study was to evaluate morbidity and mortality in preweaned dairy heifer calves based on different health, feeding, and management practices, as well as environmental factors. This study was conducted as part of the calf component of the National Animal Health Monitoring System's Dairy 2014 study, which included 104 dairy operations in 13 states. The calf component was an 18-mo longitudinal study focused on dairy heifer calves from birth to weaning; data were collected on 2,545 calves. The percentage morbidity for all calves enrolled in the study was 33.9%. Backward elimination model selection was used after univariate screening to determine which management practices and environmental factors significantly affected morbidity and mortality. The final morbidity model included birth weight, serum IgG concentration, ventilation type, and average temperature-humidity index (THI) during the preweaning period. After controlling for other independent variables in the model, calves born at a higher birth weight had a lower predicted risk of morbidity than calves with a lower birth weight. An increase in serum IgG concentration was associated with decreased morbidity. Calves housed in positive- or cross-ventilated systems had a 2.2 times higher odds of developing disease compared with calves housed in natural ventilation systems. Average THI during the preweaning period was inversely correlated with morbidity; as THI increased, the predicted morbidity risk decreased. The percent mortality for all calves enrolled in the study was 5.0%. The final mortality model included birth weight, serum IgG concentration, amount of fat/day in the liquid diet, and morbidity. After controlling for other independent variables in the model, calves born at a higher birth weight had a lower risk of mortality. An increase in serum IgG concentration decreased the risk of mortality. The odds of mortality were 3.1 times higher in calves fed ≤0.15 kg of fat/d in the liquid diet compared with calves fed ≥0.22 kg of fat/d. The odds of mortality were 4.7 times higher in calves that experienced any disease throughout the preweaning period than in calves with no disease. In summary, morbidity and mortality were both associated with birth weight and serum IgG concentration. Additionally, morbidity was associated with ventilation type and average monthly THI, and mortality was associated with amount of fat per day in the liquid diet and morbidity.

negative: Disparities in COVID-19 Reported Incidence, Knowledge, and Behavior Abstract Background: Data from the COVID-19 pandemic in the United States show large differences in hospitalizations and mortality across race and geography. However, there is limited data on health information, beliefs, and behaviors that might indicate different exposure to risk. Methods: A sample of 5,198 respondents in the United States (80% population representative, 20% oversample of hotspot areas in New York City, Seattle, New Orleans, and Detroit) was conducted from March 29th to April 13th to measure differences in knowledge, beliefs and behavior regarding COVID-19. Linear regression was used to understand racial, geographic, political, and socioeconomic differences in COVID-19 reported incidence knowledge, and behaviors after adjusting for state-specific and survey date fixed effects. Results: The largest differences in COVID-19 knowledge and behaviors are associated with race/ethnicity, gender, and age. African-Americans, men, and people <55 years old are less likely to know how the disease is spread, less likely to know symptoms of COVID-19, wash their hands less frequently, and leave the home more often. Differences by income, political orientation, and living in a hotspot area are much smaller. Conclusions: There are wide gaps in COVID-19 reported incidence, knowledge regarding disease spread and symptoms, and in social distancing behavior. The findings suggest more effort is needed to increase accurate information and encourage appropriate behaviors among minority communities, men, and younger people.

negative: Implementing shared ventilation must be scientific and ethical or it risks harm

negative: SARS-CoV-2 specific antibody responses in COVID-19 patients A new coronavirus, SARS-CoV-2, has recently emerged to cause a human pandemic. Whereas molecular diagnostic tests were rapidly developed, serologic assays are still lacking, yet urgently needed. Validated serologic assays are important for contact tracing, identifying the viral reservoir and epidemiological studies. Here, we developed serological assays for the detection of SARS-CoV-2 neutralizing, spike- and nucleocapsid-specific antibodies. Using serum samples from patients with PCR-confirmed infections of SARS-CoV-2, other coronaviruses, or other respiratory pathogenic infections, we validated and tested various antigens in different in-house and commercial ELISAs. We demonstrate that most PCR-confirmed SARS-CoV-2 infected individuals seroconverted, as revealed by sensitive and specific in-house ELISAs. We found that commercial S1 IgG or IgA ELISAs were of lower specificity while sensitivity varied between the two, with IgA showing higher sensitivity. Overall, the validated assays described here can be instrumental for the detection of SARS-CoV-2-specific antibodies for diagnostic, seroepidemiological and vaccine evaluation studies.

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

negative: Modeling and Forecasting Trend of COVID-19 Epidemic in Iran Background: COVID-19 is an emerging disease and precise data are not available in the world and Iran. this study aimed to determine the epidemic trend and prediction of COVID-19 in Iran. Methods: This study is a secondary data analysis and modeling. We used the daily reports of definitive COVID-19 patients (sampling of severe cases and hospitalization) released by Iran Ministry of Health and Medical Education. Epidemic projection models of Gompertz, Von Bertalanffy and least squared error (LSE) were used to predict the number of cases at April 3, 2020 until May 13, 2020. Results: R0 in Iran was estimated to be 4.7 that has now fallen to below 2. Given the three different scenarios, the prediction of the patients on April 3, 2020 by Von Bertalanffy, Gompertz and LSE were estimated at 48200, 52500 and 58000, respectively. The number of deceased COVID-19 patients was also estimated to be 3600 individuals using the Von growth model, 4200 ones by Gompertz's model and 4850 ones according to the LSE method. To predict and estimate the number of patients and deaths in the end of epidemic based on Von and Gompertz models, we will have 87000 cases, 4900 and 11000 deaths until 13 May and 1 June, respectively. Conclusion: The process of controlling the epidemic is tangible. If enforcement and public behavior interventions continue with current trends, the control and reduction of the COVID-19 epidemic in Iran will be flat from April 28, until July, 2020 and new cases are expected to decline from the following Iranian new year.

negative: Is There a Starling Curve for Intensive Care? Large differences exist in the provision of ICU beds worldwide, with a complicated mix of risks and benefits to the population of having either too few or too many beds. Having too few beds can result in delayed admission of patients to the ICU or no admission at all, with either scenario potentially increasing mortality. Potential societal benefits of having few beds include lower costs for health care and less futile intensive care at the end of life. With added ICU beds for a population, mortality benefit should accrue, but there is still the question of whether the addition of beds always means that more lives will be saved or whether there is a point at which no additional mortality benefit is gained. With an abundance of ICU beds may come the possibility of increasing harm in the forms of unnecessary costs, poor quality of deaths (ie, excessively intensive), and iatrogenic complications. The possibility of harm may be likened to the concept of falling off a Starling curve, which is traditionally used to describe worsening heart function when overfilling occurs. This commentary examines the possible implications of having too few or too many ICU beds and proposes the concept of a family of Starling curves as a way to conceptualize the balance of societal benefits and harms associated with different availability of ICU beds for a population.

negative: Do COVID-19 and SARS Gene Complexities and Variations Help Overcome the Knowledge Gap? A whole new pathogen, to which humans have virtually no pre-existing immunity, has caused fear all over the world. Severe acute respiratory syndrome coronavirus (SARS CoV-2) is one of the types of human novel-coronavirus of the family coronavirus. The nature of transmission of the virus makes it one of the most infectious pathogenic diseases that has ever existed. Though the human coronaviruses have existed since the discovery of the human coronavirus 229E (HCoV-229E) and human coronavirus OC43 (HCoV-OC43) in 1960, it has been a challenge to develop an effective cure as well as vaccine for the diseases associated with coronaviruses. Commonly, human coronaviruses cause illnesses such as intestinal and respiratory tract illnesses. Nevertheless, the symptoms reflected after infection from the coronaviruses take some time before being identified. Thus, viruses can replicate and cause more harm to the human body before being detected. Moreover, research continues to explain why some gene variations in some individuals increase the risk of some infectious diseases, while others are not affected. Looking at gene variations in people infected with Coronavirus Disease 2019 (COVID-19) and studying how genes influence people's response to infection will help to develop a vaccine that will help strengthen the immune system. Knowing how the human genes respond to the virus COVID-19 will help to cure people more effectively.

negative: The Impact of School Closure for COVID-19 on the US Healthcare Workforce and the Net Mortality Effects Background COVID-19 is leading to the implementation of social distancing policies around the world and in the United States, including school closures. The evidence that mandatory school closures reduce cases and ultimately mortality mostly comes from experience with influenza or from models that do not include the impact of school closure on the healthcare labor supply or the role of the healthcare labor force in reducing the per infection mortality from the pathogen. There is considerable uncertainty of the incremental effect of school closures on transmission and lives saved from school closures. The likely, but uncertain, benefits from school closure need to be weighed against uncertain, and seldom quantified, costs of healthcare worker absenteeism associated with additional child care obligations. Methods We analyze data from the US Current Population Survey to measure the potential child care obligations for US healthcare workers that will need to be addressed if school closures are employed as a social distancing measure. We account for the occupation within the healthcare sector, state, and household structure to identify the segments of the healthcare labor force that are most exposed to child care obligations from school closures. We use these estimates to identify the critical level for the importance of healthcare labor supply in increasing a patient's COVID-19 survival probability that would undo the benefits of school closures and ultimately increase cumulative mortality. Findings The US healthcare sector has some of the highest child care obligations in the United States. 29% of healthcare provider households must provide care for children 3-12. Assuming non-working adults or a sibling 13 years old or older can provide child care, leaves 15% of healthcare provider households in need of childcare during a school closure, while 7% of healthcare households are single-parent households. We document the substantial variation within the healthcare system. For example, 35% of medical assistants and 31% of nursing, psychiatric, and home health aide households have child care obligations, while only 24% of emergency medical personnel have childcare obligations. Child care obligations can vary between states by over 10 percentage points. A 15% decline in the healthcare labor force, combined with reasonable parameters for COVID-19 such as a 15% case reduction from school closings and 2% baseline mortality rate implies that a 15% loss in the healthcare labor force must decrease the survival probability per percent healthcare worker lost by 17.6% for a school closure to increase cumulative mortality. This means that the per infection mortality rate cannot increase from 2% to 2.35% when the healthcare workforce declines by 15%; otherwise, school closures will lead to a greater number of deaths than they prevent. For school closures to unambiguously provide a net reduction in COVID-19 mortality with these parameters, the school closures must reduce cases by over 25%. Conclusion School closures come with many tradeoffs. Setting aside economic costs, school closures implemented to reduce COVID-19 spread create unintended childcare obligations, which are particularly large in healthcare occupations. Detailed data are provided to help public health officials make informed decisions about the tradeoffs associated with closing schools. The results suggest that it is unclear if the potential contagion prevention from school closures justifies the potential loss of healthcare workers from the standpoint of reducing cummulative mortality.

negative: Outbreak of Novel Coronavirus (SARS-CoV-2): First Evidences From International Scientific Literature and Pending Questions On 31 December, 2019, a cluster of 27 pneumonia cases of unknown etiology was reported by Chinese health authorities in Wuhan City (China) [ ]

negative: The Influenza A Virus Endoribonuclease PA-X Usurps Host mRNA Processing Machinery to Limit Host Gene Expression Many viruses shut off host gene expression to inhibit antiviral responses. Viral proteins and host proteins required for viral replication are typically spared in this process, but the mechanisms of target selectivity during host shutoff remain poorly understood. Using transcriptome-wide and targeted reporter experiments, we demonstrate that the influenza A virus endoribonuclease PA-X usurps RNA splicing to selectively target host RNAs for destruction. Proximity-labeling proteomics reveals that PA-X interacts with cellular RNA processing proteins, some of which are partially required for host shutoff. Thus, PA-X taps into host nuclear pre-mRNA processing mechanisms to destroy nascent mRNAs shortly after their synthesis. This mechanism sets PA-X apart from other viral host shutoff proteins that target actively translating mRNAs in the cytoplasm. Our study reveals a unique mechanism of host shutoff that helps us understand how influenza viruses suppress host gene expression.

negative: Surveillance and Control of Communicable Disease in Conflicts and Disasters

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

negative: Public preferences for interventions to prevent emerging infectious disease threats: a discrete choice experiment OBJECTIVE: When faced with an emergent epidemic with high mortality and morbidity potential, policy makers must decide what public health interventions to deploy at different stages of the outbreak. However, almost nothing is known about how the public view these interventions or how they trade off risks (of disease) with inconvenience (of interventions). In this paper, we aim to understand public perceptions on pandemic interventions, as well as to identify if there are any distinct respondent preference classes. DESIGN: A discrete choice experiment. SETTING: This study was fielded in Singapore between November 2012 and February 2013. PARTICIPANTS: A random sample of 500 Singapore residents aged 21 and over, including 271 women and 229 men, was analysed. OUTCOME MEASURES: Demographic information was collected from each participant. Participants were also shown a series of pairs of alternatives, each combining interventions and morbidity, mortality and cost outcomes and declared a preference for one combination. A random utility model was developed to determine the individual’s preference for interventions and a hierarchical cluster analysis was performed to identify distinct respondent preference classes. RESULTS: On average, participants preferred more intense interventions, and preferred scenarios with fewer deaths and lower tax. The number of infections did not significantly influence respondents’ responses. We identified two broad classes of respondents: those who were mortality averse and those who were expenditure averse. Education was found to be a predictor of group membership. CONCLUSION: Overall, there was considerable support for government interventions to prevent or mitigate outbreaks of emerging infectious diseases, including those that greatly restricted individual liberties, as long as the restrictions showed a reasonable chance of reducing the adverse health effects of the outbreak.

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

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

negative: Reduction in Clostridium difficile Infection Rates after Mandatory Hospital Public Reporting: Findings from a Longitudinal Cohort Study in Canada BACKGROUND: The role of public reporting in improving hospital quality of care is controversial. Reporting of hospital-acquired infection rates has been introduced in multiple health care systems, but its relationship to infection rates has been understudied. Our objective was to determine whether mandatory public reporting by hospitals is associated with a reduction in hospital rates of Clostridium difficile infection. METHODS AND FINDINGS: We conducted a longitudinal, population-based cohort study in Ontario (Canada's largest province) between April 1, 2002, and March 31, 2010. We included all patients (>1 y old) admitted to 180 acute care hospitals. Using Poisson regression, we developed a model to predict hospital- and age-specific monthly rates of C. difficile disease per 10,000 patient-days prior to introduction of public reporting on September 1, 2008. We then compared observed monthly rates of C. difficile infection in the post-intervention period with rates predicted by the pre-intervention predictive model. In the pre-intervention period there were 33,634 cases of C. difficile infection during 39,221,113 hospital days, with rates increasing from 7.01 per 10,000 patient-days in 2002 to 10.79 in 2007. In the first calendar year after the introduction of public reporting, there was a decline in observed rates of C. difficile colitis in Ontario to 8.92 cases per 10,000 patient-days, which was significantly lower than the predicted rate of 12.16 (95% CI 11.35–13.04) cases per 10,000 patient-days (p<0.001). Over this period, public reporting was associated with a 26.7% (95% CI 21.4%–31.6%) reduction in C. difficile cases, or a projected 1,970 cases averted per year (95% CI 1,476–2,500). The effect was specific to C. difficile, with rates of community-acquired gastrointestinal infections and urinary tract infections unchanged. A limitation of our study is that this observational study design cannot rule out the influence of unmeasured temporal confounders. CONCLUSIONS: Public reporting of hospital C. difficile rates was associated with a substantial reduction in the population burden of this infection. Future research will be required to discern the direct mechanism by which C. difficile infection rates may have been reduced in response to public reporting. Please see later in the article for the Editors' Summary

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

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

negative: A phased approach to unlocking during the COVID‐19 pandemic—Lessons from trend analysis BACKGROUND: The COVID‐19 pandemic has led to radical political control of social behaviour. The purpose of this paper is to explore data trends from the pandemic regarding infection rates/policy impact and draw learning points for informing the unlocking process. METHODS: The daily published cases in England in each of 149 Upper Tier Local Authority (UTLA) areas were converted to Average Daily Infection Rate (ADIR), an R value—the number of further people infected by one infected person during their infectious phase with Rate of Change of Infection Rate (RCIR) also calculated. Stepwise regression was carried out to see what local factors could be linked to differences in local infection rates. FINDINGS: By the 19th April 2020 the infection R has fallen from 2.8 on 23rd March before the lockdown and has stabilised at about 0.8 sufficient for suppression. However, there remain significant variations between England regions. Regression analysis across UTLAs found that the only factor relating to reduction in ADIR was the historic number of confirmed number infection/000 population, There is, however, wide variation between Upper Tier Local Authorities (UTLA) areas. Extrapolation of these results showed that unreported community infection may be 150 times higher than reported cases, providing evidence that by the end of the 2nd week in April, 26.8% of the population may already have had the disease and so have increased immunity. INTERPRETATION: Analysis of current case data using infectious ratio has provided novel insight into the current national state and can be used to make better‐informed decisions about future management of restricted social behaviour and movement.

negative: Hydroxychloroquine as antiviral prophylaxis for exposed caregivers to Covid-19: an urgent appraisal is needed Abstract Background Since the onset of the new coronavirus pandemic, the world is facing a public health emergency. Repositioning hydroxychloroquine (HQ) seems to be a promising option. Many emerging evidences have converged on the effectiveness of HQ in the treatment of Covid-19 infection. In a recent paper, Gautret et al. suggested that further works are needed to determine if HQ antiviral prophylaxis is useful, especially for healthcare workers. Methods The purpose of this paper is to assess the Covid-19 exposure and risks level among caregivers. For this, we performed research on internet and PubMed by crossing the following keywords: healthcare givers, healthcare workers, doctors, nurses, coronavirus, Covid-19, mortality, infection rate, chloroquine, hydroxychloroquine. Results Data on healthcare worker's infection and mortality by Covid-19 are partial and are not systematically published. However, it seems that the infection rate varies between 3.8% and 9% depending on the country. Moreover, the mean age of this population is relatively old, especially in the OECD area. Conclusions Anti-Covid-19 HQ prophylaxis should be urgently accessed, especially for healthcare workers. It is to be hoped that HQ prophylaxis reduces the morbidity and mortality from Covid-19 infection among this population which is particularly exposed and relatively old.

negative: A decade after SARS: Strategies to control emerging coronaviruses Two novel coronaviruses have emerged in humans in the 21(st) century, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome human coronavirus (MERS-CoV), both of which cause acute respiratory distress syndrome (ARDS) and have high mortality rates. There are no clinically approved vaccines or antiviral drugs available for either of these infections; thus, a priority in the field is the development of effective therapeutic and preventive strategies that can be readily applied to new emergent strains. This review will: describe the emergence and identification of novel human coronaviruses over the last 10 years; review their key biological features, including tropism and receptor use; and summarize approaches to develop broadly effective vaccines.

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

negative: Development of antiviral therapy for severe acute respiratory syndrome Abstract A new disease, the severe acute respiratory distress syndrome (SARS), caused by the SARS coronavirus (SARS-CoV), emerged at the beginning of 2003 and rapidly spread throughout the world. Although the disease had disappeared in June 2003 its re-emergence cannot be excluded. The development of vaccines against SARS-CoV may take years. Therefore, the availability of effective antiviral drugs against SARS-CoV may be crucial for the control of future SARS outbreaks. In this review, experimental and clinical data about potential anti-SARS drugs is summarised and discussed. Animal model studies will be needed to help to determine which interventions warrant controlled clinical testing.

negative: Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS Coronavirus A novel human coronavirus (HCoV-EMC) was recently identified in the Middle East as the causative agent of a severe acute respiratory syndrome (SARS) resembling the illness caused by SARS coronavirus (SARS-CoV). Although derived from the CoV family, the two viruses are genetically distinct and do not use the same receptor. Here, we investigated whether HCoV-EMC and SARS-CoV induce similar or distinct host responses after infection of a human lung epithelial cell line. HCoV-EMC was able to replicate as efficiently as SARS-CoV in Calu-3 cells and similarly induced minimal transcriptomic changes before 12 h postinfection. Later in infection, HCoV-EMC induced a massive dysregulation of the host transcriptome, to a much greater extent than SARS-CoV. Both viruses induced a similar activation of pattern recognition receptors and the interleukin 17 (IL-17) pathway, but HCoV-EMC specifically down-regulated the expression of several genes within the antigen presentation pathway, including both type I and II major histocompatibility complex (MHC) genes. This could have an important impact on the ability of the host to mount an adaptive host response. A unique set of 207 genes was dysregulated early and permanently throughout infection with HCoV-EMC, and was used in a computational screen to predict potential antiviral compounds, including kinase inhibitors and glucocorticoids. Overall, HCoV-EMC and SARS-CoV elicit distinct host gene expression responses, which might impact in vivo pathogenesis and could orient therapeutic strategies against that emergent virus.

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

negative: Understanding the Outcomes of Supplementary Support Services in Palliative Care for Older People. A Scoping Review and Mapping Exercise. CONTEXT Supplementary support services in palliative care for older people are increasingly common, but with no recommended tools to measure outcomes, nor reviews synthesising anticipated outcomes. Common clinically focussed tools may be less appropriate. OBJECTIVE To identify stakeholder perceptions of key outcomes from supplementary palliative care support services, then map these onto outcome measurement tools to assess relevance and item redundancy. METHODS A scoping review using Arksey and O'Malley's design. EMBASE, CINAHL, MEDLINE and PSYCHinfo searched using terms relating to palliative care, qualitative research and supplementary support interventions. Papers imported into Endnote™, and Covidence™ used by two reviewers to assess against inclusion criteria. Included papers were imported into NVivo™, and thematically coded to identify key concepts underpinning outcomes. Each item within contender outcome measurement tools was assessed against each concept. RESULTS 60 included papers focused on advance care planning, guided conversations, and volunteer befriending services. Four concepts were identified: enriching relationships; greater autonomy and perceived control; knowing more; and improved mental health. Mapping concepts to contender tool items revealed issues of relevance and redundancy. Some tools had no redundant items, but mapped only to two of four outcome themes, others mapped to all concepts, but with many redundant questions. Tools such as ICECAP-SCM and McGill Quality of Life had high relevance and low redundancy. CONCLUSIONS Pertinent outcome concepts for these services and population are not well represented in commonly used outcome measurement tools, and this may have implications in appropriately measuring outcomes. This review and mapping method may have utility in fields where selecting appropriate outcome tools can be challenging.

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

negative: Comparative analyses revealed reduced spread of COVID-19 in malaria endemic countries In late 2019, SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection started in Hubei province of China and now it has spread like a wildfire in almost all parts of the world except some. WHO named the disease caused by SARS-CoV-2 as COVID-19 (CoronaVirus Disease-2019). It is very intriguing to see a mild trend of infection in some countries which could be attributed to mitigation efforts, lockdown strategies, health infrastructure, demographics and cultural habits. However, the lower rate of infection and death rates in mostly developing countries, which are not placed at higher levels in terms of healthcare facilities, is a very surprising observation. To address this issue, we hypothesize that this lower rate of infection is majorly been observed in countries which have a higher transmission/prevalence of protozoan parasite borne disease, malaria. We compared the COVID-19 spread and malaria endemicity of 108 countries which have shown at least 200 cases of COVID-19 till 18th April 2020. We found that the number of COVID-19 cases per million population correlates negatively with the malaria endemicity of respective countries. The malaria free countries not only have higher density of COVID-19 infections but also the higher case fatality rates as compared to highly malaria endemic countries. We also postulate that this phenomenon is due to natural immune response against malaria infection, which is providing a heterologous protection against the virus. Unfortunately, there is no licensed vaccine against SARS-CoV-2 yet, but this information will be helpful in design of future strategies against fast spreading COVID-19 disease.

negative: Predicting the evolution and control of COVID-19 pandemic in Portugal. The Coronavirus (COVID-19) is a world pandemic that has been affecting Portugal since 2 of March 2020. Portuguese government has been making efforts to contradict the exponential growth through social isolation measures. We have developed a mathematical model to predict the impact of such measures in the number of infected cases and peak of infection. We estimate the peak to be around 2 million infected cases by the beginning of May if no additional measures are taken. The model indicates that current measures effectively isolated 25-30% of the population, contributing for some reduction on the infection peak. Importantly, our simulations show that the infection burden can be further reduced with higher isolation degree, providing information for a second intervention.

negative: Using routinely collected data to evaluate risk factors for mortality of veal calves Abstract From 2009 to 2012 a gradual increase in on-farm mortality of Dutch veal calves was observed. In 2012, the cattle industry decided that more information was needed on risk factors for mortality in both veal herds and herds of origin to enable implementation of risk mitigating measures. Routinely collected data were available from seven different data sources and contained information from 2.4 million white veal calves that were fattened in the period between 1 January 2011 and 30 June 2014. Survival analysis techniques (Kaplan-Meier), multilevel Poisson and multilevel Logistic regression models were applied to analyse the data. Two different models were assembled in which risk factors for veal calf mortality in respectively veal herds and herds of origin were identified. Univariable and multivariable regression techniques were used to detect risk factors significantly associated with mortality of veal calves during the fattening period. During the study period, the mean mortality was 4.9% per production cycle. The probability to die was highest during the first weeks after arrival in the veal herds and declined thereafter. Important risk factors included a veal herds with a higher use of antimicrobials, hair colour as proxy for breed, certain countries of origin, veal herd management with a limited amount of supplied feed and a not having an all-in / all-out system. A higher body weight at arrival in the veal herd was associated with lower mortality as well as veal calves that were fed an above median amount of milk, roughage and concentrates. From the calves that were fattened during the study period, observations of 1.1 million calves originated from the Netherlands and were available to study risk factors for veal calf mortality associated with the herd of origin. Important risk factors included purchase, herds with high mortality rates in the quarter in which the calf was born, fast growth in herd size, high cattle replacement rates and a higher antibiotic use in the quarter of birth. Calves that originated from herds that were certified BVD-free, Salmonella-unsuspected or Paratuberculosis-unsuspected, had a lower odds to die during the subsequent fattening period in a veal herd. Veal calf mortality was influenced by risk factors at the herd of origin as well as at veal herds. Adequate collaboration between the different industries is necessary to optimize veal calf management leading to a reduction in veal calf mortality during the fattening period.

negative: Aetiology-Specific Estimates of the Global and Regional Incidence and Mortality of Diarrhoeal Diseases Commonly Transmitted through Food BACKGROUND: Diarrhoeal diseases are major contributors to the global burden of disease, particularly in children. However, comprehensive estimates of the incidence and mortality due to specific aetiologies of diarrhoeal diseases are not available. The objective of this study is to provide estimates of the global and regional incidence and mortality of diarrhoeal diseases caused by nine pathogens that are commonly transmitted through foods. METHODS AND FINDINGS: We abstracted data from systematic reviews and, depending on the overall mortality rates of the country, applied either a national incidence estimate approach or a modified Child Health Epidemiology Reference Group (CHERG) approach to estimate the aetiology-specific incidence and mortality of diarrhoeal diseases, by age and region. The nine diarrhoeal diseases assessed caused an estimated 1.8 billion (95% uncertainty interval [UI] 1.1–3.3 billion) cases and 599,000 (95% UI 472,000–802,000) deaths worldwide in 2010. The largest number of cases were caused by norovirus (677 million; 95% UI 468–1,153 million), enterotoxigenic Escherichia coli (ETEC) (233 million; 95% UI 154–380 million), Shigella spp. (188 million; 95% UI 94–379 million) and Giardia lamblia (179 million; 95% UI 125–263); the largest number of deaths were caused by norovirus (213,515; 95% UI 171,783–266,561), enteropathogenic E. coli (121,455; 95% UI 103,657–143,348), ETEC (73,041; 95% UI 55,474–96,984) and Shigella (64,993; 95% UI 48,966–92,357). There were marked regional differences in incidence and mortality for these nine diseases. Nearly 40% of cases and 43% of deaths caused by these nine diarrhoeal diseases occurred in children under five years of age. CONCLUSIONS: Diarrhoeal diseases caused by these nine pathogens are responsible for a large disease burden, particularly in children. These aetiology-specific burden estimates can inform efforts to reduce diarrhoeal diseases caused by these nine pathogens commonly transmitted through foods.

negative: Congruent epidemic models for unstructured and structured populations: Analytical reconstruction of a 2003 SARS outbreak Abstract Both the threat of bioterrorism and the natural emergence of contagious diseases underscore the importance of quantitatively understanding disease transmission in structured human populations. Over the last few years, researchers have advanced the mathematical theory of scale-free networks and used such theoretical advancements in pilot epidemic models. Scale-free contact networks are particularly interesting in the realm of mathematical epidemiology, primarily because these networks may allow meaningfully structured populations to be incorporated in epidemic models at moderate or intermediate levels of complexity. Moreover, a scale-free contact network with node degree correlation is in accord with the well-known preferred mixing concept. The present author describes a semi-empirical and deterministic epidemic modeling approach that (a) focuses on time-varying rates of disease transmission in both unstructured and structured populations and (b) employs probability density functions to characterize disease progression and outbreak controls. Given an epidemic curve for a historical outbreak, this modeling approach calls for Monte Carlo calculations (that define the average new infection rate) and solutions to integro-differential equations (that describe outbreak dynamics in an aggregate population or across all network connectivity classes). Numerical results are obtained for the 2003 SARS outbreak in Taiwan and the dynamical implications of time-varying transmission rates and scale-free contact networks are discussed in some detail.

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

negative: COPD in Asia: Where East Meets West COPD is a global health concern, and is a major cause of chronic morbidity and mortality worldwide. According to the World Health Organization, it is currently the sixth leading cause of death in the world, and further increases in the prevalence and mortality of the disease is predicted for the coming decades. These increases are mainly linked to the epidemic of tobacco exposure and indoor and outdoor air pollution in Asian countries. The burden of COPD in Asia is currently greater than that in developed Western countries, both in terms of the total number of deaths and the burden of disease, as measured in years of life lost and years spent living with disability. The types of health-care policies and the practice of medicine vary considerably among the regions of Asia and have an impact on the burden of disease. Treatment aims in Asian countries are based on evidence-based management guidelines. Barriers to the implementation of disease management guidelines are related to issues of resource conflict and lack of organizational support rather than cultural differences in medical practice. To reduce this burden of COPD in Asian countries, there is a need for a multifaceted approach in improving awareness of prevalence and disease burden, in facilitating accurate diagnosis of COPD among chronic respiratory diseases, in championing health policies that reduce the burden of the main risk factors for COPD and in the wider use of evidence-based management for COPD.

negative: Numerical investigation of gaseous pollutant cross-transmission for single-sided natural ventilation driven by buoyancy and wind Abstract Single-sided natural ventilation was numerically investigated to determine the impact of buoyancy and wind on the cross-transmission of pollution by considering six window types commonly found in multistory buildings. The goal of this study was to predict the gaseous pollutant transmission using computational fluid dynamics based on the Reynolds-averaged Navier-Stokes equations and baseline k-ω turbulence equations. The results indicated that ventilation rates generally increased with increasing wind speeds if the effects of buoyancy and wind were not suppressed; however, the re-entry ratio representing the proportion of expelled air re-entering other floors and the corresponding risk of infection decreased. If the source of the virus was on a central floor, the risk of infection was the highest on the floors closest to the source. Different window types were also considered for determining their effectiveness in controlling cross-transmission and infection risk, depending on the source location and driving force (e.g., buoyancy and wind).

negative: Genetic analysis of the SARS-coronavirus spike glycoprotein functional domains involved in cell-surface expression and cell-to-cell fusion Abstract The SARS-coronavirus (SARS-CoV) is the etiological agent of severe acute respiratory syndrome (SARS). The SARS-CoV spike (S) glycoprotein mediates membrane fusion events during virus entry and virus-induced cell-to-cell fusion. To delineate functional domains of the SARS-CoV S glycoprotein, single point mutations, cluster-to-lysine and cluster-to-alanine mutations, as well as carboxyl-terminal truncations were investigated in transient expression experiments. Mutagenesis of either the coiled-coil domain of the S glycoprotein amino terminal heptad repeat, the predicted fusion peptide, or an adjacent but distinct region, severely compromised S-mediated cell-to-cell fusion, while intracellular transport and cell-surface expression were not adversely affected. Surprisingly, a carboxyl-terminal truncation of 17 amino acids substantially increased S glycoprotein-mediated cell-to-cell fusion suggesting that the terminal 17 amino acids regulated the S fusogenic properties. In contrast, truncation of 26 or 39 amino acids eliminating either one or both of the two endodomain cysteine-rich motifs, respectively, inhibited cell fusion in comparison to the wild-type S. The 17 and 26 amino-acid deletions did not adversely affect S cell-surface expression, while the 39 amino-acid truncation inhibited S cell-surface expression suggesting that the membrane proximal cysteine-rich motif plays an essential role in S cell-surface expression. Mutagenesis of the acidic amino-acid cluster in the carboxyl terminus of the S glycoprotein as well as modification of a predicted phosphorylation site within the acidic cluster revealed that this amino-acid motif may play a functional role in the retention of S at cell surfaces. This genetic analysis reveals that the SARS-CoV S glycoprotein contains extracellular domains that regulate cell fusion as well as distinct endodomains that function in intracellular transport, cell-surface expression, and cell fusion.

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: Prevalence of Comorbidities Among Individuals With COVID-19: A Rapid Review of current Literature On February 11, 2020 WHO designated the name “COVID-19” for the disease caused by “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2), a novel virus that first occurred in Wuhan, China, but quickly turned into a global pandemic. As of June 29, 2020, it has claimed 502,947 lives and is present in more than 213 countries worldwide. Risks associated with acquiring the virus and with its severe outcomes have been reported in various studies, which has led health organizations and governments to develop and institute a variety of preventative and control measures. With constantly growing scientific understanding on this topic, updated information can help equip health and public sectors with the most current knowledge. In this literature review we explore the prevalence of comorbidity among individuals with COVID-19 and summarize our findings based on information available as of May 15, 2020. Overall, we found that comorbidities including Hypertension (27.4%), Diabetes (17.4%), and Cardiovascular Disease (8.9%) are quite prevalent in COVID-19 patients across major epicenters worldwide and is associated with increased disease severity but not clearly to fatality (OR 0.83, CI[0.60-0.99], p <0.05). Understanding of COVID-19 characteristics and association to common global health problems may provide support and direction to policy makers, clinicians, and researchers in developing shielding strategies to mitigate the COVID-19 pandemic and its severe outcomes.

negative: SARS-CoV-2 launches a unique transcriptional signature from in vitro, ex vivo, and in vivo systems One of the greatest threats to humanity is the emergence of a pandemic virus. Among those with the greatest potential for such an event include influenza viruses and coronaviruses. In the last century alone, we have observed four major influenza A virus pandemics as well as the emergence of three highly pathogenic coronaviruses including SARS-CoV-2, the causative agent of the ongoing COVID-19 pandemic. As no effective antiviral treatments or vaccines are presently available against SARS-CoV-2, it is important to understand the host response to this virus as this may guide the efforts in development towards novel therapeutics. Here, we offer the first in-depth characterization of the host transcriptional response to SARS-CoV-2 and other respiratory infections through in vitro, ex vivo, and in vivo model systems. Our data demonstrate the each virus elicits both core antiviral components as well as unique transcriptional footprints. Compared to the response to influenza A virus and respiratory syncytial virus, SARS-CoV-2 elicits a muted response that lacks robust induction of a subset of cytokines including the Type I and Type III interferons as well as a numerous chemokines. Taken together, these data suggest that the unique transcriptional signature of this virus may be responsible for the development of COVID-19.

negative: Mortality of Life‐Insured Swedish Cats during 1999–2006: Age, Breed, Sex, and Diagnosis Background: A cat life insurance database can potentially be used to study feline mortality. Hypothesis: The aim was to describe patterns of mortality in life‐insured Swedish cats. Cats: All cats (<13 years of age) with life insurance during the period 1999–2006 were included. Methods: Age‐standardized mortality rates (MR) were calculated with respect to sex (males and females), age, breed, and diagnosis. Survival to various ages is presented by time period and breed. Results: The total number of cats insured was 49,450 and the number of cat‐years at risk (CYAR) was 142,049. During the period, 6,491 cats died and of these 4,591 cats (71%) had a diagnosis, ie, were claimed for life insurance. The average annual MR was 462 deaths per 10,000 CYAR (95% confidence interval, 431–493). Sex‐specific rates did not differ significantly. The overall mortality of the Persian and the Siamese groups was higher than that of several other breeds. Overall and breed‐specific (for most breeds) survival increased with time when analyzed by 2‐year periods. The 6 most common diagnostic categories (ignoring cats recorded as dead with no diagnosis) were urinary, traumatic, neoplastic, infectious, cardiovascular, and gastrointestinal. The MR within diagnostic categories varied by age and breed. Conclusions and Clinical Importance: In this mainly purebred, insured cat population, the overall mortality varied with age and breed but not with sex. The increase in survival over time is likely a reflection of willingness to keep pet cats longer and increased access to and sophistication of veterinary care.

negative: Global Mortality Impact of the 1957–1959 Influenza Pandemic Background. Quantitative estimates of the global burden of the 1957 influenza pandemic are lacking. Here we fill this gap by modeling historical mortality statistics. Methods. We used annual rates of age- and cause-specific deaths to estimate pandemic-related mortality in excess of background levels in 39 countries in Europe, the Asia-Pacific region, and the Americas. We modeled the relationship between excess mortality and development indicators to extrapolate the global burden of the pandemic. Results. The pandemic-associated excess respiratory mortality rate was 1.9/10 000 population (95% confidence interval [CI], 1.2–2.6 cases/10 000 population) on average during 1957–1959. Excess mortality rates varied 70-fold across countries; Europe and Latin America experienced the lowest and highest rates, respectively. Excess mortality was delayed by 1–2 years in 18 countries (46%). Increases in the mortality rate relative to baseline were greatest in school-aged children and young adults, with no evidence that elderly population was spared from excess mortality. Development indicators were moderate predictors of excess mortality, explaining 35%–77% of the variance. Overall, we attribute 1.1 million excess deaths (95% CI, .7 million–1.5 million excess deaths) globally to the 1957–1959 pandemic. Conclusions. The global mortality rate of the 1957–1959 influenza pandemic was moderate relative to that of the 1918 pandemic but was approximately 10-fold greater than that of the 2009 pandemic. The impact of the pandemic on mortality was delayed in several countries, pointing to a window of opportunity for vaccination in a future pandemic.

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

negative: Viral Evasion Strategies in Type I IFN Signaling – A Summary of Recent Developments The immune system protects the organism against infections and the damage associated with them. The first line of defense against pathogens is the innate immune response. In the case of a viral infection, it induces the interferon (IFN) signaling cascade and eventually the expression of type I IFN, which then causes an antiviral state in the cells. However, many viruses have developed strategies to counteract this mechanism and prevent the production of IFN. In order to modulate or inhibit the IFN signaling cascade in their favor, viruses have found ways to interfere at every single step of the cascade, for example, by inducing protein degradation or cleavage, or by mediate protein polyubiquitination. In this article, we will review examples of viruses that modulate the IFN response and describe the mechanisms they use.

negative: Assessment of Temporary Community-Based Health Care Facilities During Arbaeenia Mass Gathering at Karbala, Iraq: Cross-Sectional Survey Study BACKGROUND: Arbaeenia mass gathering (MG) in Karbala, Iraq, is becoming one of the largest MGs in the world. The health care infrastructure in Iraq is inadequately prepared to serve the health needs of the millions of pilgrims. OBJECTIVE: This study aimed to describe the temporary health care facilities installed and run by the local community to provide health care services to Arbaeenia pilgrims in Karbala, Iraq. METHODS: A survey was conducted in all community-based health care facilities located along part of Najaf to Karbala road within Karbala governorate. A structured questionnaire was answered through an interview with the workers and direct observation. Data were collected on staff profile, type of services provided, use of basic infection control measures, medical equipment, drugs and supplies, and the most commonly encountered medical problems. RESULTS: The total number of health care facilities was 120, staffed by 659 workers. Only 18 (15.0%, 18/120) facilities were licensed, and 44.1% (53/120) of the workers were health professionals. The health care workers provided different services including dispensing drugs (370/1692, 21.87%), measuring blood pressure and blood sugar (350/1692, 20.69%), and caring for wounds and injuries (319/1692, 18.85%). Around 97% (116/120) health facilities provided services for musculoskeletal disorders and only 16.7% (20/120) provided services for injuries. The drugs available in the clinic were analgesics, drugs for gastrointestinal and respiratory diseases, and antibiotics, with an availability range of 13.3% to 100.0%. Infection control practices for individual protection, environmental sanitation, and medical waste disposal were available in a range of 18.1% to 100.0%. CONCLUSIONS: Community-based health care facilities experienced a profound shortage of trained human resources and medical supplies. They can significantly contribute to health services if they are adequately equipped and follow standardized operation procedures.

negative: Intervention strategies against COVID-19 and their estimated impact on Swedish healthcare capacity Objectives: During March 2020, the COVID-19 pandemic has rapidly spread globally, and non-pharmaceutical interventions are being used to reduce both the load on the healthcare system as well as overall mortality. Design: Individual-based transmission modelling using Swedish demographic and Geographical Information System data and conservative COVID-19 epidemiological parameters. Setting: Sweden Participants: A model to simulate all 10.09 million Swedish residents. Interventions: 5 different non-pharmaceutical public-health interventions including the mitigation strategy of the Swedish government as of 10 April; isolation of the entire household of confirmed cases; closure of schools and non-essential businesses with or without strict social distancing; and strict social distancing with closure of schools and non-essential businesses. Main outcome measures: Estimated acute care and intensive care hospitalisations, COVID-19 attributable deaths, and infections among healthcare workers from 10 April until 29 June. Findings: Our model for Sweden shows that, under conservative epidemiological parameter estimates, the current Swedish public-health strategy will result in a peak intensive-care load in May that exceeds pre-pandemic capacity by over 40-fold, with a median mortality of 96,000 (95% CI 52,000 to 183,000). The most stringent public-health measures examined are predicted to reduce mortality by approximately three-fold. Intensive-care load at the peak could be reduced by over two-fold with a shorter period at peak pandemic capacity. Conclusions: Our results predict that, under conservative epidemiological parameter estimates, current measures in Sweden will result in at least 40-fold over-subscription of pre-pandemic Swedish intensive care capacity, with 15.8 percent of Swedish healthcare workers unable to work at the pandemic peak. Modifications to ICU admission criteria from international norms would further increase mortality.

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: Giardiosis and other enteropathogenic infections: a study on diarrhoeic calves in Southern Germany BACKGROUND: Diarrhoea induces massive problems in the rearing of calves. The aim of the study was to obtain current data about the frequency of Giardia spp., Cryptosporidium spp. and Eimeria spp. in diarrhoeic calves in Southern Germany with the particular focus on giardiosis. RESULTS: 1564 samples were analysed for the three pathogens using microscopical methods. Giardia spp. was detectable in 112/1564 samples (7.2%). The mean age was 46.5 days and the odds of being infected with Giardia spp. increased slowly up to 8 times from about 12 days to 30 days of age. There appeared to be no seasonal influence on the frequency of Giardia spp. A mono-infection with Giardia spp. was diagnosed in 46 calves (2.9%) whereas 15 calves (1.0%) had a mixed-infection with Cryptosporidium spp. and 51 calves (3.3%) with Eimeria spp. Cryptosporidium spp. and Eimeria spp. could be detected in 646/1564 samples (41.3%) and 208/1564 samples (13.3%), respectively, with a mean age of 11.3 and 55.0 days, respectively. The odds of being infected with Cryptosporidium spp. increased up to 4.5 times until an age of 10 days. After that the odds decreased continuously and was approaching zero at about 30 days. The odds of being infected with Eimeria spp. increased continuously up to 30 times from about 20 days to 60 days of age. There appeared to be no significant seasonal influence on the frequency of Cryptosporidium spp.; but there was one for Eimeria spp.: the odds of being infected with Eimeria spp. in March and April decreased by about half and increased up to 2.3 times between July and September. Additionally, as requested by the veterinarians, 1282 of those samples were analysed for E. coli, Rota-, Coronavirus and Cryptosporidium spp. using an ELISA. Obtained frequencies for these pathogens were 0.9%, 37.8%, 3.4% and 45.3% with a mean age of 24.8 days, 12.1 days, 9.0 days and 12.1 days, respectively. CONCLUSIONS: The results indicate that in Southern Germany in addition to Eimeria spp., Giardia spp. seems to play a contributing role in diarrhoea in older calves, whereas Cryptosporidium spp. and Rotavirus are mostly relevant in young calves.

negative: Covid-19 is no worse in immunocompromised children, says NICE.

negative: No evidence that androgen regulation of pulmonary TMPRSS2 explains sex-discordant COVID-19 outcomes The recent emergence of SARS-CoV-2 and the subsequent COVID-19 pandemic have posed a public health crisis. Higher morbidity and mortality of men with COVID-19 may be explained by androgen-driven mechanisms. One such proposed mechanism is androgen regulation of pulmonary TMPRSS2, the host co-receptor for SARS-CoV-2. We find no evidence for increased TMPRSS2 mRNA expression in the lungs of males compared to females in humans or mice. Furthermore, in male mice, treatment with the androgen receptor antagonist enzalutamide does not decrease pulmonary TMPRSS2 expression. Nevertheless, regardless of sex, smoking significantly increases the expression of TMPRSS2, which reverts back to never-smoker levels in former smokers. Finally, we show that in mouse models, despite equivalent AR transcript levels, males express markedly higher amounts of AR protein. If a similar sex-specific regulation of AR protein occurs in human lung, androgens could play important roles in clinical outcome of COVID-19 through mechanisms other than TMPRSS2 regulation.

negative: What Has SARS Taught Us About Infection Control in Nursing Homes?

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: Household transmissions of SARS-CoV-2 in the time of unprecedented travel lockdown in China IMPORTANCE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the city of Wuhan, China, in December 2019 and then spread globally. Limited information is available for characterizing epidemiological features and transmission patterns in the regions outside of Hubei Province. Detailed data on transmission at the individual level could be an asset to understand the transmission mechanisms and respective patterns in different settings. OBJECTIVE: To reconstruct infection events and transmission clusters of SARS-CoV-2 for estimating epidemiological characteristics at household and non-household settings, including super-spreading events, serial intervals, age- and gender-stratified risks of infection in China outside of Hubei Province. DESIGN, SETTING, AND PARTICIPANTS: 9,120 confirmed cases reported online by 264 Chinese urban Health Commissions in 27 provinces from January 20 to February 19, 2020. A line-list database is established with detailed information on demographic, social and epidemiological characteristics. The infection events are categorized into the household and non-household settings. EXPOSURES: Confirmed cases of SARS-CoV-2 infections. MAIN OUTCOMES AND MEASURES: Information about demographic characteristics, social relationships, travel history, timelines of potential exposure, symptom onset, confirmation, and hospitalization were extracted from online public reports. 1,407 infection events formed 643 transmission clusters were reconstructed. RESULTS: In total 34 primary cases were identified as super spreaders, and 5 household super-spreading events were observed. The mean serial interval is estimated to be 4.95 days (standard deviation: 5.24 days) and 5.19 days (standard deviation: 5.28 days) for households and non-household transmissions, respectively. The risk of being infected outside of households is higher for age groups between 18 and 64 years, whereas the hazard of being infected within households is higher for age groups of young (<18) and elderly (>65) people. CONCLUSIONS AND RELEVANCE: The identification of super-spreading events, short serial intervals, and a higher risk of being infected outside of households for male people of age between 18 and 64 indicate a significant barrier to the case identification and management, which calls for intensive non-pharmaceutical interventions (e.g. cancellation of public gathering, limited access of public services) as the potential mitigation strategies.

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

negative: Flattening the curve before it flattens us: hospital critical care capacity limits and mortality from novel coronavirus (SARS-CoV2) cases in US counties ABSTRACT Background As of March 26, 2020, the United States had the highest number of confirmed cases of Novel Coronavirus (COVID-19) of any country in the world. Hospital critical care is perhaps the most important medical system choke point in terms of preventing deaths in a disaster scenario such as the current COVID-19 pandemic. We therefore brought together previously established disease modeling estimates of the growth of the COVID-19 epidemic in the US under various social distancing contact reduction assumptions, with local estimates of the potential critical care surge response across all US counties. Methods Estimates of spatio-temporal COVID-19 demand and medical system critical care supply were calculated for all continental US counties. These estimates were statistically summarized and mapped for US counties, regions and urban versus non-urban areas. Estimates of COVID-19 infections and patients needing critical care were calculated from March 24, 2020 to April 24, 2020 for three different estimated population levels - 0%, 25%, and 50% - of contact reduction (through actions such as social distancing). Multiple national public and private datasets were linked and harmonized in order to calculate county-level critical care bed counts that included currently available beds and those that could be made available under four surge response scenarios - very low, low, medium, and high - as well as excess deaths stemming from inaccessible critical care. Results Surge response scenarios ranged from a very low total supply 77,588 critical care beds to a high total of 278,850 critical care beds. Over the four week study period, excess deaths from inaccessible critical care ranged from 24,688 in the very low response scenario to 13,268 in the high response scenario. Northeastern and urban counties were projected to be most affected by excess deaths due to critical care shortages, and counties in New York, Colorado, and Virginia were projected to exceed their critical care bed limits despite high levels of COVID-19 contact reduction. Over the four week study period, an estimated 12,203-19,594 excess deaths stemming from inaccessible critical care could be averted through greater preventive actions such as travel restrictions, publicly imposed contact precautions, greater availability of rapid testing for COVID-19, social distancing, self-isolation when sick, and similar interventions. An estimated 4,029-11,420 excess deaths stemming from inaccessible critical care could be averted through aggressive critical care surge response and preparations, including high clearance of ICU and non-ICU critical care beds and extraordinary measures like using a single ventilator for multiple patients. Conclusions Unless the epidemic curve of COVID-19 cases is flattened over an extended period of time, the US COVID-19 epidemic will cause a shortage of critical care beds and drive up otherwise preventable deaths. The findings here support value of preventive actions to flatten the epidemic curve, as well as the value of exercising extraordinary surge capacity measures to increase access to hospital critical care for severely ill COVID-19 patients.

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: The Epidemic Process in Zoonoses and Sapronoses This chapter could also be called eco-epidemiological basics or background information for zoonoses and sapronoses. Epidemiology is the study of the process of the origin and spread of transmissible (communicable) infectious diseases of man, and their control. The modern conception of epidemiology is broader in that it also includes non-infectious diseases (such as diabetes, heart attack, cardiovascular diseases and carcinomas) and variables that influence their distribution in the human population. In both the classical and modern conception of epidemiology, these factors include variables concerning the host (age, sex, nutrition, occupation), the agent (virulence, antigenic variability), and the environment (chemical factors, contamination, emissions, temperature, precipitation and humidity, illumination, ionising radiation, noise etc.). Epidemiological data are then analysed, and the results of these studies can then be used for the prevention and control of these human diseases.

negative: COVID-19: towards controlling of a pandemic

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: Semi-quantitative visual assessment of chest radiography is associated with clinical outcomes in critically ill patients BACKGROUND: Respiratory pathology is a major driver of mortality in the intensive care unit (ICU), even in the absence of a primary respiratory diagnosis. Prior work has demonstrated that a visual scoring system applied to chest radiographs (CXR) is associated with adverse outcomes in ICU patients with Acute Respiratory Distress Syndrome (ARDS). We hypothesized that a simple, semi-quantitative CXR score would be associated with clinical outcomes for the general ICU population, regardless of underlying diagnosis. METHODS: All individuals enrolled in the Registry of Critical Illness at Brigham and Women’s Hospital between June 2008 and August 2018 who had a CXR within 24 h of admission were included. Each patient’s CXR was assigned an opacification score of 0–4 in each of four quadrants with the total score being the sum of all four quadrants. Multivariable negative binomial, logistic, and Cox regression, adjusted for age, sex, race, immunosuppression, a history of chronic obstructive pulmonary disease, a history of congestive heart failure, and APACHE II scores, were used to assess the total score’s association with ICU length of stay (LOS), duration of mechanical ventilation, in-hospital mortality, 60-day mortality, and overall mortality, respectively. RESULTS: A total of 560 patients were included. Higher CXR scores were associated with increased mortality; for every one-point increase in score, in-hospital mortality increased 10% (OR 1.10, CI 1.05–1.16, p < 0.001) and 60-day mortality increased by 12% (OR 1.12, CI 1.07–1.17, p < 0.001). CXR scores were also independently associated with both ICU length of stay (rate ratio 1.06, CI 1.04–1.07, p < 0.001) and duration of mechanical ventilation (rate ratio 1.05, CI 1.02–1.07, p < 0.001). CONCLUSIONS: Higher values on a simple visual score of a patient’s CXR on admission to the medical ICU are associated with increased in-hospital mortality, 60-day mortality, overall mortality, length of ICU stay, and duration of mechanical ventilation.

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

negative: Developing vaccines against epidemic-prone emerging infectious diseases Today’s world is characterized by increasing population density, human mobility, urbanization, and climate and ecological change. This global dynamic has various effects, including the increased appearance of emerging infectious diseases (EIDs), which pose a growing threat to global health security. Outbreaks of EIDs, like the 2013–2016 Ebola outbreak in West Africa or the current Ebola outbreak in Democratic Republic of the Congo (DRC), have not only put populations in low- and middle-income countries (LMIC) at risk in terms of morbidity and mortality, but they also have had a significant impact on economic growth in affected regions and beyond. The Coalition for Epidemic Preparedness Innovation (CEPI) is an innovative global partnership between public, private, philanthropic, and civil society organizations that was launched as the result of a consensus that a coordinated, international, and intergovernmental plan was needed to develop and deploy new vaccines to prevent future epidemics. CEPI is focusing on supporting candidate vaccines against the World Health Organization (WHO) Blueprint priority pathogens MERS-CoV, Nipah virus, Lassa fever virus, and Rift Valley fever virus, as well as Chikungunya virus, which is on the WHO watch list. The current vaccine portfolio contains a wide variety of technologies, ranging across recombinant viral vectors, nucleic acids, and recombinant proteins. To support and accelerate vaccine development, CEPI will also support science projects related to the development of biological standards and assays, animal models, epidemiological studies, and diagnostics, as well as build capacities for future clinical trials in risk-prone contexts.

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

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

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

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

negative: Prevalence of Diabetes in the 2009 Influenza A (H1N1) and the Middle East Respiratory Syndrome Coronavirus: A Systematic Review and Meta-Analysis Over the past two decades a number of severe acute respiratory infection outbreaks such as the 2009 influenza A (H1N1) and the Middle East respiratory syndrome coronavirus (MERS-CoV) have emerged and presented a considerable global public health threat. Epidemiologic evidence suggests that diabetic subjects are more susceptible to these conditions. However, the prevalence of diabetes in H1N1 and MERS-CoV has not been systematically described. The aim of this study is to conduct a systematic review and meta-analysis of published reports documenting the prevalence of diabetes in H1N1 and MERS-CoV and compare its frequency in the two viral conditions. Meta-analysis for the proportions of subjects with diabetes was carried out in 29 studies for H1N1 (n=92,948) and 9 for MERS-CoV (n=308). Average age of H1N1 patients (36.2±6.0 years) was significantly younger than that of subjects with MERS-CoV (54.3±7.4 years, P<0.05). Compared to MERS-CoV patients, subjects with H1N1 exhibited 3-fold lower frequency of cardiovascular diseases and 2- and 4-fold higher prevalence of obesity and immunosuppression, respectively. The overall prevalence of diabetes in H1N1 was 14.6% (95% CI: 12.3-17.0%; P<0.001), a 3.6-fold lower than in MERS-CoV (54.4%; 95% CI: 29.4-79.5; P<0.001). The prevalence of diabetes among H1N1 cases from Asia and North America was ~two-fold higher than those from South America and Europe. The prevalence of diabetes in MERS-CoV cases is higher than in H1N1. Regional comparisons suggest that an etiologic role of diabetes in MERS-CoV may exist distinctive from that in H1N1.

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

negative: An age-structured epidemiological model of the Belgian COVID-19 epidemic COVID-19 has prompted many countries to implement extensive social distancing to stop the rapid spread of the virus, in order to prevent overloading health care systems. Yet, the main epidemic parameters of this virus are not well understood. In the absence of broad testing or serological surveillance, it is hard to evaluate or predict the impact of different strategies to exit implemented lock-down measures. An age-structured epidemiological model was developed, which distinguishes between the younger versus older population (e.g. < 65 and >= 65). Because the illness severity is markedly different for these two populations, such a separation is necessary then estimating the model based on death and hospitalization incidence data. The model was applied to data of the Belgian epidemic and used to predict how the epidemic would react to a relaxing of social distancing measures.

negative: Influenza Influenza is one of the commonest infections in human populations, and causing substantial morbidity and mortality globally. The influenza virus is divided into different types and subtypes, three of which are currently circulating widely in humans: influenza A(H3N2) and influenza B. The virus undergoes constant evolution, leading to annual seasonal winter epidemics in temperate countries and necessitating annual updates to the vaccine. Rarely, completely new influenza viruses can emerge in human populations, giving rise to influenza pandemics. Children aged <5 years (especially those <2 years) and those with underlying illness such as cardiac, respiratory and severe neurologic disease have an increased risk of severe outcomes associated with influenza. Pregnant women have an increased risk of severe influenza. Complications may involve the respiratory tract (e.g. otitis media or pneumonia) or, less commonly, other organ systems (e.g. encephalitis or myocarditis). Specific antiviral treatment should be offered as soon as possible for hospitalized children with presumed or confirmed influenza and for influenza of any severity for children at high risk of severe complications of influenza without waiting for laboratory confirmation. Antiviral treatment is usually not warranted for uncomplicated influenza as this is usually self-limiting. Annual influenza vaccination should be offered to all individuals at increased risk for complications of influenza. Vaccine cannot be given to children aged <6 months but maternal influenza immunization during pregnancy is recommended and can confer protection to the young infant.

negative: The Infection Rate of the Coronavirus Disease 2019 (COVID-19) in Wuhan, China For the pandemic of COVID-19, the initial number of infections in Wuhan China has never been known or estimated properly. This data is critical to understand the current pandemic across the world, as well as to eliminate panic from overestimated fatality rate that has biased the public health policies of many countries. By our unique estimation with the data of a number of foreign government evacuations with thorough follow-up and etiological tests, it is safe to say that a large number of infections in Wuhan, China have not been diagnosed (the number of undiagnosed is much more than the final diagnosed number 50,333 to date).

negative: Respiratory Infections, Acute Acute respiratory tract infections are an extremely common and important source of morbidity and mortality. Despite advances in our understanding of microbial pathogens and the development of novel antimicrobial agents, acute respiratory tract infections continue to place an enormous burden on global health expenditure. Acute respiratory tract infections can be divided into infections that predominantly affect the upper respiratory tract above the vocal cords and those that affect the lower respiratory tract. The clinical features, causative pathogens, and therapies of common acute respiratory tract infections are detailed in this article.

negative: COVID-19: the gendered impacts of the outbreak

negative: Modeling the COVID-19 outbreaks and the effectiveness of the containment measures adopted across countries On March 11, 2020, the World Health Organization declared the COVID-19 outbreak, originally started in China, a global pandemic. Since then, the outbreak has indeed spread across all continents, threatening the public health of numerous countries. Although the Case Fatality Rate (CFR) of COVID-19 is relatively low when optimal level of healthcare is granted to the patients, the high percentage of severe cases developing severe pneumonia and thus requiring respiratory support is worryingly high, and could lead to a rapid saturation of Intensive Care Units (ICUs). To overcome this risk, most countries enacted COVID-19 containment measures. In this study, we use a Bayesian SEIR epidemiological model to perform a parametric regression over the COVID-19 outbreaks data in China, Italy, Belgium, and Spain, and estimate the effect of the containment measures on the basic reproduction ratio R_0. We find that the effect of these measures is detectable, but tends to be gradual, and that a progressive strengthening of these measures usually reduces the R_0 below 1, granting a decay of the outbreak. We also discuss the biases and inconsistencies present in the publicly available data on COVID-19 cases, providing an estimate for the actual number of cases in Italy on March 12, 2020. Lastly, despite the data and model's limitations, we argue that the idea of "flattening the curve" to reach herd immunity is likely to be unfeasible.

negative: Respiratory viruses in patients with influenza-like illness in Senegal: Focus on human respiratory adenoviruses BACKGROUND: Human adenoviruses (HAdVs) are highly contagious pathogens that are associated with a wide spectrum of human illnesses involving the respiratory tract. In the present study, we investigate the epidemiologic and viral molecular features of HAdVs circulating in Senegal after 4 consecutive years of sentinel surveillance of influenza-like Illness cases. METHODOLOGY AND RESULTS: From January 2012 to December 2015 swabs were collected from consenting ILI outpatients. Adenoviral detection is performed by rRT-PCR with the Anyplex(™) II RV16 Detection kit (Seegene) and molecular characterization was performed using a partial hexon gene sequence. 6381 samples were collected. More than half of patients (51.7%; 3297/6381) were children of ≤ 5 years. 1967 (30.8%) were positive for HAdV with 1561 (79.4%) found in co-infection with at least one another respiratory virus. The most common co-detections were with influenza viruses (53.1%; 1045/1967), rhinoviruses (30%; 591/1967), enteroviruses (18.5%; 364/1967) and RSV (13.5%; 266/1967). Children under 5 were the most infected group (62.2%; 1224/1967; p <0.05). We noted that HAdV was detected throughout the year at a high level with detection peaks of different amplitudes without any clear seasonality. Phylogenetic analysis revealed species HAdV-C in majority, species HAdV-B and one HAdV- 4 genome type. The 9 HAdV-B species like strains from Senegal grouped with genome types HAdV-7, HAdV-55 and HAdV-11 as shown by a phylogenetic branch with a high bootstrap value of (88%). CONCLUSION: In conclusion, the results of the present study suggest strong year-round HAdV activity in Senegal, especially in children up to 5 years of age. Molecular studies revealed that the dominant species in circulation in patients with ILI appears to be HAdV-C and HAdV-B species. The circulation of though HAdV-7 and HAdV-55 genome types is of note as these serotypes are recognized causes of more severe and even fatal acute respiratory infections.

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: Global Variability in Reported Mortality for Critical Illness during the 2009-10 Influenza A(H1N1) Pandemic: A Systematic Review and Meta-Regression to Guide Reporting of Outcomes during Disease Outbreaks PURPOSE: To determine how patient, healthcare system and study-specific factors influence reported mortality associated with critical illness during the 2009–2010 Influenza A (H1N1) pandemic. METHODS: Systematic review with meta-regression of studies reporting on mortality associated with critical illness during the 2009–2010 Influenza A (H1N1) pandemic. DATA SOURCES: Medline, Embase, LiLACs and African Index Medicus to June 2009-March 2016. RESULTS: 226 studies from 50 countries met our inclusion criteria. Mortality associated with H1N1-related critical illness was 31% (95% CI 28–34). Reported mortality was highest in South Asia (61% [95% CI 50–71]) and Sub-Saharan Africa (53% [95% CI 29–75]), in comparison to Western Europe (25% [95% CI 22–30]), North America (25% [95% CI 22–27]) and Australia (15% [95% CI 13–18]) (P<0.0001). High income economies had significantly lower reported mortality compared to upper middle income economies and lower middle income economies respectively (P<0.0001). Mortality for the first wave was non-significantly higher than wave two (P = 0.66). There was substantial variability in reported mortality among the specific subgroups of patients: unselected critically ill adults (27% [95% CI 24–30]), acute respiratory distress syndrome (37% [95% CI 32–44]), acute kidney injury (44% [95% CI 26–64]), and critically ill pregnant patients (10% [95% CI 5–19]). CONCLUSION: Reported mortality for outbreaks and pandemics may vary substantially depending upon selected patient characteristics, the number of patients described, and the region and economic status of the outbreak location. Outcomes from a relatively small number of patients from specific regions may lead to biased estimates of outcomes on a global scale.

negative: COVID-19 - Considerations for the paediatric rheumatologist The novel coronavirus SARS-CoV2 is a threat to the health and well-being of millions of lifes across the globe. A significant proportion of adult patients require hospitalisation and may develop severe life-threatening complications. Children, on the other hand, can carry and transmit the virus, but usually do not develop severe disease. Mortality in the paediatric age-group is relatively low. Differences in virus containment and clearance, as well as reduced inflammation-related tissue and organ damage may be caused by age-specific environmental and host factors. Since severe complications in adults are frequently caused by uncontrolled immune responses and a resulting "cytokine storm" that may be controlled by targeted blockade of cytokines, previously established treatment with immunosuppressive treatments may indeed protect children from complications.

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 Indian perspective of COVID-19 outbreak The emerging infection of COVID-19 was initiated from Wuhan, China, have been spread to more than 210 countries around the globe including India. The clinical symptoms of COVID-19 are very similar to other respiratory viruses. The number of laboratory-confirmed cases and associated deaths are increasing regularly in various parts of the World. Seven coronaviruses (229E, NL63, OC43, HKU1, SARS, MERS and, COVID-19) can naturally infect human beings. Out of these four (229E-CoV, NL63-CoV, OC43-CoV, HKU1-CoV) are responsible for mild upper respiratory infections, while SARS-CoV, MERS-CoV, and COVID-19 are well known for their high mortality. Few mild strains of coronaviruses are circulating in India but there is no evidence of SARS and MERS outbreaks. The COVID-19 is an emerging viral infection responsible for pandemics. Fortunately, the mortality of COVID-19 is low as compared with SARS and MERS, the majority of its cases are recovered. The death toll of COVID-19 is high even after its low mortality because COVID-19 causes a pandemic while SARS-CoV and MERS-CoV cause epidemics only. COVID-19 influenced the large segments of the world population, which led to a public health emergency of international concern, putting all health organizations on high alert. COVID-19 is the first coronavirus after Spanish Flu 1918–1919, who has extremely influenced the health system, economy, and psychology of India. The present study review is on the general continent, virology, pathogenesis, global epidemiology, clinical presentation, diagnosis, treatment and control of COVID-19 with the reference to India.

negative: Risky Bodies in the Plasma Bioeconomy: A Feminist Analysis In 2003 the UK National Blood Service introduced a policy of ‘male donor preference’ which involved women’s plasma being discarded following blood collection. The policy was based on the view that data relating to the incidence of Transfusion-Related Acute Lung Injury (TRALI) was linked to transfusion with women’s plasma. While appearing to treat female donors as equal to male donors, exclusion criteria operate after donation at the stage of processing blood, thus perpetuating myths of universality even though only certain ‘extractions’ from women are retained for use in transfusion. Many women in the UK receive a plasma-derived product called Anti-D immunoglobulin which is manufactured from pooled male plasma. This article examines ways in which gender has significance for understanding blood relations, and how the blood economy is gendered. In our study of relations between blood donors and recipients, we explore how gendered bodies are produced through the discursive and material practices within blood services. We examine both how donation policies and the manufacturing and use of blood products produces gendered blood relations.

negative: A prototype for decision support tool to help decision-makers with the strategy of handling the COVID-19 UK epidemic The primary objective of this work is to model and compare different exit scenarios from the lock-down for the COVID-19 UK epidemic. In doing so we provide an additional modelling basis for laying out the strategy options for the decision-makers. The main results are illustrated and discussed in Part I. In Part II, we describe the stochastic model that we have developed for modelling this epidemic. As argued in Part II, the developed model is more flexible than the SEIR/SEIRS models and can be used for modelling the scenarios which may be difficult or impossible to model with the SEIR/SEIRS models. To compare different scenarios for exiting from the lock-down, in Part III we provide our previous report on the same topic where similar (although not as detailed) scenarios were considered. As the possible exit dates, we have chosen May 4, May 11, May 18 and May 25. We model differently the regions with high initial reproductive number chosen to be R0=2.5, medium R0=2.3 and low R0=2.The numbers for the whole of the UK can be obtained by appropriate averaging of the numbers given in the report. Typical figures are given in Section 4. For each scenario considered, we plot the expected proportion of infected at time t and the expected number of deaths at time t. To compute the expected numbers of deaths we used the total mortality rate 0.66%. Many recent studies suggest lower values and therefore the numbers in our projections should be considered as rather pessimistic. Our analysis suggests a value around 0.5% for the mortality rate. In the model, we assume that the isolation of older and vulnerable people continues and the public carries on certain level of isolation until the end of 2020; also we assume that immunity is kept for at least a year and there is no international travel influence. Our main conclusions are: In regions with higher initial reproductive number 2.5 the proportion of susceptible at the start of the lock-down should be not smaller than 0.95, the epidemic curve in such regions is in the fast monotonic decline irrespectively of the date of the lock-down lift; In regions with lower initial reproductive number 2.0 the second mild wave can be expected, the difference between the expected mortality rates is very small for all May 2020 lifting lock-down dates; In regions with initial reproductive number 2.3, a mild second wave can be expected in the case of large proportion of susceptible at the start of the lock-down, but its severity and resulting mortality depend very little on the date of lifting the lock-down; For the overall UK epidemic, even for rather pessimistic scenarios considered, the second wave is much less pronounced (in terms of the expected mortality rate) than the first one, and the total numbers of expected deaths are within 2% for all May 2020 dates of lifting the lock-down. Moreover, by keeping R0-value after lifting the lock-down below 1.75 is likely to lead to the avoidance of a UK-wide second wave, see Section 4. We believe that the model build in this work can be considered as an important decision support tool to help decision-makers with the strategy of handling the epidemic. We invite other scholars to participate in an open discussion of the strategy options. We feel that this kind of models should be used in the short and long term management of the disease. We recommend the development of a permanent and modularised modelling suite for COVID-19 management to which additional modules can be added as anti-viral drugs and vaccination are introduced, extending the options. We trust that this work makes a start in that direction and demonstrates the advantages of a heterogeneous demographic refinement, which can only improve targeting role out of treatments.

negative: 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: Immunosuppressive therapy maintenance in a kidney transplant recipient with SARS-CoV-2 pneumonia: A case report The role of systemic inflammation is proving crucial in determining unfavorable outcome in SARS-CoV-2-infected patients. Limited data are available regarding immunosuppression management in kidney transplant recipients (KTRs) with SARS-CoV-2 pneumonia. We report a case of a 32-year-old KTR who developed SARS-CoV-2 infection and fully recovered in 15 days while maintaining standard immunosuppressive therapy.

negative: COVID-19 in Spain: age, Interleukin-6, C Reactive Protein and lymphocytes as key clues from a multicentre retrospective study SARS-CoV-2 infection has widely spread to the hugest public health challenge to date, COVID-19 pandemic. Different fatality rates among countries are probably due to unstandardized records being carried out by local health authorities. Spanish case-fatality rate is 11.86%, far higher to those reported in Asia or by other European countries. A multicenter retrospective study of demographic, clinical, laboratory and immunological features of 574 Spanish COVID-19 inpatients (59.4% males) and their outcomes was performed. 27.7% cases presented a mild curse, 42% a moderate one and 30.3%, severe. Ages ranged from 18 to 98 (average 63.2). Interleukin 6 was higher as increasing severity. On the other hand, CD8 lymphocyte count was significantly lower as severity grew and subpopulations CD4, CD8, CD19 and NK showed concordant lowering trends. Severity-related natural killer percent descents were evidenced just within aged cases. A significant severity-related decrease of CD4 lymphocytes was found in males. The use of renin-angiotensin system blockers was associated with moderate or mild disease courses. Clinical course of the disease is more severe in this study than in previous literature cohorts. Age and age-related comorbidities, such as dyslipidemia, hypertension or diabetes, were also higher. Immunosenescence might be therefore a suitable explanation for immune system effectors severity-related hampering. Adaptive immunity would go exhausted and a huge ineffective and almost deleterious innate response would account for COVID-19 severity. Hypertensive patients treated with renin-angiotensin system blockers developed milder forms of the disease.

negative: Patterns of Readmissions for Three Common Conditions Among Younger US Adults Abstract Background Thirty-day readmissions among elderly Medicare patients are an important hospital quality measure. Although plans for using 30-day readmission measures are under consideration for younger patients, little is known about readmission in younger patients or the relationship between readmissions in younger and elderly patients at the same hospital. Methods By using the 2014 Nationwide Readmissions Database, we examined readmission patterns in younger patients (18-64 years) using hierarchical models to evaluate associations between hospital 30-day, risk-standardized readmission rates in elderly Medicare patients and readmission risk in younger patients with acute myocardial infarction, heart failure, or pneumonia. Results There were 87,818, 98,315, and 103,251 admissions in younger patients for acute myocardial infarction, heart failure, and pneumonia, respectively, with overall 30-day unplanned readmission rates of 8.5%, 21.4%, and 13.7%, respectively. Readmission risk in younger patients was significantly associated with hospital 30-day risk-standardized readmission rates for elderly Medicare patients for all 3 conditions. A decrease in an average hospital's 30-day, risk-standardized readmission rates from the 75th percentile to the 25th percentile was associated with reduction in younger patients' risk of readmission from 8.8% to 8.0% (difference: 0.7%; 95% confidence interval, 0.5-0.9) for acute myocardial infarction; 21.8% to 20.0% (difference: 1.8%; 95% confidence interval, 1.4-2.2) for heart failure; and 13.9% to 13.1% (difference: 0.8%; 95% confidence interval, 0.5-1.0) for pneumonia. Conclusions Among younger patients, readmission risk was moderately associated with hospital 30-day, risk-standardized readmission rates in elderly Medicare beneficiaries. Efforts to reduce readmissions among older patients may have important areas of overlap with younger patients, although further research may be necessary to identify specific mechanisms to tailor initiatives to younger patients.

negative: Liver Disease Associated with Non-Hepatitis Viruses Abstract Hepatitis is commonly associated with certain viruses labeled as “Hepatitis” viruses. However, many other viral infections can also affect the liver ranging from mild asymptomatic elevations of aminotransferases to fulminant hepatic failure. This article will provide a brief overview on a variety of different viral infections that may be associated with significant liver pathology at least under certain conditions, for example, immunosuppression. This overview discusses key virological features, clinical presentation of associated liver disease and provides some information on diagnosis and an outline of treatment options. Thus, the overview can provide first orientation when infectious hepatitis is encountered in a patient that cannot be explained by the usual hepatitis viruses.

negative: Trends in Notifiable Infectious Diseases in China: Implications for Surveillance and Population Health Policy This study aimed to analyse trends in notifiable infectious diseases in China, in their historical context. Both English and Chinese literature was searched and diseases were categorised according to the type of disease or transmission route. Temporal trends of morbidity and mortality rates were calculated for eight major infectious diseases types. Strong government commitment to public health responses and improvements in quality of life has led to the eradication or containment of a wide range of infectious diseases in China. The overall infectious diseases burden experienced a dramatic drop during 1975–1995, but since then, it reverted and maintained a gradual upward trend to date. Most notifiable diseases are contained at a low endemic level; however, local small-scale outbreaks remain common. Tuberculosis, as a bacterial infection, has re-emerged since the 1990s and has become prevalent in the country. Sexually transmitted infections are in a rapid, exponential growth phase, spreading from core groups to the general population. Together human immunodeficiency virus (HIV), they account for 39% of all death cases due to infectious diseases in China in 2008. Zoonotic infections, such as severe acute respiratory syndrome (SARS), rabies and influenza, pose constant threats to Chinese residents and remain the most deadly disease type among the infected individuals. Therefore, second-generation surveillance of behavioural risks or vectors associated with pathogen transmission should be scaled up. It is necessary to implement public health interventions that target HIV and relevant coinfections, address transmission associated with highly mobile populations, and reduce the risk of cross-species transmission of zoonotic pathogens.

negative: COVID-19 Modelling: the Effects of Social Distancing The purpose of this article is to reach all those who find it difficult to become well informed about the repercussions of a lockdown strategy to tackle the COVID-19 pandemic and to spark discussion and thought. Here we use simple stochastic simulations to evaluate different approaches taken to tackle the crisis, along with the efficiency they will hold and the number of casualties they may incur. It is clear that the less strict the social distancing the more time it will take for life to return to normal, and the more lives will be at risk. This is shown through simulations formed by an open sourced code, which allows evaluation of the outcomes from different intervention scenarios or conditions.

negative: Measuring Physiological Stress in Australian Flying-Fox Populations Flying-foxes (pteropid bats) are the natural host of Hendra virus, a recently emerged zoonotic virus responsible for mortality or morbidity in horses and humans in Australia since 1994. Previous studies have suggested physiological and ecological risk factors for infection in flying-foxes, including physiological stress. However, little work has been done measuring and interpreting stress hormones in flying-foxes. Over a 12-month period, we collected pooled urine samples from underneath roosting flying-foxes, and urine and blood samples from captured individuals. Urine and plasma samples were assayed for cortisol using a commercially available enzyme immunoassay. We demonstrated a typical post-capture stress response in flying-foxes, established urine specific gravity as an attractive alternative to creatinine to correct urine concentration, and established population-level urinary cortisol ranges (and geometric means) for the four Australian species: Pteropus alecto 0.5–305.1 ng/mL (20.1 ng/mL); Pteropus conspicillatus 0.3–370.9 ng/mL (18.9 ng/mL); Pteropus poliocephalus 0.3–311.3 ng/mL (10.1 ng/mL); Pteropus scapulatus 5.2–205.4 ng/mL (40.7 ng/mL). Geometric means differed significantly except for P. alecto and P. conspicillatus. Our approach is methodologically robust, and has application both as a research or clinical tool for flying-foxes, and for other free-living colonial wildlife species.

negative: Acute care issues in internationally adopted children Over the past decade there has been a dramatic increase in international adoptions in the United States. While most adopted children will have common illnesses, others may have unique medical issues as a result of the conditions in their birth country requiring a broadened differential diagnosis. Knowledge of these issues is essential in the management of these patients. This review will predominately focus on infectious disease issues commonly seen in international adoptees but will also discuss other medical conditions and some of the psychosocial issues which may be encountered by caregivers in the emergency department.

negative: Evaluating the massive underreporting and undertesting of COVID-19 cases in multiple global epicenters Abstract Background With continuous global COVID-19 outbreak, differing case numbers and mortality rates are observed. While actual case numbers appear vague, mortality numbers related to COVID-19 seem more precise. In this study, we used the mortality rate as the main indicator to evaluate the extent of underreporting and underdetection of COVID-19 cases. Methods We have analyzed all available data provided by the World Health Organization on the development of international COVID-19 cases and mortality numbers on March 17th, 2020. A crude case-fatality risk (cCFR) and adjusted case-fatality risk (aCFR) was calculated for China, South Korea, Japan, Italy, France, Spain, Germany, Iran and the United States. Additionally, a fold-change (FC) was derived for each country. Results The highest aCFR and FC were detected for Spain. Based on their FC values, an extremely high number of undetected COVID-19 cases was displayed in France, the United States, Italy and Spain. For these countries, our findings indicate a detection rate of only 1-2% of total actual COVID-19 cases. Conclusions Due to limited testing capacities, mortality numbers may serve as a better indicator for COVID-19 case spread in many countries. Our data indicate that countries like France, Italy, the United States, Iran and Spain have extremely high numbers of undetected and underreported cases. Differences in testing availability and capacity, containment as well as overall health care and medical infrastructure result in significantly different mortality rates and COVID-19 case numbers for each respective country.

negative: Comparison of risk factors for viral and nonviral asthma exacerbations

negative: Epidemiology of Traumatic Brain Injury in Europe: A Living Systematic Review. This systematic review provides a comprehensive, up-to-date summary of traumatic brain injury (TBI) epidemiology in Europe, describing incidence, mortality, age, and sex distribution, plus severity, mechanism of injury, and time trends. PubMed, CINAHL, EMBASE, and Web of Science were searched in January 2015 for observational, descriptive, English language studies reporting incidence, mortality, or case fatality of TBI in Europe. There were no limitations according to date, age, or TBI severity. Methodological quality was assessed using the Methodological Evaluation of Observational Research checklist. Data were presented narratively. Sixty-six studies were included in the review. Country-level data were provided in 22 studies, regional population or treatment center catchment area data were reported by 44 studies. Crude incidence rates varied widely. For all ages and TBI severities, crude incidence rates ranged from 47.3 per 100,000, to 694 per 100,000 population per year (country-level studies) and 83.3 per 100,000, to 849 per 100,000 population per year (regional-level studies). Crude mortality rates ranged from 9 to 28.10 per 100,000 population per year (country-level studies), and 3.3 to 24.4 per 100,000 population per year (regional-level studies.) The most common mechanisms of injury were traffic accidents and falls. Over time, the contribution of traffic accidents to total TBI events may be reducing. Case ascertainment and definitions of TBI are variable. Improved standardization would enable more accurate comparisons.

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

negative: Survival of mechanically ventilated patients admitted to intensive care units: Results from a tertiary care center between 2016-2018 OBJECTIVES: To estimate the survival of adult and pediatric patients receiving mechanical ventilation and determine the associated risk factors METHODS: A retrospective cohort study was carried out in the intensive care unit (ICU) at King Abdulaziz Medical City (KAMC) and King Abdullah Children’s Specialist Hospital (KACSH), Riyadh, Saudi Arabia. The analysis includes data from medical records of all patients admitted to ICUs who received mechanical ventilation between 2016-2018. For each patient, potential risk factors were collected. The main outcome of this study was the mortality during the stay in ICU after receiving mechanical ventilation RESULTS: A total of 262 adults and 175 pediatric patients were admitted to ICUs and received mechanical ventilation during the study period. For adult patients, the overall mortality was 37%, with a median survival time of 11 days (interquartile range [IQR] 6-20 days). The main risk factors independently associated with the increased mortality rate were being aged 51-60 (odds ratio [OR] 2.6, 95% confidence interval [CI] 6.7-1.0) and factors related to ICU admission. For the pediatric population, the mortality rate was 17%, with a median survival time of 16 days (IQR 7-37 days). Prematurity with respiratory problems was the main recorded cause of initiation of mechanical ventilation (50% of patients). Neonates who had mechanical ventilation within one month of their birth and were born extremely preterm had a high mortality rate after the initiation of mechanical ventilation. CONCLUSION: Both patient age and the causes of the initiation of mechanical ventilation were influencing the survival of patients who required mechanical ventilation.

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

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: Health Inequalities, General Trends in Mortality and Morbidity, and Associated Factors All measures of health status are ultimately derived from observations of individuals. At the field level we have such measures as self-assessed health status, report of a specific disease, record of a particular death, or an individual’s test on a biomarker, such as blood pressure or serum cholesterol. The observations for individuals are combined and summarized to represent subnational geographic areas, demographic or socioeconomic groups within countries, or national populations. The summary measures, whether they are percentages, averages, or rates, apply to groups. A problem arises when the measures that are based on groups are assumed to represent individuals. The analysis becomes especially problematic when the units analyzed are geographic areas and inferences are being made about individuals from the analysis for these geographic areas.

negative: The effect of treatment on pathogen virulence Abstract The optimal virulence of a pathogen is determined by a trade-off between maximizing the rate of transmission and maximizing the duration of infectivity. Treatment measures such as curative therapy and case isolation exert selective pressure by reducing the duration of infectivity, reducing the value of duration-increasing strategies to the pathogen and favoring pathogen strategies that maximize the rate of transmission. We extend the trade-off models of previous authors, and represents the reproduction number of the pathogen as a function of the transmissibility, host contact rate, disease-induced mortality, recovery rate, and treatment rate, each of which may be influenced by the virulence. We find that when virulence is subject to a transmissibility-mortality trade-off, treatment can lead to an increase in optimal virulence, but that in other scenarios (such as the activity-recovery trade-off) treatment decreases the optimal virulence. Paradoxically, when levels of treatment rise with pathogen virulence, increasing control efforts may raise predicted levels of optimal virulence. Thus we show that conflict can arise between the epidemiological benefits of treatment and the evolutionary risks of heightened virulence.

negative: Roles of sunlight and natural ventilation for controlling infection: historical and current perspectives Summary Background Infections caught in buildings are a major global cause of sickness and mortality. Understanding how infections spread is pivotal to public health yet current knowledge of indoor transmission remains poor. Aim To review the roles of natural ventilation and sunlight for controlling infection within healthcare environments. Methods Comprehensive literature search was performed, using electronic and library databases to retrieve English language papers combining infection; risk; pathogen; and mention of ventilation; fresh air; and sunlight. Foreign language articles with English translation were included, with no limit imposed on publication date. Findings In the past, hospitals were designed with south-facing glazing, cross-ventilation and high ceilings because fresh air and sunlight were thought to reduce infection risk. Historical and recent studies suggest that natural ventilation offers protection from transmission of airborne pathogens. Particle size, dispersal characteristics and transmission risk require more work to justify infection control practices concerning airborne pathogens. Sunlight boosts resistance to infection, with older studies suggesting potential roles for surface decontamination. Conclusions Current knowledge of indoor transmission of pathogens is inadequate, partly due to lack of agreed definitions for particle types and mechanisms of spread. There is recent evidence to support historical data on the effects of natural ventilation but virtually none for sunlight. Modern practice of designing healthcare buildings for comfort favours pathogen persistence. As the number of effective antimicrobial agents declines, further work is required to clarify absolute risks from airborne pathogens along with any potential benefits from additional fresh air and sunlight.

negative: Monitoring Influenza Epidemics in China with Search Query from Baidu Several approaches have been proposed for near real-time detection and prediction of the spread of influenza. These include search query data for influenza-related terms, which has been explored as a tool for augmenting traditional surveillance methods. In this paper, we present a method that uses Internet search query data from Baidu to model and monitor influenza activity in China. The objectives of the study are to present a comprehensive technique for: (i) keyword selection, (ii) keyword filtering, (iii) index composition and (iv) modeling and detection of influenza activity in China. Sequential time-series for the selected composite keyword index is significantly correlated with Chinese influenza case data. In addition, one-month ahead prediction of influenza cases for the first eight months of 2012 has a mean absolute percent error less than 11%. To our knowledge, this is the first study on the use of search query data from Baidu in conjunction with this approach for estimation of influenza activity in China.

negative: Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study Summary Background Middle East respiratory syndrome (MERS) is a new human disease caused by a novel coronavirus (CoV). Clinical data on MERS-CoV infections are scarce. We report epidemiological, demographic, clinical, and laboratory characteristics of 47 cases of MERS-CoV infections, identify knowledge gaps, and define research priorities. Methods We abstracted and analysed epidemiological, demographic, clinical, and laboratory data from confirmed cases of sporadic, household, community, and health-care-associated MERS-CoV infections reported from Saudi Arabia between Sept 1, 2012, and June 15, 2013. Cases were confirmed as having MERS-CoV by real-time RT-PCR. Findings 47 individuals (46 adults, one child) with laboratory-confirmed MERS-CoV disease were identified; 36 (77%) were male (male:female ratio 3·3:1). 28 patients died, a 60% case-fatality rate. The case-fatality rate rose with increasing age. Only two of the 47 cases were previously healthy; most patients (45 [96%]) had underlying comorbid medical disorders, including diabetes (32 [68%]), hypertension (16 [34%]), chronic cardiac disease (13 [28%]), and chronic renal disease (23 [49%]). Common symptoms at presentation were fever (46 [98%]), fever with chills or rigors (41 [87%]), cough (39 [83%]), shortness of breath (34 [72%]), and myalgia (15 [32%]). Gastrointestinal symptoms were also frequent, including diarrhoea (12 [26%]), vomiting (ten [21%]), and abdominal pain (eight [17%]). All patients had abnormal findings on chest radiography, ranging from subtle to extensive unilateral and bilateral abnormalities. Laboratory analyses showed raised concentrations of lactate dehydrogenase (23 [49%]) and aspartate aminotransferase (seven [15%]) and thrombocytopenia (17 [36%]) and lymphopenia (16 [34%]). Interpretation Disease caused by MERS-CoV presents with a wide range of clinical manifestations and is associated with substantial mortality in admitted patients who have medical comorbidities. Major gaps in our knowledge of the epidemiology, community prevalence, and clinical spectrum of infection and disease need urgent definition. Funding None.

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

negative: An Internet-Based Epidemiological Investigation of the Outbreak of H7N9 Avian Influenza A in China Since Early 2013 BACKGROUND: In early 2013, a new type of avian influenza, H7N9, emerged in China. It quickly became an issue of great public concern and a widely discussed topic on the Internet. A considerable volume of relevant information was made publicly available on the Internet through various sources. OBJECTIVE: This study aimed to describe the outbreak of H7N9 in China based on data openly available on the Internet and to validate our investigation by comparing our findings with a well-conducted conventional field epidemiologic study. METHODS: We searched publicly accessible Internet data on the H7N9 outbreak primarily from government and major mass media websites in China up to February 10, 2014. Two researchers independently extracted, compared, and confirmed the information of each confirmed H7N9 case using a self-designed data extraction form. We summarized the epidemiological and clinical characteristics of confirmed H7N9 cases and compared them with those from the field study. RESULTS: According to our data updated until February 10, 2014, 334 confirmed H7N9 cases were identified. The median age was 58 years and 67.0% (219/327) were males. Cases were reported in 15 regions in China. Five family clusters were found. Of the 16.8% (56/334) of the cases with relevant data, 69.6% (39/56) reported a history of exposure to animals. Of the 1751 persons with a close contact with a confirmed case, 0.6% (11/1751) of them developed respiratory symptoms during the 7-day surveillance period. In the 97.9% (327/334) of the cases with relevant data, 21.7% (71/327) died, 20.8% (68/327) were discharged from a hospital, and 57.5% (188/327) were of uncertain status. We compared our findings before February 10, 2014 and those before December 1, 2013 with those from the conventional field study, which had the latter cutoff date of ours in data collection. Our study showed most epidemiological and clinical characteristics were similar to those in the field study, except for case fatality (71/327, 21.7% for our data before February 10; 45/138, 32.6% for our data before December 1; 47/139, 33.8% for the field study), time from illness onset to first medical care (4 days, 3 days, and 1 day), and time from illness onset to death (16.5 days, 17 days, and 21 days). CONCLUSIONS: Findings from our Internet-based investigation were similar to those from the conventional field study in most epidemiological and clinical aspects of the outbreak. Importantly, publicly available Internet data are open to any interested researchers and can thus greatly facilitate the investigation and control of such outbreaks. With improved efforts for Internet data provision, Internet-based investigation has a great potential to become a quick, economical, novel approach to investigating sudden issues of great public concern that involve a relatively small number of cases like this H7N9 outbreak.

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

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

negative: COVID-19 and the difficulty of inferring epidemiological parameters from clinical data Knowing the infection fatality ratio (IFR) is of crucial importance for evidence-based epidemic management: for immediate planning; for balancing the life years saved against the life years lost due to the consequences of management; and for evaluating the ethical issues associated with the tacit willingness to pay substantially more for life years lost to the epidemic, than for those to other diseases. Against this background Verity et al. (2020, Lancet Infections Diseases) have rapidly assembled case data and used statistical modelling to infer the IFR for COVID-19. We have attempted an in-depth statistical review of their approach, to identify to what extent the data are sufficiently informative about the IFR to play a greater role than the modelling assumptions, and have tried to identify those assumptions that appear to play a key role. Given the difficulties with other data sources, we provide a crude alternative analysis based on the Diamond Princess Cruise ship data and case data from China, and argue that, given the data problems, modelling of clinical data to obtain the IFR can only be a stop-gap measure. What is needed is near direct measurement of epidemic size by PCR and/or antibody testing of random samples of the at risk population.

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: Molecular and serological surveillance of canine enteric viruses in stray dogs from Vila do Maio, Cape Verde BACKGROUND: Infections caused by canine parvovirus, canine distemper virus and canine coronavirus are an important cause of mortality and morbidity in dogs worldwide. Prior to this study, no information was available concerning the incidence and prevalence of these viruses in Cape Verde archipelago. RESULTS: To provide information regarding the health status of the canine population in Vila do Maio, Maio Island, Cape Verde, 53 rectal swabs were collected from 53 stray dogs during 2010 and 93 rectal swabs and 88 blood samples were collected from 125 stray dogs in 2011. All rectal swabs (2010 n = 53; 2011 n = 93) were analysed for the presence of canine parvovirus, canine distemper virus and canine coronavirus nucleic acids by quantitative PCR methods. Specific antibodies against canine distemper virus and canine parvovirus were also assessed (2011 n = 88). From the 2010 sampling, 43.3% (23/53) were positive for canine parvovirus DNA, 11.3% (6/53) for canine distemper virus RNA and 1.9% (1/53) for canine coronavirus RNA. In 2011, the prevalence values for canine parvovirus and canine coronavirus were quite similar to those from the previous year, respectively 44.1% (41/93), and 1.1% (1/93), but canine distemper virus was not detected in any of the samples analysed (0%, 0/93). Antibodies against canine parvovirus were detected in 71.6% (63/88) blood samples and the seroprevalence found for canine distemper virus was 51.1% (45/88). CONCLUSIONS: This study discloses the data obtained in a molecular and serological epidemiological surveillance carried out in urban populations of stray and domestic animals. Virus transmission and spreading occurs easily in large dog populations leading to high mortality rates particularly in unvaccinated susceptible animals. In addition, these animals can act as disease reservoirs for wild animal populations by occasional contact. Identification of susceptible wildlife of Maio Island is of upmost importance to evaluate the risk of pathogen spill over from domestic to wild animals in Cape Verde and to evaluate the associated threat to the wild susceptible species.

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

negative: A joint analysis of influenza-associated hospitalizations and mortality in Hong Kong, 1998–2013 Influenza viruses may cause severe human infections leading to hospitalization or death. Linear regression models were fitted to population-based data on hospitalizations and deaths. Surveillance data on influenza virus activity permitted inference on influenza-associated hospitalizations and deaths. The ratios of these estimates were used as a potential indicator of severity. Influenza was associated with 431 (95% CrI: 358–503) respiratory deaths and 12,700 (95% CrI: 11,700–13,700) respiratory hospitalizations per year. Majority of the excess deaths occurred in persons ≥65 y of age. The ratios of deaths to hospitalizations in adults ≥65 y were significantly higher for influenza A(H1N1) and A(H1N1)pdm09 compared to A(H3N2) and B. Substantial disease burden associated with influenza viruses were estimated in Hong Kong particularly among children and elderly in 1998–2013. Infections with influenza A(H1N1) was suggested to be more serious than A(H3N2) in older adults.

negative: Effect of thermal control of dry fomites on regulating the survival of human pathogenic bacteria responsible for nosocomial infections We monitored the survival of human pathogenic bacteria [Escherichia coli (ATCC), extended-spectrum β-lactamase-producing E. coli (Clinical isolate), New Delhi metallo-β-lactamase-producing E. coli (clinical isolate), Staphylococcus aureus (ATCC)] on dry materials (vinyl chloride, aluminum, plastic, stainless steel) at distinct temperatures (room temperature or 15°C–37°C). These bacteria favored a lower temperature for their prolonged survival on the dry fomites, regardless of the material type. Interestingly, when mixed with S. aureus, E. coli survived for a longer time at a lower temperature. Cardiolipin, which can promote the survival of S. aureus in harsh environments, had no effect on maintaining the survival of E. coli. Although the trends remained unchanged, adjusting the humidity from 40% to 60% affected the survival of bacteria on dry surfaces. Scanning electron microscopic analysis revealed no morphological differences in these bacteria immediately before or after one day of dry conditions. In addition, ATP assessment, a method used to visualize high-touch surfaces in hospitals, was not effective at monitoring bacterial dynamics. A specialized handrail device fitted with a heater, which was maintained at normal human body core temperature, successfully prohibited the prolonged survival of bacteria [Enterococcus faecalis (ATCC), E. coli (ATCC), Pseudomonas aeruginosa (ATCC), S. aureus (ATCC), Acinetobacter baumannii (clinical isolate), and Serratia marcescens (clinical isolate)], with the exception of spore-forming Bacillus subtilis (from our laboratory collection) and the yeast-like fungus Candida albicans (from our laboratory collection)] on dry surfaces. Taken together, we concluded that the tested bacteria favor lower temperatures for their survival in dry environments. Therefore, the thermal control of dry fomites has the potential to control bacterial survival on high-touch surfaces in hospitals.

negative: Influence of Obesity on Pneumococcus Infection Risk in the Elderly Obesity negatively affects immune function and host defense mechanisms. Obesity is associated with chronic activation of the innate immune system and consequent local and systemic inflammation which contribute to pathologic conditions such as type-2 diabetes mellitus, cancer, psoriasis, atherosclerosis, and inflammatory bowel disease. Individuals with obesity have increased susceptibility to contract viral, bacterial, and fungal infections and respond sub-optimally to vaccination. In this review, we summarize research findings on the effects of obesity on immune responses to respiratory tract infections (RTI), focusing on Streptococcus pneumoniae (“pneumococcus”) infection, which is a major cause of morbidity and mortality in the US, causing community-acquired infections such as pneumonia, otitis media and meningitis. We show that the risk of infection is higher in elderly individuals and also in individuals of certain ethnic groups, although in a few reports obesity has been associated with better survival of individuals admitted to hospital with pneumococcus infection, a phenomenon known as “obesity paradox.” We discuss factors that are associated with increased risk of pneumococcal infection, such as recent infection with RTI, chronic medical conditions, and immunosuppressive medications.

negative: Comparative Analysis of COVID-19 Transmission Patterns in Three Chinese Regions vs. South Korea,Italy and Iran Background: The outbreak of Coronavirus 2019 (COVID-19) began in January 2020 in the city of Wuhan (Hubei province, China). It took about 2 months for China to get this infectious disease under control in its epicenter at Wuhan. Since February 2020, COVID-19 has been spreading around the world, becoming widespread in a number of countries. The timing and nature of government actions in response to the pandemic has varied from country to country, and their role in affecting the spread of the disease has been debated. Method: The present study proposed a modified susceptible-exposed-infected-removed model (SEIR) model to perform a comparative analysis of the temporal progress of disease spread in six regions worldwide: three Chinese regions (Zhejiang, Guangdong and Xinjiang) vs. three countries (South Korea, Italy and Iran). For each region we developed detailed timelines of reported infections and outcomes, along with government-implemented measures to enforce social distancing. Simulations of the imposition of strong social distancing measures were used to evaluate the impact that these measures might have had on the duration and severity of COVID-19 outbreaks in the three countries. Results: The main results of this study are as follows: (a) an empirical COVID-19 growth law provides an excellent fit to the disease data in all study regions and potentially could be of more general validity; (b) significant differences exist in the spread characteristics of the disease among the three regions of China and between the three regions of China and the three countries; (c) under the control measures implemented in the Chinese regions (including the immediate quarantine of infected patients and their close contacts, and considerable restrictions on social contacts), the transmission rate of COVID-19 followed a modified normal distribution function, and it reached its peak after 1 to 2 days and then was reduced to zero 11, 11 and 18 days after a 1st-Level Response to Major Public Health Emergency was declared in Zhejiang, Guangdong and Xinjiang, respectively; moreover, the epidemic control times in Zhejiang, Guangdong and Xinjiang showed that the epidemic reached an "inflection point" after 9, 12 and 17 days, respectively, after a 1st-Level Response was issued; (d) an empirical COVID-19 law provided an excellent fit to the disease data in the six study regions, and the law can be potentially of more general validity; and (e) the curves of infected cases in South Korea, Italy and Iran would had been significantly flattened and shrunken at a relatively earlier stage of the epidemic if similar preventive measures as in the Chinese regions had been also taken in the above three countries on February 25th, February 25th and March 8th, respectively: the simulated maximum number of infected individuals in South Korea, Italy and Iran would had been 4480 cases (March 9th, 2020), 2335 cases (March 10th) and 6969 cases (March 20th), instead of the actual (reported) numbers of 7212 cases (March 9th), 8514 cases (March 10th, 2020) and 11466 cases (March 20th), respectively; moreover, up to March 29th, the simulated reduction in the accumulated number of infected cases would be 1585 for South Korea, 93490 for Italy and 23213 for Iran, respectively, accounting for 16.41% (South Korea), 95.70% (Italy) and 60.59% (Iran) of the accumulated number of actual reported infected cases. Conclusions: The implemented measures in China were very effective for controlling the spread of COVID-19. These measures should be taken as early as possible, including the early identification of all infection sources and eliminating transmission pathways. Subsequently, the number of infected cases can be controlled at a low level, and existing medical resources could be sufficient for maintaining higher cure rates and lower mortality rate compared to the current situations in these countries. The proposed model can account for these prevention and control measures by properly adjusting its parameters, it computes the corresponding variations in disease transmission rate during the outbreak period, and it can provide valuable information for public health decision-making purposes.

negative: Human agency and infection rates: implications for social distancing during epidemics Social distancing is an important measure in controlling epidemics. This paper presents a simple theoretical model focussed on the implications of the wide range in interaction rates between individuals, both within the workplace and in the social setting. The model is based on well-mixed populations and so is not intended for studying geographic spread. The model shows that epidemic growth rate is largely determined by the upper interactivity quantiles of society, implying that the most efficient methods of epidemic control are interaction capping approaches rather than overall reductions in interaction. The theoretical model can also be applied to look at the dynamics of epidemic progression under various scenarios. The theoretical model suggests that with no intervention herd immunity would be achieved with a lower overall infection rate than if variation in interaction rate is ignored, because by this stage almost all the most interactive members of society would have had the infection; however the overall mortality with such an approach is very high. Scenarios for mitigation and suppression suggest that, by using interactivity capping, it should be possible to control an epidemic without extreme sanctions on the majority of the population if R0 of the uncontrolled infection is 2.4. However to control the infection rate to a specific level will always require the switching on and off of measures and for this reason eradication is likely to be a less costly policy in the long run. While social distancing alone can be used for eradication it is not be a good mechanism on its own to prevent reinfection. The use of robust testing, quarantining, and contact tracing would strengthen any social distancing measures, speed up eradication, and be a better tool for prevention of infection or reinfection.

negative: Exercise against SARS-CoV-2 (COVID-19): Does workout intensity matter? (A mini review of some indirect evidence related to obesity) ABSTRACT SARS-CoV-2 (COVID-19) is a new virus causing respiratory illness outbreak. Nowadays, COVID-19 has spread to several countries around the world and is presently a major global concern. It appears that no certain effective pharmaceutical agent is currently available for it. It seems that obesity is one of the biggest risk factors related to COVID-19 hospitalization and critical illness. The strengthening of the body systems by non-drug ways is very important especially in obese people. On the basis of some indirect evidence, it seems that moderate physical activity can be recommended as a non-pharmacological, inexpensive, and viable way to cope with corona. On the other hand, recommending higher intensity exercise needs further consideration to make final decision in this regard.

negative: Temporal Trends of In-Hospital Mortality in Patients Treated with Intra-Aortic Balloon Pumping: A Nationwide Population Study in Taiwan, 1998-2008 Intra-aortic balloon pumping (IABP) is widely used for hemodynamic support in critical patients with cardiogenic shock (CS). We examined whether the in-hospital mortality of patients in Taiwan treated with IABP has recently declined. We used Taiwan’s National Health Insurance Research Database to retrospectively review the in-hospital all-cause mortality of 9952 (7146 men [71.8%]) 18-year-old and older patients treated with IABP between 1998 and 2008. The mortality rate was 13.84% (n = 1377). The urbanization levels of the hospitals, and the number of days in the intensive care unit, of hospitalization, and of IABP treatment, and prior percutaneous coronary intervention (PCI) were associated with mortality. Seven thousand six hundred thirty-five patients (76.72%) underwent coronary artery bypass grafting (CABG) surgery, and 576 (5.79%) underwent high-risk PCI with IABP treatment. The number of patients treated with IABP significantly increased during this decade (p(trend) < 0.0001), the in-hospital all-cause mortality for patients treated with IABP significantly decreased (p(trend) = 0.0243), but the in-hospital all-cause mortality of patients who underwent CABG and PCI plus IABP did not decrease. In conclusion, the in-hospital mortality rate of IABP treatment decreased annually in Taiwan during the study period. However, high-risk patients who underwent coronary revascularization with IABP had a higher and unstable in-hospital mortality rate.

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: The current COVID-19 wave will likely be mitigated in the second-line European countries Objective. Countries presently apply different strategies to control the COVID-19 outbreak. Differences in population structures, decision making, health systems and numerous other factors result in various trajectories in terms of mortality at country scale. Our objective in this manuscript is to disentangle the future of second-line European countries (i.e. countries that present, today, a moderate death rate) with respect to the current COVID-19 wave. Method. We propose a data-driven approach, grounded on a mixture model, to forecast the dynamics of the number of deaths from COVID-19 in a given focal country using data from countries that are ahead in time in terms of COVID-19-induced mortality. In this approach, the mortality curves of ahead-in-time countries are used to build predictors, which are then used as the components of the mixture model. This approach was applied to eight second-line European countries (Austria, Denmark, Germany, Ireland, Poland, Portugal, Romania and Sweden), using Belgium, France, Italy, Netherlands, Spain, Switzerland, United Kingdom as well as the Hubei province in China to build predictors. For this analysis, we used data pooled by the Johns Hopkins University Center for Systems Science and Engineering. Results. In general, the second-line European countries tend to follow relatively mild mortality curves (typically, those of Switzerland and Hubei) rather than fast and severe ones (typically, those of Spain, Italy, Belgium, France and the United Kingdom). From a methodological viewpoint, the performance of our forecasting approach is about 80% up to 8 days in the future, as soon as the focal country has accumulated at least two hundreds of deaths. Discussion. Our results suggest that the continuation of the current COVID-19 wave across Europe will likely be mitigated, and not as strong as it was in most of the front-line countries first impacted by the wave.

negative: Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study OBJECTIVE: To characterise the clinical features of patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United Kingdom during the growth phase of the first wave of this outbreak who were enrolled in the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) World Health Organization (WHO) Clinical Characterisation Protocol UK (CCP-UK) study, and to explore risk factors associated with mortality in hospital. DESIGN: Prospective observational cohort study with rapid data gathering and near real time analysis. SETTING: 208 acute care hospitals in England, Wales, and Scotland between 6 February and 19 April 2020. A case report form developed by ISARIC and WHO was used to collect clinical data. A minimal follow-up time of two weeks (to 3 May 2020) allowed most patients to complete their hospital admission. PARTICIPANTS: 20 133 hospital inpatients with covid-19. MAIN OUTCOME MEASURES: Admission to critical care (high dependency unit or intensive care unit) and mortality in hospital. RESULTS: The median age of patients admitted to hospital with covid-19, or with a diagnosis of covid-19 made in hospital, was 73 years (interquartile range 58-82, range 0-104). More men were admitted than women (men 60%, n=12 068; women 40%, n=8065). The median duration of symptoms before admission was 4 days (interquartile range 1-8). The commonest comorbidities were chronic cardiac disease (31%, 5469/17 702), uncomplicated diabetes (21%, 3650/17 599), non-asthmatic chronic pulmonary disease (18%, 3128/17 634), and chronic kidney disease (16%, 2830/17 506); 23% (4161/18 525) had no reported major comorbidity. Overall, 41% (8199/20 133) of patients were discharged alive, 26% (5165/20 133) died, and 34% (6769/20 133) continued to receive care at the reporting date. 17% (3001/18 183) required admission to high dependency or intensive care units; of these, 28% (826/3001) were discharged alive, 32% (958/3001) died, and 41% (1217/3001) continued to receive care at the reporting date. Of those receiving mechanical ventilation, 17% (276/1658) were discharged alive, 37% (618/1658) died, and 46% (764/1658) remained in hospital. Increasing age, male sex, and comorbidities including chronic cardiac disease, non-asthmatic chronic pulmonary disease, chronic kidney disease, liver disease and obesity were associated with higher mortality in hospital. CONCLUSIONS: ISARIC WHO CCP-UK is a large prospective cohort study of patients in hospital with covid-19. The study continues to enrol at the time of this report. In study participants, mortality was high, independent risk factors were increasing age, male sex, and chronic comorbidity, including obesity. This study has shown the importance of pandemic preparedness and the need to maintain readiness to launch research studies in response to outbreaks. STUDY REGISTRATION: ISRCTN66726260.

negative: Spatial modelling of contribution of individual level risk factors for mortality from Middle East respiratory syndrome coronavirus in the Arabian Peninsula BACKGROUND: Middle East respiratory syndrome coronavirus is a contagious respiratory pathogen that is contracted via close contact with an infected subject. Transmission of the pathogen has occurred through animal-to-human contact at first followed by human-to-human contact within families and health care facilities. DATA AND METHODS: This study is based on a retrospective analysis of the Middle East respiratory syndrome coronavirus outbreak in the Kingdom of Saudi Arabia between June 2012 and July 2015. A Geoadditive variable model for binary outcomes was applied to account for both individual level risk factors as well spatial variation via a fully Bayesian approach. RESULTS: Out of 959 confirmed cases, 642 (67%) were males and 317 (33%) had died. Three hundred and sixty four (38%) cases occurred in Ar Riyad province, while 325 (34%) cases occurred in Makkah. Individuals with some comorbidity had a significantly higher likelihood of dying from MERS-CoV compared with those who did not suffer comorbidity [Odds ratio (OR) = 2.071; 95% confidence interval (CI): 1.307, 3.263]. Health-care workers were significantly less likely to die from the disease compared with non-health workers [OR = 0.372, 95% CI: 0.151, 0.827]. Patients who had fatal clinical experience and those with clinical and subclinical experiences were equally less likely to die from the disease compared with patients who did not have fatal clinical experience and those without clinical and subclinical experiences respectively. The odds of dying from the disease was found to increase as age increased beyond 25 years and was much higher for individuals with any underlying comorbidities. CONCLUSION: Interventions to minimize mortality from the Middle East respiratory syndrome coronavirus should particularly focus individuals with comorbidity, non-health-care workers, patients with no clinical fatal experience, and patients without any clinical and subclinical experiences.

negative: How do environmental, economic and health factors influence regional vulnerability to COVID-19? We have studied the correlations between twelve environmental, economic and health variables, by carrying out a statistical analysis of the fatality rate of COVID-19 in 14 countries. Our statistical analysis indicates that, among the 12 variables, the diabetes percentage of the total population and the extent of the population ages 65 and older in each country are correlated most strongly with the total number of deaths in them. Although the strength of the correlations between the variables and the total ND may change as the ongoing pandemic evolves, the study highlights the importance of integrating regional-specific variables in the modelling efforts aimed at projecting how the spread of the virus may influence different parts of the world.

negative: A Poisson Kalman filter for disease surveillance An optimal filter for Poisson observations is developed as a variant of the traditional Kalman filter. Poisson distributions are characteristic of infectious diseases, which model the number of patients recorded as presenting each day to a health care system. We develop both a linear and nonlinear (extended) filter. The methods are applied to a case study of neonatal sepsis and postinfectious hydrocephalus in Africa, using parameters estimated from publicly available data. Our approach is applicable to a broad range of disease dynamics, including both noncommunicable and the inherent nonlinearities of communicable infectious diseases and epidemics.

negative: Comparison of influenza disease burden in older populations of Hong Kong and Brisbane: the impact of influenza and pneumococcal vaccination BACKGROUND: Influenza and pneumococcal vaccine uptake in the older population aged 65 years or over of Hong Kong dramatically increased since the 2003 SARS outbreak. This study is aimed to evaluate the impact of increased coverage of influenza and pneumococcal vaccines by comparing the change of disease burden in the older population of Hong Kong, with the burden in the older population of Brisbane with relatively high vaccine coverage in the past fifteen years. METHODS: Time series segmented regression models were applied to weekly numbers of cause-specific mortality or hospitalization of Hong Kong and Brisbane. Annual excess rates of mortality or hospitalization associated with influenza in the older population were estimated for the pre-SARS (reference period), post-SARS and post-pandemic period, respectively. The rate ratios (RRs) between these periods were also calculated to assess the relative change of disease burden. RESULTS: Compared to the pre-SARS period, excess rates of mortality associated with influenza during the post-SARS period in Hong Kong decreased for cardiorespiratory diseases (RR = 0.90, 95% CI 0.80, 1.01), stroke (RR = 0.74, 95% CI 0.50, 1.09), and ischemic heart diseases (RR = 0.45, 95% CI 0.34, 0.58). The corresponding RRs in Brisbane were 0.79 (95% CI 0.54, 1.15), 0.33 (0.13, 0.80), and 1.09 (0.62, 1.90), respectively. Only the mortality of ischemic heart diseases showed a greater reduction in Hong Kong than in Brisbane. During the post-pandemic period, excess rates of all-cause mortality increased in Hong Kong, but to a lesser extent than in Brisbane (RR = 1.41 vs 2.39). CONCLUSION: A relative decrease (or less of an increase) of influenza disease burden was observed in the older population of Hong Kong after increased coverage of influenza and pneumococcal vaccines in this population, as compared to those of Brisbane where vaccination rates remained stable. The lack of significant findings in some disease categories highlights the challenges of evaluating the benefits of vaccination at the population level. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-019-3735-7) contains supplementary material, which is available to authorized users.

negative: Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia BACKGROUND: In the recent outbreak of novel coronavirus infection in Wuhan, China, significantly abnormal coagulation parameters in severe novel coronavirus pneumonia (NCP) cases were a concern. OBJECTIVES: To describe the coagulation feature of patients with NCP. METHODS: Conventional coagulation results and outcomes of 183 consecutive patients with confirmed NCP in Tongji hospital were retrospectively analyzed. RESULTS: The overall mortality was 11.5%, the non‐survivors revealed significantly higher D‐dimer and fibrin degradation product (FDP) levels, longer prothrombin time and activated partial thromboplastin time compared to survivors on admission (P < .05); 71.4% of non‐survivors and 0.6% survivors met the criteria of disseminated intravascular coagulation during their hospital stay. CONCLUSIONS: The present study shows that abnormal coagulation results, especially markedly elevated D‐dimer and FDP are common in deaths with NCP.

negative: NKG2A and COVID-19: another brick in the wall

negative: Extracorporeal membrane oxygenation for severe Middle East respiratory syndrome coronavirus BACKGROUND: Middle East respiratory syndrome (MERS) is caused by a coronavirus (MERS‐CoV) and is characterized by hypoxemic respiratory failure. The objective of this study is to compare the outcomes of MERS-CoV patients before and after the availability of extracorporeal membrane oxygenation (ECMO) as a rescue therapy in severely hypoxemic patients who failed conventional strategies. METHODS: We collected data retrospectively on MERS-CoV patients with refractory respiratory failure from April 2014 to December 2015 in 5 intensive care units (ICUs) in Saudi Arabia. Patients were classified into two groups: ECMO versus conventional therapy. Our primary outcome was in-hospital mortality; secondary outcomes included ICU and hospital length of stay. RESULTS: Thirty-five patients were included; 17 received ECMO and 18 received conventional therapy. Both groups had similar baseline characteristics. The ECMO group had lower in-hospital mortality (65 vs. 100%, P = 0.02), longer ICU stay (median 25 vs. 8 days, respectively, P < 0.01), and similar hospital stay (median 41 vs. 31 days, P = 0.421). In addition, patients in the ECMO group had better PaO2/FiO2 at days 7 and 14 of admission to the ICU (124 vs. 63, and 138 vs. 36, P < 0.05), and less use of norepinephrine at days 1 and 14 (29 vs. 80%; and 36 vs. 93%, P < 0.05). CONCLUSIONS: ECMO use, as a rescue therapy, was associated with lower mortality in MERS patients with refractory hypoxemia. The results of this, largest to date, support the use of ECMO as a rescue therapy in patients with severe MERS-CoV.

negative: Bioterrorism and children Unique concerns with infection control and vaccination Treatment of child victims of a bioterrorism attack is complicated because they may be more vulnerable to the agents used and may suffer more complications from the treatment strategies. Isolation and other infection control measures can be psychologically harmful to young children and may require that they undergo sedation. Most of the recommended antibiotics and antiviral treatments for bioterror agents have not been approved for use in children, and children undergoing smallpox vaccination have a higher incidence of complications than adults. Pediatric anesthesiologists should expect to be part of the pediatric care team and must be careful to observe infection control procedures to limit the spread of disease caused by bioterror attack.

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

negative: Implementing the comprehensive unit-based safety program model to improve the management of mechanically ventilated patients in Saudi Arabia BACKGROUND: Ventilator-associated events are common in mechanically ventilated patients. They are associated with more days on mechanical ventilation, longer intensive care unit (ICU) stay, and increased risk of mortality. Theoretically, interventions that prevent ventilator-associated events should also reduce associated morbidity. We evaluated the Comprehensive Unit-based Safety Program approach to improve the care of mechanically ventilated patients. METHODS: All mechanically ventilated patients admitted to the ICU between October 1, 2015, and October 31, 2016, were prospectively monitored for the development of ventilator-associated events according to the National Healthcare Safety Network criteria. A process care bundle (endotracheal intubation with subglottic suctioning, head-of-bed elevation ≥30°, target sedation scores, daily spontaneous awakening trials, spontaneous breathing trials), daily delirium assessment, and an early mobility protocol were instituted. The bundle compliance, ventilator-associated events rates, ICU length of stay, and mortality rate were noted. The database allowed viewing of current rates, trends, and averages of all participating sites. RESULTS: In the study period, 2,321 patients were admitted to the ICU, and 1,231 required mechanical ventilation (10,342 ventilator days). There were 115 ventilator-associated events: 82 ventilator-associated conditions, 15 infection-related ventilator-associated conditions, and 18 possible cases of ventilator-associated pneumonia. The ICU mortality rate was 13.3%, compared with 28.7% for those mechanically ventilated patients with ventilator-associated events (P = .0001). There was increased compliance for spontaneous awakening trials (51.5%-76.9%, P = .0008) and spontaneous breathing trials (54.2%-72.2%, P = .02) and a decrease in infection-related ventilator-associated conditions (4.2-3.5 per 1,000 days), possible cases of ventilator-associated pneumonia (2.1-1.7 per 1,000 days), ICU mortality (45.3%-19.1%, P = .045), and ventilator-associated events associated mortality rates (33.3%-8.3%, P < .37). Physical therapy participation and mobility were 60.8% and 26.4%, respectively. CONCLUSION: The implementation of a multipronged program like the Comprehensive Unit-based Safety Program could improve the care processes and outcomes of mechanically ventilated patients.

negative: Proposals for the classification of human rhinovirus species A, B and C into genotypically assigned types Human rhinoviruses (HRVs) frequently cause mild upper respiratory tract infections and more severe disease manifestations such as bronchiolitis and asthma exacerbations. HRV is classified into three species within the genus Enterovirus of the family Picornaviridae. HRV species A and B contain 75 and 25 serotypes identified by cross-neutralization assays, although the use of such assays for routine HRV typing is hampered by the large number of serotypes, replacement of virus isolation by molecular methods in HRV diagnosis and the poor or absent replication of HRV species C in cell culture. To address these problems, we propose an alternative, genotypic classification of HRV-based genetic relatedness analogous to that used for enteroviruses. Nucleotide distances between 384 complete VP1 sequences of currently assigned HRV (sero)types identified divergence thresholds of 13, 12 and 13 % for species A, B and C, respectively, that divided inter- and intra-type comparisons. These were paralleled by 10, 9.5 and 10 % thresholds in the larger dataset of >3800 VP4 region sequences. Assignments based on VP1 sequences led to minor revisions of existing type designations (such as the reclassification of serotype pairs, e.g. A8/A95 and A29/A44, as single serotypes) and the designation of new HRV types A101–106, B101–103 and C34–C51. A protocol for assignment and numbering of new HRV types using VP1 sequences and the restriction of VP4 sequence comparisons to type identification and provisional type assignments is proposed. Genotypic assignment and identification of HRV types will be of considerable value in the future investigation of type-associated differences in disease outcomes, transmission and epidemiology.

negative: ORBiT: Oak Ridge biosurveillance toolkit for public health dynamics BACKGROUND: The digitization of health-related information through electronic health records (EHR) and electronic healthcare reimbursement claims and the continued growth of self-reported health information through social media provides both tremendous opportunities and challenges in developing effective biosurveillance tools. With novel emerging infectious diseases being reported across different parts of the world, there is a need to build systems that can track, monitor and report such events in a timely manner. Further, it is also important to identify susceptible geographic regions and populations where emerging diseases may have a significant impact. METHODS: In this paper, we present an overview of Oak Ridge Biosurveillance Toolkit (ORBiT), which we have developed specifically to address data analytic challenges in the realm of public health surveillance. In particular, ORBiT provides an extensible environment to pull together diverse, large-scale datasets and analyze them to identify spatial and temporal patterns for various biosurveillance-related tasks. RESULTS: We demonstrate the utility of ORBiT in automatically extracting a small number of spatial and temporal patterns during the 2009-2010 pandemic H1N1 flu season using claims data. These patterns provide quantitative insights into the dynamics of how the pandemic flu spread across different parts of the country. We discovered that the claims data exhibits multi-scale patterns from which we could identify a small number of states in the United States (US) that act as "bridge regions" contributing to one or more specific influenza spread patterns. Similar to previous studies, the patterns show that the south-eastern regions of the US were widely affected by the H1N1 flu pandemic. Several of these south-eastern states act as bridge regions, which connect the north-east and central US in terms of flu occurrences. CONCLUSIONS: These quantitative insights show how the claims data combined with novel analytical techniques can provide important information to decision makers when an epidemic spreads throughout the country. Taken together ORBiT provides a scalable and extensible platform for public health surveillance.

negative: The Pediatric Asthmatic The incidence of allergies and asthma in the Western world has been increasing over the past 30 years. However, more recent data suggests that over the past 5–10 years, the overall global trends of asthma incidence have begun to stabilize (1). Urbanization and industrialization has contributed to the increase in developed countries, but the reasons for this are still unclear. Asthma is estimated to be responsible for 1 in every 250 deaths worldwide. Many of these deaths are preventable, and specific issues have been identified that may contribute to this high mortality rate. Factors that contribute to high mortality and morbidity include slow access to care and medications, inadequate environmental control of allergens and irritants, dietary changes, genetic variations, cultural barriers, lack of education amongst patients and providers, insufficient resources, and improper use of health care dollars.

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: Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. BACKGROUND As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016. METHODS We estimated prevalence and incidence for 328 diseases and injuries and 2982 sequelae, their non-fatal consequences. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between incidence, prevalence, remission, and cause of death rates for each condition. For some causes, we used alternative modelling strategies if incidence or prevalence needed to be derived from other data. YLDs were estimated as the product of prevalence and a disability weight for all mutually exclusive sequelae, corrected for comorbidity and aggregated to cause level. We updated the Socio-demographic Index (SDI), a summary indicator of income per capita, years of schooling, and total fertility rate. GBD 2016 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). FINDINGS Globally, low back pain, migraine, age-related and other hearing loss, iron-deficiency anaemia, and major depressive disorder were the five leading causes of YLDs in 2016, contributing 57·6 million (95% uncertainty interval [UI] 40·8-75·9 million [7·2%, 6·0-8·3]), 45·1 million (29·0-62·8 million [5·6%, 4·0-7·2]), 36·3 million (25·3-50·9 million [4·5%, 3·8-5·3]), 34·7 million (23·0-49·6 million [4·3%, 3·5-5·2]), and 34·1 million (23·5-46·0 million [4·2%, 3·2-5·3]) of total YLDs, respectively. Age-standardised rates of YLDs for all causes combined decreased between 1990 and 2016 by 2·7% (95% UI 2·3-3·1). Despite mostly stagnant age-standardised rates, the absolute number of YLDs from non-communicable diseases has been growing rapidly across all SDI quintiles, partly because of population growth, but also the ageing of populations. The largest absolute increases in total numbers of YLDs globally were between the ages of 40 and 69 years. Age-standardised YLD rates for all conditions combined were 10·4% (95% UI 9·0-11·8) higher in women than in men. Iron-deficiency anaemia, migraine, Alzheimer's disease and other dementias, major depressive disorder, anxiety, and all musculoskeletal disorders apart from gout were the main conditions contributing to higher YLD rates in women. Men had higher age-standardised rates of substance use disorders, diabetes, cardiovascular diseases, cancers, and all injuries apart from sexual violence. Globally, we noted much less geographical variation in disability than has been documented for premature mortality. In 2016, there was a less than two times difference in age-standardised YLD rates for all causes between the location with the lowest rate (China, 9201 YLDs per 100 000, 95% UI 6862-11943) and highest rate (Yemen, 14 774 YLDs per 100 000, 11 018-19 228). INTERPRETATION The decrease in death rates since 1990 for most causes has not been matched by a similar decline in age-standardised YLD rates. For many large causes, YLD rates have either been stagnant or have increased for some causes, such as diabetes. As populations are ageing, and the prevalence of disabling disease generally increases steeply with age, health systems will face increasing demand for services that are generally costlier than the interventions that have led to declines in mortality in childhood or for the major causes of mortality in adults. Up-to-date information about the trends of disease and how this varies between countries is essential to plan for an adequate health-system response. FUNDING Bill & Melinda Gates Foundation, and the National Institute on Aging and the National Institute of Mental Health of the National Institutes of Health.

negative: SARS in Taiwan: an overview and lessons learned Summary Objectives: This report aims to describe the epidemiology of severe acute respiratory syndrome (SARS) in Taiwan between March and July 2003, and to examine the public health response. Methods: Surveillance for SARS was initiated on 14 March 2003. Response activities are described for the isolation of patients; contact tracing; quarantine of contact persons; fever screening for inbound and outbound passengers at the airport; and hospital infection control as assessed by mobile SARS containment teams. Results: Between 14 March and 30 July 2003 a total of 668 probable cases of SARS were reported. Of the 668 cases, 181 (27%) were fatal. Compared to the survivors, fatal cases were more likely to be older (p <0.001), male (p <0.05), exposed through hospital contact (p <0.001), and have a coexisting medical disorder (p <0.001). Between 28 March and 30 July a total of 151,270 persons were quarantined. Among them, 46 (3.0/10,000) were subsequently classified as being probable SARS cases. At the time of the mobile team assessments, 46 (53%) hospitals had implemented WHO infection control recommendations. Conclusions: In this outbreak, an emergency plan consisted of patient isolation and strict hospital infection control.

negative: ECR 2012 Book of Abstracts - A - Postergraduate Educational Programme

negative: Research on the Influence of Effective Distance Between Cities on the Cross-regional Transmission of COVID-19 The COVID-19 epidemic in China has been effectively controlled. It is of great significance to study the law of cross-regional spread of the epidemic, for the prevention and control of the COVID-19 in the future in China and other countries or regions. In this study, the cross-regional connection intensity between cities was characterized based on the probability and the effective distance of the shortest path tree, and the empirical analysis was carried out based on the high-frequency data such as the cases of COVID 19 outbreaks. It is concluded that the higher the intensity of inter-city connection, the larger scale the cross-regional spread of the epidemic.

negative: A model for COVID-19 with isolation, quarantine and testing as control measures In this article we propose a compartmental model for the dynamics of Coronavirus Disease 2019 (COVID-19). We take into account the presence of asymptomatic infections and the main policies that have been adopted so far to contain the epidemic: isolation (or social distancing) of a portion of the population, quarantine for confirmed cases and testing. We model isolation by separating the population in two groups: one composed by key-workers that keep working during the pandemic and have a usual contact rate, and a second group consisting of people that are enforced/recommended to stay at home. We refer to quarantine as strict isolation, and it is applied to confirmed infected cases. In the proposed model, the proportion of people in isolation, the level of contact reduction and the testing rate are control parameters that can vary in time, representing policies that evolve in different stages. We obtain an explicit expression for the basic reproduction number R0 in terms of the parameters of the disease and of the control policies. In this way we can quantify the effect that isolation and testing have in the evolution of the epidemic. We present a series of simulations to illustrate different realistic scenarios. From the expression of R0 and the simulations we conclude that isolation (social distancing) and testing among asymptomatic cases are fundamental actions to control the epidemic, and the stricter these measures are and the sooner they are implemented, the more lives can be saved. Additionally, we show that people that remain in isolation significantly reduce their probability of contagion, so risk groups should be recommended to maintain a low contact rate during the course of the epidemic.

negative: Abstract Presentations from the AABB Annual Meeting Boston, MA, October 13–16, 2018

negative: 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.

negative: Performance Characteristics of the Abbott Architect SARS-CoV-2 IgG Assay and Seroprevalence Testing in Idaho Coronavirus disease-19 (COVID19), the novel respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with severe morbidity and mortality. The rollout of diagnostic testing in the United States was slow, leading to numerous cases that were not tested for SARS-CoV-2 in February and March 2020, necessitating the use of serological testing to determine past infections. Here, we evaluated the Abbott SARS-CoV-2 IgG test for detection of anti-SARS-CoV-2 IgG antibodies by testing 3 distinct patient populations. We tested 1,020 serum specimens collected prior to SARS-CoV-2 circulation in the United States and found one false positive, indicating a specificity of 99.90%. We tested 125 patients who tested RT-PCR positive for SARS-CoV-2 for which 689 excess serum specimens were available and found sensitivity reached 100% at day 17 after symptom onset and day 13 after PCR positivity. Alternative index value thresholds for positivity resulted in 100% sensitivity and 100% specificity. We then tested 4,856 individuals from Boise, Idaho collected over one week in April 2020 as part of the Crush the Curve initiative and detected 87 positives for a positivity rate of 1.79%. These data demonstrate excellent analytical performance of the Abbott SARS-CoV-2 IgG test as well as the limited circulation of the virus on the West Coast. We expect the availability of high-quality serological testing will be a key tool in the fight against SARS-CoV-2.

negative: Structural disorder in the proteome and interactome of Alkhurma virus (ALKV) Infection by the Alkhurma virus (ALKV) leading to the Alkhurma hemorrhagic fever is a common thread in Saudi Arabia, with no efficient treatment or prevention available as of yet. Although the rational drug design traditionally uses information on known 3D structures of viral proteins, intrinsically disordered proteins (i.e., functional proteins that do not possess unique 3D structures), with their multitude of disorder-dependent functions, are crucial for the biology of viruses. Here, viruses utilize disordered regions in their invasion of the host organisms and in hijacking and repurposing of different host systems. Furthermore, the ability of viruses to efficiently adjust and accommodate to their hostile habitats is also intrinsic disorder-dependent. However, little is currently known on the level of penetrance and functional utilization of intrinsic disorder in the ALKV proteome. To fill this gap, we used here multiple computational tools to evaluate the abundance of intrinsic disorder in the ALKV genome polyprotein. We also analyzed the peculiarities of intrinsic disorder predisposition of the individual viral proteins, as well as human proteins known to be engaged in interaction with the ALKV proteins. Special attention was paid to finding a correlation between protein functionality and structural disorder. To the best of our knowledge, this work represents the first systematic study of the intrinsic disorder status of ALKV proteome and interactome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00018-018-2968-8) contains supplementary material, which is available to authorized users.

negative: AI-assisted CT imaging analysis for COVID-19 screening: Building and deploying a medical AI system in four weeks The sudden outbreak of novel coronavirus 2019 (COVID-19) increased the diagnostic burden of radiologists. In the time of an epidemic crisis, we hoped artificial intelligence (AI) to help reduce physician workload in regions with the outbreak, and improve the diagnosis accuracy for physicians before they could acquire enough experience with the new disease. Here, we present our experience in building and deploying an AI system that automatically analyzes CT images to detect COVID-19 pneumonia features. Different from conventional medical AI, we were dealing with an epidemic crisis. Working in an interdisciplinary team of over 30 people with medical and / or AI background, geographically distributed in Beijing and Wuhan, we were able to overcome a series of challenges in this particular situation and deploy the system in four weeks. Using 1,136 training cases (723 positives for COVID-19) from five hospitals, we were able to achieve a sensitivity of 0.974 and specificity of 0.922 on the test dataset, which included a variety of pulmonary diseases. Besides, the system automatically highlighted all lesion regions for faster examination. As of today, we have deployed the system in 16 hospitals, and it is performing over 1,300 screenings per day.

negative: Harnessing Mechanistic Knowledge on Beneficial Versus Deleterious IFN-I Effects to Design Innovative Immunotherapies Targeting Cytokine Activity to Specific Cell Types Type I interferons (IFN-I) were identified over 50 years ago as cytokines critical for host defense against viral infections. IFN-I promote anti-viral defense through two main mechanisms. First, IFN-I directly reinforce or induce de novo in potentially all cells the expression of effector molecules of intrinsic anti-viral immunity. Second, IFN-I orchestrate innate and adaptive anti-viral immunity. However, IFN-I responses can be deleterious for the host in a number of circumstances, including secondary bacterial or fungal infections, several autoimmune diseases, and, paradoxically, certain chronic viral infections. We will review the proposed nature of protective versus deleterious IFN-I responses in selected diseases. Emphasis will be put on the potentially deleterious functions of IFN-I in human immunodeficiency virus type 1 (HIV-1) infection, and on the respective roles of IFN-I and IFN-III in promoting resolution of hepatitis C virus (HCV) infection. We will then discuss how the balance between beneficial versus deleterious IFN-I responses is modulated by several key parameters including (i) the subtypes and dose of IFN-I produced, (ii) the cell types affected by IFN-I, and (iii) the source and timing of IFN-I production. Finally, we will speculate how integration of this knowledge combined with advanced biochemical manipulation of the activity of the cytokines should allow designing innovative immunotherapeutic treatments in patients. Specifically, we will discuss how induction or blockade of specific IFN-I responses in targeted cell types could promote the beneficial functions of IFN-I and/or dampen their deleterious effects, in a manner adapted to each disease.

negative: Chapter 3 Measuring, Monitoring, and Evaluating the Health of a Population Abstract Public health depends on information derived from monitoring population health status to identify community health problems, and to diagnose and investigate health problems and hazards in the community. These depend on vital statistics and disease reporting systems, including for non-communicable diseases, injuries, risk factors, health care resources, utilization of resources, and special disease registries such as for cancer, birth defects, and many others. Information technology and computerization allow data systems to be linked to assess the impact of health conditions and utilization of services providing vital information for epidemiological and economic analyses for policy development. Epidemiology and its associated quantitative disciplines of biostatistics and demography are augmented by social and behavioral qualitative research methods. The disciplines of health systems research provide evidence from population health monitoring crucial to policy and priority determination. This introductory chapter is augmented in subsequent chapters, and by specialized courses in public health education programs.

negative: Perception of emergent epidemic of COVID-2019 / SARS CoV-2 on the Polish Internet Problem: Due to the spread of SARS CoV-2 virus infection and COVID-2019 disease, there is an urgent need to analyze COVID-2019 epidemic perception in Poland. This would enable authorities for preparation of specific actions minimizing public health and economic risks. Methods: We study the perception of COVID-2019 epidemic in Polish society using quantitative analysis of its digital footprints on the Internet (on Twitter, Google, YouTube, Wikipedia and electronic media represented by Event Registry) from January 2020 to 12.03.2020 (before and after official introduction to Poland on 04.03.2020). To this end we utilize data mining, social network analysis, natural language processing techniques. Each examined internet platform was analyzed for representativeness and composition of the target group. Results: We identified three major cluster of the interest before disease introduction on the topic COVID-2019: China- and Italy-related peaks on all platforms, as well as a peak on social media related to the recent special law on combating COVID-2019. Besides, there was a peak in interest on the day of officially confirmed introduction as well as an exponential increase of interest when the Polish government declared war against disease with a massive mitigation program. From sociolingistic perspective, we found that concepts and issues of threat, fear and prevention prevailed before introduction. After introduction, practical concepts about disease and epidemic dominate. Twitter reflected the clear, structural division of the Polish political sphere. We were able to identify potential sources of misinformation as well as key actors (especially early adopters) and influencers. Conclusions: Traditional and social media not only reflect reality, but also create it. Polish authorities, having a reliable analysis of the perception of the problem, could optimally prepare and manage the social dimension of the current epidemic and future ones. Due to filter bubbles observed on Twitter, public information campaigns might have less impact on society than expected. For greater penetration, it might be necessary to diversify information channels to reach as many people as possible which might already be happening. Moreover, it might be necessary to prevent the spread of disinformation, which is now possible due to the special law on combating COVID-2019.

negative: Field trial evaluation of a reo-coronavirus calf diarrhea vaccine. Field trials were conducted using an experimental, modified live virus, oral vaccine for prevention of reo- and coronavirus calf diarrhea. Prior to the trials, one or both of the specific causative agents were identified from affected calves in each participating herd. In 21 herds, sequential trials were conducted in which results of uninterrupted vaccination were compared with disease rates during a preceding or subsequent control period. In these herds there was a statistically significant reduction in the morbidity and mortality from disease in 1,598 vaccinates compared with the rates in 829 prevaccination control calves. Morbidity and mortality in 206 post-vaccination control calves rose marginally above the rates in the same vaccinates. In 26 other herds, where double blind trials were conducted, rates of morbidity and mortality from disease were virtually the same for 1,080 vaccinated calves and 355 placebo calves. Vaccinates in the sequential trials had the lowest morbidity and mortality rates of any test group in either field trial format. In a selected dairy herd, both field trial formats were implemented and the results compared. In the double blind trial, vaccinates and placebo calves had comparable rates of morbidity and mortality from disease. When a sequential trial was later implemented, a statistically significant reduction in morbidity and mortality occurred in vaccinates compared with rates in control calves.

negative: COVID‐19 and rationally layered social distancing I would like to thank Dr. Thomson for the very pertinent and relevant points that he raised in his thoughtful letter Where are we now with COVID-19? [1]. As my response will illustrate, and in what probably will become a defining feature of conversations surrounding COVID-19 for quite some time, attempts to answer will only make room for more questions. As COVID-19 is unfolding, every day is marked by novel developments. Since the editorial went to press [2], the outbreak has expanded considerably. Over 128,000 individuals were infected worldwide as of March 13, 2020, leading to 4720 deaths [3]. In early March, while the outbreak in China appeared to start to subside [4], it started to amplify in Europe and the United States. The first fatality in the United States occurred on February 29, 2020 in a suburb of Seattle. On March 4m the first death was reported outside WA state, in CA, and was the 11th death in the United States. On March 6, the first two fatalities were reported in Florida. On March 11, 2020, the World Health Organization declared the outbreak a pandemic [5].

negative: The First 75 Days of Novel Coronavirus (SARS-CoV-2) Outbreak: Recent Advances, Prevention, and Treatment The recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, previously known as 2019-nCoV) outbreak has engulfed an unprepared world amidst a festive season. The zoonotic SARS-CoV-2, believed to have originated from infected bats, is the seventh member of enveloped RNA coronavirus. Specifically, the overall genome sequence of the SARS-CoV-2 is 96.2% identical to that of bat coronavirus termed BatCoV RaTG13. Although the current mortality rate of 2% is significantly lower than that of SARS (9.6%) and Middle East respiratory syndrome (MERS) (35%), SARS-CoV-2 is highly contagious and transmissible from human to human with an incubation period of up to 24 days. Some statistical studies have shown that, on average, one infected patient may lead to a subsequent 5.7 confirmed cases. Since the first reported case of coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 on December 1, 2019, in Wuhan, China, there has been a total of 60,412 confirmed cases with 1370 fatalities reported in 25 different countries as of February 13, 2020. The outbreak has led to severe impacts on social health and the economy at various levels. This paper is a review of the significant, continuous global effort that was made to respond to the outbreak in the first 75 days. Although no vaccines have been discovered yet, a series of containment measures have been implemented by various governments, especially in China, in the effort to prevent further outbreak, whilst various medical treatment approaches have been used to successfully treat infected patients. On the basis of current studies, it would appear that the combined antiviral treatment has shown the highest success rate. This review aims to critically summarize the most recent advances in understanding the coronavirus, as well as the strategies in prevention and treatment.

negative: 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: Molecular Diagnosis of Pneumonia Using Multiplex Real-Time PCR Assay RespiFinder® SMART 22 FAST in a Group of Moroccan Infants BACKGROUND: In Morocco, pediatric pneumonia remains a serious public health problem, as it constitutes the first cause of mortality due to infectious diseases. The etiological diagnosis of acute respiratory tract infections is difficult. Therefore, it is necessary to use Multiplex real-time polymerase chain reaction assay tests in a routine setting for exact and fast identification. OBJECTIVES: In this paper, we present the clinical results of pediatric pneumonia and describe their etiology by using molecular diagnosis. Study design: Tracheal secretion was collected from infants presenting respiratory distress isolated or associated with systemic signs, attending the unit of Neonatology between December 1, 2016, and Mai 31, 2018. Samples were tested with the multiplex RespiFinder® SMART 22 FAST which potentially detects 18 viruses and 4 bacteria. RESULTS: Of the 86 infants considered in this study (mean age 31 ± 19 days) suspected of acute respiratory tract infections, 71 (83%) were positive for one or multiple viruses or/and bacteria. The majority of acute respiratory tract infections had a viral origin (95%): respiratory syncytial viruses (A and B) (49%), rhinovirus (21%), coronaviruses 229E (11%), humain metapneumovirus (5%), influenza A (3%), influenza H1N1 (1%), adenovirus (2%), and parainfluenza virus type 4 (2%). Among our patients, 6% had Mycoplasma pneumoniae. Coinfections were not associated with severe respiratory symptoms. CONCLUSION: The clinical spectrum of respiratory infections is complex and often nonspecific. Thus, the early and fast detection of related causative agents is crucial. The use of multiplex real time polymerase chain reaction may help choose an accurate treatment, reduce the overall use of unnecessary antibiotics, preserve intestinal flora, and decrease nosocomial infection by reducing the length of hospitalization.

negative: COVID-19 Pandemic: Global Impact and Potential Implications for Cardiovascular Disease in Canada BACKGROUND: Literature indicates that cardiovascular disease (CVD, including stroke), older age, and availability of healthcare resources impact COVID-19 case fatality rates (CFR). The cumulative effect of COVID-19 CFR in global CVD populations and the extrapolated impact on access to healthcare services in the CVD population in Canada are not fully known. This study explored the relationships of factors that may impact COVID-19 CFR and estimated the potential indirect impact of COVID-19 on Canadian healthcare resources. METHODS: Country-level epidemiological data were analyzed to study the correlation, main effect, and interaction between COVID-19 CFR and: a) proportion of the population with CVD, b) proportion of the population ≥ 65 years, and c) availability of essential health services as defined by the World Health Organization Universal Health Coverage (UHC) index. For indirect implications on healthcare resources, estimates of the volume of postponed coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI) and valve surgeries in Ontario were calculated. RESULTS: Positive correlations were found between COVID-19 CFR and a) proportion of the population with CVD (ρ=0.40, p=0.001), b) proportion of the population ≥ 65 years (ρ=0.43, p=0.0005) and c) UHC index (ρ=0.27, p=0.03). For every 1% increase in proportion of the population ≥ 65 years or proportion of the population with CVD, COVID-19 CFR was 9% and 19% higher, respectively. Approximately 1,252 procedures would be postponed monthly in Ontario due to current public health measures. CONCLUSIONS: Countries with more prevalent CVD reported higher COVID-19 CFR. Strain on healthcare resources is likely in Canada.

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: CryptoDex: A randomised, double-blind, placebo-controlled phase III trial of adjunctive dexamethasone in HIV-infected adults with cryptococcal meningitis: study protocol for a randomised control trial BACKGROUND: Cryptococcal meningitis (CM) is a severe AIDS-defining illness with 90-day case mortality as high as 70% in sub-Saharan Africa, despite treatment. It is the leading cause of death in HIV patients in Asia and Africa. No major advance has been made in the treatment of CM since the 1970s. The mainstays of induction therapy are amphotericin B and flucytosine, but these are often poorly available where the disease burden is highest. Adjunctive treatments, such as dexamethasone, have had dramatic effects on mortality in other neurologic infections, but are untested in CM. Given the high death rates in patients receiving current optimal treatment, and the lack of new agents on the horizon, adjuvant treatments, which offer the potential to reduce mortality in CM, should be tested. The principal research question posed by this study is as follows: does adding dexamethasone to standard antifungal therapy for CM reduce mortality? Dexamethasone is a cheap, readily available, and practicable intervention. METHOD: A double-blind placebo-controlled trial with parallel arms in which patients are randomised to receive either dexamethasone or placebo, in addition to local standard of care. The study recruits patients in both Asia and Africa to ensure the relevance of its results to the populations in which the disease burden is highest. The 10-week mortality risk in the control group is expected to be between 30% and 50%, depending on location, and the target hazard ratio of 0.7 corresponds to absolute risk reductions in mortality from 30% to 22%, or from 50% to 38%. Assuming an overall 10-week mortality of at least 30% in our study population, recruitment of 824 patients will be sufficient to observe the expected number of deaths. Allowing for some loss to follow-up, the total sample size for this study is 880 patients. To generate robust evidence across both continents, we aim to recruit roughly similar numbers of patients from each continent. The primary end point is 10-week mortality. Ethical approval has been obtained from Oxford University’s Tropical Research Ethics Committee (OxTREC), and as locally mandated at each site. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number: ISRCTN59144167 26-July-2012

negative: In utero infection with porcine reproductive and respiratory syndrome virus modulates leukocyte subpopulations in peripheral blood and bronchoalveolar fluid of surviving piglets Abstract It is well known that piglets congenitally infected with porcine reproductive and respiratory syndrome virus (PRRSV) can be viremic at birth, and that preweaning mortality due to secondary infections often increases during acute outbreaks of PRRS. Therefore, an immunosuppressive effect of in utero infection has been suggested. The aim of the present study was to characterise the changes of leukocyte populations in piglets surviving in utero infection with PRRSV. A total of 27 liveborn uninfected control piglets and 22 piglets infected transplacentally with a Danish strain of PRRSV were included. At 2 and 4 weeks of age, 21 of 22 (96%) and 7 of 14 (50%) examined infected piglets were still viremic, whereas PRRSV could not be detected in the six infected piglets examined at 6 weeks of age. Flow cytometry analysis was used to determine the phenotypic composition of leukocytes in peripheral blood and bronchoalveolar lavage fluid (BALF) of 2-, 4- and 6-week-old infected piglets and age-matched uninfected controls. The key observation in the present study is that high levels of CD8+ cells constitute a dominant feature in peripheral blood and BALF of piglets surviving in utero infection with PRRSV. In BALF, the average high level of CD8+ cells in 2-week-old infected piglets (33.4±12.6%) was followed by a decline to 7.3±3.0 and 11.1±3.0% at 4 and 6 weeks of age. BALF of control piglets contained 1.6±0.9, 2.3±1.8 and 1.9±0.5% CD8+ cells, only. In peripheral blood, however, the average number of CD8+ cells remained at high levels in the infected piglets throughout the post-natal experimental period (2.8±1.9, 2.9±1.8 and 3.2±1.7×106 CD8+ cells/ml at 2, 4 and 6 weeks, respectively). In the controls, the average levels of CD8+ cells were 0.9±0.2, 1.9±1.7 and 1.6±0.5×106/ml, respectively. Furthermore, the numbers of CD2+, CD4+CD8+ and SLA-classII+ cells, respectively, in peripheral blood, together with the levels of CD2+ and CD3+ cells in BALF were increased in the infected piglets infected in utero compared to the uninfected controls. The kinetic analyses carried out in the present study reflect that in utero infection with PRRSV modulates immune cell populations in peripheral blood and BALF of surviving piglets. The observed changes are characterised by high levels of CD8+ cells supporting an important role of these cells in PRRSV infection. The present results, however, do not support the existence of post-natal immunosuppression following in utero infection with PRRSV.

negative: Pneumonia severity index in viral community acquired pneumonia in adults Pneumonia severity index (PSI) is an important scoring system that can assess the severity of community acquired pneumonia and determine admission status. However, there is a lack of research on whether this scoring system can be applied to viral community acquired pneumonia. The purpose of this study was to evaluate the usefulness of PSI in viral community acquired pneumonia. This retrospective cohort study included 1,434 adult patients (aged ≥18 years) who were admitted to the emergency department of a university hospital during 2013–2015 because of community-acquired pneumonia. Viral infections were diagnosed by multiplex PCR. Patients diagnosed with non-viral community-acquired pneumonia were included in the control group (N = 1,173). The main outcome was 30-day all-cause mortality. multivariate Cox regression analyses were performed to calculate the risk of death. Respiratory viruses were detected in 261 (18.2%) patients with community-acquired pneumonia. Two types of respiratory viruses were detected in 7 cases. Of the 254 cases detected with only one virus, 62 were influenza A, 18 were influenza B, 65 were rhinovirus, 35 were respiratory syncytial virus, 25 were metapneumovirus, 20 were parainfluenza, 17 were coronavirus, 7 were bocavirus, and 5 were adenovirus. Mortality was not significantly different between patients with respiratory virus and those without respiratory virus; the 30-day all-cause mortality rates were 20.3% and 22.4%, respectively (P = 0.45). Mortality rate increased with an increasing PSI score with or without respiratory viral infection. Pulmonary severity index was significantly associated with mortality adjusted for respiratory virus detection (hazard ratio = 1.024, 95% confidence interval = 1.020–1.028). Pneumonia severity index score is an important factor for assessing the prognosis of patients with community-acquired pneumonia, regardless of respiratory virus detection.

negative: 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.

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: Essential care of critical illness must not be forgotten in the COVID-19 pandemic

negative: Health System Resource Gaps and Associated Mortality from Pandemic Influenza across Six Asian Territories BACKGROUND: Southeast Asia has been the focus of considerable investment in pandemic influenza preparedness. Given the wide variation in socio-economic conditions, health system capacity across the region is likely to impact to varying degrees on pandemic mitigation operations. We aimed to estimate and compare the resource gaps, and potential mortalities associated with those gaps, for responding to pandemic influenza within and between six territories in Asia. METHODS AND FINDINGS: We collected health system resource data from Cambodia, Indonesia (Jakarta and Bali), Lao PDR, Taiwan, Thailand and Vietnam. We applied a mathematical transmission model to simulate a “mild-to-moderate” pandemic influenza scenario to estimate resource needs, gaps, and attributable mortalities at province level within each territory. The results show that wide variations exist in resource capacities between and within the six territories, with substantial mortalities predicted as a result of resource gaps (referred to here as “avoidable” mortalities), particularly in poorer areas. Severe nationwide shortages of mechanical ventilators were estimated to be a major cause of avoidable mortalities in all territories except Taiwan. Other resources (oseltamivir, hospital beds and human resources) are inequitably distributed within countries. Estimates of resource gaps and avoidable mortalities were highly sensitive to model parameters defining the transmissibility and clinical severity of the pandemic scenario. However, geographic patterns observed within and across territories remained similar for the range of parameter values explored. CONCLUSIONS: The findings have important implications for where (both geographically and in terms of which resource types) investment is most needed, and the potential impact of resource mobilization for mitigating the disease burden of an influenza pandemic. Effective mobilization of resources across administrative boundaries could go some way towards minimizing avoidable deaths.

negative: Epidemiological features of and changes in incidence of infectious diseases in China in the first decade after the SARS outbreak: an observational trend study Summary Background The model of infectious disease prevention and control changed significantly in China after the outbreak in 2003 of severe acute respiratory syndrome (SARS), but trends and epidemiological features of infectious diseases are rarely studied. In this study, we aimed to assess specific incidence and mortality trends of 45 notifiable infectious diseases from 2004 to 2013 in China and to investigate the overall effectiveness of current prevention and control strategies. Methods Incidence and mortality data for 45 notifiable infectious diseases were extracted from a WChinese public health science data centre from 2004 to 2013, which covers 31 provinces in mainland China. We estimated the annual percentage change in incidence of each infectious disease using joinpoint regression. Findings Between January, 2004, and December, 2013, 54 984 661 cases of 45 infectious diseases were reported (average yearly incidence 417·98 per 100 000). The infectious diseases with the highest yearly incidence were hand, foot, and mouth disease (114·48 per 100 000), hepatitis B (81·57 per 100 000), and tuberculosis (80·33 per 100 000). 132 681 deaths were reported among the 54 984 661 cases (average yearly mortality 1·01 deaths per 100 000; average case fatality 2·4 per 1000). Overall yearly incidence of infectious disease was higher among males than females and was highest among children younger than 10 years. Overall yearly mortality was higher among males than females older than 20 years and highest among individuals older than 80 years. Average yearly incidence rose from 300·54 per 100 000 in 2004 to 483·63 per 100 000 in 2013 (annual percentage change 5·9%); hydatid disease (echinococcosis), hepatitis C, and syphilis showed the fastest growth. The overall increasing trend changed after 2009, and the annual percentage change in incidence of infectious disease in 2009–13 (2·3%) was significantly lower than in 2004–08 (6·2%). Interpretation Although the overall incidence of infectious diseases was increasing from 2004, the rate levelled off after 2009. Effective prevention and control strategies are needed for diseases with the highest incidence—including hand, foot, and mouth disease, hepatitis B, and tuberculosis—and those with the fastest rates of increase (including hydatid disease, hepatitis C, and syphilis). Funding Chinese Ministry of Science and Technology, National Natural Science Foundation (China).

negative: Expression of the recombinant anchorless N-terminal domain of mouse hepatitis virus (MHV) receptor makes hamster of human cells susceptible to MHV infection. Mouse hepatitis virus (MHV) receptor, the receptor for the murine coronavirus MHV, was expressed in MHV-resistant hamster and human cells as a series of mutant, recombinant glycoproteins with carboxy-terminal deletions lacking the cytoplasmic tail, transmembrane domain, and various amounts of the immunoglobulin constant-region-like domains. The soluble receptor glycoproteins containing the N-terminal virus-binding domain were released into the supernatant medium and inactivated the infectivity of MHV-A59 virions in a concentration-dependent manner. Surprisingly, some of the anchorless glycoproteins were found on the plasma membranes of transfected cells by flow cytometry, and these cells were rendered susceptible to infection with three strains of MHV. Thus, in the cells in which the anchorless, recombinant receptor glycoprotein is synthesized, some of the protein is bound to an unidentified moiety on the plasma membrane, which allows it to serve as a functional virus receptor.

negative: Evolution, antigenicity and pathogenicity of global porcine epidemic diarrhea virus strains Emerging and re-emerging coronaviruses cause morbidity and mortality in human and animal populations, resulting in serious public and animal health threats and economic losses. The ongoing outbreak of a highly contagious and deadly porcine epidemic diarrhea virus (PEDV) in Asia, the Americas and Europe is one example. Genomic sequence analyses of PEDV variants have revealed important insights into the evolution of PEDV. However, the antigenic variations among different PEDV strains are less explored, although they may contribute to the failure of PEDV vaccines in Asian countries. In addition, the evolution of PEDV results in variants with distinct genetic features and virulence differences; thus PEDV can serve as a model to explore the molecular mechanisms of coronavirus evolution and pathogenesis. In this article, we review the evolution, antigenic relationships and pathologic features of PEDV strains. This information and review of researches will aid in the development of strategies for control and prevention of PED.

negative: A demographic scaling model for estimating the total number of COVID-19 infections Background: The total number of COVID-19 infections is critical information for decision makers when assessing the progress of the pandemic, its implications, and policy options. Despite efforts to carefully monitor the COVID-19 pandemic, the reported number of confirmed cases is likely to underestimate the actual number of infections. We aim to estimate the total number of COVID-19 infections in a straightforward manner using a demographic scaling approach based on life tables. Methods: We use data on total number of COVID-19 attributable deaths, population counts, and life tables as well as information on infection fatality rates as reported in Verity et al. (2020) for Hubei, China. We develop a scaling approach based on life tables and remaining life expectancy to map infection fatality rates between two countries to account for differences in their age structure, health status, and the health care system. The scaled infection fatality rates can be used in combination with COVID-19 attributable deaths to calculate estimates of the total number of infected. We also introduce easy to apply formulas to quantify the bias that would be required in death counts and infection fatality rates in order to reproduce a certain estimate of infections. Findings: Across the 10 countries with most COVID-19 deaths as of April 17, 2020, our estimates suggest that the total number of infected is approximately 4 times the number of confirmed cases. The uncertainty, however, is high, as the lower bound of the 95% prediction interval suggests on average twice as many infections than confirmed cases, and the upper bound 10 times as many. Country-specific variation is high. For Italy, our estimates suggest that the total number of infected is approximately 1 million, or almost 6 times the number of confirmed cases. For the U.S., our estimate of 1.4 million is close to being twice as large as the number of confirmed cases, and the upper bound of 3 million is more than 4 times the number of confirmed cases. For Germany, where testing has been comparatively extensive, we estimate that the total number of infected is only 1.2 times (upper bound: 3 times) than the number of confirmed cases. Comparing our results with findings from local seroprevalence studies and applying our bias formulas shows that some of their infection estimates would only be possible if just a small fraction of COVID-19 related deaths were recorded, indicating that these seroprevalence estimates might not be representative for the total population. Interpretation: As many countries lack population based seroprevalence studies, straightforward demographic adjustment can be used to deliver useful estimates of the total number of infected cases. Our results imply that the total number COVID-19 cases may be approximately 4 times (95%: 2 to 10 times) that of the confirmed cases. Although these estimates are uncertain and vary across countries, they indicate that the COVID-19 pandemic is much more broadly spread than what confirmed cases would suggest, and the number of asymptomatic cases or cases with mild symptoms may be high. In cases in which estimates from local seroprevalence studies or from simulation models exist, our approach can provide a simple benchmark to assess the quality of those estimates.

negative: Preoperative nutritional status is an important predictor of survival in patients undergoing surgery for renal cell carcinoma. BACKGROUND The role of malnutrition has not been well studied in patients undergoing surgery for renal cell carcinoma (RCC). OBJECTIVE Our aim was to evaluate whether nutritional deficiency (ND) is an important determinant of survival following surgery for RCC. DESIGN, SETTING, AND PARTICIPANTS A total of 369 consecutive patients underwent surgery for locoregional RCC from 2003 to 2008. ND was defined as meeting one of the following criteria: body mass index <18.5 kg/m(2), albumin <3.5 g/dl, or preoperative weight loss ≥ 5% of body weight. INTERVENTION All patients underwent radical or partial nephrectomy. MEASUREMENTS Primary outcomes were overall and disease-specific mortality. Covariates included age, Charlson comorbidity index (CCI), preoperative anemia, tumor stage, Fuhrman grade, and lymph node status. Multivariate analysis was performed using a Cox proportional hazards model. Mortality rates were estimated using the Kaplan-Meier product-limit method. RESULTS AND LIMITATIONS Eighty-five patients (23%) were categorized as ND. Three-year overall and disease-specific survival were 58.5% and 80.4% in the ND cohort compared with 85.4% and 94.7% in controls, respectively (p<0.001). ND remained a significant predictor of overall mortality (hazard ratio [HR]: 2.41, 95% confidence interval [CI], 1.40-4.18) and disease-specific mortality (HR: 2.76; 95% CI, 1.17-6.50) after correcting for age, CCI, preoperative anemia, stage, grade, and nodal status. This study is limited by its retrospective nature. CONCLUSIONS ND is associated with higher mortality in patients undergoing surgery for locoregional RCC, independent of key clinical and pathologic factors. Given this mortality risk, it may be important to address nutritional status preoperatively and counsel patients appropriately.

negative: Infectious Disease Risk Across the Growing Human-Non Human Primate Interface: A Review of the Evidence Most of the human pandemics reported to date can be classified as zoonoses. Among these, there is a long history of infectious diseases that have spread from non-human primates (NHP) to humans. For millennia, indigenous groups that depend on wildlife for their survival were exposed to the risk of NHP pathogens' transmission through animal hunting and wild meat consumption. Usually, exposure is of no consequence or is limited to mild infections. In rare situations, it can be more severe or even become a real public health concern. Since the emergence of acquired immune deficiency syndrome (AIDS), nobody can ignore that an emerging infectious diseases (EID) might spread from NHP into the human population. In large parts of Central Africa and Asia, wildlife remains the primary source of meat and income for millions of people living in rural areas. However, in the past few decades the risk of exposure to an NHP pathogen has taken on a new dimension. Unprecedented breaking down of natural barriers between NHP and humans has increased exposure to health risks for a much larger population, including people living in urban areas. There are several reasons for this: (i) due to road development and massive destruction of ecosystems for agricultural needs, wildlife and humans come into contact more frequently; (ii) due to ecological awareness, many long distance travelers are in search of wildlife discovery, with a particular fascination for African great apes; (iii) due to the attraction for ancient temples and mystical practices, others travelers visit Asian places colonized by NHP. In each case, there is a risk of pathogen transmission through a bite or another route of infection. Beside the individual risk of contracting a pathogen, there is also the possibility of starting a new pandemic. This article reviews the known cases of NHP pathogens' transmission to humans whether they are hunters, travelers, ecotourists, veterinarians, or scientists working on NHP. Although pathogen transmission is supposed to be a rare outcome, Rabies virus, Herpes B virus, Monkeypox virus, Ebola virus, or Yellow fever virus infections are of greater concern and require quick countermeasures from public health professionals.

negative: Global patterns of zoonotic disease in mammals As the frequency and prevalence of zoonotic diseases increase worldwide, investigating how mammal host distributions determine patterns of human disease and predicting which regions are at greatest risk for future zoonotic disease emergence are two goals which both require better understanding the current distributions of zoonotic hosts and pathogens. Here we review the existing data about mammalian host species, comparing and contrasting these patterns against global maps of zoonotic hosts from all 27 orders of terrestrial mammals. We discuss the zoonotic potential of host species from the top six most species-rich mammal groups, and review the literature to identify analytical and conceptual gaps that must be addressed to improve our ability to generate testable predictions about zoonotic diseases originating from wild mammals.

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

negative: AMS 3.0: prediction of post-translational modifications BACKGROUND: We present here the recent update of AMS algorithm for identification of post-translational modification (PTM) sites in proteins based only on sequence information, using artificial neural network (ANN) method. The query protein sequence is dissected into overlapping short sequence segments. Ten different physicochemical features describe each amino acid; therefore nine residues long segment is represented as a point in a 90 dimensional space. The database of sequence segments with confirmed by experiments post-translational modification sites are used for training a set of ANNs. RESULTS: The efficiency of the classification for each type of modification and the prediction power of the method is estimated here using recall (sensitivity), precision values, the area under receiver operating characteristic (ROC) curves and leave-one-out tests (LOOCV). The significant differences in the performance for differently optimized neural networks are observed, yet the AMS 3.0 tool integrates those heterogeneous classification schemes into the single consensus scheme, and it is able to boost the precision and recall values independent of a PTM type in comparison with the currently available state-of-the art methods. CONCLUSIONS: The standalone version of AMS 3.0 presents an efficient way to indentify post-translational modifications for whole proteomes. The training datasets, precompiled binaries for AMS 3.0 tool and the source code are available at http://code.google.com/p/automotifserver under the Apache 2.0 license scheme.

negative: Higher virulence of COVID-19 in the air-polluted regions of eight severely affected countries COVID-19 has spread in all continents in a span of just over three months, escalating into a pandemic that poses several humanitarian as well as scientific challenges. We here investigated the geographical character of the infection and correlate it with several annual satellite and ground indexes of air quality in China, Iran, Italy, Spain, France, Germany, U.K. and U.S.A. Adjusting for population size, we find more viral infections in those areas afflicted by high PM 2.5 and Nitrogen Dioxide values. Higher mortality was also correlated with relatively poor air quality. In Italy, the correspondence between the Po valley pollution and SARS-CoV-2 infections and induced mortality was the starkest, originating right in the most polluted European area. Air pollution appears to be for this disease a risk factor similar to smoking. This suggests the detrimental impact climate change will have on the trajectory of future respiratory epidemics.

negative: As COVID-19 cases, deaths and fatality rates surge in Italy, underlying causes require investigation. COVID-19 case fatalities surged during the month of March 2020 in Italy, reaching over 10,000 by 28 March 2020. This number exceeds the number of fatalities in China (3,301) recorded from January to March, even though the number of diagnosed cases was similar (85,000 Italy vs. 80,000 China). Case Fatality Rates (CFR) could be somewhat unreliable because the estimation of total case numbers is limited by several factors, including insufficient testing and limitations in test kits and materials, such as NP swabs and PPE for testers. Sero prevalence of SARS-CoV-2 antibodies may help in more accurate estimations of the total number of cases. Nevertheless, the disparity in the differences in the total number of fatalities between Italy and China suggests investigation into several factors, such as demographics, sociological interactions, availability of medical equipment (ICU beds and PPE), variants in immune proteins (e.g., HLA, IFNs), past immunity to related CoVs, and mutations in SARS-CoV-2, could impact survival of severe COVID-19 illness survival and the number of case fatalities.

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

negative: Nosocomial Infection in the Intensive Care Unit

negative: TREC-COVID: Rationale and Structure of an Information Retrieval Shared Task for COVID-19 TREC-COVID is an information retrieval (IR) shared task initiated to support clinicians and clinical research during the COVID-19 pandemic. IR for pandemics breaks many normal assumptions, which can be seen by examining nine important basic IR research questions related to pandemic situations. TREC-COVID differs from traditional IR shared task evaluations with special considerations for the expected users, IR modality considerations, topic development, participant requirements, assessment process, relevance criteria, evaluation metrics, iteration process, projected timeline, and the implications of data use as a post-task test collection. This article describes how all these were addressed for the particular requirements of developing IR systems under a pandemic situation. Finally, initial participation numbers are also provided, which demonstrate the tremendous interest the IR community has in this effort.

negative: Characterization of Plasmodium vivax-associated admissions to reference hospitals in Brazil and India BACKGROUND: The benign character formerly attributed to Plasmodium vivax infection has been dismantled by the increasing number of reports of severe disease associated with infection with this parasite, prompting the need for more thorough and comprehensive characterization of the spectrum of resulting clinical complications. Endemic areas exhibit wide variations regarding severe disease frequency. This study, conducted simultaneously in Brazil and India, constitutes, to our knowledge, the first multisite study focused on clinical characterization of P. vivax severe disease. METHODS: Patients admitted with P. vivax mono-infection at reference centers in Manaus (Amazon - Brazil) and Bikaner (Rajasthan - India), where P. vivax predominates, were submitted to standard thorough clinical and laboratory evaluations in order to characterize clinical manifestations and identify concurrent co-morbidities. RESULTS: In total, 778 patients (88.0% above 12 years old) were hospitalized at clinical discretion with PCR-confirmed P. vivax mono-infection (316 in Manaus and 462 in Bikaner), of which 197 (25.3%) presented at least one severity criterion as defined by the World Health Organization (2010). Hyperlactatemia, respiratory distress, hypoglycemia, and disseminated intravascular coagulation were more frequent in Manaus. Noteworthy, pregnancy status was associated as a risk factor for severe disease (OR = 2.03; 95% CI = 1.2-3.4; P = 0.007). The overall case fatality rate was 0.3/1,000 cases in Manaus and 6.1/1,000 cases in Bikaner, with all deaths occurring among patients fulfilling at least one severity criterion. Within this subgroup, case fatality rates increased respectively to 7.5% in Manaus and 4.4% in Bikaner. CONCLUSION: P. vivax-associated severity is not negligible, and although lethality observed for complicated cases was similar, the overall fatality rate was about 20-fold higher in India compared to Brazil, highlighting the variability observed in different settings. Our observations highlight that pregnant women and patients with co-morbidities need special attention when infected by this parasite due to higher risk of complications. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-015-0302-y) contains supplementary material, which is available to authorized users.

negative: SARS-CoV-2 will continue to circulate in the human population: an opinion from the point of view of the virus-host relationship At the population level, the virus-host relationship is not set up to end with the complete elimination of either or both. Pathogen-resistant individuals will always remain in the host population. In turn, the virus can never completely eliminate the host population, because evolutionarily such an event is a dead end for the virus as an obligate intracellular parasite. A certain existential balance exists in the virus-host relationship. Against this backdrop, viral epidemics and pandemics only become manifest and egregious to human beings when tens and hundreds of thousands of people die and the question emerges what caused the high mortality peaks on the death chart. The answer seems clear; the emerging strain of the virus is new to the host population, and new mutations of the virus and natural selection will lead to a survival of only genetically resistant individuals in a host population. The dangers inherent to a novel virus are due to new features generally inthe molecular structure of proteins, which enable the virus to infect the cells of the host organism more intensively, dramatically challenging host immunity, and thus be transmitted more readily in the host population. In this article, we will concentrate on the facts currently available about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has caused COVID-19 (coronavirus disease 2019) pandemic and try to predict its development and consequences based on the virus-host relationship. In fact, only two scenarios will occur simultaneously in the very near future: people who are genetically resistant to the virus will get sick, recover, and develop immunity, while people who are sensitive to the virus will need drugs and vaccines, which will have to be researched and developed if they are to recover. If the pandemic does not stop, in a few decades it is anticipated that SARS-CoV-2 will become as safe as the four non-severe acute respiratory syndrome human coronaviruses (HCoV-NL63, HCoV-HKU1, HCoV-OC43, and HCoV-229E) currently circulating but causing low mortality in the human population.

negative: Blood Still Kills: Six Strategies to Further Reduce Allogeneic Blood Transfusion-Related Mortality After reviewing the relative frequency of the causes of allogeneic blood transfusion-related mortality in the United States today, we present 6 possible strategies for further reducing such transfusion-related mortality. These are (1) avoidance of unnecessary transfusions through the use of evidence-based transfusion guidelines, to reduce potentially fatal (infectious as well as noninfectious) transfusion complications; (2) reduction in the risk of transfusion-related acute lung injury in recipients of platelet transfusions through the use of single-donor platelets collected from male donors, or female donors without a history of pregnancy or who have been shown not to have white blood cell (WBC) antibodies; (3) prevention of hemolytic transfusion reactions through the augmentation of patient identification procedures by the addition of information technologies, as well as through the prevention of additional red blood cell alloantibody formation in patients who are likely to need multiple transfusions in the future; (4) avoidance of pooled blood products (such as pooled whole blood–derived platelets) to reduce the risk of transmission of emerging transfusion-transmitted infections (TTIs) and the residual risk from known TTIs (especially transfusion-associated sepsis [TAS]); (5) WBC reduction of cellular blood components administered in cardiac surgery to prevent the poorly understood increased mortality seen in cardiac surgery patients in association with the receipt of non–WBC-reduced (compared with WBC-reduced) transfusion; and (6) pathogen reduction of platelet and plasma components to prevent the transfusion transmission of most emerging, potentially fatal TTIs and the residual risk of known TTIs (especially TAS).

negative: Trends and Patterns of Burden of Disease and Injuries in Korea Using Disability-Adjusted Life Years BACKGROUND: It is extremely important to objectively take a view of population health to provide useful information to decision makers, health-sector leaders, researchers, and informed citizens. This study aims to examine the burden of disease in Korea as of 2015, and to study how the burden of disease changes with the passage of time. METHODS: We used results from the Korean National Burden of Disease and Injuries Study 2015 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive disability-adjusted life years (DALYs) by gender and age groups from 2007 to 2015. DALYs were calculated as the sum of the years of life lost (YLLs) and the years lived with disability (YLDs). RESULTS: In 2015, the burden of disease for Korean people was calculated at 29,476 DALYs per 100,000 population. DALYs caused by low back pain were the highest, followed by diabetes mellitus and chronic obstructive pulmonary disease. The burden of disease showed a consistently increasing trend from 2007 to 2015. Although YLLs have been on the decrease since 2011, the increase in YLDs has contributed to the overall rise in DALYs. The DALYs per 100,000 population in 2015 increased by 28.1% compared to 2007. CONCLUSION: As for the diseases for which the burden of disease is substantially increasing, it is needed to establish appropriate policies in a timely manner. The results of this study are expected to be the basis for prioritizing public health and health care policies in Korea.

negative: [Quick simultaneous analyses are important when MERS-coronavirus infection is suspected]. In September 2012 a novel coronavirus (CoV) caused severe respiratory tract infections in patients from The Arabian Peninsula. It was named Middle East respiratory syndrome (MERS)-CoV. Here, a small series of case stories illustrates how simultaneous analyses for MERS-CoV and other agents of infections at the loca l laboratory resulted in rapid rejection of suspicion of MERS and establishment of the true cause of disease. Relevant treatment was initiated and the patients were discharged from hospital.

negative: Pediatric COVID-19: Systematic review of the literature OBJECTIVES: There is limited data regarding the demographics and clinical features of SARS-CoV-2 infection in children. This information is especially important as pneumonia is the single leading cause of death in children worldwide. This Systematic Review aims to elucidate a better understanding of the global impact of COVID-19 on the pediatric population. METHODS: A systematic review of the literature was performed in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to gain insight into pediatric COVID-19 epidemiology. Specifically, Pubmed and Google Scholar databases were searched to identify any relevant article with a focus on Pediatric Covid 19, Pediatric Covid-19, Pediatric SARS-COV-2, and Pediatric Coronavirus 19. References within the included articles were reviewed. All articles that met criteria where analyzed for demographics, clinical, laboratory, radiographic, treatment and outcomes data. RESULTS: Ten studies including two case series and 8 retrospective chart reviews, altogether describing a total of 2914 pediatric patients with COVID-19 were included in this systematic review. Of the patients whose data was available, 56% were male, the age range was 1â¯day to 17â¯years, 79% were reported to have no comorbidities, and of the 21% with comorbidities, the most common were asthma, immunosupression, and cardiovascular disease. Of pediatric patients that were tested and positive for an infection with SARS-CoV-2, patients were asymptomatic, 14.9% of the time. Patients presented with cough (48%), fever (47%) and sore throat/pharyngitis (28.6%), more commonly than with upper respiratory symptoms/rhinorrhea/sneezing/nasal congestion (13.7%), vomiting/nausea (7.8%) and diarrhea (10.1%). Median lab values including those for WBC, lymphocyte count and CRP, were within the reference ranges with the exception of procalcitonin levels, which were slightly elevated in children with COVID-19 (median procalcitonin levels ranged from 0.07 to 0.5â¯ng/mL. Computed tomography (CT) results suggest that unilateral CT imaging findings are present 36% of cases while 64% of pediatric patients with COVID-19 had bilateral findings. Of the studies with age specific hospitalization data available, 27.0% of patients hospitalized were infants under 1â¯year of age. Various treatment regimens including interferon, antivirals, and hydroxychloroquine therapies have been trialed on the pediatric population but there are currently no studies showing efficacy of one regimen over the other. The mortality rate of children that were hospitalized with COVID-19 was 0.0018%. CONCLUSION: In contrast to adults, most infected children appear to have a milder course and have better outcomes overall. Additional care may be needed for children with comorbidities and younger children. This review also suggests that unilateral CT chest imaging findings were seen in 36.4% pediatric COVID-19 patients. This is particularly concerning as the work-up of pediatric patients with cough may warrant a bronchoscopy to evaluate for airway foreign bodies. Extra precautions need to be taken with personal protective equipment for these cases, as aerosolizing procedures may be a method of viral transmission. LEVEL OF EVIDENCE: 4 (Systematic Review).

negative: Risks of Death and Severe Disease in Patients With Middle East Respiratory Syndrome Coronavirus, 2012–2015 Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging pathogen, first recognized in 2012, with a high case fatality risk, no vaccine, and no treatment beyond supportive care. We estimated the relative risks of death and severe disease among MERS-CoV patients in the Middle East between 2012 and 2015 for several risk factors, using Poisson regression with robust variance and a bootstrap-based expectation maximization algorithm to handle extensive missing data. Increased age and underlying comorbidity were risk factors for both death and severe disease, while cases arising in Saudi Arabia were more likely to be severe. Cases occurring later in the emergence of MERS-CoV and among health-care workers were less serious. This study represents an attempt to estimate risk factors for an emerging infectious disease using open data and to address some of the uncertainty surrounding MERS-CoV epidemiology.

negative: Tracing DAY-ZERO and Forecasting the Fade out of the COVID-19 Outbreak in Lombardy, Italy: A Compartmental Modelling and Numerical Optimization Approach. Italy currently constitutes the epicenter of the novel coronavirus disease (COVID-19) pandemic, having surpassed China's death toll. The disease is sweeping through Lombardy, which remains in lockdown since the 8th of March. As of the same day, the isolation measures taken in Lombardy have been extended to the entire country. Here, we provide estimates for: (a) the DAY-ZERO of the outbreak in Lombardy, Italy; (b) the actual number of exposed/infected cases in the total population; (c) the basic reproduction number (R0); (d) the "effective" per-day disease transmission; and, importantly, (e) a forecast for the fade out of the outbreak, on the basis of the COVID-19 Community Mobility Reports released by Google on March 29. Methods. To deal with the uncertainty in the number of actual exposed/ infected cases in the total population, we address a compartmental Susceptible/ Exposed/ Infectious/ Recovered/ Dead (SEIRD) model with two compartments of infectious persons: one modelling the total cases in the population and another modelling the confirmed cases. The parameters of the model corresponding to the recovery period, the time from the onset of symptoms to death, the case fatality ratio, and the time from exposure to the time that an individual starts to be infectious, have been set as reported from clinical studies on COVID-19. For the estimation of the DAY-ZERO of the outbreak in Lombardy, as well as of the ``effective" per-day transmission rate for which no clinical data are available, we have used the SEIRD simulator to fit the numbers of new daily cases from February 21 to the 8th of March, the lockdown day of Lombardy and of all Italy. This was accomplished by solving a mixed-integer optimization problem with the aid of genetic algorithms. Based on the computed values, we also provide an estimation of the basic reproduction number $R_0$. Furthermore, based on an estimation for the reduction in the "effective" transmission rate of the disease as of March 8 that reflects the suspension of almost all activities in Italy, we ran the simulator to forecast the fade out of the epidemic. For this purpose, we considered the reduction in mobility in Lombardy as released on March 29 by Google COVID-19 Community Mobility Reports, the effect of social distancing, and the draconian measures taken by the government on March 20 and March 21, 2020. Results. Based on the proposed methodological procedure, we estimated that the DAY-ZERO was most likely between January 5 and January 23 with the most probable date the 15th of January 2020. The actual cumulative number of exposed cases in the total population in Lombardy on March 8 was of the order of 15 times the confirmed cumulative number of infected cases. The "effective" per-day disease transmission rate for the period until March 8 was found to be 0.686 (95% CI:0.660, 0.713), while the basic reproduction number R0 was found to be 4.51 (95% CI: 4.14, 4.90). Importantly, simulations show that the COVID-19 pandemic in Lombardy is expected to fade out by the end of May - early June, 2020, if the draconian, as of March 20 and March 21, measures are maintained.

negative: Protecting workers aged 60-69 years from COVID-19

negative: A Pilot Study of Pulmonary Segmentectomy With Indocyanine Green Near-Infrared Angiography. OBJECTIVES Video-assisted thoracoscopic surgery (VATS) pulmonary segmentectomy is commonly used in treating small ground-glass opacity (GGO) nodules in lung. The identification of the intersegmental plane is one of the challenges. In this pilot study, we aimed to evaluate the feasibility of indocyanine green (ICG) angiography in VATS segmentectomy. METHODS Nineteen GGO patients were enrolled, and VATS segmentectomy with ICG near-infrared angiography were performed between July 2017 and December 2017. Conventional 3-port VATS was used. ICG was injected intravenously after dominant arties were ligated. Intersegmental plane was identified and divided by stapler and electrocautery. RESULTS All patients had perfect intersegmental plane visualization. The mean operation time was 140.8 minutes, and the mean blood loss was 23.7 mL. No complications due to ICG occurred. The mean chest tube duration was 4.6 days. No severe complications occurred in the perioperative period. The mean chest tube drainage duration was 4.6 days. Prolonged postoperative air leak (>5 days), which required no surgical intervention, occurred in 2 cases. There were no severe complications or in-hospital deaths. CONCLUSIONS VATS segmentectomy with ICG near-infrared angiography is a reasonable treatment option to treat small GGO in lung, especially due to its good surgical view maintenance.

negative: The role of afferent pulmonary innervation in poor prognosis of acute respiratory distress syndrome in COVID-19 patients and proposed use of resiniferatoxin (RTX) to improve patient outcomes in advanced disease state: A review Abstract Acute respiratory distress is one of the major causes of mortality associated with COVID-19 disease. Many patients will require intensive care with ventilatory support. Despite progress and best efforts, the mortality rates projected remain high. Historical data outlook points towards 80% expected fatality for patients progressing to advanced pulmonary disease, even when hospitalized in the intensive care unit. This is particularly true among the patient population over 65. Novel life-saving strategies are desperately needed to mitigate the high mortality that will be associated with the late stage SARS-CoV-2 viral infection associated with the fatal respiratory distress. We hypothesize that the morbidity, severity of the disease, and underlying physiological events leading to mortality are closely linked to the TRPV1 expressing neuronal system (afferent/efferent neurons) in the lungs. TRPV1 expressing cells are responsible for pain transmission, inflammation and immunomodulation throughout the entire pulmonary system and are modulating the processes associated with localized cytokine release (storm) and overall rapid disease progression. We suggest that therapeutic approaches targeting TRPV1 containing nerve fibers in the lungs will modulate the inflammatory and immune signal activity, leading to reduced mortality and better overall outcomes. We also propose to further explore the use of resiniferatoxin (RTX), an ultra-potent TRPV1 agonist currently in clinical trials for cancer and osteoarthritis pain, as a possible ablating agent of TRPV1 positive pulmonary pathways in patients with advanced COVID-19 disease.

negative: Phylogenetic analysis of a highly conserved region of the polymerase gene from 11 coronaviruses and development of a consensus polymerase chain reaction assay Abstract Viruses in the genus Coronavirus are currently placed in three groups based on antigenic cross-reactivity and sequence analysis of structural protein genes. Consensus polymerase chain reaction (PCR) primers were used to obtain cDNA, then cloned and sequenced a highly conserved 922 nucleotide region in open reading frame (ORF) 1b of the polymerase (pol) gene from eight coronaviruses. These sequences were compared with published sequences for three additional coronaviruses. In this comparison, it was found that nucleotide substitution frequencies (per 100 nucleotides) varied from 46.40 to 50.13 when viruses were compared among the traditional coronavirus groups and, with one exception (the human coronavirus (HCV) 229E), varied from 2.54 to 15.89 when compared within these groups. (The substitution frequency for 229E, as compared to other members of the same group, varied from 35.37 to 35.72.) Phylogenetic analysis of these pol gene sequences resulted in groupings which correspond closely with the previously described groupings, including recent data which places the two avian coronaviruses—infectious bronchitis virus (IBV) of chickens and turkey coronavirus (TCV)—in the same group [Guy, J.S., Barnes, H.J., Smith L.G., Breslin, J., 1997. Avian Dis. 41:583–590]. A single pair of degenerate primers was identified which amplify a 251 bp region from coronaviruses of all three groups using the same reaction conditions. This consensus PCR assay for the genus Coronavirus may be useful in identifying as yet unknown coronaviruses.

negative: Mortality Rates of Human Metapneumovirus and Respiratory Syncytial Virus Lower Respiratory Tract Infections in Hematopoietic Cell Transplantation Recipients Abstract Human metapneumovirus (HMPV), a common respiratory virus, can cause severe disease in pre- and post-hematopoietic cell transplantation (HCT) recipients. We conducted a retrospective cohort analysis in HCT patients with HMPV (n = 23) or respiratory syncytial virus (n = 23) detected in bronchoalveolar lavage samples by reverse transcription PCR between 2006 and 2011 to determine disease characteristics and factors associated with outcome. Mortality rates at 100 days were 43% for both HMPV and respiratory syncytial virus lower respiratory tract disease. Steroid therapy, oxygen requirement >2 L or mechanical ventilation, and bone marrow as cell source were significant risk factors for overall and virus-related mortality in multivariable models, whereas the virus type was not. The presence of centrilobular/nodular radiographic infiltrates was a possible protective factor for mechanical ventilation. Thus, HMPV lower respiratory tract disease is associated with high mortality in HCT recipients. Earlier detection in combination with new antiviral therapy is needed to reduce mortality among HCT recipients.

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

negative: Human rhinovirus spatial-temporal epidemiology in rural coastal Kenya, 2015-2016, observed through outpatient surveillance Background: Human rhinovirus (HRV) is the predominant cause of upper respiratory tract infections, resulting in a significant public health burden. The virus circulates as many different types (168), each generating strong homologous, but weak heterotypic, immunity. The influence of these features on transmission patterns of HRV in the community is understudied. Methods: Nasopharyngeal swabs were collected from patients with symptoms of acute respiratory infection (ARI) at nine out-patient facilities across a Health and Demographic Surveillance System between December 2015 and November 2016. HRV was diagnosed by real-time RT-PCR, and the VP4/VP2 genomic region of the positive samples sequenced. Phylogenetic analysis was used to determine the HRV types. Classification models and G-test statistic were used to investigate HRV type spatial distribution. Demographic characteristics and clinical features of ARI were also compared. Results: Of 5,744 NPS samples collected, HRV was detected in 1057 (18.4%), of which 817 (77.3%) were successfully sequenced. HRV species A, B and C were identified in 360 (44.1%), 67 (8.2%) and 390 (47.7%) samples, respectively. In total, 87 types were determined: 39, 10 and 38 occurred within species A, B and C, respectively. HRV types presented heterogeneous temporal patterns of persistence. Spatially, identical types occurred over a wide distance at similar times, but there was statistically significant evidence for clustering of types between health facilities in close proximity or linked by major road networks. Conclusion: This study records a high prevalence of HRV in out-patient presentations exhibiting high type diversity. Patterns of occurrence suggest frequent and independent community invasion of different types. Temporal differences of persistence between types may reflect variation in type-specific population immunity. Spatial patterns suggest either rapid spread or multiple invasions of the same type, but evidence of similar types amongst close health facilities, or along road systems, indicate type partitioning structured by local spread.

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: The Impact of Covid‐19 Pandemic on Elderly Mental Health

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: SARS-CoV-2 and SARS-CoV differ in their cell tropism and drug sensitivity profiles SARS-CoV-2 is a novel coronavirus currently causing a pandemic. We show that the majority of amino acid positions, which differ between SARS-CoV-2 and the closely related SARS-CoV, are differentially conserved suggesting differences in biological behaviour. In agreement, novel cell culture models revealed differences between the tropism of SARS-CoV-2 and SARS-CoV. Moreover, cellular ACE2 (SARS-CoV-2 receptor) and TMPRSS2 (enables virus entry via S protein cleavage) levels did not reliably indicate cell susceptibility to SARS-CoV-2. SARS-CoV-2 and SARS-CoV further differed in their drug sensitivity profiles. Thus, only drug testing using SARS-CoV-2 reliably identifies therapy candidates. Therapeutic concentrations of the approved protease inhibitor aprotinin displayed anti-SARS-CoV-2 activity. The efficacy of aprotinin and of remdesivir (currently under clinical investigation against SARS-CoV-2) were further enhanced by therapeutic concentrations of the proton pump inhibitor omeprazole (aprotinin 2.7-fold, remdesivir 10-fold). Hence, our study has also identified anti-SARS-CoV-2 therapy candidates that can be readily tested in patients.

negative: Patient and health system delays before registration among migrant patients with tuberculosis who were transferred out in China BACKGROUND: Early diagnosis and treatment is vital for effective tuberculosis (TB) management especially among migrant populations who are a vulnerable group. We aimed to study factors associated with delay before registration at country level among registered migrant TB patients in China (2014–15) who were transferred out (during treatment) through web-based TB information management system (TBIMS). METHODS: This was a cross sectional study involving review of TBIMS data. Delays (in days) were classified as follows: patient delay (from symptom onset to first doctor visit), health system delay (from first doctor visit to treatment initiation, divided into health system diagnosis and treatment delay before and after date of diagnosis respectively), diagnosis delay (from symptom onset to diagnosis) and total delay (from symptom onset to treatment initiation). Linear regression was used to build a predictive model (forward stepwise) for the socio-demographic, clinical and health system related factors associated with delay: one model for each type of delay. Delays were log transformed and included in the model. RESULTS: The median (IQR) patient delay, health system delay and total delay was 16 (6, 34), two (0, 6) and 22 (11, 41) days respectively. Factors associated with long patient, diagnosis and total delay were: female gender, age ≥ 65 years, sputum smear positive pulmonary TB and registration at referral hospital. Treatment initiation delay was significantly higher among those registered in referral hospitals, unemployed and previously treated. Among migrant patients having permanent residence out of province, health system diagnosis delay was significantly higher while treatment initiation delay after diagnosis was significantly lower when compared to patients having permanent residence within the prefecture. CONCLUSION: Among migrant population with TB, patient delay contributed to the total delay. The factors identified including the need for improved coordination between referral hospitals and national programme have to be addressed if China has to end TB. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12913-018-3583-y) contains supplementary material, which is available to authorized users.

negative: Expert recommendations on blood purification treatment protocol for patients with severe COVID-19 Recommendation and consensus Abstract Coronavirus disease (COVID-19) was first diagnosed in Wuhan in December 2019. The World Health Organization defined the subsequent outbreak of COVID-19 worldwide as a public health emergency of international concern. Epidemiological data indicate that at least 20% of COVID-19 patients have severe disease. In addition to impairment of the respiratory system, acute kidney injury (AKI) is a major complication. Immune damage mediated by cytokine storms and concomitant AKI is a key factor for poor prognosis. Based on previous experience of blood purification for patients with severe acute respiratory syndrome and Middle East respiratory syndrome combined with clinical front-line practice, we developed a blood purification protocol for patients with severe COVID-19. This protocol is divided into four major steps. The first step is to assess whether patients with severe COVID-19 require blood purification. The second step is to prescribe a blood purification treatment for patients with COVID-19. The third step is to monitor and adjust parameters of blood purification. The fourth step is to evaluate the timing of discontinuation of blood purification. It is expected that blood purification will play a key role in effectively reducing the mortality of patients with severe COVID-19 through the standardized implementation of the present protocol.

negative: The Effect of Large-Scale Anti-Contagion Policies on the Coronavirus (COVID-19) Pandemic Governments around the world are responding to the novel coronavirus (COVID-19) pandemic with unprecedented policies designed to slow the growth rate of infections. Many actions, such as closing schools and restricting populations to their homes, impose large and visible costs on society. In contrast, the benefits of these policies, in the form of infections that did not occur, cannot be directly observed and are currently understood through process-based simulations. Here, we compile new data on 1,659 local, regional, and national anti-contagion policies recently deployed in the ongoing pandemic across localities in China, South Korea, Iran, Italy, France, and the United States (US). We then apply reduced-form econometric methods, commonly used to measure the effect of policies on economic growth, to empirically evaluate the effect that these anti-contagion policies have had on the growth rate of infections. In the absence of any policy actions, we estimate that early infections of COVID-19 exhibit exponential growth rates of roughly 42% per day. We find that anti-contagion policies collectively have had significant effects slowing this growth. Our results suggest that similar policies may have different impacts on different populations, but we obtain consistent evidence that the policy packages now deployed are achieving large, beneficial, and measurable health outcomes. We estimate that, to date, current policies have already prevented or delayed on the order of 62 million infections across these six countries. These findings may help inform whether or when these ongoing policies should be lifted or intensified, and they can support decision-making in the other 180+ countries where COVID-19 has been reported.

negative: Correcting under-reported COVID-19 case numbers: estimating the true scale of the pandemic The COVID-19 virus has spread worldwide in a matter of a few months, while healthcare systems struggle to monitor and report current cases. Testing results have struggled with the relative capabilities, testing policies and preparedness of each affected country, making their comparison a non-trivial task. Since severe cases, which more likely lead to fatal outcomes, are detected at a higher rate than mild cases, the reported virus mortality is likely inflated in most countries. Lockdowns and changes in human behavior modulate the underlying growth rate of the virus. Under-sampling of infection cases may lead to the under-estimation of total cases, resulting in systematic mortality estimation biases. For healthcare systems worldwide it is important to know the expected number of cases that will need treatment. In this manuscript, we identify a generalizable growth rate decay reflecting behavioral change. We propose a method to correct the reported COVID-19 cases and death numbers by using a benchmark country (South Korea) with near-optimal testing coverage, with considerations on population demographics. We extrapolate expected deaths and hospitalizations with respect to observations in countries that passed the exponential growth curve. By applying our correction, we predict that the number of cases is highly under-reported in most countries and a significant burden on worldwide hospital capacity.

negative: Diseases and pathogens associated with mortality in Ontario beef feedlots. This study determined the prevalence of diseases and pathogens associated with mortality or severe morbidity in 72 Ontario beef feedlots in calves that died or were euthanized within 60 days after arrival. Routine pathologic and microbiologic investigations, as well as immunohistochemical staining for detection of bovine viral diarrhea virus (BVDV) antigen, were performed on 99 calves that died or were euthanized within 60 days after arrival. Major disease conditions identified included fibrinosuppurative bronchopneumonia (49%), caseonecrotic bronchopneumonia or arthritis (or both) caused by Mycoplasma bovis (36%), viral respiratory disease (19%), BVDV-related diseases (21%), Histophilus somni myocarditis (8%), ruminal bloat (2%), and miscellaneous diseases (8%). Viral infections identified were BVDV (35%), bovine respiratory syncytial virus (9%), bovine herpesvirus-1 (6%), parainfluenza-3 virus (3%), and bovine coronavirus (2%). Bacteria isolated from the lungs included M. bovis (82%), Mycoplasma arginini (72%), Ureaplasma diversum (25%), Mannheimia haemolytica (27%), Pasteurella multocida (19%), H. somni (14%), and Arcanobacterium pyogenes (19%). Pneumonia was the most frequent cause of mortality of beef calves during the first 2 months after arrival in feedlots, representing 69% of total deaths. The prevalence of caseonecrotic bronchopneumonia caused by M. bovis was similar to that of fibrinosuppurative bronchopneumonia, and together, these diseases were the most common causes of pneumonia and death. M. bovis pneumonia and polyarthritis has emerged as an important cause of mortality in Ontario beef feedlots.

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

negative: Ventilation Techniques and Risk for Transmission of Coronavirus Disease, Including COVID-19: A Living Systematic Review of Multiple Streams of Evidence BACKGROUND: Mechanical ventilation is used to treat respiratory failure in coronavirus disease 2019 (COVID-19). PURPOSE: To review multiple streams of evidence regarding the benefits and harms of ventilation techniques for coronavirus infections, including that causing COVID-19. (PROSPERO registration: CRD42020178187) DATA SOURCES: 21 standard, World Health Organization–specific and COVID-19–specific databases, without language restrictions, until 1 May 2020. STUDY SELECTION: Studies of any design and language comparing different oxygenation approaches in patients with coronavirus infections, including severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS), or with hypoxemic respiratory failure. Animal, mechanistic, laboratory, and preclinical evidence was gathered regarding aerosol dispersion of coronavirus. Studies evaluating risk for virus transmission to health care workers from aerosol-generating procedures (AGPs) were included. DATA EXTRACTION: Independent and duplicate screening, data abstraction, and risk of bias assessment (GRADE for certainty of evidence and AMSTAR 2 for included systematic reviews). DATA SYNTHESIS: 123 studies were eligible (45 on COVID-19, 70 on SARS, 8 on MERS), but only 5 studies (1 on COVID-19, 3 on SARS, 1 on MERS) adjusted for important confounders. A study in hospitalized patients with COVID-19 reported slightly higher mortality with noninvasive ventilation (NIV) than with invasive mechanical ventilation (IMV), but 2 opposing studies, 1 in patients with MERS and 1 in patients with SARS, suggest a reduction in mortality with NIV (very low-certainty evidence). Two studies in patients with SARS report a reduction in mortality with NIV compared with no mechanical ventilation (low-certainty evidence). Two systematic reviews suggest a large reduction in mortality with NIV compared with conventional oxygen therapy. Other included studies suggest increased odds of transmission from AGPs. LIMITATION: Direct studies in COVID-19 are limited and poorly reported. CONCLUSION: Indirect and low-certainty evidence suggests that use of NIV, similar to IMV, probably reduces mortality but may increase the risk for transmission of COVID-19 to health care workers. PRIMARY FUNDING SOURCE: World Health Organization.

negative: Ranking hazards pertaining to human health concerns from land application of anaerobic digestate Abstract Anaerobic digestion (AD) has been identified as one of the cleanest producers of green energy. AD typically uses organic materials as feedstock and, through a series of biological processes, produces methane. Farmyard manure and slurry (FYM&S) are important AD feedstock and are typically mixed with agricultural waste, grass and/or food wastes. The feedstock may contain many different pathogens which can survive the AD process and hence also possibly be present in the final digestate. In this study, a semi-quantitative screening tool was developed to rank pathogens of potential health concern emerging from AD digestate. A scoring system was used to categorise likely inactivation during AD, hazard pathways and finally, severity as determined from reported human mortality rates, number of global human-deaths and infections per 100,000 populations. Five different conditions including mesophilic and thermophilic AD and three different pasteurisation conditions were assessed in terms of specific pathogen inactivation. In addition, a number of scenarios were assessed to consider foodborne incidence data from Ireland and Europe and to investigate the impact of raw FYM&S application (without AD and pasteurisation). A sensitivity analysis revealed that the score for the mortality rate (S3) was the most sensitive parameter (rank coefficient 0.49) to influence the final score S; followed by thermal inactivation score (S1, 0.25) and potential contamination pathways (S2, 0.16). Across all the scenarios considered, the screening tool prioritised Cryptosporidium parvum, Salmonella spp., norovirus, Streptococcus pyogenes, enteropathogenic E. coli (EPEC), Mycobacterium spp., Salmonella typhi (followed by S. paratyphi), Clostridium spp., Listeria monocytogenes and Campylobacter coli as the highest-ranking pathogens of human health concern resulting from AD digestate in Ireland. This tool prioritises potentially harmful pathogens which can emerge from AD digestate and highlights where regulation and intervention may be required.

negative: Significant Transplantation-Related Mortality from Respiratory Virus Infections within the First One Hundred Days in Children after Hematopoietic Stem Cell Transplantation Abstract Respiratory viral infections (RVI) are important in hematopoietic stem cell transplantations (HSCT) and knowledge regarding incidence, morbidity, mortality, and long-term pulmonary complications is limited. We report a study to evaluate incidence and outcomes, both short and long-term, of RVI in children receiving HSCT. Between January 2000 and December 2012, 844 patients underwent hematopoietic stem cell transplantation (HSCT) at the Hospital for Sick Children: 491 were allogeneic and 353 were autologous. When screening for causes of death in the first year after HSCT in the 844 patients, we found that RVI as a cause of death was only evident in the first 100 days after HSCT. Fifty-four (6.5%) patients were found to have an RVI within the first 100 days after HSCT (allogeneic = 32, autologous = 22). Upper and lower respiratory tract infections were documented in 31 (57%) and 23 (43%) patients, respectively. Viruses were parainfluenza (35%), respiratory syncytial virus (28%), influenza (22%), adenovirus (7%), human metapneumovirus (4%), coronavirus (2%), and rhinovirus (2%). Three patients relapsed with their primary disease before day 100 and were excluded. The overall mortality for the remaining 51 patients was 10% (allogeneic = 4, autologous = 1). All 5 deaths were directly attributable to RVI and all 5 deaths occurred in patients with a lower respiratory tract infection. The remaining patients were followed for a median of 4.3 years (range, 1.4 to 11.8) and no chronic pulmonary complications were observed. A clear seasonal pattern for contracting RVI was evident with 65% of total RVI occurring between October and March (35 of 427 versus 19 of 417, P = .03). Given the significant mortality from RVI and the challenges in preventing them, choosing the time to start HSCT, whenever possible, may help prevent RVI and improve outcomes.

negative: Progress and challenges in maternal health in western China: a Countdown to 2015 national case study BACKGROUND: China is one of the few Countdown countries to have achieved Millennium Development Goal 5 (75% reduction in maternal mortality ratio between 1990 and 2015). We aimed to examine the health systems and contextual factors that might have contributed to the substantial decline in maternal mortality between 1997 and 2014. We chose to focus on western China because poverty, ethnic diversity, and geographical access represent particular challenges to ensuring universal access to maternal care in the region. METHODS: In this systematic assessment, we used data from national census reports, National Statistical Yearbooks, the National Maternal and Child Health Routine Reporting System, the China National Health Accounts report, and National Health Statistical Yearbooks to describe changes in policies, health financing, health workforce, health infrastructure, coverage of maternal care, and maternal mortality by region between 1997 and 2014. We used a multivariate linear regression model to examine which contextual and health systems factors contributed to the regional variation in maternal mortality ratio in the same period. Using data from a cross-sectional survey in 2011, we also examined equity in access to maternity care in 42 poor counties in western China. FINDINGS: Maternal mortality declined by 8·9% per year between 1997 and 2014 (geometric mean ratio for each year 0·91, 95% CI 0·91–0·92). After adjusting for GDP per capita, length of highways, female illiteracy, the number of licensed doctors per 1000 population, and the proportion of ethnic minorities, the maternal mortality ratio was 118% higher in the western region (2·18, 1·44–3·28) and 41% higher in the central region (1·41, 0·99–2·01) than in the eastern region. In the rural western region, the proportion of births in health facilities rose from 41·9% in 1997 to 98·4% in 2014. Underpinning such progress was the Government's strong commitment to long-term strategies to ensure access to delivery care in health facilities—eg, professionalisation of maternity care in large hospitals, effective referral systems for women medically or socially at high risk, and financial subsidies for antenatal and delivery care. However, in the poor western counties, substantial disparity by education level of the mother existed in access to health facility births (44% of illiterate women vs 100% of those with college or higher education), antenatal care (17% vs 69%) had at least four visits), and caesarean section (8% vs 44%). INTERPRETATION: Despite remarkable progress in maternal survival in China, substantial disparities remain, especially for the poor, less educated, and ethnic minority groups in remote areas in western China. Whether China's highly medicalised model of maternity care will be an answer for these populations is uncertain. A strategy modelled after China's immunisation programme, whereby care is provided close to the women's homes, might need to be explored, with township hospitals taking a more prominent role. FUNDING: Government of Canada, UNICEF, and the Bill & Melinda Gates Foundation.

negative: Chapter Three Epidemiology and Biostatistics Abstract Epidemiology and biostatistics are the cornerstone of public health and preventive medicine. These practices use mathematical, scientific, and social methods to monitor disease trends and provide intervention to prevent future disease. [147 questions.]

negative: Integrating Genome-based Informatics to Modernize Global Disease Monitoring, Information Sharing, and Response The rapid advancement of genome technologies holds great promise for improving the quality and speed of clinical and public health laboratory investigations and for decreasing their cost. The latest generation of genome DNA sequencers can provide highly detailed and robust information on disease-causing microbes, and in the near future these technologies will be suitable for routine use in national, regional, and global public health laboratories. With additional improvements in instrumentation, these next- or third-generation sequencers are likely to replace conventional culture-based and molecular typing methods to provide point-of-care clinical diagnosis and other essential information for quicker and better treatment of patients. Provided there is free-sharing of information by all clinical and public health laboratories, these genomic tools could spawn a global system of linked databases of pathogen genomes that would ensure more efficient detection, prevention, and control of endemic, emerging, and other infectious disease outbreaks worldwide.

negative: Mortality of people with intellectual disabilities during the 2017/2018 influenza epidemic in the Netherlands: potential implications for the COVID-19 pandemic BACKGROUND: Data on the development of Covid-19 among people with intellectual disabilities (IDs) are scarce and it is uncertain to what extent general population data applies to people with ID. To give an indication of possible implications, this study investigated excess mortality patterns during a previous influenza epidemic. METHODS: Using Dutch population and mortality registers, a historical cohort study was designed to compare mortality during the 2017-2018 influenza epidemic with mortality in the same period in the three previous years. People with ID were identified by entitlements to residential ID-care services as retrieved from a national database. RESULTS: Data covered the entire adult Dutch population (12.6 million; GenPop), of which 91 064 individuals were identified with an ID. During the influenza epidemic, mortality among people with ID increased almost three times as much than in the GenPop (15.2% vs. 5.4%), and more among male individuals with ID (+19.5%) than among female individuals with ID (+10.6%), as compared with baseline. In both cohorts, comparable increases in mortality within older age groups and due to respiratory causes were seen. Particularly in the ID-cohort, excess deaths also occurred in younger age groups, due to endocrine diseases and ID-specific causes. CONCLUSIONS: During the 2017-2018 influenza epidemic, excess mortality among people with ID was three times higher than in the general Dutch population, appeared more often at young age and with a broader range of underlying causes. These findings suggest that a pandemic may disproportionally affect people with ID while population data may not immediately raise warnings. Early detection of diverging patterns and faster implementation of tailored strategies therefore require collection of good quality data.

negative: Is there evidence that BCG vaccination has non-specific protective effects for COVID 19 infections or is it an illusion created by lack of testing? The goal of this paper is to showcase that the COVID-19 disease pattern is evolving and to study the relationship between mandatory BCG policy and caseload/million or death/per million. We analyze seven recent publications on the impact of BCG vaccinations on the development of COVID19 illness and extend presented findings using the latest data from April 10, 2020. We analyze data from 98 countries and we extend existing models by adding the dimension of COVID-19-related testing conducted by the analyzed countries. Similarly to prior studies, we find that COVID-19 attributable case and death incidences across countries share a relationship with the BCG vaccination inclusion in the national immunization program of a country when testing is not taken into consideration. However, this relationship vanishes when we add the dimension of testing. We observe that case and death incidences conditional on testing do not get affected by the BCG vaccination inclusion in the national immunization program of a country. Therefore, we show that there is no statistical evidence to support the assertion that inclusion of BCG vaccination in national immunization program (NIP) has any impact of COVID 19 infections (cases) or mortality.

negative: Hospital Mortality – a neglected but rich source of information supporting the transition to higher quality health systems in low and middle income countries BACKGROUND: There is increasing focus on the strength of primary health care systems in low and middle-income countries (LMIC). There are important roles for higher quality district hospital care within these systems. These hospitals are also sources of information of considerable importance to health systems, but this role, as with the wider roles of district hospitals, has been neglected. KEY MESSAGES: As we make efforts to develop higher quality health systems in LMIC we highlight the critical importance of district hospitals focusing here on how data on hospital mortality offers value: i) in understanding disease burden; ii) as part of surveillance and impact monitoring; iii) as an entry point to exploring system failures; and iv) as a lens to examine variability in health system performance and possibly as a measure of health system quality in its own right. However, attention needs paying to improving data quality by addressing reporting gaps and cause of death reporting. Ideally enabling the collection of basic, standardised patient level data might support at least simple case-mix and case-severity adjustment helping us understand variation. Better mortality data could support impact evaluation, benchmarking, exploration of links between health system inputs and outcomes and critical scrutiny of geographic variation in quality and outcomes of care. Improved hospital information is a neglected but broadly valuable public good. CONCLUSION: Accurate, complete and timely hospital mortality reporting is a key attribute of a functioning health system. It can support countries’ efforts to transition to higher quality health systems in LMIC enabling national and local advocacy, accountability and action.

negative: Modeling behavioral change and COVID-19 containment in Mexico: A trade-off between lockdown and compliance Abstract Sanitary Emergency Measures (SEM) were implemented in Mexico on March 30th, 2020 requiring the suspension of non-essential activities. This action followed a Healthy Distance Sanitary action on March 23rd, 2020. The aim of both measures was to reduce community transmission of COVID-19 in Mexico by lowering the effective contact rate. Using a modification of the Kermack-McKendrick SEIR model we explore the effect of behavioral changes required to lower community transmission by introducing a time-varying contact rate, and the consequences of disease spread in a population subject to suspension of non-essential activities. Our study shows that there exists a trade-off between the proportion of the population under SEM and the average time an individual is committed to all the behavioral changes needed to achieve an effective social distancing. This trade-off generates an optimum value for the proportion of the population under strict mitigation measures, significantly below 1 in some cases, that minimizes maximum COVID-19 incidence. We study the population-level impact of three key factors: the implementation of behavior change control measures, the time horizon necessary to reduce the effective contact rate and the proportion of people under SEM in combating COVID-19. Our model is fitted to the available data. The initial phase of the epidemic, from February 17th to March 23rd, 2020, is used to estimate the contact rates, infectious periods and mortality rate using both confirmed cases (by date of symptoms initiation), and daily mortality. Data on deaths after march 23rd, 2020 is used to estimate the mortality rate after the mitigation measures are implemented. Our simulations indicate that the most likely dates for maximum incidence are between late May and early June, 2020 under a scenario of high SEM compliance and low SEM abandonment rate.

negative: Chapter 6 Sources of Harm Prescription Drugs, Surgery, and Infections Abstract Most medical harm is from prescription drugs, surgery, and healthcare-acquired infections. Although the full extent of medical harm remains to be accurately gauged, estimates of incidence have tended to grow larger with each successive detailed assessment. Estimates of the extent of harm in the United States published by the Institutes of Medicine in 2000, which at the time were so shocking as to be disbelieved by some authorities, have since been consistently eclipsed by further detailed analyses. Recent studies show that harm from drugs and infections individually exceeds estimates of what was previously thought to be the total of healthcare-related harm from all causes. The emergence of antibiotic-resistant microorganisms, due primarily to the use, misuse, and overuse of antibiotics, is a particularly ominous threat to future personal and population health.

negative: Chapter 12 Planning and Managing Health Systems Abstract Health systems are complex organizations. They are often the largest single employer in a country, with expenditures of public and private money of 4–17 percent of gross domestic product. Overall and individual facility management requires mission statements, objectives, targets, budgets, activities planning, human interaction, services delivery, and quality assurance. Health organization involves a vast complex of stakeholders and participants, suppliers and purchasers, regulators and direct providers, and individual patients, and their decision-making. These include pyramidal and network organizations and ethical decision-making based on public interest, resource allocations, priority selection, and assurance of certain codes of law and ethical conduct. This chapter discusses how complex organizations work, with potential for application in health, and the motivations of workers and of the population being served. Organization theory helps in devising methods to integrate relevant factors to become more effective in defining and achieving goals and missions.

negative: The virology and pathogenesis of feline infectious peritonitis

negative: Healthcare-Associated Pneumonia: Don't Forget About Respiratory Viruses! Introduction: Healthcare-associated infections are an important cause of morbidity and mortality, are among the most common adverse events in healthcare, and of them, pneumonia is the most commonly reported. Our objective was to evaluate the incidence and clinical outcome of respiratory viruses in hospital-acquired pneumonia (HAP). Methods: This was a prospective cohort study, include patients aged between 0 and 18 who fulfilled Centers for Diseases Control and Prevention (CDC) criteria for HAP. Demographic and clinical data were obtained, and a nasopharyngeal swab specimen was taken for the detection of respiratory viruses. All included patients were monitored until discharge to collect data on the need for mechanical ventilation, intensive care unit (ICU) admission, and mortality. All-cause 30-day mortality was also ascertained. Results: Four thousand three hundred twenty-seven patients were followed for 42,658 patient-days and 5,150 ventilator-days. Eighty-eight patients (2.03%) met the CDC criteria for HAP, 63 patients were included, and clinical and epidemiological characteristics showed no statistically significant differences between patients with virus associated healthcare-associated pneumonia (VAHAP) and those with non-viral healthcare-associated pneumonia (NVHAP). At least one respiratory virus was detected in 65% [95% CI (53–77)] of episodes of HAP, with a single viral pathogen observed in 53.9% and coinfection with 2 viruses in 11.1% of cases. The outcome in terms of ICU admission, mechanical ventilation and the 30-day mortality did not show a significant difference between groups. Conclusions: In two-thirds of the patients a respiratory virus was identified. There was no difference in mortality or the rest of the clinical outcome variables. About half of the patients required mechanical ventilation and 10% died, which emphasizes the importance of considering these pathogens in nosocomial infections, since their identification can influence the decrease in hospital costs and be taken into account in infection control policies.

negative: Le nouveau Coronavirus Covid-19 : quels risques ophtalmiques ?

negative: ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy Background: As the outbreak of coronavirus disease 2019 (COVID-19) progresses, prognostic markers for early identification of high-risk individuals are an urgent medical need. Italy has the highest rate of SARS-CoV-2 infection, the highest number of deaths, and the highest mortality rate among large countries. Worldwide, a more severe course of COVID-19 is associated with older age, comorbidities, and male sex. Hence, we searched for possible genetic components of the peculiar severity of COVID-19 among Italians, by looking at expression levels and variants in ACE2 and TMPRSS2 genes, which are crucial for viral infection. Methods: Exome and SNP array data from a large Italian cohort representative of the country's population were used to compare the burden of rare variants and the frequency of polymorphisms with European and East Asian populations. Moreover, we looked into gene expression databases to check for sex-unbalanced expression. Results: While we found no significant evidence that ACE2 is associated with disease severity/sex bias in the Italian population, TMPRSS2 levels and genetic variants proved to be possible candidate disease modulators, contributing to the observed epidemiological data among Italian patients. Conclusions: Our analysis suggests a role for TMPRSS2 variants and expression levels in modulating COVID-19 severity, a hypothesis that fosters a rapid experimental validation on large cohorts of patients with different clinical manifestations.

negative: Burden and changes in HIV/AIDS morbidity and mortality in Southern Africa Development Community Countries, 1990–2017 BACKGROUND: The 16 Southern Africa Development Community (SADC) countries remain the epicentre of the HIV/AIDS epidemic with the largest number of people living with HIV/AIDS. Anti-retroviral treatment (ART) has improved survival and prevention of mother-to-child transmission (PMTCT) of HIV, but the disease remains a serious cause of mortality. We conducted a descriptive epidemiological analysis of HIV/AIDS burden for the 16 SADC countries using secondary data from the Global Burden of Diseases, Injuries and Risk Factor (GBD) Study. METHODS: The GBD study is a systematic, scientific effort by the Institute for Health Metrics and Evaluation (IHME) to quantify the comparative magnitude of health loss due to diseases, injuries, and risk factors by age, sex, and geographies for specific points in time. We analyzed the following outcomes: mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to HIV/AIDS for SADC. Input data for GBD was extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service utilisation, disease notifications, and other sources. Country- and cause-specific HIV/AIDS-related death rates were calculated using the Cause of Death Ensemble model (CODEm) and spatiotemporal Gaussian process regression (ST-GPR). Deaths were multiplied by standard life expectancy at each age-group to calculate YLLs. Cause-specific mortality was estimated using a Bayesian meta-regression modelling tool, DisMod-MR. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases to calculate YLDs. Crude and age-adjusted rates per 100,000 population and changes between 1990 and 2017 were determined for each country. RESULTS: In 2017, HIV/AIDS caused 336,175 deaths overall in SADC countries, and more than 20 million DALYs. This corresponds to a 3-fold increase from 113,631 deaths (6,915,170 DALYs) in 1990. The five leading countries with the proportion of deaths attributable to HIV/AIDS in 2017 were Botswana at the top with 28.7% (95% UI; 23.7–35.2), followed by South Africa 28.5% (25.8–31.6), Lesotho, 25.1% (21.2–30.4), eSwatini 24.8% (21.3–28.6), and Mozambique 24.2% (20.6–29.3). The five countries had relative attributable deaths that were at least 14 times greater than the global burden of 1.7% (1.6–1.8). Similar patterns were observed with YLDs, YLLs, and DALYs. Comoros, Seychelles and Mauritius were on the lower end, with attributable proportions less than 1%, below the global proportion. CONCLUSIONS: Great progress in reducing HIV/AIDS burden has been achieved since the peak but more needs to be done. The post-2005 decline is attributed to PMTCT of HIV, resources provided through the US President’s Emergency Plan For AIDS Relief (PEPFAR), and behavioural change. The five countries with the highest burden of HIV/AIDS as measured by proportion of death attributed to HIV/AIDS and age-standardized mortaility rate were Botswana, South Africa, Lesotho, eSwatini, and Mozambique. SADC countries should cooperate, work with donors, and embrace the UN Fast-Track approach, which calls for frontloading investment from domestic or other sources to prevent and treat HIV/AIDS. Robust tracking, testing, and early treatment are required, as well as refinement of individual treatment strategies for transient individuals in the region.

negative: Vaccines for emerging infectious diseases: Lessons from MERS coronavirus and Zika virus The past decade and a half has been characterized by numerous emerging infectious diseases. With each new threat, there has been a call for rapid vaccine development. Pathogens such as the Middle East Respiratory Syndrome coronavirus (MERS-CoV) and the Zika virus represent either new viral entities or viruses emergent in new geographic locales and characterized by novel complications. Both serve as paradigms for the global spread that can accompany new pathogens. In this paper, we review the epidemiology and pathogenesis of MERS-CoV and Zika virus with respect to vaccine development. The challenges in vaccine development and the approach to clinical trial design to test vaccine candidates for disease entities with a changing epidemiology are discussed.

negative: Radiation therapy considerations during the COVID-19 Pandemic: Literature review and expert opinions

negative: Abstracts from the 11th International Congress of Behavioral Medicine

negative: Monitoring the propagation of COVID-19-pandemic first waves A phenomenological approach is proposed to monitor the propagation of the COVID-19-pandemic first waves. A large set of data collected at a worldwide scale during the first months of 2020 is compiled into series of semi-logarithmic plots, for a selection of thirty-two countries from the five continents. Three regimes are identified in the propagation of an epidemic wave: a pre-epidemic regime 1, an exponential-growth regime 2, and a resorption regime 3. A two-parameters scaling of the first-wave death variation reported in China is used to fit those reported in other countries. Comparison is made between the propagation of the pandemic in different countries, which are classified in four groups, from group A where the pandemic first waves were contained efficiently, to group D where the pandemic first waves widely spread. Group A is mainly composed of Asian countries, where fast and efficient measures have been applied. Group D is composed of Western-Europe countries and the United States of America, where late decisions and confused political communication (pandemic seriousness, protection masks, herd immunity etc.) led to significant death tolls. The threat of large resurging epidemic waves after a hasty lockdown lift is discussed, in particular for the countries from group D, where the number of contagious people remained high in the beginning of May 2020. The situation is opposite in Asian countries from group A, where the number of contagious people was successfully maintained to a low level. In particular, the results obtained by Hong Kong and South Korea are highlighted, and the measures taken there are presented as virtuous examples that other countries may follow.

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

negative: Nepal’s First Case of COVID-19 and public health response

negative: Outcomes in Patients with COVID-19 Infection Taking ACEI/ARB PURPOSE OF REVIEW: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the aggressive coronavirus disease (COVID-19) pandemic. Recently, investigators have stipulated that COVID-19 patients receiving angiotensin-converting-enzyme inhibitors (ACEI) may be subject to poorer outcomes. This editorial presents the available evidence to guide treatment practices during this pandemic. RECENT FINDINGS: Recent studies from Wuhan cohorts provide valuable information about COVID-19. A cohort with 52 critically ill patients revealed cardiac injury in 12% of patients. Worse outcomes appear to be more prevalent in patients with hypertension and diabetes mellitus (DM), possibly due to overexpression of angiotensin-converting enzyme 2 (ACE2) receptor in airway alveolar epithelial cells. Investigators suspect that SARS-CoV-2 uses the ACE2 receptor to enter the lungs in a mechanism similar to SARS-CoV. Several hypotheses have been proposed to date regarding the net effect of ACEI/ARB on COVID-19 infections. Positive effects include ACE2 receptor blockade, disabling viral entry into the heart and lungs, and an overall decrease in inflammation secondary to ACEI/ARB. Negative effects include a possible retrograde feedback mechanism, by which ACE2 receptors are upregulated. SUMMARY: Even though physiological models of SARS-CoV infection show a theoretical benefit of ACEI/ARB, these findings cannot be extrapolated to SARS-CoV-2 causing COVID-19. Major cardiology scientific associations, including ACC, HFSA, AHA, and ESC Hypertension Council, have rejected these correlation hypotheses. After an extensive literature review, we conclude that there is no significant evidence to support an association for now, but given the rapid evolvement of this pandemic, findings may change.

negative: An in vivo cell-based assay for investigating the specific interaction between the SARS-CoV N-protein and its viral RNA packaging sequence Abstract The SARS-CoV nucleocapsid (N) protein serves multiple functions in viral replication, transcription, and assembly of the viral genome complex. Coronaviruses specifically package genomic RNA into assembled virions, and in SARS-CoV, it is reported that this process is driven by an interaction between the N-protein and a packaging signal encoded within the viral RNA. While recent studies have uncovered the sequence of this packaging signal, little is known about the specific interaction between the N-protein and the packaging signal sequence, and the mechanisms by which this interaction drives viral genome packaging. In this study, we developed a novel in vivo cell-based assay for examining this interaction between the N-protein and packaging signal RNA for SARS-CoV, as well as other viruses within the coronaviridae family. Our results demonstrate that the N-protein specifically recognizes the SARS-CoV packaging signal with greater affinity compared to signals from other coronaviruses or non-coronavirus species. We also use deletion mapping to identify a 151-nt region within the packaging signal sequence that is critical for N-protein-RNA binding, and conversely, we show that both the N-terminal and C-terminal domains of the N protein are necessary for recognizing the packaging RNA. These results describe, for the first time, in vivo evidence for an interaction between the SARS-CoV N-protein and its packaging signal RNA, and demonstrate the feasibility of using this cell-based assay to further probe viral RNA-protein interactions in future studies.

negative: COVID-19: Forecasting short term hospital needs in France Europe is now considered as the epicenter of the SARS-CoV-2 pandemic, France being among the most impacted country. In France, there is an increasing concern regarding the capacity of the healthcare system to sustain the outbreak, especially regarding intensive care units (ICU). The aim of this study was to estimate the dynamics of the epidemic in France, and to assess its impact on healthcare resources for each French metropolitan Region. We developed a deterministic, age-structured, Susceptible-Exposed-Infectious-Removed (SEIR) model based on catchment areas of each COVID-19 referral hospitals. We performed one month ahead predictions (up to April 14, 2020) for three different scenarios (R0=1.5, R0=2.25, R0=3), where we estimated the daily number of COVID-19 cases, hospitalizations and deaths, the needs in ICU beds per Region and the reaching date of ICU capacity limits. At the national level, the total number of infected cases is expected to range from 22,872 in the best case (R0=1.5) to 161,832 in the worst case (R0=3), while the total number of deaths would vary from 1,021 to 11,032, respectively. At the regional level, all ICU capacities may be overrun in the worst scenario. Only seven Regions may lack ICU beds in the mild scenario (R0=2.25) and only one in the best case. In the three scenarios, Corse may be the first Region to see its ICU capacities overrun. The two other Regions, whose capacity will be overrun shortly after are Grand-Est and Bourgogne-Franche-Comté. Our analysis shows that, even in the best case scenario, the French healthcare system will very soon be overwhelmed. While drastic social distancing measures may temper our results, a massive reorganization leading to an expansion of French ICU capacities seems to be necessary to manage the coming wave of critically affected COVID-19 patients.

negative: Urbanization and International Trade and Investment Policies as Determinants of Noncommunicable Diseases in Sub-Saharan Africa There are three dominant globalization pathways affecting noncommunicable diseases in Sub-Saharan Africa (SSA): urbanization, trade liberalization, and investment liberalization. Urbanization carries potential health benefits due to improved access to an increased variety of food imports, although for the growing number of urban poor, this has often meant increased reliance on cheap, highly processed food commodities. Reduced barriers to trade have eased the importation of such commodities, while investment liberalization has increased corporate consolidation over global and domestic food chains. Higher profit margins on processed foods have promoted the creation of ‘obesogenic’ environments, which through progressively integrated global food systems have been increasingly ‘exported’ to developing nations. This article explores globalization processes, the food environment, and dietary health outcomes in SSA through the use of trend analyses and structural equation modelling. The findings are considered in the context of global barriers and facilitators for healthy public policy.

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: Human parainfluenza virus circulation, United States, 2011–2019 Abstract Background Human parainfluenza viruses (HPIVs) cause upper and lower respiratory tract illnesses, most frequently among infants and young children, but also in the elderly. While seasonal patterns of HPIV types 1–3 have been described, less is known about national patterns of HPIV-4 circulation. Objectives To describe patterns of HPIVs circulation in the United States (US). Study design We used data from the National Respiratory and Enteric Virus Surveillance System (NREVSS), a voluntary passive laboratory-based surveillance system, to characterize the epidemiology and circulation patterns of HPIVs in the US during 2011–2019. We summarized the number of weekly aggregated HPIV detections nationally and by US census region, and used a subset of data submitted to NREVSS from public health laboratories and several clinical laboratories during 2015–2019 to analyze differences in patient demographics. Results During July 2011 - June 2019, 2,700,135 HPIV tests were reported; 122,852 (5 %) were positive for any HPIV including 22,446 for HPIV-1 (18 %), 17,474 for HPIV-2 (14 %), 67,649 for HPIV-3 (55 %), and 15,283 for HPIV-4 (13 %). HPIV testing increased substantially each year. The majority of detections occurred in children aged ≤ 2 years (36 %) with fluctuations in the distribution of age by type. Conclusions HPIVs were detected year-round during 2011–2019, with type-specific year-to-year variations in circulation patterns. Among HPIV detections where age was known, the majority were aged ≤ 2 years. HPIV-4 exhibited an annual fall-winter seasonality, both nationally and regionally. Continued surveillance is needed to better understand national patterns of HPIV circulation.

negative: Spread of Mutant Middle East Respiratory Syndrome Coronavirus with Reduced Affinity to Human CD26 during the South Korean Outbreak The newly emerging Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe respiratory infection with a high mortality rate (~35%). MERS-CoV has been a global threat due to continuous outbreaks in the Arabian peninsula and international spread by infected travelers since 2012. From May to July 2015, a large outbreak initiated by an infected traveler from the Arabian peninsula swept South Korea and resulted in 186 confirmed cases with 38 deaths (case fatality rate, 20.4%). Here, we show the rapid emergence and spread of a mutant MERS-CoV with reduced affinity to the human CD26 receptor during the South Korean outbreak. We isolated 13 new viral genomes from 14 infected patients treated at a hospital and found that 12 of these genomes possess a point mutation in the receptor-binding domain (RBD) of viral spike (S) protein. Specifically, 11 of these genomes have an I529T mutation in RBD, and 1 has a D510G mutation. Strikingly, both mutations result in reduced affinity of RBD to human CD26 compared to wild-type RBD, as measured by surface plasmon resonance analysis and cellular binding assay. Additionally, pseudotyped virus bearing an I529T mutation in S protein showed reduced entry into host cells compared to virus with wild-type S protein. These unexpected findings suggest that MERS-CoV adaptation during human-to-human spread may be driven by host immunological pressure such as neutralizing antibodies, resulting in reduced affinity to host receptor, and thereby impairs viral fitness and virulence, rather than positive selection for a better affinity to CD26.

negative: Understanding COVID-19 spreading through simulation modeling and scenarios comparison: preliminary results. Since late 2019 the world is facing the rapid spreading of a novel viral disease (SARS-CoV-2) provoked by the coronavirus 2 infection (COVID-19), declared pandemic last 12 March 2020. As of 27 March 2020, there were more than 500,000 confirmed cases and 23,335 deaths worldwide. In those places with a rapid growth in numbers of sick people in need of hospitalization and intensive care, this demand has over-saturate the medical facilities and, in turn, rise the mortality rate. In the absence of a vaccine, classical epidemiological measures such as testing, quarantine and physical distancing are ways to reduce the growing speed of new infections. Thus, these measures should be a priority for all governments in order to minimize the morbidity and mortality associated to this disease. System dynamics is widely used in many fields of the biological sciences to study and explain changing systems. The system dynamics approach can help us understand the rapid spread of an infectious disease such as COVID-19 and also generate scenarios to test the effect of different control measures. The aim of this study is to provide an open model (using STELLA® from Iseesystems) that can be customized to any area/region and by any user, allowing them to evaluate the different behavior of the COVID-19 dynamics under different scenarios. Thus, our intention is not to generate a model to accurately predict the evolution of the disease nor to supplant others more robust -official and non-official- from governments and renowned institutions. We believe that scenarios comparison can be an effective tool to convince the society of the need of a colossal and unprecedented effort to reduce new infections and ultimately, fatalities.

negative: Low serum 25-hydroxyvitamin D levels are associated with increased risk of viral coinfections in wheezing children

negative: Incidence of COVID-19 and Connections with Air Pollution Exposure: Evidence from the Netherlands The fast spread of severe acute respiratory syndrome coronavirus 2 has resulted in the emergence of several hot-spots around the world. Several of these are located in areas associated with high levels of air pollution. This study investigates the relationship between exposure to particulate matter and COVID-19 incidence in 355 municipalities in the Netherlands. The results show that atmospheric particulate matter with diameter less than 2.5 is a highly significant predictor of the number of confirmed COVID-19 cases and related hospital admissions. The estimates suggest that expected COVID-19 cases increase by nearly 100 percent when pollution concentrations increase by 20 percent. The association between air pollution and case incidence is robust in the presence of data on health-related preconditions, proxies for symptom severity, and demographic control variables. The results are obtained with ground-measurements and satellite-derived measures of atmospheric particulate matter as well as COVID-19 data from alternative dates. The findings call for further investigation into the association between air pollution and SARS-CoV-2 infection risk. If particulate matter plays a significant role in COVID-19 incidence, it has strong implications for the mitigation strategies required to prevent spreading.

negative: Second waves, social distancing, and the spread of COVID-19 across America We recently described a dynamic causal model of a COVID-19 outbreak within a single region. Here, we combine several of these (epidemic) models to create a (pandemic) model of viral spread among regions. Our focus is on a second wave of new cases that may result from loss of immunity--and the exchange of people between regions--and how mortality rates can be ameliorated under different strategic responses. In particular, we consider hard or soft social distancing strategies predicated on national (Federal) or regional (State) estimates of the prevalence of infection in the population. The modelling is demonstrated using timeseries of new cases and deaths from the United States to estimate the parameters of a factorial (compartmental) epidemiological model of each State and, crucially, coupling between States. Using Bayesian model reduction, we identify the effective connectivity between States that best explains the initial phases of the outbreak in the United States. Using the ensuing posterior parameter estimates, we then evaluate the likely outcomes of different policies in terms of mortality, working days lost due to lockdown and demands upon critical care. The provisional results of this modelling suggest that social distancing and loss of immunity are the two key factors that underwrite a return to endemic equilibrium.

negative: 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: A review of vaccine research and development: Human acute respiratory infections() Worldwide, acute respiratory infections (ARIs) constitute the leading cause of acute illnesses, being responsible for nearly 4 million deaths every year, mostly in young children and infants in developing countries. The main infectious agents responsible for ARIs include influenza virus, respiratory syncytial virus (RSV), parainfluenza virus type 3 (PIV-3), Streptococcus pneumoniae and Haemophilus influenzae. While effective vaccines against influenza, H. influenzae type b (Hib) and S. pneumoniae infections have been available for several years, no vaccine is available at present against illnesses caused by RSV, PIV-3, metapneumovirus or any of the three novel coronaviruses. In addition, the threat constituted by the multiple outbreaks of avian influenza during the last few years is urgently calling for the development of new influenza vaccines with broader spectrum of efficacy, which could provide immunity against an avian influenza virus pandemic. This article reviews the state of the art in vaccine R&D against ARIs and attempts to address these basic public health questions.

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: 89 Severe Acute Respiratory Syndrome (SARS) Abstract Severe acute respiratory syndrome (SARS) first appeared in November 2002 and ultimately resulted in 8096 probable human infections and 774 deaths worldwide. By July 2003, the global outbreak was declared over. A new coronavirus, SARS-associated coronavirus (SARS-CoV), was identified as the causative agent; this virus appeared to have a zoonotic origin, as genetically similar coronaviruses have been identified in several animal species. The global response to the outbreak was extensive. Within a short period, the pathogen had been identified, new diagnostic tests were developed, surveillance systems were created, infection control and prevention measures were instituted, and transmission among humans stopped. It is unclear if and when person-to-person SARS-CoV transmission will reappear. However, procedures have been established by public health organizations, including the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC), to help guide diagnosis, reporting, surveillance, and prevention.

negative: Population vulnerability to COVID-19 in Europe: a burden of disease analysis Background: Evidence has emerged showing that elderly people and those with pre-existing chronic health conditions may be at higher risk of developing severe health consequences from COVID-19. In Europe, this is of particular relevance with ageing populations living with non-communicable diseases, multi-morbidity and frailty. Published estimates of Years Lived with Disability (YLD) from the Global Burden of Disease (GBD) study help to characterise the extent of these effects. Our aim was to identify the countries across Europe that have populations at highest risk from COVID-19 by using estimates of population age structure and YLD for health conditions linked to severe illness from COVID-19. Methods: Population and YLD estimates from GBD 2017 were extracted for 45 countries in Europe. YLD was restricted to a list of specific health conditions associated with being at risk of developing severe consequences from COVID-19 based on guidance from the United Kingdom Government. This guidance also identified individuals aged 70 years and above as being at higher risk of developing severe health consequences. Study outcomes were defined as: (i) proportion of population aged 70 years and above; and (ii) rate of YLD for COVID-19 for vulnerable health conditions across all ages. Bivariate groupings were established for each outcome and combined to establish overall population-level vulnerability. Results: Countries with the highest proportions of elderly residents were Italy, Greece, Germany, Portugal and Finland. When assessments of population-level YLD rates for COVID-19 vulnerable health conditions were made the highest rates were observed for Bulgaria, Czech Republic, Croatia, Hungary and Bosnia and Herzegovina. A bivariate analysis indicated that the countries at high-risk across both measures of vulnerability were: Bulgaria; Portugal; Latvia; Lithuania; Greece; Germany; Estonia; and Sweden. Conclusion: Routine estimates of population structures and non-fatal burden of disease measures can be usefully combined to create composite indicators of vulnerability for rapid assessments, in this case to severe health consequences from COVID-19. Countries with available results for sub-national regions within their country, or national burden of disease studies that also use sub-national levels for burden quantifications, should consider using non-fatal burden of disease estimates to estimate geographical vulnerability to COVID-19.

negative: Incorporating and Addressing Testing Bias Within Estimates of Epidemic Dynamics for SARS-CoV-2 The disease burden of SARS-CoV-2 as measured by tests from various countries present varying estimates of infection and fatality rates. Models based on these acquired data may suffer from systematic errors and large estimation variances due to the biases associated with testing and lags between the infection and death counts. Here, we present an augmented compartment model to predict epidemic dynamics while explicitly modeling for the sampling bias involved in testing. Our simulations show that sampling biases in favor of patients with higher disease manifestation could significantly affect direct estimates of infection and fatality rates calculated from the numbers of confirmed cases and deaths, and serological testing can partially mitigate these biased estimates. We further recommend a strategy to obtain unbiased estimates, calculating the dependence of expected confidence on a randomized sample size, showing that relatively small sample sizes can provide statistically significant estimates for SARS-CoV-2 related death rates.

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: Chapter 2 Expanding the Concept of Public Health Abstract Ancient societies recognized the needs of sanitation, food safety, workers’ health, and medical care to protect against disease and to promote well-being and civic prosperity. New energies and knowledge since the eighteenth century produced landmark discoveries such as prevention of scurvy and vaccination against smallpox. The biological germ theory and competing miasma theory each proved effective in sanitation, and immunization in control of infectious diseases. Non-communicable diseases as the leading causes of mortality have responded to innovative preventive care of health risk factors, smoking, hypertension, obesity, physical inactivity, unhealthful diets, and diabetes mellitus. Health promotion proved effective to modern public health in tackling disease origins, individual behavior, and social and economic conditions. The global burden of infectious and non-communicable diseases, aging and chronic illness faces rising costs and still inadequate prevention. The evolution of concepts of public health will have to address these new challenges of population health.

negative: Laboratory diagnosis of emerging human coronavirus infections – the state of the art The three unprecedented outbreaks of emerging human coronavirus (HCoV) infections at the beginning of the twenty-first century have highlighted the necessity for readily available, accurate and fast diagnostic testing methods. The laboratory diagnostic methods for human coronavirus infections have evolved substantially, with the development of novel assays as well as the availability of updated tests for emerging ones. Newer laboratory methods are fast, highly sensitive and specific, and are gradually replacing the conventional gold standards. This presentation reviews the current laboratory methods available for testing coronaviruses by focusing on the coronavirus disease 2019 (COVID-19) outbreak going on in Wuhan. Viral pneumonias typically do not result in the production of purulent sputum. Thus, a nasopharyngeal swab is usually the collection method used to obtain a specimen for testing. Nasopharyngeal specimens may miss some infections; a deeper specimen may need to be obtained by bronchoscopy. Alternatively, repeated testing can be used because over time, the likelihood of the SARS-CoV-2 being present in the nasopharynx increases. Several integrated, random-access, point-of-care molecular devices are currently under development for fast and accurate diagnosis of SARS-CoV-2 infections. These assays are simple, fast and safe and can be used in the local hospitals and clinics bearing the burden of identifying and treating patients.

negative: Dynamic and Cell-Infiltratable Hydrogels as Injectable Carrier of Therapeutic Cells and Drugs for Treating Challenging Bone Defects [Image: see text] Biopolymeric hydrogels have been widely used as carriers of therapeutic cells and drugs for biomedical applications. However, most conventional hydrogels cannot be injected after gelation and do not support the infiltration of cells because of the static nature of their network structure. Here, we develop unique cell-infiltratable and injectable (Ci-I) gelatin hydrogels, which are physically cross-linked by weak and highly dynamic host–guest complexations and are further reinforced by limited chemical cross-linking for enhanced stability, and then demonstrate the outstanding properties of these Ci-I gelatin hydrogels. The highly dynamic network of Ci-I hydrogels allows injection of prefabricated hydrogels with encapsulated cells and drugs, thereby simplifying administration during surgery. Furthermore, the reversible nature of the weak host–guest cross-links enables infiltration and migration of external cells into Ci-I gelatin hydrogels, thereby promoting the participation of endogenous cells in the healing process. Our findings show that Ci-I hydrogels can mediate sustained delivery of small hydrophobic molecular drugs (e.g., icaritin) to boost differentiation of stem cells while avoiding the adverse effects (e.g., in treatment of bone necrosis) associated with high drug dosage. The injection of Ci-I hydrogels encapsulating mesenchymal stem cells (MSCs) and drug (icaritin) efficiently prevented the decrease in bone mineral density (BMD) and promoted in situ bone regeneration in an animal model of steroid-associated osteonecrosis (SAON) of the hip by creating the microenvironment favoring the osteogenic differentiation of MSCs, including the recruited endogenous cells. We believe that this is the first demonstration on applying injectable hydrogels as effective carriers of therapeutic cargo for treating dysfunctions in deep and enclosed anatomical sites via a minimally invasive procedure.

negative: IFN-α2a or IFN-β1a in combination with ribavirin to treat Middle East respiratory syndrome coronavirus pneumonia: a retrospective study OBJECTIVES: Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with significant mortality. We examined the utility of plasma MERS-CoV PCR as a prognostic indicator and compared the efficacies of IFN-α2a and IFN-β1a when combined with ribavirin in reducing MERS-CoV-related mortality rates. METHODS: We retrospectively analysed 32 patients with confirmed MERS-CoV infection, admitted between April 2014 and June 2014, by positive respiratory sample RT–PCR. Plasma MERS-CoV RT–PCR was performed at the time of diagnosis for 19 patients. RESULTS: The overall mortality rate was 69% (22/32). Ninety percent (9/10) of patients with positive plasma MERS-CoV PCR died compared with 44% (4/9) of those with negative plasma MERS-CoV PCR. Mortality rate in patients who received IFN-α2a was 85% (11/13) compared with 64% (7/11) in those who received IFN-β1a (P = 0.24). The mortality rate in patients with renal failure (14), including 8 on haemodialysis, was 100%. Age >50 years and diabetes mellitus were found to be significantly associated with mortality (OR = 26.1; 95% CI 3.58–190.76; P = 0.001 and OR = 15.74; 95% CI 2.46–100.67; P = 0.004, respectively). The median duration of viral shedding in patients who recovered was 11 days (range 6–38 days). Absence of fever was noted in 5/32 patients. CONCLUSIONS: Plasma MERS-CoV RT–PCR may serve as an effective tool to predict MERS-CoV-associated mortality. Older age and comorbid conditions may have contributed to the lack of efficacy of IFN-α2a or IFN-β1a with ribavirin in treating MERS-CoV. Absence of fever should not exclude MERS-CoV.

negative: COVID-19 and obesity—lack of clarity, guidance, and implications for care

negative: Alisporivir inhibits MERS- and SARS-coronavirus replication in cell culture, but not SARS-coronavirus infection in a mouse model Abstract Currently, there is no registered treatment for infections with emerging zoonotic coronaviruses like SARS- and MERS-coronavirus. We here report that in cultured cells low-micromolar concentrations of alisporivir, a non-immunosuppressive cyclosporin A-analog, inhibit the replication of four different coronaviruses, including MERS- and SARS-coronavirus. Ribavirin was found to further potentiate the antiviral effect of alisporivir in these cell culture-based infection models, but this combination treatment was unable to improve the outcome of SARS-CoV infection in a mouse model. Nevertheless, our data provide a basis to further explore the potential of Cyp inhibitors as host-directed, broad-spectrum inhibitors of coronavirus replication.

negative: Pathogenic T cells and inflammatory monocytes incite inflammatory storm in severe COVID-19 patients Pathogenic human coronavirus infections, such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV), cause high morbidity and mortality1, 2 Recently, a severe pneumonia-associated respiratory syndrome caused by a new coronavirus (SARS-CoV-2) was reported at December 2019 in the city Wuhan, Hubei province, China3, 4, 5, which was also named as pneumonia-associated respiratory syndrome (PARS)6 and can cause coronavirus disease 2019 (COVID-19) to seriously endanger human health Up to 24th of February 2020, at least 77779 cases have been reported with 2666 fatal cases according to the report from China CDC However, the immune mechanism that potential orchestrated acute mortality from COVID-19 patients is still unknown Here we show that after the SARS-CoV-2 infection, CD4+ T lymphocytes are rapidly activated to become pathogenic T helper (Th) 1 cells and generate GM-CSF etc The cytokines environment induces inflammatory CD14+CD16+ monocytes with high expression of IL-6 and accelerate the inflammation Given that large amount of inflammatory cells infiltrations have been observed in lungs from severe COVID-19 patients7, 8, these aberrant pathogenic Th1 cells and inflammatory monocytes may enter the pulmonary circulation in huge numbers and play an immune damaging role to causing lung functional disability and quick mortality Our results demonstrate that excessive non-effective host immune responses by pathogenic T cells and inflammatory monocytes may associate with severe lung pathology Thus, we suggest that monoclonal antibodies targeting GM-CSF or interleukin 6 may be effective in blocking inflammatory storms and, therefore, be a promising treatment of severe COVID-19 patients

negative: Viet Nam. Attention in this discussion of Viet Nam focuses on the following: history of the demographic situation; the government's overall approach to population problems; population data systems and development planning; institutional arangements for the integration of population within development planning; the government's view of the importance of population policy in achieving development objectives; population size, growth, and natural increase; morbidity and mortality; fertility; international migration; and spatial distribution. Relatively little information has been available on demographic trends in Viet Nam due to the absence of any major survey or census until the last few decades. The government increasingly has been concerned about the high rate of population growth and is working to change the situation through programs directed at fertility reduction. As part of its program for overall social and economic restructuring, the government seeks to give special attention to health problems, particularly those relating to maternal and child health and environmental sanitation. Population censuses in Viet Nam have been undertaken only in the last 2 decades, with censuses conducted in the North in 1960 and 1974. No population census was undertaken in the South, and any population information available was based upon the periodic population and household surveys conducted alternately in different provinces, cities, and rural areas during 1962, 1967, 1971, and 1974. The government considers the formulation and implementation of population policy to be a critical variable for realizing national development objectives. The population of Viet Nam has grown considerably since the 1950s, increasing from over 30 million in 1950 to 35.4 million in 1960 and reaching 43.1 million by 1970, according to UN estimates. 1979 census results indicate that the population of Viet Nam had reached 52.7 million. The current rate of growth is estimated at 2.2%. The government perceives the current rate of population growth as unsatisfactory because it is too high. The official government policy is to take steps to reduce the rate of population growth as rapidly as possible. All 3 demographic factors--mortality, fertility, and spatial distribution--are viewed as subject to direct policy intervention to achieve this goal. Rates of morbidity and mortality have declined considerably in the past few decades. The government reports a decline in the crude death rate from 12.2 in 1957 to 7.0 in 1980 and an increase in the life expectancy at birth from 34 years in 1936 to 60 in 1978. UN estimates are considerably higher. According to UN estimates, the infant mortality rate was 90.3/1000 live births during 1975-80 for Viet Nam as a whole. The current mortality and morbidity situation is considered to be unacceptable. The government estimates the crude birthrate as 29.3/1000 in 1980, an unsatisfactory level. The government perceives the present levels and trends of immigration as not significant and satisfactory and the spatial distribution as inappropriate.

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

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: Exploring Causal relationship between risk factors and vulnerability to COVID-19Cases of Italy, Spain, France, Greece, Portugal, Morocco and South Africa Even though the infection rate of COVID-19 is very high as of today 31 May: 5,819,962 confirmed cases worldwide, the death rate is only about 6.23%, 362,786 deaths as for the same date. Furthermore, the rate of total infected cases is extremely different from one country to another as well as for the rate of mortality. Therefore, there may be some factors that possibly amplify the rate of infection from one country to another as well as for the rate of mortality due to COVID-19. In the literature, we have found multiple identified risk factors responsible for vulnerability to COVID19, we have chosen pertinent key risk factors for our study: Median-age, age>65 years old, weight, population density, diabetics, International arrivals, median temperature between March and May.

negative: Comparative features of a coronavirus isolated from a cheetah with feline infectious peritonitis Abstract A coronavirus which was isolated from a cheetah (Acinonyx jubatus) that succumbed to feline infectious peritonitis was characterized in vitro. The virus was determined to be highly cell-associated with Crandell feline kidney (CrFK) cells and was routinely maintained as a persistent infection (CrFK 83–4497). The cheetah coronavirus was compared with other members of the feline coronavirus group including the feline enteric coronavirus (FECV) 79–1683 and the feline infectious peritonitis viruses (FIPV), 79–1146, and UCD-1. The cheetah coronavirus was demonstrated to have a restricted host-cell range with limited cytopathic effect. Indirect immunofluorescence with antisera to FIPV UCD-1 revealed the concentration of viral antigens in the perinuclear region of cells infected with the cheetah coronavirus. Ultrastructural studies of the cheetah coronavirus indicated a limited number of immature viral particles within cytoplasmic vesicles and at the cell surface. This was in contrast to electron microscopy results of FECV 79–1683 and FIPV 79–1146, which had numerous mature virus particles within the cytoplasmic vesicles, as well as at the cell surface. The cheetah coronavirus was tentatively placed in the feline coronavirus family based upon its antigenic reactivity by immunofluorescence; however, the possibility that it represents a unique coronavirus of cheetahs should not be dismissed without further analyses at the host and genomic levels.

negative: Characterization of turkey coronavirus from turkey poults with acute enteritis Abstract The present study was to characterize turkey coronavirus associated with turkey poult enteritis and mortality. Intestinal contents or intestines from affected turkey poults and inoculated turkey embryos contained coronaviruses as revealed by electron microscopy or were positive for turkey coronavirus by immunofluorescent antibody assay. Sucrose density gradient ultracentrifugation of the virus-containing intestinal homogenate yielded two opalescent bands corresponding to the buoyant densities of 1.14–1.15 and 1.18–1.20g/ml, respectively. Coronaviral particles from intestinal contents or the sucrose density gradient preparation were mainly spherical in shape and had envelope and central depression. They were surrounded by a fringe of regularly spaced petal-shaped projections attached to the particles by a short stalk. Purified viruses hemagglutinated rabbit erythrocytes with a titer of 16. Major protein bands of purified viruses analyzed by SDS-PAGE were located at 200, 100–110, 50–60, and 30–35kDa. The patterns of protein bands were consistent with those of Minnesota or Quebec turkey coronavirus isolates. A 568bp nucleotide fragment of turkey coronavirus spike protein gene was amplified from RNA of inoculated turkey embryo intestine or purified virus. Sequence analysis of the 568bp PCR product revealed high degree of identity with the corresponding spike protein gene sequence of human and bovine coronaviruses. The results indicated that turkey coronavirus was associated with turkey poults with acute enteritis.

negative: Defining high-value information for COVID-19 decision-making Initial projections from the first generation of COVID-19 models focused public attention on worst-case scenarios in the absence of decisive policy action. These underscored the imperative for strong and immediate measures to slow the spread of infection. In the coming weeks, however, as policymakers continue enlisting models to inform decisions on COVID-19, answers to the most difficult and pressing policy questions will be much more sensitive to underlying uncertainties. In this study, we demonstrate a model-based approach to assessing the potential value of reducing critical uncertainties most salient to COVID-19 decision-making and discuss priorities for acquiring new data to reduce these uncertainties. We demonstrate how information about the impact of non-pharmaceutical interventions could narrow prediction intervals around hospitalizations over the next few weeks, while information about the prevalence of undetected cases could narrow prediction intervals around the timing and height of the peak of the epidemic.

negative: Global Influenza Hospital-based Surveillance Network (GIHSN): results of surveillance of influenza and other respiratory viruses in hospitalised patients in Brazil, 2015 BACKGROUND: Influenza-like illness occurs annually worldwide, with peak timing and severity varying seasonally, resulting in significant annual mortality. OBJECTIVES: There were three objectives: (1) to describe the epidemiological and clinical features of hospitalised patients with severe acute respiratory infection caused by influenza and other respiratory viruses (ORVs); (2) to report the influenza seasonality in the region and (3) to correlate findings of influenza circulation and immunisation time in Brazil. PATIENTS/METHODS: This study took place in three Brazilian hospitals located in cities with different climatic conditions (Curitiba (south), Rio de Janeiro (south-east) and Fortaleza (north-east)). Patients presenting with an acute process with indication for admission consisting of a predefined set of conditions potentially associated with recent influenza infection were enrolled. RESULTS: We screened 1666 patients, with 595 meeting the inclusion criteria. Influenza viruses and ORVs were detected in 6.5% and 59% of patients, respectively. Influenza-positive cases fell into the severe spectrum as compared with those with ORVs (30% vs 11%), but without any difference in mortality rates. Epidemiological results revealed variations in the peak time of influenza infections between north-east (Fortaleza) and south (Curitiba) Brazil, basically following the rain period of each region. In north-east Brazil, viral circulation was prevalent in the first 4 months of the year, indicating that the vaccination campaign occurred in a postseasonal period, possibly explaining the low effectiveness. CONCLUSIONS: The active-surveillance model is a valuable tool for investigating respiratory virus impact on hospitalised patients, with influenza-infection monitoring enabling implementation of adequate preventive measures.

negative: And now for something completely different: from 2019-nCoV and COVID-19 to 2020-nMan

negative: Middle East respiratory syndrome The Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonotic pathogen that was first identified in humans in Saudi Arabia and Jordan in 2012. Intermittent sporadic cases, community clusters, and nosocomial outbreaks of MERS-CoV continue to occur. Between April 2012 and December 2019, 2499 laboratory-confirmed cases of MERS-CoV infection, including 858 deaths (34·3% mortality) were reported from 27 countries to WHO, the majority of which were reported by Saudi Arabia (2106 cases, 780 deaths). Large outbreaks of human-to-human transmission have occurred, the largest in Riyadh and Jeddah in 2014 and in South Korea in 2015. MERS-CoV remains a high-threat pathogen identified by WHO as a priority pathogen because it causes severe disease that has a high mortality rate, epidemic potential, and no medical countermeasures. This Seminar provides an update on the current knowledge and perspectives on MERS epidemiology, virology, mode of transmission, pathogenesis, diagnosis, clinical features, management, infection control, development of new therapeutics and vaccines, and highlights unanswered questions and priorities for research, improved management, and prevention.

negative: COSRE: Community Exposure Risk Estimator for the COVID-19 Pandemic Due to the complexities of virus genotypes and the stochastic contacts in human society, it is a big challenge to estimate the potential risks of getting exposed to a widely spreading virus. To allow the public to be aware of the exposure risks in their daily activities, we proposed a birthday-paradox-based probability model and implement it into a web-based system named COSRE for estimating community exposure risks of public gathering during a pandemic. The exposure risk means the probability of people meeting potential COVID hosts in public places like grocery stores, gyms, libraries, restaurants, coffee shops, office suits, etc. The model has three inputs: the real-time potential active patients, the population in local communities, and the customer counts in the room. With COSRE, people can explore the possible impacts of the pandemic by doing spatiotemporal analysis, e.g., moving through time and testing a different number of people to see the changes of risks as the pandemic unfolds. The system has the potential to advance our ability to know the accurate exposure risks in various communities and allow us to make plans with improved preparedness and precise responses for the pandemic. We use spatial analysis tools and drew the county-level exposure risks of the United States from April 1 to May 15. The experiment shows that the estimation model is very promising to assist people to be more specifically precise about their safety control in daily routine and social lives and help businesses to dynamically adjust their COVID-19 policies to accelerate their recovery.

negative: Pandemic simulation of antivirals + school closures: buying time until strain-specific vaccine is available A strain-specific vaccine is unlikely to be available in the early phases of a potential H5N1 avian influenza pandemic. It could be months and at the current production rate may not provide timely protection to the population. Intervention strategies that control the spread of infection will be necessary in this situation, such as the use of the US stockpile of antiviral medication coupled with a 6-month school closure. The agent-based simulation model, EpiSimS, was used to assess the impact of this intervention strategy followed by three different vaccine approaches: (1) 2-dose, 80% effective, (2) 1-dose, 30% effective, and (3) 1 dose, 80% effective. Simulations show that the combination of antivirals, school closures, and a strain-specific vaccine can reduce morbidity and mortality while in effect. A significant second infection wave can occur with current vaccine technology once school closures are relaxed, though an ideal vaccine is able to contain it. In our simulations, worker absenteeism increases in all cases mostly attributed to household adults staying home with children due to the school closures.

negative: The Australian response to the COVID-19 pandemic and diabetes – lessons learned The COVID-19 pandemic has had a significant impact on the economy and health system of most countries in the world and this is also true of Australia. Australia has not seen the huge surge of COVID-19 positive cases and subsequent hospitalisations and deaths experienced in other parts of the world. However there have been important social and health strategies to “flatten” the curve, to reduce infections and to manage those infected. These have included closure of international and interstate borders, local lockdown measures, physical distancing, shift to work from home, closure of non-essential businesses and full or partial closure of all schools and tertiary education facilities. From the diabetes care perspective, there was a significant and concerted diversion of hospital resources and staff to COVID-19 specific activities. Reduced access to primary care, diagnostic and hospital services for diabetes, combined with fear of exposure to the virus in these settings, led to a significant drop in access to usual diabetes care. Provision of outpatient and private sector diabetes services via telehealth was encouraged and supported by expanded and new government subsidies. Importantly, for the first time, there was government funded subsidy for care delivered via the telephone and inclusion of credentialled diabetes educators in funded telephone/telehealth support. The Australian health professional and consumer organisations worked cooperatively producing guidelines, position statements and other educational resources specific for the COVID-19 setting. Once the COVID-19 pandemic is over, review of all the changes will be important, determining which should be permanently implemented. The learnings from COVID-19 should help prepare Australia for future pandemics or other major health crises.

negative: SARS: Systematic Review of Treatment Effects BACKGROUND: The SARS outbreak of 2002–2003 presented clinicians with a new, life-threatening disease for which they had no experience in treating and no research on the effectiveness of treatment options. The World Health Organization (WHO) expert panel on SARS treatment requested a systematic review and comprehensive summary of treatments used for SARS-infected patients in order to guide future treatment and identify priorities for research. METHODS AND FINDINGS: In response to the WHO request we conducted a systematic review of the published literature on ribavirin, corticosteroids, lopinavir and ritonavir (LPV/r), type I interferon (IFN), intravenous immunoglobulin (IVIG), and SARS convalescent plasma from both in vitro studies and in SARS patients. We also searched for clinical trial evidence of treatment for acute respiratory distress syndrome. Sources of data were the literature databases MEDLINE, EMBASE, BIOSIS, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to February 2005. Data from publications were extracted and evidence within studies was classified using predefined criteria. In total, 54 SARS treatment studies, 15 in vitro studies, and three acute respiratory distress syndrome studies met our inclusion criteria. Within in vitro studies, ribavirin, lopinavir, and type I IFN showed inhibition of SARS-CoV in tissue culture. In SARS-infected patient reports on ribavirin, 26 studies were classified as inconclusive, and four showed possible harm. Seven studies of convalescent plasma or IVIG, three of IFN type I, and two of LPV/r were inconclusive. In 29 studies of steroid use, 25 were inconclusive and four were classified as causing possible harm. CONCLUSIONS: Despite an extensive literature reporting on SARS treatments, it was not possible to determine whether treatments benefited patients during the SARS outbreak. Some may have been harmful. Clinical trials should be designed to validate a standard protocol for dosage and timing, and to accrue data in real time during future outbreaks to monitor specific adverse effects and help inform treatment.

negative: An analysis of the health status of the United Arab Emirates: the ‘Big 4’ public health issues BACKGROUND: The United Arab Emirates (UAE) is a rapidly developing country composed of a multinational population with varying educational backgrounds, religious beliefs, and cultural practices, which pose a challenge for population-based public health strategies. A number of public health issues significantly contribute to morbidity and mortality in the UAE. This article summarises the findings of a panel of medical and public health specialists from UAE University and various government health agencies commissioned to report on the health status of the UAE population. METHODS: A systematic literature search was conducted to retrieve peer-reviewed articles on health in the UAE, and unpublished data were provided by government health authorities and local hospitals. RESULTS: The panel reviewed and evaluated all available evidence to list and rank (1=highest priority) the top four main public health issues: 1) Cardiovascular disease accounted for more than 25% of deaths in 2010; 2) Injury caused 17% of mortality for all age groups in 2010; 3) Cancer accounted for 10% of all deaths in 2010, and the incidence of all cancers is projected to double by 2020; and 4) Respiratory disorders were the second most common non-fatal condition in 2010. CONCLUSION: The major public health challenges posed by certain personal (e.g. ethnicity, family history), lifestyle, occupational, and environmental factors associated with the development of chronic disease are not isolated to the UAE; rather, they form part of a global health problem, which requires international collaboration and action. Future research should focus on population-based public health interventions that target the factors associated with the development of various chronic diseases.

negative: Preliminary epidemiological analysis on children and adolescents with novel coronavirus disease 2019 outside Hubei Province, China: an observational study utilizing crowdsourced data Background: The outbreak of coronavirus disease 2019 (COVID-19) continues to expand across the world. Though both the number of cases and mortality rate in children and adolescents is reported to be low in comparison to adults, limited data has been reported on the outbreak with respect to pediatric patients. To elucidate information, we utilized crowdsourced data to perform a preliminary epidemiologic analysis of pediatric patients with COVID-19 Methods: In this observational study, data was collected from two open-access, line list crowdsourced online databases. Pediatric cases of COVID-19 were defined as patients ≤19 years of age with a laboratory confirmed diagnosis. The primary outcomes were case counts and cumulative case counts. Secondary outcomes included days between symptoms onset and first medical care and days between first medical care and reporting. Tertiary outcomes were rate of travel to Wuhan, rate of infected family members and rates of symptoms. Results: A total of 82 patients were included. The median age was 10 [IQR: 5-15] years. Patients from mainland China (outside Hubei) accounted for 46.3% of cases, while the remaining 53.7% of cases were international. Males and females accounted for 52.4% and 32.9% of cases, respectively, with the remaining 14.6% being designated as unknown. A male skew persisted across subgroup analyses by age group (p=1.0) and location (inside/outside China) (p=0.22). While the number of reported international cases has been steadily increasing over the study period, the number of reported cases in China rapidly decreased from the start point. The median reporting delay was 3 [IQR: 2-4.8] days. The median delay between symptom onset and first seeking medical care was 1 [IQR: 0-3.25] day. In international cases, time to first seeking medical care was a median of 2.5 days longer than in China (p=0.04). When clinical features were reported, fever was the most common presentation (68.0%), followed by cough (36.0%). Conclusions: The number of reported international pediatric COVID-19 cases is rapidly increasing. COVID-19 infections are, to-date, more common in males than females in both the children and adolescent age groups. Additionally, this male predominance remains the case both inside and outside of China. Crowdsourced data enabled early analysis of epidemiologic variables in pediatric patients with COVID-19. Further data sharing is required to enable analyses that are required to understand the course of this infection in children.

negative: Excess mortality from seasonal influenza is negligible below the age of 50 in Israel: implications for vaccine policy PURPOSE: Evaluation of the severity of pandemic influenza requires reliable estimates of mortality attributable to the seasonal influenza. METHODS: Excess age-specific mortality during periods of influenza activity was evaluated in Israel during the period 1999–2006 for three death categories. For each respiratory year, the lowest monthly moving average for the mortality rate was subtracted from each month in the period of influenza activity. Average mortality rates in years with minimal influenza activity were deducted from corresponding months to exclude winter mortality unrelated to influenza. The sums of these results were used as estimates of excess mortality rates. RESULTS: Overall excess mortality rates ranged from 7.7 to 36.1 per 100,000 for all causes, and from 4.4 to 24.4 per 100,000 for respiratory and circulatory causes. Influenza was associated with an average of 869 (range 280–1,516) deaths annually from respiratory and circulatory diseases during seasons with significant influenza activity. About 90% of the influenza-associated mortality from respiratory and circulatory diseases was in the age group 65+ years and about 1% in the age group <50 years. The age group <50 years accounted for an annual average of seven deaths from respiratory and circulatory diseases. CONCLUSION: Annual mortality associated with seasonal influenza is highly variable. Under the age of 50 years, there is minimal seasonal influenza associated mortality. This information provides an important baseline for evaluating the severity of the A(H1N1) 2009 influenza pandemic, where persons under 50 years of age were often disproportionately represented.

negative: A Meta-Analysis of the Association between Gender and Protective Behaviors in Response to Respiratory Epidemics and Pandemics Respiratory infectious disease epidemics and pandemics are recurring events that levy a high cost on individuals and society. The health-protective behavioral response of the public plays an important role in limiting respiratory infectious disease spread. Health-protective behaviors take several forms. Behaviors can be categorized as pharmaceutical (e.g., vaccination uptake, antiviral use) or non-pharmaceutical (e.g., hand washing, face mask use, avoidance of public transport). Due to the limitations of pharmaceutical interventions during respiratory epidemics and pandemics, public health campaigns aimed at limiting disease spread often emphasize both non-pharmaceutical and pharmaceutical behavioral interventions. Understanding the determinants of the public’s behavioral response is crucial for devising public health campaigns, providing information to parametrize mathematical models, and ultimately limiting disease spread. While other reviews have qualitatively analyzed the body of work on demographic determinants of health-protective behavior, this meta-analysis quantitatively combines the results from 85 publications to determine the global relationship between gender and health-protective behavioral response. The results show that women in the general population are about 50% more likely than men to adopt/practice non-pharmaceutical behaviors. Conversely, men in the general population are marginally (about 12%) more likely than women to adopt/practice pharmaceutical behaviors. It is possible that factors other than pharmaceutical/non-pharmaceutical status not included in this analysis act as moderators of this relationship. These results suggest an inherent difference in how men and women respond to epidemic and pandemic respiratory infectious diseases. This information can be used to target specific groups when developing non-pharmaceutical public health campaigns and to parameterize epidemic models incorporating demographic information.

negative: Knowledge synthesis from 100 million biomedical documents augments the deep expression profiling of coronavirus receptors The COVID-19 pandemic demands assimilation of all available biomedical knowledge to decode its mechanisms of pathogenicity and transmission. Despite the recent renaissance in unsupervised neural networks for decoding unstructured natural languages, a platform for the real-time synthesis of the exponentially growing biomedical literature and its comprehensive triangulation with deep omic insights is not available. Here, we present the nferX platform for dynamic inference from over 45 quadrillion possible conceptual associations extracted from unstructured biomedical text, and their triangulation with Single Cell RNA-sequencing based insights from over 25 tissues. Using this platform, we identify intersections between the pathologic manifestations of COVID-19 and the comprehensive expression profile of the SARS-CoV-2 receptor ACE2. We find that tongue keratinocytes, airway club cells, and ciliated cells are likely underappreciated targets of SARS-CoV-2 infection, in addition to type II pneumocytes and olfactory epithelial cells. We further identify mature small intestinal enterocytes as a possible hotspot of COVID-19 fecal-oral transmission, where an intriguing maturation-correlated transcriptional signature is shared between ACE2 and the other coronavirus receptors DPP4 (MERS-CoV) and ANPEP (α-coronavirus). This study demonstrates how a holistic data science platform can leverage unprecedented quantities of structured and unstructured publicly available data to accelerate the generation of impactful biological insights and hypotheses. The nferX Platform Single-cell resource - https://academia.nferx.com/

negative: Bills of Mortality: tracking disease in early modern London

negative: A case of improved oxygenation in SARS-CoV-2 positive patient on nasal cannula undergoing prone positioning Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality worldwide. It has placed societal and financial burden on the globe. Its rapid progressions from mild URI symptoms to severe acute respiratory distress syndrome (ARDS) in a matter of days is the underlying reason as to why the world is struggling to keep up with ventilator production. In this case report, we went about proning a corona virus positive patient for 6–8hrs as a potential early intervention to prevent progression to ARDS. Our patient was initially in acute hypoxemic respiratory failure and placed on nasal cannula. He was started on hydroxychloroquine and azithromycin with no improvement of symptoms. However within the span of few hours of proning he experienced significant symptomatic relief with improvement of oxygenation. His oxygen saturation improved drastically and eventually was taken off of nasal cannula and discharged within span of one day of proning.

negative: 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: Important Steps to Control COVID-19/SARS-CoV-2 Infection Elderly patients are having high mortality rates from COVID-19/SARS-CoV-2 infection compared to younger patients. The SARS-CoV-2 virus uses the ACE2 receptor as the entry point to the host cells. ARBs/ACEIs which are widely used in elderly patients, have been found to be associated with overexpression of ACE2.To decrease the severity of COVID-19 infection, ARB/ACEI should be switched to another class drug not known to cause a rise in ACE2 until the COVID-19 infection subsides. Specific human immunoglobulin can be tried for COVID-19 patients with critical conditions under supervision.

negative: Preliminary study to identify severe from moderate cases of COVID-19 using NLR&RDW-SD combination parameter Objectives: Investigate the characteristics and rules of hematology changes in patients with COVID-19, and explore the possibility to identify moderate and severe patients using conventional hematology parameters or combined parameters. Methods: The clinical data of 45 moderate and severe type patients with 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 the two groups were analyzed, and the combination parameters with best diagnostic performance were selected using the LDA method. Results: Of the 45 patients with COVID-19 (35 moderate and 10 severe cases), 23 were male and 22 female, aged 16-62 years. The most common clinical symptoms were fever (89%) and dry cough (60%). As the disease progressed, WBC, Neu#, NLR, PLR, RDW-CV and RDW-SD parameters in the severe group were significantly higher than that in the moderate group (P<0.05); meanwhile, Lym#, Eos#, HFC%, RBC, HGB and HCT parameters in the severe group were significantly lower than that in the moderate group (P<0.05). For NLR, the AUC, the best cut-off value, the sensitivity and the specificity were 0.890, 13.39, 83.3% and 82.4% respectively, and for PLR , the AUC, the best cut-off, the sensitivity and the specificity were 0.842, 267.03, 83.3% and 74.0% respectively. The combined parameter NLR&RDW-SD had the best diagnostic efficiency (AUC was 0.938) and when the cut-off value was 1.046, the sensitivity and the specificity were 90.0% and 84.7% respectively, followed by the fitting 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 parameter NLR&RDW-SD is the best hematology index and can help clinicians to predict the severity of COVID-19 patients, and it can be used as a useful indicator to help prevent and control the epidemic.

negative: SARS – CoV -2: reasons of epidemiology of severe ill disease cases and therapeutic approach using trivalent vaccine (tetanus, diphtheria and Bordetella pertussis) Abstract The novel coronavirus COVID-19 follows transmission route and clinical presentation of all community-acquired coronaviruses. Instead, the rate of transmission is significative higher, with a faster spread of the virus responsible of the worldwide outbreak and a significative higher mortality rate due to the development of a severe lung injury. Most noteworthy is the distribution of death rate among age groups. Children and younger people are almost protected from severe clinical presentation. Possible explanation of this phenomenon could be the ability of past vaccinations (especially tetanic, diphtheria toxoids and inactivated bacteria as pertussis) to stimulate immune system and to generate a scattered immunity against non-self antigens in transit, as coronaviruses and other community-circulating viruses and make immune system readier to develop specific immunity against COVID-19. The first support to this hypothesis is the distribution of mortality rate during historical pandemics (“Spanish flu” 1918, “Asian flu” 1956 and “the Hong Kong flu” 1968) among age groups before and after the introduction of vaccines. The immunological support to the hypothesis derives from recent studies about immunotherapy for malignancies, which propose the use of oncolytic vaccines combined with toxoids in order to exploit CD4+ memory T cell recall in supporting the ongoing anti-tumour response. According to this hypothesis vaccine formulations (tetanus, diphtheria, Bordetella pertussis) could be re-administrate after the first contact with Covid-19, better before the development of respiratory severe illness and of course before full-blown ARDS (Acute Respiratory Distress Syndrome). The CD4+ memory exploiting could help immune system to recall immunity of already know antigens against coronaviruses, avoiding or limiting “lung crash” until virus specific immunity develops and making it faster and prolonged. Finally, this administration could be helpful not only in already infected patients, but also before infection. In fact, people could have an immune system more ready when the contact with the COVID-19 will occur.

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

negative: A model to forecast regional demand for COVID-19 related hospital beds COVID-19 threatens to overwhelm hospital facilities throughout the United States. We created an interactive, quantitative model that forecasts demand for COVID-19 related hospitalization based on county-level population characteristics, data from the literature on COVID-19, and data from online repositories. Using this information as well as user inputs, the model estimates a time series of demand for intensive care beds and acute care beds as well as the availability of those beds. The online model is designed to be intuitive and interactive so that local leaders with limited technical or epidemiological expertise may make decisions based on a variety of scenarios. This complements high-level models designed for public consumption and technically sophisticated models designed for use by epidemiologists. The model is actively being used by several academic medical centers and policy makers, and we believe that broader access will continue to aid community and hospital leaders in their response to COVID-19. Link to online model: https://surf.stanford.edu/covid-19-tools/covid-19/

negative: 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.

negative: Comparing SARS-CoV-2 with SARS-CoV and influenza pandemics The objective of this Personal View is to compare transmissibility, hospitalisation, and mortality rates for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with those of other epidemic coronaviruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), and pandemic influenza viruses. The basic reproductive rate (R0) for SARS-CoV-2 is estimated to be 2·5 (range 1·8-3·6) compared with 2·0-3·0 for SARS-CoV and the 1918 influenza pandemic, 0·9 for MERS-CoV, and 1·5 for the 2009 influenza pandemic. SARS-CoV-2 causes mild or asymptomatic disease in most cases; however, severe to critical illness occurs in a small proportion of infected individuals, with the highest rate seen in people older than 70 years. The measured case fatality rate varies between countries, probably because of differences in testing strategies. Population-based mortality estimates vary widely across Europe, ranging from zero to high. Numbers from the first affected region in Italy, Lombardy, show an all age mortality rate of 154 per 100â000 population. Differences are most likely due to varying demographic structures, among other factors. However, this new virus has a focal dissemination; therefore, some areas have a higher disease burden and are affected more than others for reasons that are still not understood. Nevertheless, early introduction of strict physical distancing and hygiene measures have proven effective in sharply reducing R0 and associated mortality and could in part explain the geographical differences.

negative: Genomic epidemiology of SARS-CoV-2 in Guangdong Province, China Highlights: 1) 1.6 million molecular diagnostic tests identified 1,388 SARS-CoV-2 infections in Guangdong Province, China, by 19th March 2020; 2) Virus genomes can be recovered using a variety of sequencing approaches from a range of patient samples. 3) Genomic analyses reveal multiple virus importations into Guangdong Province, resulting in genetically distinct clusters that require careful interpretation. 4) Large-scale epidemiological surveillance and intervention measures were effective in interrupting community transmission in Guangdong Summary: COVID-19 is caused by the SARS-CoV-2 coronavirus and was first reported in central China in December 2019. Extensive molecular surveillance in Guangdong, China's most populous province, during early 2020 resulted in 1,388 reported RNA positive cases from 1.6 million tests. In order to understand the molecular epidemiology and genetic diversity of SARS-CoV-2 in China we generated 53 genomes from infected individuals in Guangdong using a combination of metagenomic sequencing and tiling amplicon approaches. Combined epidemiological and phylogenetic analyses indicate multiple independent introductions to Guangdong, although phylogenetic clustering is uncertain due to low virus genetic variation early in the pandemic. Our results illustrate how the timing, size and duration of putative local transmission chains were constrained by national travel restrictions and by the province's large-scale intensive surveillance and intervention measures. Despite these successes, COVID-19 surveillance in Guangdong is still required as the number of cases imported from other countries is increasing.

negative: Role of a Habitat's Air Humidity in Covid-19 Mortality Transient local over-dry environment might be a contributor and an explanation for the observed asynchronous local rises in Covid-19 mortality. We propose that a habitat's air humidity negatively correlate with Covid-19 morbidity and mortality, and support this hypothesis on the example of publicly available data from German federal states.

negative: 2264. The Burden of Respiratory Viral Illness in HIV-Infected Patients BACKGROUND: Among individuals living with human immunodeficiency virus (HIV), pulmonary complications are the most frequent cause of morbidity and mortality. Although bacterial and fungal pathogens are well-described etiologies of lung disease, the role of respiratory viruses remains poorly understood. We sought to describe the burden of respiratory viral illness in HIV-infected inpatients admitted to our tertiary care center. METHODS: All HIV-infected inpatients from August 2015 to March 2018 were approached if they presented with respiratory symptoms, defined as cough, dyspnea, sore throat, rhinorrhea, wheezing, or stridor. Eighty patients were enrolled. After obtaining informed consent, nasopharyngeal swabs and blood were collected. If the subject underwent bronchoscopy per the treating physician, excess bronchoalveolar lavage (BAL) sample was collected. Demographic and clinical data were recorded for each subject. Multiplex PCR testing of all respiratory samples was performed. RESULTS: Of the 70 HIV-infected patients that have undergone complete analysis, 23 (33%) tested positive for respiratory viruses. Of these, 11 (48%) were positive for rhinovirus, 3 were positive for influenza A (13%), 2 for parainfluenza 3 (9%), 2 for coronavirus (9%), and one each tested positive for adenovirus, parainfluenza 4, respiratory syncytial virus and influenza B. One patient had co-infection with rhinovirus and human metapneumovirus. Patients infected with a respiratory virus had severe illness as nearly half (10/23; 48%) required intensive care, 5 (22%) required mechanical ventilation, 4 (17%) were discharged to a higher level of care, and 3 (13%) died. CONCLUSION: The role of respiratory viruses on the lung health of HIV-infected patients is poorly defined. In this study, respiratory viruses were identified in over a third of HIV-infected inpatients, representing a substantial disease burden. Moreover, these patients demonstrated significant disease severity. Given these findings, there is a need for future studies of viral infections in HIV-infected individuals to elucidate mechanisms of susceptibility to reduce the burden of pulmonary morbidity in this vulnerable population. DISCLOSURES: All authors: No reported disclosures.

negative: Clinical characteristics and outcomes of hospitalised patients with COVID-19 treated in Hubei (epicenter) and outside Hubei (non-epicenter): A Nationwide Analysis of China BACKGROUND: During the outbreak of coronavirus disease 2019 (COVID-19), consistent and considerable differences in disease severity and mortality rate of patients treated in Hubei province compared to those in other parts of China has been observed. We sought to compare the clinical characteristics and outcomes of patients being treated inside and outside Hubei province, and explore the factors underlying these differences. METHODS: Collaborating with the National Health Commission, we established a retrospective cohort to study hospitalised COVID-19 cases in China. Clinical characteristics, the rate of severe events and deaths, and the time to critical illness (invasive ventilation or intensive care unit admission or death) were compared between patients in and outside of Hubei. The impact of Wuhan-related exposure (a presumed key factor that drove the severe situation in Hubei, as Wuhan is the epicenter as well the administrative center of Hubei province) and the duration between symptom onset and admission on prognosis were also determined. RESULTS: Upon data cut-off (Jan 31st, 2020), 1590 cases from 575 hospitals in 31 provincial administrative regions were collected (core cohort). The overall rate of severe cases and mortality was 16.0% and 3.2%, respectively. Patients in Hubei (predominantly with Wuhan-related exposure, 597/647, 92.3%) were older (mean: 49.7 versus 44.9 years), had more cases with comorbidity (32.9% versus 19.7%), higher symptomatic burden, abnormal radiologic manifestations, and, especially, a longer waiting time between symptom onset and admission (5.7 versus 4.5 days) compared with patients outside Hubei. Patients in Hubei [severe event rate 23.0% versus 11.1%, death rate 7.3% versus 0.3%, hazards ratio (HR) for critical illness 1.59, 95%CI 1.05–2.41] have a poorer prognosis compared with patients outside of Hubei after adjusting for age and comorbidity. However, among patients outside of Hubei, the duration from symptom onset to hospitalisation (mean: 4.4 versus 4.7 days) and prognosis (HR 0.84, 95%CI 0.40–1.80) were similar between patients with or without Wuhan-related exposure. In the overall population, the waiting time, but neither treated in Hubei nor Wuhan-related exposure, remained an independent prognostic factor (HR 1.05, 1.01–1.08). CONCLUSION: There were more severe cases and poorer outcomes for COVID-19 patients treated in Hubei, which might be attributed to the prolonged duration of symptom onset to hospitalisation in the epicenter. Future studies to determine the reason for delaying hospitalisation are warranted.

negative: Host Range and Emerging and Reemerging Pathogens An updated literature survey identified 1,407 recognized species of human pathogen, 58% of which are zoonotic. Of the total, 177 are regarded as emerging or reemerging. Zoonotic pathogens are twice as likely to be in this category as are nonzoonotic pathogens. Emerging and reemerging pathogens are not strongly associated with particular types of nonhuman hosts, but they are most likely to have the broadest host ranges. Emerging and reemerging zoonoses are associated with a wide range of drivers, but changes in land use and agriculture and demographic and societal changes are most commonly cited. However, although zoonotic pathogens do represent the most likely source of emerging and reemerging infectious disease, only a small minority have proved capable of causing major epidemics in the human population.

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: Increased Mortality Rate Associated with Chikungunya Epidemic, Ahmedabad, India A total of 3,056 excess deaths epidemiologically linked to chikungunya occurred in 2006.

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

negative: Lower Respiratory Tract Diseases Caused by Common Respiratory Viruses among Stem Cell Transplantation Recipients: A Single Center Experience in Korea PURPOSE: To describe the incidence, clinical courses, and risk factors for mortality of lower respiratory tract diseases (LRDs) caused by common respiratory viruses (CRVs) in stem cell transplantation (SCT) recipients. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 1038 patients who received SCT between January 2007 and August 2011 at a single center in Korea. RESULTS: Seventy-one CRV-LRDs were identified in 67 (6.5%) patients. The human parainfluenza virus (HPIV) was the most common causative pathogen of CRV-LRDs at 100 days [cumulative incidence estimate, 23.5%; 95% confidence interval (CI), 3.3–43.7] and 1 year (cumulative incidence estimate, 69.2%; 95% CI, 45.9–92.5) following SCT. The 30-day overall mortality rates due to influenza-LRDs, respiratory syncytial virus-LRDs, HPIV-LRDs, and human rhinovirus-LRDs were 35.7, 25.8, 31.6, and 42.8%, respectively. Co-pathogens in respiratory specimens were detected in 23 (33.8%) patients. The overall mortality at day 30 after CRV-LRD diagnosis was 32.8% (22/67). High-dose steroid usage (p=0.025), a severe state of immunodeficiency (p=0.033), and lymphopenia (p=0.006) were significantly associated with death within 30 days following CRV-LRD diagnosis in a univariate analysis. Multivariate logistic regression analysis revealed that high-dose steroid usage [odds ratio (OR), 4.05; 95% CI, 1.12–14.61; p=0.033] and lymphopenia (OR, 6.57; 95% CI, 1.80–24.03; p=0.004) were independent risk factors for mortality within 30 days of CRV-LRDs. CONCLUSION: CRV-LRDs among SCT recipients showed substantially high morbidity and mortality rates. Therefore, the implement of an active diagnostic approaches for CRV infections is required for SCT recipients with respiratory symptoms, especially those receiving high-dose steroids or with lymphopenia.

negative: Association Between BCG Policy is Significantly Confounded by Age and is Unlikely to Alter Infection or Mortality Rates Recently a number of publications looked at the association between COVID-19 morbidity and mortality on one hand and countries' policies with respect to BCG vaccination on the other. This connection arises from differences in the rates of infection in countries where BCG vaccination is mandatory compared to countries where mandatory vaccination no longer exists or was never implemented in the first place. In at least 2 preprint publications the authors expressed the view that the "known immunological benefits" of BCG vaccination may be behind the biological mechanism of such observation. One study accounted for different income levels in different groups. Another study did not attempted to do so, instead exploring the differences between countries where a booster shot is given vs others where no such practice exists (finding no connection). Both of these studies did not explore other potential confounding factors. Meanwhile the press has focused on these headlines and pushed the narrative that BCG vaccination is causally linked to infection and mortality rates. This poses a serious challenge, demonstrated by the recently initiated clinical trials on BCG vaccination within the COVID19 context. This study shows that population age is a very significant confounding factor that explains the rates of infections much better and has a solid biology mechanism which explains this correlation. It suggests that BCG vaccination may have little or no causal link to infection rates and advises that any follow up studies should control for several confounding factors, such as population age, ethnicity, rates of certain chronic diseases, time from community spread start date, major public policy decisions and income levels.

negative: Malaria in China: a longitudinal population-based surveillance study This study aims to ascertain the long-term epidemic trends of malaria and evaluates the probability of achieving the eradication goal by 2020 in China. Data on malaria incidence and deaths were extracted from the China Information System for Disease Control and Prevention. The epidemic trends by sex, age and spatial distribution and predictions of malaria were estimated by using Joinpoint and Poisson regressions. From 1950 to 2016, 227 668 374 malaria cases were reported in China, with an annualised average incidence of 337.02 (336.98–337.07, 95% confidence interval (CI)) per 100 000 population. The incidence decreased with an average annual per cent change (AAPC) of −11.4% (−16.6 to −6.0). There were 36 085 malaria deaths, with an annualised average mortality of 0.534 (0.529–0.540) per 1 000 000 population. The mortality decreased with an AAPC of −8.7% (−13.7 to −3.4). The predicted number of malaria cases and deaths for 2020 is 2 562 and 10, respectively, and zero for indigenous cases. The disease burden of malaria dramatically decreased in China. Though, the goal of malaria elimination is realistic by 2020 in China, routine clinical and entomological surveillance should be continually conducted, especially for the cross-border areas and imported malaria cases.

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: Digital Surveillance: A Novel Approach to Monitoring the Illegal Wildlife Trade A dearth of information obscures the true scale of the global illegal trade in wildlife. Herein, we introduce an automated web crawling surveillance system developed to monitor reports on illegally traded wildlife. A resource for enforcement officials as well as the general public, the freely available website, http://www.healthmap.org/wildlifetrade, provides a customizable visualization of worldwide reports on interceptions of illegally traded wildlife and wildlife products. From August 1, 2010 to July 31, 2011, publicly available English language illegal wildlife trade reports from official and unofficial sources were collected and categorized by location and species involved. During this interval, 858 illegal wildlife trade reports were collected from 89 countries. Countries with the highest number of reports included India (n = 146, 15.6%), the United States (n = 143, 15.3%), South Africa (n = 75, 8.0%), China (n = 41, 4.4%), and Vietnam (n = 37, 4.0%). Species reported as traded or poached included elephants (n = 107, 12.5%), rhinoceros (n = 103, 12.0%), tigers (n = 68, 7.9%), leopards (n = 54, 6.3%), and pangolins (n = 45, 5.2%). The use of unofficial data sources, such as online news sites and social networks, to collect information on international wildlife trade augments traditional approaches drawing on official reporting and presents a novel source of intelligence with which to monitor and collect news in support of enforcement against this threat to wildlife conservation worldwide.

negative: Strategy for the practice of digestive and oncological surgery during the Covid-19 epidemic()() The Covid-19 pandemic is changing the organization of healthcare and has a direct impact on digestive surgery. Healthcare priorities and circuits are being modified. Emergency surgery is still a priority. Functional surgery is to be deferred. Laparoscopic surgery must follow strict rules so as not to expose healthcare professionals (HCPs) to added risk. The question looms large in cancer surgery–go ahead or defer? There is probably an added risk due to the pandemic that must be balanced against the risk incurred by deferring surgery. For each type of cancer–colon, pancreas, oesogastric, hepatocellular carcinoma–morbidity and mortality rates are stated and compared with the oncological risk incurred by deferring surgery and/or the tumour doubling time. Strategies can be proposed based on this comparison. For colonic cancers T1-2, N0, it is advisable to defer surgery. For advanced colonic lesions, it seems judicious to undertake neoadjuvant chemotherapy and then wait. For rectal cancers T3-4 and/or N+, chemoradiotherapy is indicated, short radiotherapy must be discussed (followed by a waiting period) to reduce time of exposure in the hospital and to prevent infections. Most complex surgery with high morbidity and mortality–oesogastric, hepatic or pancreatic–is most often best deferred.

negative: Understanding Economic and Health Factors Impacting the Spread of COVID-19 Disease The rapid spread of the Coronavirus 2019 disease (COVID-19) had drastically impacted life all over the world. While some economies are actively recovering from this pestilence, others are experiencing fast and consistent disease spread, compelling governments to impose social distancing measures that have put a halt on routines, especially in densely-populated areas. Aiming at bringing more light on key economic and public health factors affecting the disease spread, this initial study utilizes a quantitative statistical analysis based on the most recent publicly-available COVID-19 datasets. The study had shown and explained multiple significant relationships between the COVID-19 data and other country-level statistics. We have also identified and statistically profiled four major country-level clusters with relation to different aspects of COVID-19 development and country-level economic and health indicators. Specifically, this study has identified potential COVID-19 under-reporting traits as well as various economic factors that impact COVID-19 Diagnosis, Reporting, and Treatment. Based on the country clusters, we have also described the four disease development scenarios, which are tightly knit to country-level economic and public health factors. Finally, we have highlighted the potential limitation of reporting and measuring COVID-19 and provided recommendations on further in-depth quantitative research.

negative: Asthma in the elderly: what we know and what we have yet to know In the past, asthma was considered mainly as a childhood disease. However, asthma is an important cause of morbidity and mortality in the elderly nowadays. In addition, the burden of asthma is more significant in the elderly than in their younger counterparts, particularly with regard to mortality, hospitalization, medical costs or health-related quality of life. Nevertheless, asthma in the elderly is still been underdiagnosed and undertreated. Therefore, it is an imperative task to recognize our current challenges and to set future directions. This project aims to review the current literature and identify unmet needs in the fields of research and practice for asthma in the elderly. This will enable us to find new research directions, propose new therapeutic strategies, and ultimately improve outcomes for elderly people with asthma. There are data to suggest that asthma in older adults is phenotypically different from young patients, with potential impact on the diagnosis, assessment and management in this population. The diagnosis of AIE in older populations relies on the same clinical findings and diagnostic tests used in younger populations, but the interpretation of the clinical data is more difficult. The challenge today is to encourage new research in AIE but to use the existing knowledge we have to make the diagnosis of AIE, educate the patient, develop a therapeutic approach to control the disease, and ultimately provide a better quality of life to our elderly patients.

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: COVID-19 Infection: Implications for Perioperative and Critical Care Physicians Healthcare systems worldwide are responding to Coronavirus Disease 2019 (COVID-19), an emerging infectious syndrome caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus. Patients with COVID-19 can progress from asymptomatic or mild illness to hypoxemic respiratory failure or multisystem organ failure, necessitating intubation and intensive care management. Healthcare providers, and particularly anesthesiologists, are at the frontline of this epidemic, and they need to be aware of the best available evidence to guide therapeutic management of patients with COVID-19 and to keep themselves safe while doing so. Here, the authors review COVID-19 pathogenesis, presentation, diagnosis, and potential therapeutics, with a focus on management of COVID-19–associated respiratory failure. The authors draw on literature from other viral epidemics, treatment of acute respiratory distress syndrome, and recent publications on COVID-19, as well as guidelines from major health organizations. This review provides a comprehensive summary of the evidence currently available to guide management of critically ill patients with COVID-19.

negative: New Insights of Emerging SARS-CoV-2: Epidemiology, Etiology, Clinical Features, Clinical Treatment, and Prevention Since the first reports that the novel coronavirus was showing human-to-human transmission characteristics and asymptomatic cases, the number of patients with associated pneumonia has continued to rise and the epidemic has grown. It now threatens the health and lives of people across the world. The governments of many countries have attached great importance to the prevention of SARS-CoV-2, via research into the etiology and epidemiology of this newly emerged disease. Clinical signs, treatment, and prevention characteristics of the novel coronavirus pneumonia have been receiving attention worldwide, especially from medical personnel. However, owing to the different experimental methods, sample sizes, sample sources, and research perspectives of various studies, results have been inconsistent, or relate to an isolated aspect of the virus or the disease it causes. Currently, systematic summary data on the novel coronavirus are limited. This review combines experimental and clinical evidence into a systematic analysis and summary of the current progress of research into SARS-CoV-2, from multiple perspectives, with the aim of gaining a better overall understanding of the disease. Our report provides important information for current clinicians, for the prevention and treatment of COVID-19 pneumonia.

negative: Commentary on Ferguson, et al., “Impact of Non-pharmaceutical Interventions (NPIs) to Reduce COVID-19 Mortality and Healthcare Demand” A recent manuscript (Ferguson et al. in Impact of non-pharmaceutical interventions (NPIs) to reduce COVID-19 mortality and healthcare demand, Imperial College COVID-19 Response Team, London, 2020. https://www.imperial.ac.uk/media/imperial-college/medicine/sph/ide/gida-fellowships/Imperial-College-COVID19-NPI-modelling-16-03-2020.pdf) from Imperial College modelers examining ways to mitigate and control the spread of COVID-19 has attracted much attention. In this paper, we will discuss a coarse taxonomy of models and explore the context and significance of the Imperial College and other models in contributing to the analysis of COVID-19.

negative: A severe influenza season in Austria and its impact on the paediatric population: mortality and hospital admission rates, november 2017 - march 2018 BACKGROUND: In Austria paediatric influenza-associated hospitalisations and deaths have never been systematically monitored. We examined the influenza season 2017/18 in terms of hospitalisation and mortality in the Austrian paediatric population and put the results into perspective of the available data from the last 15 years. METHODS: Cases of influenza-associated hospitalisations and deaths for season 2017/18 in children below 18 years were retrospectively collected from 12 and 33 Austrian hospitals, respectively. Hospitalisation and mortality rates for the whole Austrian paediatric population were estimated, adjusting for the population in each catchment area. Two Austrian databases were queried for hospitalisations and deaths associated with influenza during 2002–2016. Rough estimate of the vaccination coverage was calculated from a survey on 100 inpatients. RESULTS: Influenza-related paediatric hospitalisation rate in season 2017/18 was estimated as 128 (CI: 122–135) per 100,000 children, much higher than the national average of 40 per 100,000 over the years 2002–2016. There were nine reported influenza-associated deaths among children, resulting in mortality rate of 0.67 (CI: 0.32–1.21) per 100,000 children. CONCLUSIONS: Reported influenza-associated hospitalisations and fatalities demonstrate a high burden of influenza in the Austrian paediatric population corresponding with very low vaccination coverage.

negative: iGPCR-Drug: A Web Server for Predicting Interaction between GPCRs and Drugs in Cellular Networking Involved in many diseases such as cancer, diabetes, neurodegenerative, inflammatory and respiratory disorders, G-protein-coupled receptors (GPCRs) are among the most frequent targets of therapeutic drugs. It is time-consuming and expensive to determine whether a drug and a GPCR are to interact with each other in a cellular network purely by means of experimental techniques. Although some computational methods were developed in this regard based on the knowledge of the 3D (dimensional) structure of protein, unfortunately their usage is quite limited because the 3D structures for most GPCRs are still unknown. To overcome the situation, a sequence-based classifier, called “iGPCR-drug”, was developed to predict the interactions between GPCRs and drugs in cellular networking. In the predictor, the drug compound is formulated by a 2D (dimensional) fingerprint via a 256D vector, GPCR by the PseAAC (pseudo amino acid composition) generated with the grey model theory, and the prediction engine is operated by the fuzzy K-nearest neighbour algorithm. Moreover, a user-friendly web-server for iGPCR-drug was established at http://www.jci-bioinfo.cn/iGPCR-Drug/. For the convenience of most experimental scientists, a step-by-step guide is provided on how to use the web-server to get the desired results without the need to follow the complicated math equations presented in this paper just for its integrity. The overall success rate achieved by iGPCR-drug via the jackknife test was 85.5%, which is remarkably higher than the rate by the existing peer method developed in 2010 although no web server was ever established for it. It is anticipated that iGPCR-Drug may become a useful high throughput tool for both basic research and drug development, and that the approach presented here can also be extended to study other drug – target interaction networks.

negative: COVID-19 pneumonia manifestations at the admission on chest ultrasound, radiographs, and CT: single-center study and comprehensive radiologic literature review PURPOSE: To investigate the imaging features of emerging COVID-19 pneumonia on chest ultrasound (US), radiographs (CXR) and computed tomography (CT) examinations performed at admission and to provide a comprehensive radiological literature review on ongoing radiological data from recent publications. MATERIALS AND METHODS: In this retrospective single-center study, we enrolled consecutive patients from February 15, 2020, to March 15, 2020, with laboratory-confirmed SARS-CoV-2 hospitalized in Valduce Hospital (Como, Italy). Multi-modality imaging findings were evaluated and compared. Literature research was conducted through a methodical search on Pubmed and Embase databases. RESULTS: Fifty-eight patients (36 men, 22 women; age range, 18–98 years) were included in the study. Among these, chest US, CXR, and CT were performed respectively in twenty-two, thirty-two and forty-two patients. Lung US findings were consistent with diffuse B lines (100%) and subpleural consolidations (27.3%). CXR showed prevalent manifestations of consolidations (46.9%) and hazy increased opacities (37.5%). Typical CT features included bilateral and multilobar ground-glass opacities (GGO) with (59.5%) and without (35.7%) consolidations having a predominantly peripheral distribution (64.3%). Other imaging features included crazy paving pattern (57.1%), fibrous stripes (50%), subpleural lines (35.7%), architectural distortion (28.6%), air bronchogram sign (26.2%), vascular thickening (23.8%) and nodules (2.4%). Also, enlarged lymph nodes (14.3 %) and pleural effusion (7.1%) were observed. The literature review identified twenty-six original studies supporting our imaging chest findings. CONCLUSION: The spectrum of chest imaging manifestations of COVID-19 pneumonia upon admission includes B-lines and consolidations on US, consolidations and hazy increased opacities on CXR, and multifocal GGO with consolidations on CT.

negative: Guidelines for preventing respiratory illness in older adults aged 60 years and above living in long-term care: A rapid review of clinical practice guidelines Background: The overall objective of this rapid review was to identify infection protection and control recommendations from published clinical practice guidelines (CPGs) for adults aged 60 years and older in long-term care settings Methods: Comprehensive searches in MEDLINE, EMBASE, the Cochrane Library, and relevant CPG publishers/repositories were carried out in early March 2020. Title/abstract and full-text screening, data abstraction, and quality appraisal (AGREE-II) were carried out by single reviewers. Results: A total of 17 relevant CPGs were identified, published in the USA (n=8), Canada (n=6), Australia (n=2), and the United Kingdom (n=1). All of the CPGs dealt with infection control in long-term care facilities (LTCF) and addressed various types of viral respiratory infections (e.g., influenza, COVID-19, severe acute respiratory syndrome). Ten or more CPGs recommended the following infection control measures in LTCF: hand hygiene (n=13), wearing personal protective equipment (n=13), social distancing or isolation (n=13), disinfecting surfaces (n=12), droplet precautions (n=12), surveillance and evaluation (n=11), and using diagnostic testing to confirm illness (n=10). While only two or more CPGs recommended these infection control measures: policies and procedures for visitors, staff and/or residents (n=9), respiratory hygiene/cough etiquette (n=9), providing supplies (n=9), staff and/or residents education (n=8), increasing communication (n=6), consulting or notifying health professionals (n=6), appropriate ventilation practices (n=2), and cohorting equipment (n=2). Ten CPGs also addressed management of viral respiratory infections in LTCF and recommended antiviral chemoprophylaxis (n=10) and one CPG recommended early mobilization of residents. Conclusion: The recommendations from current guidelines overall seem to support environmental measures for infection prevention and antiviral chemoprophylaxis for infection management as the most appropriate first-line response to viral respiratory illness in long-term care.

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

negative: Aminopeptidase N Knockout Pigs Are Not Resistant to Porcine Epidemic Diarrhea Virus Infection

negative: Extensive multiplex PCR diagnostics reveal new insights into the epidemiology of viral respiratory infections Viral respiratory infections continue to pose a major global healthcare burden. At the community level, the co-circulation of respiratory viruses is common and yet studies generally focus on single aetiologies. We conducted the first comprehensive epidemiological analysis to encompass all major respiratory viruses in a single population. Using extensive multiplex PCR diagnostic data generated by the largest NHS board in Scotland, we analysed 44230 patient episodes of respiratory illness that were simultaneously tested for 11 virus groups between 2005 and 2013, spanning the 2009 influenza A pandemic. We measured viral infection prevalence, described co-infections, and identified factors independently associated with viral infection using multivariable logistic regression. Our study provides baseline measures and reveals new insights that will direct future research into the epidemiological consequences of virus co-circulation. In particular, our study shows that (i) human coronavirus infections are more common during influenza seasons and in co-infections than previously recognized, (ii) factors associated with co-infection differ from those associated with viral infection overall, (iii) virus prevalence has increased over time especially in infants aged <1 year, and (iv) viral infection risk is greater in the post-2009 pandemic era, likely reflecting a widespread change in the viral population that warrants further investigation.

negative: Global Burden of Infectious Diseases Systematic efforts to quantify and monitor the burden of specific health conditions in populations, at the national level, started in the mid-1950s for malaria, poliomyelitis, and influenza in the United States. Comprehensive surveillance of morbidity and mortality for dozens of conditions has since been well established in the United States and in other industrialized countries. However, despite the clear need for epidemiological data to inform health policies, reliable and comprehensive health statistics are not available in many developing countries. International efforts to assess and monitor the burden of certain diseases have been limited in the past to a small number of infectious diseases in the context of global eradication programs – smallpox, poliomyelitis, guinea worm, and, more recently, HIV/AIDS, severe acute respiratory syndrome (SARS), and avian flu influenza A (H5N1). The Global Burden of Disease Study (GBD), published in 1996, filled an important gap in our knowledge of population health status. It created a common metric, the disability-adjusted life year (DALY), to estimate morbidity and mortality for eight regions that collectively span the world’s population, generating comparable information on incidence and prevalence in global health. However, patterns of disease, disability, and risk factors have since changed significantly and new data on their distribution are available. Furthermore, the unprecedented money and attention now pouring into international health has made an accurate assessment of global health patterns a matter of utmost urgency. The new Global Burden of Diseases, Injuries, and Risk Factors (GBD 2005) project, which began in 2007, represents the first major effort at a systematic revision of estimates in health for every region in the world comprehensively, and will ensure that that the global health community bases its research and policies on complete, valid, and reliable information. Burden of disease estimates provided in this article are for 2001 – the year for which the most recent estimates of the global burden of disease and risk factors are currently available. Causes of deaths were categorized into three main groups: group I (infectious diseases and maternal, perinatal, and nutritional conditions), group II (noncommunicable diseases), and group III (injuries). Accordingly, estimates of the global burden of infectious diseases are provided in the context of the overall burden from other conditions, diseases, and injuries. The relative importance of the burden of infectious diseases was forecasted to change by 2020. As the epidemiological transition progresses worldwide, a decline in the burden of infectious diseases is expected as the burden of noncommunicable diseases and injuries gradually increases. The pace of the epidemiological transition, however, varies greatly among regions so that the projected decreases in the burden of infectious diseases are expected to vary between regions. Trends in the global burden due to specific infectious diseases projected to 2020 also vary among specific conditions. The global burden of HIV/AIDS, for instance, is expected to greatly increase, whereas the global burden due to respiratory infections and diarrheal diseases is expected to decrease. Contrary to expectations, the global burden of malaria has increased in recent years.

negative: Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. BACKGROUND Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI). METHODS We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2016. We calculated DALYs by summing years of life lost and years of life lived with disability for each location, age group, sex, and year. We estimated HALE using age-specific death rates and years of life lived with disability per capita. We explored how DALYs and HALE differed from expected trends when compared with the SDI: the geometric mean of income per person, educational attainment in the population older than age 15 years, and total fertility rate. FINDINGS The highest globally observed HALE at birth for both women and men was in Singapore, at 75·2 years (95% uncertainty interval 71·9-78·6) for females and 72·0 years (68·8-75·1) for males. The lowest for females was in the Central African Republic (45·6 years [42·0-49·5]) and for males was in Lesotho (41·5 years [39·0-44·0]). From 1990 to 2016, global HALE increased by an average of 6·24 years (5·97-6·48) for both sexes combined. Global HALE increased by 6·04 years (5·74-6·27) for males and 6·49 years (6·08-6·77) for females, whereas HALE at age 65 years increased by 1·78 years (1·61-1·93) for males and 1·96 years (1·69-2·13) for females. Total global DALYs remained largely unchanged from 1990 to 2016 (-2·3% [-5·9 to 0·9]), with decreases in communicable, maternal, neonatal, and nutritional (CMNN) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the five lowest ratios of observed to expected age-standardised DALY rates in 2016, were Nicaragua, Costa Rica, the Maldives, Peru, and Israel. The leading three causes of DALYs globally were ischaemic heart disease, cerebrovascular disease, and lower respiratory infections, comprising 16·1% of all DALYs. Total DALYs and age-standardised DALY rates due to most CMNN causes decreased from 1990 to 2016. Conversely, the total DALY burden rose for most NCDs; however, age-standardised DALY rates due to NCDs declined globally. INTERPRETATION At a global level, DALYs and HALE continue to show improvements. At the same time, we observe that many populations are facing growing functional health loss. Rising SDI was associated with increases in cumulative years of life lived with disability and decreases in CMNN DALYs offset by increased NCD DALYs. Relative compression of morbidity highlights the importance of continued health interventions, which has changed in most locations in pace with the gross domestic product per person, education, and family planning. The analysis of DALYs and HALE and their relationship to SDI represents a robust framework with which to benchmark location-specific health performance. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform health policies, health system improvement initiatives, targeted prevention efforts, and development assistance for health, including financial and research investments for all countries, regardless of their level of sociodemographic development. The presence of countries that substantially outperform others suggests the need for increased scrutiny for proven examples of best practices, which can help to extend gains, whereas the presence of underperforming countries suggests the need for devotion of extra attention to health systems that need more robust support. FUNDING Bill & Melinda Gates Foundation.

negative: Prevalence of Underlying Diseases in Hospitalized Patients with COVID-19: a Systematic Review and Meta-Analysis INTRODUCTION: In the beginning of 2020, an unexpected outbreak due to a new corona virus made the headlines all over the world. Exponential growth in the number of those affected makes this virus such a threat. The current meta-analysis aimed to estimate the prevalence of underlying disorders in hospitalized COVID-19 patients. METHODS: A comprehensive systematic search was performed on PubMed, Scopus, Web of science, and Google scholar, to find articles published until 15 February 2020. All relevant articles that reported clinical characteristics and epidemiological information of hospitalized COVID-19 patients were included in the analysis. RESULTS: The data of 76993 patients presented in 10 articles were included in this study. According to the meta-analysis, the pooled prevalence of hypertension, cardiovascular disease, smoking history and diabetes in people infected with SARS-CoV-2 were estimated as 16.37% (95%CI: 10.15%-23.65%), 12.11% (95%CI 4.40%-22.75%), 7.63% (95%CI 3.83%-12.43%) and 7.87% (95%CI 6.57%-9.28%), respectively. CONCLUSION: According to the findings of the present study, hypertension, cardiovascular diseases, diabetes mellitus, smoking, chronic obstructive pulmonary disease (COPD), malignancy, and chronic kidney disease were among the most prevalent underlying diseases among hospitalized COVID-19 patients, respectively.

negative: Practical Strategies Against the Novel Coronavirus and COVID-19—the Imminent Global Threat The last month of 2019 harbingered the emergence of a viral outbreak that is now a major public threat globally. COVID-19 was first diagnosed and confirmed in a couple of cases with unknown pneumonia; the patients lived in, or travelled to, Wuhan, the capital of China's Hubei province. People now face a complex challenge that deserves urgent intervention by all involved in medical healthcare globally. Conventional antiviral therapies or vaccines are the most referred means of tackling the virus, but we think establishing these ideal management strategies is presently far-fetched. In-house isolation or quarantine of suspected cases to keep hospital admissions manageable and prevent in-hospital spread of the virus, and promoting general awareness about transmission routes are the practical strategies used to tackle the spread of COVID-19. Cases with weakened or compromised immune systems—for example, elderly individuals, young children, and those with pre-existing conditions such as diabetes, cancer, hypertension, and chronic respiratory diseases—are particularly more susceptible to COVID-19. Hopefully, cumulative data using whole-genome sequencing of the SARS-CoV-2 genome in parallel with mathematical modeling will help the molecular biologists to understand unknown features of the pathogenesis and epidemiology of COVID-19.

negative: Is investing in religious institutions a viable pathway to reduce mortality in the population? There is established and consistent findings from epidemiologic studies, among individuals, that religion— broadly assessed through frequency of attending worship services—is associated with lower all-cause and cause-specific mortality attributed to suicide, alcohol, cardiovascular disease and cancer. Religious norms, social support, character, virtue, compassion, love, generosity, and religious community are among some mechanisms purported to explain lower mortality, on aggregate. The religious ecology or characteristics of religion within an area or geographic level (e.g., county, ZIP-code, country), has been linked with overall and cause-specific mortality, but directions of findings are mixed. Mechanisms to explain the links between the religious ecology and mortality included social integration, civic engagement, and social control. The manuscript (SSM-D-19-03928R2) adds a fresh and timely perspective by investigating another mechanism: investment in local healthcare spending. The study found some support of an indirect association from county-level religious denominational composition, through investments in health spending, on Black and White all-cause mortality rates. Should society or government invest finances in religious institutions to indirectly improve population health? This work adds evidence to debate that question. Future work on the topic will need to address several conceptual and methodological challenges. Conceptually, is investigating the market share of religious denominations (i.e., % Catholics vs % Protestants) relevant today given diversity in population and declining trends of worship attendance? Is mortality the most relevant for moving policy or should the focus be on well-being? Methodologically, are there alternate observable measures religious investments/spending in the local economy? Mechanisms, challenges, and opportunities for social epidemiology research on this topic are discussed.

negative: NUEVOS VIRUS RESPIRATORIOS EN PEDIATRÍA RESUMEN Las infecciones respiratorias continúan siendo la mayor causa de morbimortalidad en pediatría. Los virus constituyen los agentes infecciosos más frecuentes, actualmente con los avances en las técnicas diagnósticas se han sumado “nuevos virus” entre los que destacan Metapneumovirus (MPVh), Bocavirus (BoVh) y Coronavirus (CoVh), que son el objetivo de este artículo. SUMMARY Acute lower respiratory infection is still the leading cause of global morbility and mortality in children. Viruses are the most frequent pathogen, currently the most common viral etiology VRS, although recently due to advances in diagnostic techniques new viruses have been added, that includes Metapneumovirus (hMPV), Bocavirus (hBoV) and Coronavirus (hCoV), which are the purpose of this review.

negative: Problems of calf rearing in connection with their mortality and optimal growth: A review Abstract Protection of calves against enteric and respiratory disorders is dependent on the passive immunity that the calf has received, its innate resistance to infection, the burden of infection in the environment and the nutrition of the calf. Superimposed on these, are the effects of management and physical environment. The plane of nutrition required for dairy heifers during rearing depends on the age at first calving, and for meat animals depends on the carcass weight and fat deposition required at a particular slaughter date in relation to time of birth.

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: Abstracts from the 36th Annual Meeting of the Society of General Internal Medicine

negative: A molecular epidemiological perspective of rhinovirus types circulating in Amsterdam from 2007 to 2012 Abstract Rhinoviruses (RVs) are frequently detected respiratory viruses that cause mild common cold symptoms, but may also lead to more severe respiratory tract infections. The large number of RV types, classified into species A, B and C, hampers clear insights into the epidemiology and clinical significance of each RV type. The aim of this study was to map the circulation of RV types in the Amsterdam area. RV-positive nasopharyngeal and oropharyngeal samples, collected from 2007 to 2012 in the Academic Medical Centre (Amsterdam, the Netherlands), were typed based on the sequence of the region coding for capsid proteins VP4 and VP2. RV-A, RV-B and RV-C were found in proportions of of 52.4% (334/637), 11.3% (72/637), and 36.2% (231/637), respectively. We detected 129 of the 167 currently classified types. RVs circulated throughout the entire year with a peak in the autumn and a decline in the summer. Some RV types were observed throughout the entire sampling period and others had a more seasonal pattern. Nine RV-A and four RV-B novel provisionally assigned types were identified. This study provides an insight into the molecular epidemiology of RVs in the Amsterdam area. The RVs circulating are diverse and include several provisionally new types.

negative: The effects of environmental stressors on the mortality of the oldest old male population in Hong Kong, 1977-2006. Although age-sex-specific mortality rates were decreasing over the years, such a trend was not observed for the male population aged 85 or above (the oldest old) in Hong Kong. Despite literature suggesting that environmental stressors were associated with higher mortality, the adverse effects of socioeconomic and political events were seldom included. Hence, this study explored the relationship between environmental stressors covering adverse weather conditions as well as key socioeconomic and political events and fluctuations in the oldest old mortality rates in Hong Kong during the period 1977 to 2006. The oldest old mortality rates in Hong Kong were observed to have a likelihood of being associated with these environmental stressors. Furthermore, men appeared to be more susceptible to these risk factors than did women. More care and attention should be given to the oldest old men, in particular, during periods of socioeconomic or political upheavals. A cohort study would be useful to study these stressors in greater detail.

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

negative: Analysis of codon usage and evolutionary rates of the 2019-nCoV genes Severe acute respiratory syndrome coronavirus 2 (2019-nCoV), which first broke out in Wuhan (China) in December of 2019, causes a severe acute respiratory illness with a mortality ranging from 3% to 6%. To better understand the evolution of the newly emerging 2019-nCoV, in this paper, we analyze the codon usage pattern of 2019-nCoV. For this purpose, we compare the codon usage of 2019-nCoV with that of other 30 viruses belonging to the subfamily of orthocoronavirinae. We found that 2019-nCoV shows a rich composition of AT nucleotides that strongly influences its codon usage, which appears to be not optimized to human host. Then, we study the evolutionary pressures influencing the codon usage and evolutionary rates of the sequences of five conserved genes that encode the corresponding proteins (viral replicase, spike, envelope, membrane and nucleocapsid) characteristic of coronaviruses. We found different patterns of both mutational bias and nature selection that affect the codon usage of these genes at different extents. Moreover, we show that the two integral membrane proteins proteins (matrix and envelope) tend to evolve slowly by accumulating nucleotide mutations on their genes. Conversely, genes encoding nucleocapsid (N), viral replicase and spike proteins are important targets for the development of vaccines and antiviral drugs, tend to evolve faster as compared to other ones. Taken together, our results suggest that the higher evolutionary rate observed for these two genes could represent a major barrier in the development of antiviral therapeutics 2019-nCoV.

negative: Lifestyle acquired immunity, decentralized intelligent infrastructures and revised healthcare expenditures may limit pandemic catastrophe: a lesson from COVID-19 Human race has often faced pandemic with substantial number of fatalities. As COVID-19 pandemic reached and endured in every corner on earth, countries with moderate to strong healthcare support and expenditure seemed to struggle in containing disease transmission and casualties. COVID-19 affected countries have variability in demographic, socioeconomic and life style health indicators. At this context it is important to find out at what extent these parametric variations are actually modulating disease outcomes. To answer this, we have selected demographic, socioeconomic and health indicators e.g. population density, percentage of urban population, median age, health expenditure per capita, obesity, diabetes prevalence, alcohol intake, tobacco use, case fatality of non communicable diseases (NCDs) as independent variables. Countries were grouped according to these variables and influence on dependent variables e.g. COVID-19 test positive, case fatality and case recovery rates were statistically analyzed. The results suggest that countries with variable median age has significantly different outcome on test positive rate (P<0.01). Both median age (P=0.0397) and health expenditure per capita (P=0.0041) has positive relation with case recovery. Increasing number of test per 100K population showed positive and negative relation with number of positives per 100K population (P=0.0001) and percentage of test positives (P<0.0001) respectively. Alcohol intake per capita in liter (P=0.0046), diabetes prevalence (P=0.0389) and NCDs mortalities (P=0.0477) also showed statistical relation with case fatality rate. Further analysis revealed that countries with high healthcare expenditure along with high median age and increased urban population showed more case fatality but also had better recovery rate. Investment in health sector alone is insufficient in controlling pandemic severity. Intelligent and sustainable healthcare both in urban and rural settings and healthy lifestyle acquired immunity may reduce disease transmission and comorbidity induced fatalities respectively.

negative: How will country-based mitigation measures influence the course of the COVID-19 epidemic?

negative: SARS, emerging infections, and bioterrorism preparedness

negative: On Determining the Age Distribution of COVID-19 Pandemic Pandemics tend to have higher occurrence (morbidity) in younger individuals but higher mortality for the elderly. The higher rate of mortality of COVID-19 in elderly individuals has been discussed in many reports. However, this pandemic is a double-edged sword as this comment shows higher morbidity rates in elderly as well. This is shown by comparing the age distribution of cases in China and South Korea to the relative populations. In every case, the relative number of elderly contracting the virus is far higher than the proportion of elderly in the population. This is unlike past pandemics and shows that aging populations are at an even higher risk than the perceived age dependent rates may imply.

negative: Changing pattern of premature mortality burden over 6 years of rapid growth of the economy in suburban south-west China: 1998–2003 Summary Background This study was conducted in Kunming, the capital of Yunnan, a poor province in south-west China experiencing rapid economic growth. The study examined the short-term trend in premature mortality burden from common causes of death in a suburban region between 1998 and 2003. Methods Years of life lost (YLL) per 1000 population and mortality rate per 100,000 population were calculated from medical death certificates, and broken down by cause of death, sex and year without age weighting but with a discounting rate of 3%. Results Non-communicable diseases contributed over 80% of all causes of YLL, with a slightly increasing trend. The combined rate for communicable, maternal, prenatal and nutritional deficiencies declined from 4.7 to 2.4 per 1000 population. Remarkably, declining trends in YLL were also seen for chronic obstructive pulmonary disease, drug use and road traffic accidents, whereas increasing trends were seen for ischaemic heart disease (IHD) and liver cancer (males). The YLL rate for stroke, self-inflicted injuries, lung cancer and stomach cancer fluctuated over time. Conclusions The region should focus on further control of IHD and liver cancer.

negative: Respiratory Viral Infections in Transplant Recipients Respiratory viral infections (RVIs) are common among the general population; however, these often mild viral illnesses can lead to serious morbidity and mortality among recipients of hematopoietic stem cell and solid organ transplantation. The disease spectrum ranges from asymptomatic or mild infections to life-threatening lower respiratory tract infection or long-term airflow obstruction syndromes. Progression to lower respiratory tract infection or to respiratory failure is determined by the intrinsic virulence of the specific viral pathogen as well as various host factors, including the type of transplantation, status of the host’s immune dysfunction, the underlying disease, and other comorbidities. This chapter focuses on the epidemiology, clinical manifestations, diagnosis, and management of RVIs in this susceptible population and includes respiratory syncytial virus, parainfluenza virus, human metapneumovirus, influenza virus, human coronavirus, and human rhinovirus. The optimal management of these infections is limited by the overall paucity of available treatment, highlighting the need for new antiviral drug or immunotherapies.

negative: Dynamics and Control of Diseases in Networks with Community Structure The dynamics of infectious diseases spread via direct person-to-person transmission (such as influenza, smallpox, HIV/AIDS, etc.) depends on the underlying host contact network. Human contact networks exhibit strong community structure. Understanding how such community structure affects epidemics may provide insights for preventing the spread of disease between communities by changing the structure of the contact network through pharmaceutical or non-pharmaceutical interventions. We use empirical and simulated networks to investigate the spread of disease in networks with community structure. We find that community structure has a major impact on disease dynamics, and we show that in networks with strong community structure, immunization interventions targeted at individuals bridging communities are more effective than those simply targeting highly connected individuals. Because the structure of relevant contact networks is generally not known, and vaccine supply is often limited, there is great need for efficient vaccination algorithms that do not require full knowledge of the network. We developed an algorithm that acts only on locally available network information and is able to quickly identify targets for successful immunization intervention. The algorithm generally outperforms existing algorithms when vaccine supply is limited, particularly in networks with strong community structure. Understanding the spread of infectious diseases and designing optimal control strategies is a major goal of public health. Social networks show marked patterns of community structure, and our results, based on empirical and simulated data, demonstrate that community structure strongly affects disease dynamics. These results have implications for the design of control strategies.

negative: Care of the Surgical ICU Patient with Chronic Obstructive Pulmonary Disease and Pulmonary Hypertension Chronic obstructive pulmonary disease (COPD) is a progressive chronic disease characterized by airflow limitation that is frequently progressive and associated with respiratory impairment. As the fourth leading cause of death in the United States and Europe, COPD results in a substantial and ever increasing economic and social burden [1]. Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are frequently encountered in the intensive care unit (ICU). Although there is no standardized definition, AECOPD are characterized by a significant change in patient symptoms from baseline accompanied by overall increased airway resistance [2]. These exacerbations carry a significant risk to patients, with 10 % in-hospital mortality and 1-year and 2-year all-cause mortality rates of 43 % and 49 %, respectively, in patients with hypercapnic exacerbations [3]. Other studies note in-hospital mortality rates as high as 30 % with worse outcomes associated with older age, severity of respiratory and non-respiratory organ dysfunction, and hospital length of stay [4]. Given that patients transferred to the ICU with AECOPD are at high risk for complications and adverse outcomes, early diagnosis and management are critical to improve patient outcomes and survival in this population.

negative: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may be harmful in patients with diabetes during COVID-19 pandemic Abstract The novel coronavirus disease 2019 (COVID-19) outbreak once again demonstrated the importance of the renin-angiotensin system (RAS) in patients with diabetes. Activation of the RAS increases in patients with diabetes. The virus attaches to the ACE2 enzyme at low cytosolic pH values and enters into the cell and causes infection. Especially in the presence of diabetes mellitus and accompanying comorbid conditions such as hypertension, obesity, old age, and smoking, cytosolic pH is low, thus the virus easily may enter the cell by attaching to ACE2. ACEIs and ARBs lead to a reduction in angiotensin II level by increasing the ACE2 level, thus they cause a low cytosolic pH. Increased cardiac ACE2 levels due to ACEIs and ARBs can trigger cardiac arrhythmias and myocarditis by causing the virus to easily enter the heart tissue. There is ACE2 activity in the rostral ventrolateral medulla in the brain stem. The release of angiotensin 1-7 in the brain stem leads to the activation of the sympathetic nervous system. This activation causes systemic vasoconstriction and the patient’s blood pressure increases. The most important event is the increased sympathetic activity via the central stimulation, this activity increases pulmonary capillary leaking, causing the ARDS. As the cytosolic pH, which is already low in patients with diabetes will decrease further with the mechanisms mentioned above, the viral load will increase and the infection will be exacerbated. As a result, the use of ACEIs and ARBs in patients with diabetes can lead to increased morbidity and mortality of COVID-19.

negative: The role of age distribution, time lag between reporting and death and healthcare system capacity on case fatality estimates of COVID-19 European countries report large differences in coronavirus disease (COVID-19) case fatality risk (CFR). CFR estimates depend on demographic characteristics of the cases, time lags between reporting of infections and deaths and infrastructural characteristics, such as healthcare and surveillance capacities. We discuss the impact of these factors on the CFR estimates for Germany, Italy, France, and Spain for the COVID-19 pandemic from early March to mid-April, 2020. We found that, first, a large proportion of the difference in CFRs can be attributed to different age structures of the cases. Second, lags of 5-10 days between day of case report and death should be used, since these provide the most constant estimates. Third, for France, Italy, and Spain, intensive care beds occupied by COVID-19 patients were positively associated with fatality risks of hospitalized cases. Our results highlight that cross-country comparisons of crude CFR estimates can be misleading and should be avoided.

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

negative: Severe leukopenia in Staphylococcus aureus-necrotizing, community-acquired pneumonia: risk factors and impact on survival BACKGROUND: Necrotizing pneumonia attributed to Panton-Valentine leukocidin-positive Staphylococcus aureus has mainly been reported in otherwise healthy children and young adults, with a high mortality rate. Erythroderma, airway bleeding, and leukopenia have been shown to be predictive of mortality. The objectives of this study were to define the characteristics of patients with severe leukopenia at 48-h hospitalization and to update our data regarding mortality predicting factors in a larger population than we had previously described. METHODS: It was designed as a case-case study nested in a cohort study. A total of 148 cases of community-acquired, necrotizing pneumonia were included. The following data were collected: basic demographic information, medical history, signs and symptoms, radiological findings and laboratory results during the first 48 h of hospitalization. The study population was divided into 2 groups: (1) with severe leukopenia (leukocyte count ≤3,000 leukocytes/mL, n=62) and (2) without severe leukopenia (>3,000 leukocytes/mL, n=86). RESULTS: Median age was 22 years, and the male-to-female gender ratio was 1.5. The overall in-hospital mortality rate was 41.2%. Death occurred in 75.8% of severe leukopenia cases with median survival time of 4 days, and in 16.3% of cases with leukocyte count >3,000/mL (P<0.001). Multivariate analysis indicated that the factors associated with severe leukopenia were influenza-like illness (adjusted odds ratio (aOR) 4.45, 95% CI (95% confidence interval) 1.67-11.88, P=0.003), airway bleeding (aOR 4.53, 95% CI 1.85-11.13, P=0.001) and age over 30 years (aOR 2.69, 95% CI 1.08-6.68, P=0.033). A personal history of furuncles appeared to be protective (OR 0.11, 95% CI 0.01-0.96, P=0.046). CONCLUSION: S. aureus-necrotizing pneumonia is still an extremely severe disease in patients with severe leukopenia. Some factors could distinguish these patients, allowing better initial identification to initiate adapted, rapid administration of appropriate therapy.

negative: Mortality among dentists in Taiwan, 1985–2009 Background/Purpose Controversy exists in the literature regarding whether dentists with multiple occupational exposures suffer from premature mortality. A cohort mortality study was conducted to evaluate the survival outcome and determine if potential exposure to harmful agents leads to premature mortality among dentists. Methods Using the Life Table Analysis System, we calculated standardized mortality ratios (SMRs) for a cohort of 11,700 dentists affiliated with the Taiwan Dental Association. These dentists were followed from 1985–2009. Reference rates were derived from cause-, gender-, and age-specific mortality rates of the general population of Taiwan and 18,664 Taiwanese internists, who were considered to be more socioeconomically proximal to dentists. A Cox proportional hazard model was also constructed to determine multiple risk factors associated with mortality. Results Compared with the general population, dentists in Taiwan consistently demonstrated reduced from all-cause mortality. However, compared with internists, significant and excess mortality were observed in dentists for overall mortality (SMR=1.13; 95% confidence interval [CI]=1.00–1.26), drowning (SMR=6.62; 95% CI=2.15–15.45), and heart diseases (SMR=1.66; 95% CI=1.22–2.21). After adjusting for other risk factors, the Cox model showed an increased hazard ratio of 1.17 (95% CI=1.01–1.37) for dentists. Conclusion Taiwanese dentists demonstrated significant elevated SMRs for overall causes, drowning, and heart diseases. Careful precaution should be taken to reduce these trends. Future studies are also needed for in-depth exploration of the mechanisms regarding how professional stress and exposure contribute to the increased risk of mortality in Taiwanese dentists.

negative: Applying the balanced scorecard to local public health performance measurement: deliberations and decisions BACKGROUND: All aspects of the heath care sector are being asked to account for their performance. This poses unique challenges for local public health units with their traditional focus on population health and their emphasis on disease prevention, health promotion and protection. Reliance on measures of health status provides an imprecise and partial picture of the performance of a health unit. In 2004 the provincial Institute for Clinical Evaluative Sciences based in Ontario, Canada introduced a public-health specific balanced scorecard framework. We present the conceptual deliberations and decisions undertaken by a health unit while adopting the framework. DISCUSSION: Posing, pondering and answering key questions assisted in applying the framework and developing indicators. Questions such as: Who should be involved in developing performance indicators? What level of performance should be measured? Who is the primary intended audience? Where and how do we begin? What types of indicators should populate the health status and determinants quadrant? What types of indicators should populate the resources and services quadrant? What type of indicators should populate the community engagement quadrant? What types of indicators should populate the integration and responsiveness quadrants? Should we try to link the quadrants? What comparators do we use? How do we move from a baseline report card to a continuous quality improvement management tool? SUMMARY: An inclusive, participatory process was chosen for defining and creating indicators to populate the four quadrants. Examples of indicators that populate the four quadrants of the scorecard are presented and key decisions are highlighted that facilitated the process.

negative: Midwives in a pandemic: A call for solidarity and compassion

negative: Coronavirus outbreak in cheetahs: Lessons for SARS

negative: 1.22 Bioethical Issues in Medicinal Chemistry and Drug Treatment The use of drugs to treat human disease is a pursuit that extends back into our evolutionary ancestors. Drugs are powerful substances with a great capacity to cause harm if misused or overused. Even when used correctly, pharmaceuticals can elicit disputes about their relative harms and benefits in specific situations. The establishment of modern intermediaries – physicians or pharmacists – in the allocation of the most powerful drugs increases the potential for conflict between those who control the resource and those who desire access to it. The size and influence of the pharmaceutical–industrial complex places disproportionate power in those whose interests lie in promoting and expanding pharmaceutical use in society. The expense of certain drugs complicates equitable allocation, and the concentration of pharmaceutical power in Western, industrialized countries promotes research and drug discovery disproportionately for diseases that are prevalent in the wealthier nations. The increasing sophistication of drug action challenges the traditional model of using drugs as a means to treat pathological conditions and processes, and raises the specter of lifestyle and enhancement uses of pharmaceuticals. New means of drug discovery – such as the use of stem cells – have elicited debate about the relative values placed on the status of the embryo and the potential treatment for intractable conditions that could result from stem cell research. Finally, the overall emphasis on drugs as the first line defense against what ails us has provoked some societal soul-searching. In this chapter, we review some of the ethical issues attendant to drug production and distribution, including issues of safety, justice, economic inequality, and the changing demands for drugs that exceed therapeutic uses. Suggestions are made to make pharmaceutical companies more responsive to these issues and to make oversight bodies more responsible for their roles.

negative: The COVID-19 pandemic: implications for the cytology laboratory The coronavirus disease 2019 (COVID-19) is a pandemic caused by the SARS-CoV-2 virus. The infection has predominantly respiratory transmission and is transmitted through large droplets or aerosols, and less commonly by contact with infected surfaces or fomites. The alarming spread of the infection and the severe clinical disease that it may cause have led to the widespread institution of social distancing measures. Because of repeated exposure to potentially infectious patients and specimens, health care and laboratory personnel are particularly susceptible to contract COVID-19. This review paper provides an assessment of the current state of knowledge about the disease and its pathology, and the potential presence of the virus in cytology specimens. It also discusses the measures that cytology laboratories can take to function during the pandemic, and minimize the risk to their personnel, trainees, and pathologists. In addition, it explores potential means to continue to educate trainees during the COVID-19 pandemic.

negative: War, Refugees, Migration, and Public Health: Do Infectious Diseases Matter?

negative: Open Data Resources for Fighting COVID-19 We provide an insight into the open data resources pertinent to the study of the spread of Covid-19 pandemic and its control. We identify the variables required to analyze fundamental aspects like seasonal behaviour, regional mortality rates, and effectiveness of government measures. Open data resources, along with data-driven methodologies, provide many opportunities to improve the response of the different administrations to the virus. We describe the present limitations and difficulties encountered in most of the open-data resources. To facilitate the access to the main open-data portals and resources, we identify the most relevant institutions, at a world scale, providing Covid-19 information and/or auxiliary variables (demographics, mobility, etc.). We also describe several open resources to access Covid-19 data-sets at a country-wide level (i.e. China, Italy, Spain, France, Germany, U.S., etc.). In an attempt to facilitate the rapid response to the study of the seasonal behaviour of Covid-19, we enumerate the main open resources in terms of weather and climate variables. CONCO-Team: The authors of this paper belong to the CONtrol COvid-19 Team, which is composed of different researches from universities of Spain, Italy, France, Germany, United Kingdom and Argentina. The main goal of CONCO-Team is to develop data-driven methods for the better understanding and control of the pandemic.

negative: Hyperoxia: At what level of SpO2 is a patient safe? A study in mechanically ventilated ICU patients. BACKGROUND Concerns have been expressed regarding a possible association between arterial hyperoxia and adverse outcomes in critically ill patients. Oxygen status is commonly monitored noninvasively by peripheral saturation monitoring (SpO2). However, the risk of hyperoxia above specific SpO2 levels in critically ill patients is unknown. The purpose of this study was to determine a threshold value of SpO2 above which the prevalence of arterial hyperoxia distinctly increases. METHODS This is a cross-sectional study in adult mechanically ventilated intensive care patients in a tertiary referral center. In 100 patients, we collected 200 arterial blood gases (ABG) and simultaneously registered SpO2 levels, as well as hemodynamic and ventilation parameters and vasoactive medication. Patients under therapeutic hypothermia were excluded. RESULTS The risk of arterial hyperoxia, defined as PaO2>100mmHg or >125mmHg, was negligible when SpO2 was ≤95% or ≤96%, respectively. The majority (89% and 54%, respectively for PaO2>100mmHg and 125mmHg) of ICU patients with SpO2 of 100% had arterial hyperoxia. The relation between SpO2 and PaO2 was not clearly affected by hemodynamic or other clinical variables (pH, pCO2, body temperature, recent blood transfusion). CONCLUSION In critically ill patients, the prevalence of arterial hyperoxia increases when SpO2 is >95%. Above this saturation level, supplemental oxygen should be administered with caution in patients potentially susceptible to adverse effects of hyperoxia.

negative: Down Syndrome and COVID-19: A Perfect Storm? People with Down syndrome show signs of chronic immune dysregulation, including a higher prevalence of autoimmune disorders, increased rates of hospitalization during respiratory viral infections, and higher mortality rates from pneumonia and sepsis. At the molecular and cellular levels, they show markers of chronic autoinflammation, including interferon hyperactivity, elevated levels of many inflammatory cytokines and chemokines, and changes in diverse immune cell types reminiscent of inflammatory conditions observed in the general population. However, the impact of this immune dysregulation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and CoV disease of 2019 (COVID-19) remains unknown. This Perspective outlines why individuals with Down syndrome should be considered an at-risk population for severe COVID-19. Specifically, the immune dysregulation caused by trisomy 21 may result in an exacerbated cytokine release syndrome relative to that observed in the euploid population, thus justifying additional monitoring and specialized care for this vulnerable population.

negative: International Society for Disease Surveillance Conference 2011: Building the Future of Public Health Surveillance: Building the Future of Public Health Surveillance

negative: The value of mitigating epidemic peaks of COVID-19 for more effective public health responses

negative: Respiratory Infections, Acute Abstract Acute respiratory tract infections are an extremely common and important source of morbidity and mortality. Despite advances in our understanding of microbial pathogens and the development of novel antimicrobial agents, acute respiratory tract infections continue to place an enormous burden on global health expenditure. Acute respiratory tract infections can be divided into infections that predominantly affect the upper respiratory tract above the vocal cords and those that affect the lower respiratory tract. The clinical features, causative pathogens, and therapies of common acute respiratory tract infections are detailed in this article.

negative: Critical Care during the Coronavirus Crisis – challenges and considerations for the cardiothoracic and vascular anesthesia community

negative: A Promising Anti-Cytokine-Storm Targeted Therapy for COVID-19: The Artificial-Liver Blood-Purification System

negative: Cancer and COVID-19: what do we really know?

negative: Newborn calf welfare: A review focusing on mortality rates Calf mortality control is vitally important for farmers, not only to improve animal welfare, but also to increase productivity. High calf mortality rates can be related to larger numbers of calves in a herd, employee performance, severe weather, and the neonatal period covering the first 4 weeks of life. Although the basic premise of preventing newborn calf mortality is early detection and treatment of calves at risk for failure of passive transfer of immunoglobulins, calf mortality due to infectious diseases such as acute diarrhea increases in the presence of these physical and psychological stressors. This suggests that farmers should not ignore the effects of secondary environmental factors. For prevention rather than cure, the quality of the environment should be improved, which will improve not only animal welfare but also productivity. This paper presents a review of the literature on newborn calf mortality and discusses its productivity implications.

negative: Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host–Virus Interaction, and Proposed Neurotropic Mechanisms [Image: see text] The recent outbreak of coronavirus infectious disease 2019 (COVID-19) has gripped the world with apprehension and has evoked a scare of epic proportion regarding its potential to spread and infect humans worldwide. As we are in the midst of an ongoing pandemic of COVID-19, scientists are struggling to understand how it resembles and differs from the severe acute respiratory syndrome coronavirus (SARS-CoV) at the genomic and transcriptomic level. In a short time following the outbreak, it has been shown that, similar to SARS-CoV, COVID-19 virus exploits the angiotensin-converting enzyme 2 (ACE2) receptor to gain entry inside the cells. This finding raises the curiosity of investigating the expression of ACE2 in neurological tissue and determining the possible contribution of neurological tissue damage to the morbidity and mortality caused by COIVD-19. Here, we investigate the density of the expression levels of ACE2 in the CNS, the host–virus interaction and relate it to the pathogenesis and complications seen in the recent cases resulting from the COVID-19 outbreak. Also, we debate the need for a model for staging COVID-19 based on neurological tissue involvement.

negative: Climate effect on COVID-19 spread rate: an online surveillance tool Background: COVID-19 outbreak poses an unprecedented challenge for societies, healthcare organizations and economies. In the present analysis we coupled climate data with COVID-19 spread rates worldwide, and in a single country (USA). Methods: Data of confirmed COVID-19 cases was derived from the COVID-19 Global Cases by the CSSE at Johns Hopkins University up to March 19, 2020. We assessed disease spread by two measures: replication rate (RR), the slope of the logarithmic curve of confirmed cases, and the rate of spread (RoS), the slope of the linear regression of the logarithmic curve. Results: Based on predefined criteria, the mean COVID-19 RR was significantly lower in warm climate countries (0.12± 0.02) compared with cold countries (0.24± 0.01), (P<0.0001). Similarly, RoS was significantly lower in warm climate countries 0.12± 0.02 vs. 0.25± 0.01 than in cold climate countries (P<0.001). In all countries (independent of climate classification) both RR and RoS displayed a moderate negative correlation with temperature R= -0.69, 95% confidence interval [CI], -0.87 to -0.36; P<0.001 and R= -0.72, 95% confidence interval [CI], -0.87 to -0.36; P<0.001, respectively. We identified a similar moderate negative correlation with the dew point temperature. Additional climate variables did not display a significant correlation with neither RR nor RoS. Finally, in an ancillary analysis, COVID-19 intra-country model using an inter-state analysis of the USA did not identify yet correlation between climate parameters and RR or RoS as of March, 19, 2020. Conclusions: Our analysis suggests a plausible negative correlation between warmer climate and COVID-19 spread rate as defined by RR and RoS worldwide. This initial correlation should be interpreted cautiously and be further validated over time, the pandemic is at different stages in various countries as well as in regions within these countries. As such, some associations may be more affected by local transmission patterns rather than by climate. Importantly, we provide an online surveillance dashboard (https://covid19.net.technion.ac.il/) to further assess the association between climate parameters and outbreak dynamics worldwide as time goes by

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: Role of Antidiarrhoeal Drugs as Adjunctive Therapies for Acute Diarrhoea in Children Acute diarrhoea is a leading cause of child mortality in developing countries. Principal pathogens include Escherichia coli, rotaviruses, and noroviruses. 90% of diarrhoeal deaths are attributable to inadequate sanitation. Acute diarrhoea is the second leading cause of overall childhood mortality and accounts for 18% of deaths among children under five. In 2004 an estimated 1.5 million children died from diarrhoea, with 80% of deaths occurring before the age of two. Treatment goals are to prevent dehydration and nutritional damage and to reduce duration and severity of diarrhoeal episodes. The recommended therapeutic regimen is to provide oral rehydration solutions (ORS) and to continue feeding. Although ORS effectively mitigates dehydration, it has no effect on the duration, severity, or frequency of diarrhoeal episodes. Adjuvant therapy with micronutrients, probiotics, or antidiarrhoeal agents may thus be useful. The WHO recommends the use of zinc tablets in association with ORS. The ESPGHAN/ESPID treatment guidelines consider the use of racecadotril, diosmectite, or probiotics as possible adjunctive therapy to ORS. Only racecadotril and diosmectite reduce stool output, but no treatment has yet been shown to reduce hospitalisation rate or mortality. Appropriate management with validated treatments may help reduce the health and economic burden of acute diarrhoea in children worldwide.

negative: Comparison of different exit scenarios from the lock-down for COVID-19 epidemic in the UK and assessing uncertainty of the predictions We model further development of the COVID-19 epidemic in the UK given the current data and assuming different scenarios of handling the epidemic. In this research, we further extend the stochastic model suggested in [1] and incorporate in it all available to us knowledge about parameters characterising the behaviour of the virus and the illness induced by it. The models we use are flexible, comprehensive, fast to run and allow us to incorporate the following: - time-dependent strategies of handling the epidemic; - spatial heterogeneity of the population and heterogeneity of development of epidemic in different areas; - special characteristics of particular groups of people, especially people with specific medical pre-histories and elderly. Standard epidemiological models such as SIR and many of its modifications are not flexible enough and hence are not precise enough in the studies that requires the use of the features above. Decision-makers get serious benefits from using better and more flexible models as they can avoid of nuanced lock-downs, better plan the exit strategy based on local population data, different stages of the epidemic in different areas, making specific recommendations to specific groups of people; all this resulting in a lesser impact on economy, improved forecasts of regional demand upon NHS allowing for intelligent resource allocation.

negative: Infection control and biosecurity in equine disease control Infectious diseases are an important cause of morbidity and mortality in horses, along with economic costs and broader impacts associated with the loss of members of a species that generates income, acts as a working animal and is a companion. Endemic diseases continue to challenge, emerging diseases are an ever‐present threat and outbreaks can be both destructive and disruptive. While infectious diseases can never be completely prevented, measures can be introduced to restrict the entry of pathogens into a population or limit the implications of the presence of a pathogen. Objective research regarding infection control and biosecurity in horses is limited, yet a variety of practical infection prevention and control measures can be used. Unfortunately, infection control can be challenging, because of the nature of the equine industry (e.g. frequent horse movement) and endemic pathogens, but also because of lack of understanding or motivation to try to improve practices. Recognition of the basic concepts of infection control and biosecurity, and indeed the need for measures to control infectious diseases, is the foundation for successful infection prevention and control.

negative: Gendered effects on inflammation reaction and outcome of COVID‐19 patients in Wuhan BACKGROUND: The rapid outbreak of coronavirus disease 2019 (COVID‐19) has turned into a public health emergency of international concern. Epidemiological research showed that gender was associated with the severity of COVID‐19, but the underlying mechanism of gender predisposition remains poorly understood. We aim to study the gendered differences in inflammation reaction, and the association with severity and mortality of COVID‐19. METHODS: In this retrospective study, we enrolled 548 COVID‐19 inpatients from Tongji Hospital from January 26 to February 5, 2020, and followed up to March 3, 2020. Epidemiological, demographic and clinical features, and inflammatory indexes were collected and compared between males and females. Cox proportional hazard regression model was applied to identify gendered effect on mortality of COVID‐19 after adjusting age, comorbidity and smoking history. Multiple linear regression method was used to explore the influence of sex on inflammation reaction. RESULTS: Males had higher mortality than females did (22.2% vs. 10.4%), with the HR of 1.923 (95% CI, 1.181‐3.130); elder age and comorbidity were significantly associated with decease of COVID‐19 patients. Excess inflammation reaction was related to severity of COVID‐19. Male patients had greater inflammation reaction, with higher levels of IL‐10, TNF‐α, LDH, ferritin and hsCRP, but lower lymphocyte count than females adjusted by age and comorbidity. CONCLUSIONS: Gender, age, and comorbidity are critical risk factors for mortality of COVID‐19. Excess innate immunity and proinflammation activity, and deficiency in adaptive immunity response promote males especially elder males to develop cytokine storm, causing potential ARDS, multiple organ failure and decease. This article is protected by copyright. All rights reserved.

negative: Air Pollution Reduction and Mortality Benefit during the COVID-19 Outbreak in China To control the novel coronavirus disease (COVID-19) outbreak, China undertook stringent traffic restrictions and self-quarantine measures. We herein examine the change in air pollution levels and the potentially avoided cause-specific mortality during this massive population quarantine episode. We found that, due to the quarantine, NO2 dropped by 22.8 μg/m3 and 12.9 μg/m3 in Wuhan and China, respectively. PM2.5 dropped by 1.4 μg/m3 in Wuhan but decreased by 18.9 μg/m3 across 367 cities. Our findings show that interventions to contain the COVID-19 outbreak led to air quality improvements that brought health benefits which outnumbered the confirmed deaths due to COVID-19 in China

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: 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: Decontamination of Bacillus subtilis var. niger spores on selected surfaces by chlorine dioxide gas. OBJECTIVE Chlorine dioxide (CD) gas has been used as a fumigant in the disinfection of biosafety laboratories. In this study, some experiments were conducted to assess the inactivation of spores inoculated on six materials [stainless steel (SS), painted steel (PS), polyvinyl chlorid (PVC), polyurethane (PU), glass (GS), and cotton cloth (CC)] by CD gas. The main aims of the study were to determine the sporicidal efficacy of CD gas and the effect of prehumidification before decontamination on sporicidal efficacy. METHODS Material coupons (1.2 cm diameter of SS, PS, and PU; 1.0 cm×1.0 cm for PVC, GS, and CC) were contaminated with 10 μl of Bacillus subtilis var. niger (ATCC 9372) spore suspension in mixed organic burden and then dried in a biosafety cabinet for 12 h. The spores were recovered by soaking the coupons in 5 ml of extraction liquid for 1 h and then vortexing the liquid for 1 min. RESULTS The log reductions in spore numbers on inoculated test materials exposed to CD gas [0.080% (volume ratio, v/v) for 3 h] were in the range of from 1.80 to 6.64. Statistically significant differences were found in decontamination efficacies on test material coupons of SS, PS, PU, and CC between with and without a 1-h prehumidification treatment. With the extraction method, there were no statistically significant differences in the recovery ratios between the porous and non-porous materials. CONCLUSIONS The results reported from this study could provide information for developing decontamination technology based on CD gas for targeting surface microbial contamination.

negative: Pneumonia Incidence and Mortality in Mainland China: Systematic Review of Chinese and English Literature, 1985–2008 BACKGROUND: Pneumonia is a leading infectious disease killer worldwide, yet the burden in China is not well understood as much of the data is published in the non-English literature. METHODOLOGY/PRINCIPAL FINDINGS: We systematically reviewed the Chinese- and English-language literature for studies with primary data on pneumonia incidence and mortality in mainland China. Between 1985 and 2008, 37 studies met the inclusion criteria. The quality of the studies was highly variable. For children <5 years, incidence ranged from 0.06–0.27 episodes per person-year and mortality ranged from 184–1,223 deaths per 100,000 population. Overall incidence and mortality were stable or decreased over the study period and were higher in rural compared to urban areas. CONCLUSIONS/SIGNIFICANCE: Pneumonia continues to be a major public health challenge in young children in China, and estimates of pneumonia incidence and mortality vary widely. Reliable surveillance data and new prevention efforts may be needed to achieve and document additional declines, especially in areas with higher incidence and mortality such as rural settings.

negative: Travel health risk perceptions of Chinese international students in Australia – Implications for COVID-19 Abstract Background International students frequently return to their country of origin to visit friends and relatives (VFR), and are at increased risk of travel-associated infections. Little is known of their travel health seeking behaviours. China is the biggest source of international students studying in Australia and the unprecedented epidemic of COVID-19 in China makes this an important area of research. Methods Focus groups of Chinese international students were conducted to explore travel health-related knowledge, attitudes and practices. Eligible participants were studying in Sydney, and had travelled to China and Hong Kong to visit friends and relatives in the preceding 18 months. A variety of topics were explored, using a focus group guide. Thematic analysis was undertaken on the transcripts using nVivo software. The list of codes and themes were not pre-determined but developed through content analysis. Results Two focus groups were held with a total of 28 participants. Risk perception about VFR travel was generally low among Chinese international students. Pre-travel healthcare was not sought. Students strongly relied on the Internet, social media, parents and friends in China for travel health advice. Conclusion This research provides insights into Chinese international students as VFR travellers. It confirms students could be a risk population for importations of infections such as COVID-19 because of low risk perception and lack of seeking travel health advice. This can inform health promotion strategies for students.

negative: A study of non-prescription usage of antibiotics in the upper respiratory tract infections in the urban population

negative: Angiotensin II Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors Usage is Associated with Improved Inflammatory Status and Clinical Outcomes in COVID-19 Patients With Hypertension With the capability of inducing elevated expression of ACE2, the cellular receptor for SARS-CoV-2, angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors (ARBs/ACEIs) treatment may have a controversial role in both facilitating virus infection and reducing pathogenic inflammation. We aimed to evaluate the correlation of ARBs/ACEIs usage with the pathogenesis of COVID-19 in a retrospective, single-center study. 126 COVID-19 patients with preexisting hypertension at Hubei Provincial Hospital of Traditional Chinese Medicine (HPHTCM) in Wuhan from January 5 to February 22, 2020 were retrospectively allocated to ARBs/ACEIs group (n=43) and non-ARBs/ACEIs group (n=83) according to their antihypertensive medication. 125 age- and sex-matched COVID-19 patients without hypertension were randomly selected as non-hypertension controls. In addition, the medication history of 1942 hypertension patients that were admitted to HPHTCM from November 1 to December 31, 2019 before COVID-19 outbreak were also reviewed for external comparison. Epidemiological, demographic, clinical and laboratory data were collected, analyzed and compared between these groups. The frequency of ARBs/ACEIs usage in hypertension patients with or without COVID-19 were comparable. Among COVID-19 patients with hypertension, those received either ARBs/ACEIs or non-ARBs/ACEIs had comparable blood pressure. However, ARBs/ACEIs group had significantly lower concentrations of CRP (p=0.049) and procalcitonin (PCT, p=0.008). Furthermore, much lower proportion of critical patients (9.3% vs 22.9%; p=0.061), and a lower death rate (4.7% vs 13.3%; p=0.216) were observed in ARBs/ACEIs group than non-ARBs/ACEIs group, although these differences failed to reach statistical significance. Our findings thus support the use of ARBs/ACEIs in COVID-19 patients with preexisting hypertension.

negative: COVID-19 target: A specific target for novel coronavirus detection An ongoing outbreak of pneumonia associated with a novel coronavirus has been reported worldwide and become a global health problem; hence, the diagnosis and differentiation of this virus from other types of coronavirus is essential to control of the disease. To this end, the analysis of genomics data plays a vital role in introducing a stronger target and consequently provides better results in laboratory examinations. The modified comparative genomics approach helps us to find novel specific targets by comparing two or more sequences on the nucleotide collection database. We, for the first time, detected ORF8 gene as a potential target for the detection of the novel coronavirus. Unlike previous reported genes (RdRP, E and N genes), ORF8 is entirely specific to the novel coronavirus (COVID-19) and has no cross-reactivity with other kinds of coronavirus. Accordingly, ORF8 gene can be used as an additional confirmatory assay.

negative: Impact of international travel dynamics on domestic spread of 2019-nCoV in India: origin-based risk assessment in importation of infected travelers The recent pandemic caused by the 2019 outbreak of novel coronavirus (2019-nCoV or COVID-19) has affected more than 3.0 million people resulting ~ 212,000 deaths across 215 countries/territories as on 28th April 2020. The importation of the cases owing to enormous international travels from the affected countries is the foremost reason for local cycle of transmission. For a country like India, the second most populous country in the world with ~ 1.35 billion population, the management and control of 2019-nCoV domestic spread heavily relied on effective screening and strict quarantine of passengers arriving at various international airports in India from affected countries. Here, by extracting the data from FLIRT, an online airline database for more than 800 airlines, and scanning more than 180,000 flights and 39.9 million corresponding passenger seats during 4th – 25th March, we show that India experienced the highest risk index of importing the passengers from middle eastern airports. Contrary to perception, travelers from China imposed lowest risk of importing the infected cases in India. This is clearly evident form the fact that while the number of infected cases were on the peak in China India was one of the least affected countries. The number of cases in India started exhibiting a sharp increase in the infected cases only after the European countries and USA recorded large number of infected cases. We further argue that while the number of cases in middle eastern countries may still be very low, the airports in middle eastern countries, particularly Dubai, being one of the largest transit hubs for international passengers, including arriving in India, might have posed a higher risk of getting infected with 2019-nCoV. We suggest that any future travel related disease infection screening at the airports should critically assess the passengers from major transit hubs in addition to affected country of origin.

negative: Insectivorous bats carry host specific astroviruses and coronaviruses across different regions in Germany Abstract Recently several infectious agents with a zoonotic potential have been detected in different bat species. However, there is still a lack of knowledge on the transmission dynamics within and between bat species, as well as from bats to other mammals. To better understand these processes, it is important to compare the phylogenetic relationships between different agents to that of their respective hosts. In this study, we analysed more than 950 urine, faeces and oral swab samples collected from 653 bats from mainly four species (Myotis nattereri, Myotis bechsteinii, Myotis daubentonii, and Plecotus auritus) for the presence of coronavirus, paramyxovirus and astrovirus related nucleic acids located in three different regions of Germany. Using hemi-nested reverse transcriptase (RT)-PCR amplification of fragments within the highly conserved regions of the respective RNA dependent RNA polymerase (RdRp) genes, we detected astrovirus sequences at an overall detection rate of 25.8% of the analysed animals, with a maximum of 65% in local populations. The detection rates for coronaviruses and paramyxoviruses were distinctly lower, ranging between 1.4% and 3.1%. Interestingly, the sequence similarities in samples collected from the same bat species in different geographical areas were distinctly larger than the sequence similarities between samples from different species sampled at the same location. This indicates that host specificity may be more important than host ecology for the presence of certain viruses in bats.

negative: Burden of lower respiratory infections in the Eastern Mediterranean Region between 1990 and 2015: findings from the Global Burden of Disease 2015 study OBJECTIVES: We used data from the Global Burden of Disease 2015 study (GBD) to calculate the burden of lower respiratory infections (LRIs) in the 22 countries of the Eastern Mediterranean Region (EMR) from 1990 to 2015. METHODS: We conducted a systematic analysis of mortality and morbidity data for LRI and its specific etiologic factors, including pneumococcus, Haemophilus influenzae type b, Respiratory syncytial virus, and influenza virus. We used modeling methods to estimate incidence, deaths, and disability-adjusted life-years (DALYs). We calculated burden attributable to known risk factors for LRI. RESULTS: In 2015, LRIs were the fourth-leading cause of DALYs, causing 11,098,243 (95% UI 9,857,095–12,396,566) DALYs and 191,114 (95% UI 170,934–210,705) deaths. The LRI DALY rates were higher than global estimates in 2015. The highest and lowest age-standardized rates of DALYs were observed in Somalia and Lebanon, respectively. Undernutrition in childhood and ambient particulate matter air pollution in the elderly were the main risk factors. CONCLUSIONS: Our findings call for public health strategies to reduce the level of risk factors in each age group, especially vulnerable child and elderly populations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00038-017-1007-0) contains supplementary material, which is available to authorized users.

negative: Access to Care for Dementia patients suffering from COVID-19

negative: Human parainfluenza virus type 4 infection in Chinese children with lower respiratory tract infections: A comparison study Abstract Background Human parainfluenza viruses (HPIVs) are a leading cause of acute respiratory tract infections (ARTIs). Although HPIV-4 has been associated with mild ARTIs for years, recent investigations have also associated HPIV-4 infection with severe respiratory syndromes and with outbreaks of ARTIs in children. Objectives To characterize the role of HPIV-4 and its clinical features in children with acute lower respiratory tract infections (ALRTIs) in Beijing, China. Study design Nasopharyngeal aspirates were collected from 2009 hospitalized children with ALRTIs between March 2007 and April 2010. RT-PCR and PCR analyses were used to identify HPIV types and other known respiratory viruses. Results HPIVs were detected in 246 (12.2%) patients, of whom 25 (10.2%) were positive for HPIV-4, 11 (4.5%) for HPIV-2, 51 (20.7%) for HPIV-1, 151 (61.4%) for HPIV-3, and 8 (3.3%) were co-detected with different types of HPIVs. Like HPIV-3, HPIV-4 was detected in spring, summer, and late fall over the study period. Seasonal incidence varied for HPIV-1 and -2. The median patient age was 20 months for HPIV-4 infections and 7–11 months for HPIV-1, -2, and -3 infections, but the clinical manifestations did not differ significantly between HPIV-1, -2, -3, and -4 infections. Moreover, co-detection of HPIV-4 (44%) with other respiratory viruses was lower than that of HPIV-1 (62.7%), HPIV-2 (63.6%), and HPIV-3 (72.7%). Conclusions HPIV-4 plays an important role in Chinese paediatric ALRTIs. The epidemiological and clinical characteristics reported here improve our understanding of the pathogenesis associated with HPIV-4.

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: Evidence-Based Medicine in the Intensive Care Unit

negative: Serology characteristics of SARS-CoV-2 infection since the exposure and post symptoms onset Background Timely diagnosis of SARS-CoV-2 infection is the prerequisite for treatment and preventive quarantine. The serology characteristics and complement diagnosis value of antibody test to RNA test needs to be demonstrated. Method A patient cohort study was conducted at the first affiliated hospital of Zhejiang University, China. Serial sera of COVID-19 patients were collected and total antibody (Ab), IgM and IgG antibody against SARS-CoV-2 were detected. The antibody dynamics during the infection were described. Results The seroconversion rate for Ab, IgM and IgG in COVID-19 patients was 98.8% (79/80), 93.8% (75/80) and 93.8% (75/80), respectively. The first detectible serology marker is total antibody and followed by IgM and IgG, with a median seroconversion time of 15, 18 and 20 day post exposure (d.p.e) or 9, 10 and 12 days post onset, separately. The antibody levels increased rapidly since 6 d.p.o and accompanied with the decline of viral load. For patients in the early stage of illness (0-7d.p.o),Ab showed the highest sensitivity (64.1%) compared to the IgM and IgG (33.3% for both, p<0.001). The sensitivities of Ab, IgM and IgG detection increased to 100%, 96.7% and 93.3% two weeks later, respectively. Conclusions Typical acute antibody response is induced during the SARS-CoV-2 infection. The serology testing provides important complementation to RNA test for pathogenic specific diagnosis and helpful information to evaluate the adapted immunity status of patient. It should be strongly recommended to apply well-validated antibody tests in the clinical management and public health practice to improve the control of COVID-19 infection.

negative: Projecting the Spread of COVID19 for Germany We model the evolution of the number of individuals that are reported to be sick with COVID-19 in Germany. Our theoretical framework builds on a continuous time Markov chain with four states: healthy without infection, sick, healthy after recovery or after infection but without symptoms and dead. Our quantitative solution matches the number of sick individuals up to the most recent observation and ends with a share of sick individuals following from infection rates and sickness probabilities. We employ this framework to study inter alia the expected peak of the number of sick individuals in a scenario without public regulation of social contacts. We also study the effects of public regulations. For all scenarios we report the expected end of the CoV-2 epidemic. We have four general findings: First, current epidemiological thinking implies that the long-run effects of the epidemic only depend on the aggregate long-run infection rate and on the individual risk to turn sick after an infection. Any measures by individuals and the public therefore only influence the dynamics of spread of CoV-2. Second, predictions about the duration and level of the epidemic must strongly distinguish between the officially reported numbers (Robert Koch Institut, RKI) and actual numbers of sick individuals. Third, given the current (scarce) medical knowledge about long-run infection rate and individual risks to turn sick, any prediction on the length (duration in months) and strength (e.g. maximum numbers of sick individuals on a given day) is subject to a lot of uncertainty. Our predictions therefore offer robustness analyses that provide ranges on how long the epidemic will last and how strong it will be. Fourth, public interventions that are already in place and that are being discussed can lead to more and less severe outcomes of the epidemic. If an intervention takes place too early, the epidemic can actually be stronger than with an intervention that starts later. Interventions should therefore be contingent on current infection rates in regions or countries. Concerning predictions about COVID-19 in Germany, we find that the long-run number of sick individuals (that are reported to the RKI), once the epidemic is over, will lie between 500 thousand and 5 million individuals. While this seems to be an absurdly large range for a precise projection, this reflects the uncertainty about the long-run infection rate in Germany. If we assume that Germany will follow the good scenario of Hubei (and we are even a bit more conservative given discussions about data quality), we will end up with 500 thousand sick individuals over the entire epidemic. If by contrast we believe (as many argue) that once the epidemic is over 70% of the population will have been infected (and thereby immune), we will end up at 5 million cases. Defining the end of the epidemic by less than 100 newly reported sick individuals per day, we find a large variation depending on the effectiveness of governmental pleas and regulations to reduce social contacts. An epidemic that is not influenced by public health measures would end mid June 2020. With public health measures lasting for few weeks, the end is delayed by around one month or two. The advantage of the delay, however, is to reduce the peak number of individuals that are simultaneously sick. When we believe in long-run infection rates of 70%, this number is equally high for all scenarios we went through and well above 1 million. When we can hope for the Hubei-scenario, the maximum number of sick individuals will be around 200 thousand only. Whatever value of the range of long-run infection rates we want to assume, the epidemic will last at least until June, with extensive and potentially future public health measures, it will last until July. In the worst case, it will last until end of August. We emphasize that all projections are subject to uncertainty and permanent monitoring of observed incidences are taken into account to update the projection. The most recent projections are available at https://www.macro.economics.uni-mainz.de/corona-blog/.

negative: The Politics of Disease Epidemics: a Comparative Analysis of the SARS, Zika, and Ebola Outbreaks Over the past few decades, disease outbreaks have become increasingly frequent and widespread. The epicenters of these outbreaks have differed, and could be linked to different economic contexts. Arguably, the responses to these outbreaks have been “political” and inherently burdensome to marginalized populations. Key lessons can be learned from exploring the narratives about the different epidemics in varying income settings. Based on a review of the published medical, social, and political literature, which was accessed using four electronic databases—PubMed, Sociological Abstracts, Scholars Portal, and Web of Science, the overall objective of this paper discuss scholars’ narratives on the “politics” of Ebola in a low-income setting, Zika virus in a middle-income setting, and SARS in a high-income setting. Various themes of the politics of epidemics were prominent in the literature. The narratives demonstrated the influence of power in whose narratives and what narratives are presented in the literature. While marginalized populations were reported to have borne the brunt of all disease outbreaks in the different contexts, the prevalence of their narratives within the reviewed literature was limited. Regardless of income setting, there is a need to give voice to the most marginalized communities during an epidemic. The experiences and narratives of those most vulnerable to an epidemic—specifically poor communities—need to be represented in the literature. This could contribute to mitigating some of the negative impact of the politics in epidemics.

negative: The effect of New Neonatal Porcine Diarrhoea Syndrome (NNPDS) on average daily gain and mortality in 4 Danish pig herds BACKGROUND: The study evaluated the effect of New Neonatal Porcine Diarrhoea Syndrome (NNPDS) on average daily gain (ADG) and mortality and described the clinical manifestations in four herds suffering from the syndrome. NNPDS is a diarrhoeic syndrome affecting piglets within the first week of life, which is not caused by enterotoxigenic Escherichia coli (ETEC), Clostridium perfringens (C. perfringens) type A/C, Clostridium difficile (C. difficile), rotavirus A, coronavirus, Cystoisospora suis, Strongyloides ransomi, Giardia spp or Cryptosporidium spp. RESULTS: Piglets were estimated to have a negative ADG of 9 and 14 g when diarrhoeic for 1 day and >1 day respectively. However, if only diarrhoeic on the day of birth, no negative effect on ADG was seen. Piglets originating from severely affected litters were estimated to have a reduced ADG of 38 g. The study did not show an overall effect of diarrhoea on mortality, but herd of origin, sow parity, birth weight, and gender were significantly associated with mortality. In one of the herds, approximately 25% of the diarrhoeic piglets vs. 6% of the non-diarrhoeic piglets died, and 74% of necropsied piglets were diagnosed with enteritis. These findings indicate that the high mortality seen in this herd was due to diarrhoea. CONCLUSIONS: NNPDS negatively affected ADG in piglets, and even piglets that were diarrhoeic for one day only experienced a reduction in ADG. However, the study showed that diarrhoea restricted to the day of birth did not affect ADG and suggested this phenomenon to be unrelated to the syndrome. Since the diarrhoeal status of the litter had important effects on ADG, future research on NNPDS probably ought to focus on piglets from severely affected litters. The study showed important dissimilarities in the course of diarrhoea between the herds, and one herd was considerably more affected than the others. Within this herd, NNPDS seemed to be associated with a higher mortality, whereas in general the study did not show lethal effects of NNPDS.

negative: Preparedness for COVID-19 in the oncology community in Africa

negative: COVID-19: How to Relax Social Distancing If You Must Following the April 16, 2020 release of the Opening Up America Again guidelines for relaxing COVID-19 social distancing policies, local leaders are concerned about future pandemic waves and lack robust strategies for tracking and suppressing transmission. Here, we present a framework for monitoring COVID-19 hospitalization data to project risks and trigger shelter-in-place orders to prevent overwhelming healthcare surges while minimizing the duration of costly lockdowns. Assuming the relaxation of social distancing increases the risk of infection ten-fold, the optimal strategy for Austin, Texas--the fastest-growing large city in the US--will trigger a total of 135 [90% prediction interval: 126-141] days of sheltering, allow schools to open in the fall, and result in an expected 2929 deaths [90% prediction interval: 2837-3026] by September 2021, which is 29% the annual mortality rate. In the months ahead, policy makers are likely to face difficult choices and the extent of public restraint and cocooning of vulnerable populations may save or cost thousands of lives.

negative: Save the ICU and save lives during the COVID-19 pandemic Appropriate critical care delivery for Coronavirus disease 2019 (COVID-19) is a cornerstone in saving lives. Earlier publications worldwide demonstrate higher mortality among patients receiving mechanical ventilation in intensive care units during “surges” in the number of cases. In contrast, lower mortality outcomes are evident in Japan using CRISIS [CRoss Icu Searchable Information System] data by the national registry, Japan ECMOnet for COVID-19. This highlights the need for scientific analysis of the medical factors contributing to high survival rates and social factors associated with low case “surges,” to gain insight into protective strategies for possible coming waves in the COVID-19 pandemic.

negative: Recommendations for coronavirus infection in rheumatic diseases treated with biologic therapy Abstract The Coronavirus-associated disease, that was first identified in 2019 in China (CoViD-19), is a pandemic caused by a bat-derived beta-coronavirus, named SARS-CoV2. It shares homology with SARS and MERS-CoV, responsible for past outbreaks in China and in Middle East. SARS-CoV2 spread from China where the first infections were described in December 2019 and is responsible for the respiratory symptoms that can lead to acute respiratory distress syndrome. A cytokine storm has been shown in patients who develop fatal complications, as observed in past coronavirus infections. The management includes ventilatory support and broad-spectrum antiviral drugs, empirically utilized, as a targeted therapy and vaccines have not been developed. Based upon our limited knowledge on the pathogenesis of CoViD-19, a potential role of some anti-rheumatic drugs may be hypothesized, acting as direct antivirals or targeting host immune response. Antimalarial drugs, commonly used in rheumatology, may alter the lysosomal proteases that mediates the viral entry into the cell and have demonstrated efficacy in improving the infection. Anti-IL-1 and anti-IL-6 may interfere with the cytokine storm in severe cases and use of tocilizumab has shown good outcomes in a small cohort. Baricitinib has both antiviral and anti-inflammatory properties. Checkpoints inhibitors such as anti-CD200 and anti-PD1 could have a role in the treatment of CoViD-19. Rheumatic disease patients taking immunosuppressive drugs should be recommended to maintain the chronic therapy, prevent infection by avoiding social contacts and pausing immunosuppressants in case of infection. National and international registries are being created to collect data on rheumatic patients with CoViD-19.

negative: Epidemiology of Human and Animal Viral Diseases Viral disease epidemiology is the study of the determinants, dynamics, and distribution of viral diseases in populations. The risk of infection or disease in a population is determined by characteristics of the virus, the host, and the host population, as well as behavioral, environmental, and ecological factors that affect virus transmission from one host to another. Viral disease epidemiology has come to have a major role in clarifying the etiologic role of particular viruses and viral variants as the cause of specific diseases, in improving our understanding of the overall nature of specific viral diseases, and in determining factors affecting host susceptibility and immunity, in unraveling modes of transmission, in clarifying the interaction of viruses with environmental determinants of disease, in determining the safety, efficacy, and utility of vaccines and antiviral drugs, and especially in alerting and directing disease prevention and control actions. Information on incidence, prevalence, and morbidity and mortality rates contributes directly to the establishment of priorities for prevention and control programs, whether this involves vaccine or drug development and delivery, environmental and hygienic improvements, enhancement of nutritional status, personal or community behavior, agricultural and food processing enhancements, reservoir host and vector control, and international cooperation and communication.

negative: Incidence, Risks, and Types of Infections in Pediatric Long-term Care Facilities. Importance The population of infants, children, and adolescents cared for at pediatric long-term care facilities is increasing in complexity and size and thus consumes substantial health care resources. Infections are a significant cause of morbidity and mortality in this population, but few recent data describe their incidence and effects. Objectives To describe the types of infections diagnosed in residents of pediatric long-term care facilities, calculate infection rates, and identify risk factors for respiratory tract infections (RTIs). Design, Setting, and Participants This prospective cohort study, which was part of a larger trial called Keep It Clean for Kids, was conducted from September 1, 2012, to December 31, 2015, at 3 pediatric long-term care facilities in New York. Residents of the facilities who were 21 years or younger and either residents or admitted during the study period (n = 717) were enrolled in the study. Medical records were reviewed to identify infections diagnosed by site clinicians. Main Outcomes and Measures Incidence of infections, such as RTIs; skin and soft-tissue infections; chronic comorbid conditions, including neurologic and respiratory disorders; and device use, including gastrostomy tubes and tracheostomies, was determined. Risk factors for RTIs were assessed by generalized linear mixed method regression modeling. Results The 717 residents had a median (interquartile range) age at enrollment of 2.6 (0.4-9.1) years; 358 (49.9%) were male. Four hundred twenty-eight residents (59.7%) had feeding tubes and 215 (30.0%) had tracheostomies. Most chronic comorbid conditions were musculoskeletal or ambulation (532 residents [74.2%]), neurologic (505 [70.4%]), respiratory (361 [50.3%]), and gastrointestinal (230 [32.1%]) disorders, and 460 residents (64.2%) had 4 or more chronic comorbid conditions. Site clinicians diagnosed 2052 infections during the 3-year study period. Respiratory tract infections were most common and were diagnosed in 1291 residents (62.9%). The overall infection rate was 5.3 infections per 1000 resident-days, and RTI rates were 3.3 infections per 1000 resident-days. Overall infection rates and rates of RTI, skin and soft-tissue infection, urinary tract infection, and bloodstream infection varied among the 3 sites. In the multivariable model, younger age (incidence rate ratio [IRR], 1.05; 95% CI, 1.03-1.06), increased number of chronic comorbid conditions (IRR, 1.12; 95% CI, 1.06-1.19), and the use of feeding tubes (IRR, 1.34; 95% CI, 1.03-1.64) and tracheostomies (IRR, 1.40; 95% CI, 1.17-1.69) were associated with RTIs. Conclusions and Relevance In this study, RTIs were the most common infections diagnosed, but modifiable risk factors for RTIs were not identified. Future work should focus on optimizing infection prevention and control strategies to reduce infections, particularly RTIs, in the pediatric long-term care population.

negative: Comment évaluer, orienter et suivre un patient ayant une pneumonie aiguë communautaire ? Une exacerbation de bronchopneumopathie chronique obstructive ?: Évaluation des facteurs de risque d'acquisition, d'évolution compliquée et/ou de mortalité, des signes de gravité. Choix du lieu de la prise en charge et orientation du suivi The purpose of this review was to analyze the literature concerning community-acquired pneumonia (CAP) and acute exacerbations of chronic obstructive pulmonary disease (AECOPD) published in the last five years. CAP and AECOPD are frequent diseases that are to this day still associated with high morbidity and mortality rates. Patient management, especially the choice of the management environment, outpatient or intensive care, depends on the knowledge and recognition of predictors of complications, mortality risk factors, and severity signs to the extent that predictive algorithms have been established. However, research and publications concerning discharge criteria and follow-up of CAP and AECOPD patients is more sparse.

negative: Identification of anti-viral activity of the cardenolides, Na+/K+-ATPase inhibitors, against porcine transmissible gastroenteritis virus Abstract A series of naturally occurring cardenolides that exhibit potent anti-transmissible gastroenteritis virus (TGEV) activity in swine testicular (ST) cells has been identified. In an immunofluorescence assay, these cardenolides were found to diminish the expressions of TGEV nucleocapsid and spike protein, which was used as an indication for viral replication; block TGEV infection induced apoptosis and cytopathic effects; and impart the same trend of inhibitory activity against Na+/K+-ATPase as for anti-TGEV activity. The viral titer inhibition was found to take place in a dose-dependent manner. Knocking down expression of Na+/K+-ATPase, the cellular receptor of cardenolides, in ST cells was found to significantly impair the susceptibility of ST cells to TGEV infectivity. Thus, we have identified Na+/K+-ATPase as an anti-viral drug target and its antagonists, cardenolides, a novel class of anti- TGEV agents.

negative: Survival of porcine epidemic diarrhea virus (PEDV) in thermally treated feed ingredients and on surfaces BACKGROUND: Infection with Porcine Epidemic Diarrhea Virus (PEDV) causes vomiting, diarrhea, and dehydration in young pigs. The virus made its first appearance in the U.S. in 2013, where it caused substantial neonatal mortality and economic losses in the U.S. pork industry. Based on outbreak investigations, it is hypothesized that the virus could be transmitted through contaminated feed or contaminated feed surfaces. This potential risk created a demand for research on the inactivation kinetics of PEDV in different environments. Therefore, the objective of this study was to evaluate the survival of PEDV in 9 different feed ingredients when exposed to 60, 70, 80, and 90 °C, as well as the survival on four different surfaces (galvanized steel, stainless steel, aluminum, and plastic). RESULTS: Overall, there were no differences (P > 0.05) in virus survival among the different feed matrices studied when thermally processed at 60 to 90 °C for 5, 10, 15, or 30 min. However, the time necessary to achieve a one log reduction in virus concentration was less (P < 0.05) when ingredients were exposed to temperatures from 70 °C (3.7 min), 80 °C (2.4 min), and 90 °C (2.3 min) compared with 60 °C (4.4 min). The maximum inactivation level (3.9 log) was achieved when heating all ingredients at 90 °C for 30 min. There were no differences in the amount of time necessary to cause a one log reduction in PEDV concentration among the different surfaces. CONCLUSIONS: The results of this study showed that PEDV survival among the 9 feed ingredients evaluated was not different when exposed to thermal treatments for up to 30 min. However, different combinations of temperature and time resulted in achieving a 3 to 4 log reduction of PEDV in all feed ingredients evaluated. Finally, PEDV survival was similar on galvanized steel, stainless steel, aluminum and plastic.

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

negative: Epidemiological Determinants of COVID-19-Related Patient Outcomes in Different Countries and Plan of Action: A Retrospective Analysis Current development around the pandemic of novel coronavirus disease 2019 (COVID-19) presents a significant healthcare resource burden threatening to overwhelm the available nationwide healthcare infrastructure. It is essential to consider, especially for resource-limited nations, strategizing the coordinated response to handle this crisis effectively and preparing for the upcoming emergence of calamity caused by this yet-to-know disease entity. Relevant epidemiological data were retrieved from currently available online reports related to COVID-19 patients. The correlation coefficient was calculated by plotting dependant variables - the number of COVID-19 cases and the number of deaths due to COVID 19 on the Y-axis and independent variables - critical-care beds per capita, the median age of the population of the country, the number of COVID-19 tests per million population, population density (persons per square km), urban population percentage, and gross domestic product (GDP) expense on health care - on the X-axis. After analyzing the data, both the fatality rate and the total number of COVID-19 cases were found to have an inverse association with the population density with the variable - the number of cases of COVID-19 - achieving a statistical significance (p-value 0.01). The negative correlation between critical care beds and the fatality rate is well-justified, as intensive care unit (ICU) beds and ventilators are the critical elements in the management of complicated cases. There was also a significant positive correlation between GDP expenses on healthcare by a country and the number of COVID-19 cases being registered (p-value 0.008), although that did not affect mortality (p-value 0.851). This analysis discusses the overview of various epidemiological determinants possibly contributing to the variation in patient outcomes across regions and helps improve our understanding to develop a plan of action and effective control measures in the future.

negative: Systematic Survey of Zoonotic and Sapronotic Microbial Agents Viruses, bacteria, fungi, protozoa, and metazoa (parasitic worms and arthropods) are among the aetiological agents of zoonoses and sapronoses. Our survey only concerns the agents of microbial diseases (i.e., not the metazoan invasions and infestations), and is arranged according to systematic position. In addition, a new zoonotic disease caused by prions – variant of Creutzfeld-Jakob disease – is included.

negative: The impact of a pathogenic bacterium on a social carnivore population 1. The long‐term ecological impact of pathogens on group‐living, large mammal populations is largely unknown. We evaluated the impact of a pathogenic bacterium, Streptococcus equi ruminatorum, and other key ecological factors on the dynamics of the spotted hyena Crocuta crocuta population in the Ngorongoro Crater, Tanzania. 2. We compared key demographic parameters during two years when external signs of bacterial infection were prevalent (‘outbreak’) and periods of five years before and after the outbreak when such signs were absent or rare. We also tested for density dependence and calculated the basic reproductive rate R (0) of the bacterium. 3. During the five pre‐outbreak years, the mean annual hyena mortality rate was 0·088, and annual population growth was relatively high (13·6%). During the outbreak, mortality increased by 78% to a rate of 0·156, resulting in an annual population decline of 4·3%. After the outbreak, population size increased moderately (5·1%) during the first three post‐outbreak years before resuming a growth similar to pre‐outbreak levels (13·9%). We found no evidence that these demographic changes were driven by density dependence or other ecological factors. 4. Most hyenas showed signs of infection when prey abundance in their territory was low. During the outbreak, mortality increased among adult males and yearlings, but not among adult females – the socially dominant group members. These results suggest that infection and mortality were modulated by factors linked to low social status and poor nutrition. During the outbreak, we estimated R (0) for the bacterium to be 2·7, indicating relatively fast transmission. 5. Our results suggest that the short‐term ‘top–down’ impact of S. equi ruminatorum during the outbreak was driven by ‘bottom–up’ effects on nutritionally disadvantaged age–sex classes, whereas the longer‐term post‐outbreak reduction in population growth was caused by poor survival of juveniles during the outbreak and subsequent poor recruitment of breeding females. These results suggest synergistic effects of ‘bottom–up’ and ‘top–down’ processes on host population dynamics.

negative: COVID-19 and cardiovascular disease: What we know, what we think we know, and what we need to know

negative: Proceedings of Réanimation 2020, the French Intensive Care Society International Congress

negative: Geographical disparities in emergency department presentations for acute respiratory infections and risk factors for presenting: a population-based cohort study of Western Australian children INTRODUCTION: Studies examining acute respiratory infections (ARIs) in emergency department (EDs), particularly in rural and remote areas, are rare. This study aimed to examine the burden of ARIs among Aboriginal and non-Aboriginal children presenting to Western Australian (WA) EDs from 2002 to 2012. METHOD: Using a retrospective population-based cohort study linking ED records to birth and perinatal records, we examined presentation rates for metropolitan, rural and remote Aboriginal and non-Aboriginal children from 469 589 births. We used ED diagnosis information to categorise presentations into ARI groups and calculated age-specific rates. Negative binomial regression was used to investigate association between risk factors and frequency of ARI presentation. RESULTS: Overall, 26% of presentations were for ARIs. For Aboriginal children, the highest rates were for those aged <12 months in the Great Southern (1233 per 1000 child-years) and Pilbara regions (1088 per 1000 child-years). Rates for non-Aboriginal children were highest in children <12 months in the Southwest and Kimberley (400 and 375 per 1000 child-years, respectively). Presentation rates for ARI in children from rural and remote WA significantly increased over time in all age groups <5 years. Risk factors for children presenting to ED with ARI were: male, prematurity, caesarean delivery and residence in the Kimberley region and lower socio-economic areas. CONCLUSION: One in four ED presentations in WA children are for ARIs, representing a significant out-of-hospital burden with some evidence of geographical disparity. Planned linkages with hospital discharge and laboratory detection data will aid in assessing the sensitivity and specificity of ARI diagnoses in ED.

negative: Viral Infection in the Development and Progression of Pediatric Acute Respiratory Distress Syndrome Viral infections are an important cause of pediatric acute respiratory distress syndrome (ARDS). Numerous viruses, including respiratory syncytial virus (RSV) and influenza A (H1N1) virus, have been implicated in the progression of pneumonia to ARDS; yet the incidence of progression is unknown. Despite acute and chronic morbidity associated with respiratory viral infections, particularly in “at risk” populations, treatment options are limited. Thus, with few exceptions, care is symptomatic. In addition, mortality rates for viral-related ARDS have yet to be determined. This review outlines what is known about ARDS secondary to viral infections including the epidemiology, the pathophysiology, and diagnosis. In addition, emerging treatment options to prevent infection, and to decrease disease burden will be outlined. We focused on RSV and influenza A (H1N1) viral-induced ARDS, as these are the most common viruses leading to pediatric ARDS, and have specific prophylactic and definitive treatment options.

negative: An ecological study of socioeconomic predictors in detection of COVID-19 cases across neighborhoods in New York City Abstract Background: New York City was the first major urban center of the COVID-19 pandemic in the USA. Cases are clustered in the city, with certain neighborhoods experiencing more cases than others. We investigate whether potential socioeconomic factors can explain between-neighborhood variation in the number of detected COVID-19 cases. Methods: Data were collected from 177 Zip Code Tabulation Areas (ZCTA) in New York City (99.9% of the population). We fit multiple Bayesian Besag-York-Mollié (BYM) mixed models using positive COVID-19 tests as the outcome and a set of 10 representative economic, demographic, and health-care associated ZCTA-level parameters as potential predictors. The BYM model includes both spatial and nonspatial random effects to account for clustering and overdispersion. Results: Multiple different regression approaches indicated a consistent, statistically significant association between detected COVID-19 cases and dependent (under 18 or 65+ years old) population, male to female ratio, and median household income. In the final model, we found that an increase of only 1% in dependent population is associated with a 2.5% increase in detected COVID-19 cases (95% confidence interval (CI): 1.6% to 3.4%, p < 0.0005). An increase of 1 male per 100 females is associated with a 1.0% (95% CI: 0.6% to 1.5%, p < 0.0005) increases in detected cases. A decrease of $10,000 median household income is associated with a 2.5% (95% CI: 1.0% to 4.1% p = 0.002) increase in detected COVID-19 cases. Conclusions: Our findings indicate associations between neighborhoods with a large dependent population, those with a high proportion of males, and low-income neighborhoods and detected COVID-19 cases. Given the elevated mortality in aging populations, the study highlights the importance of public health management during and after the current COVID-19 pandemic. Further work is warranted to fully understand the mechanisms by which these factors may have affected the number of detected cases, either in terms of the true number of cases or access to testing.

negative: Measuring progress and projecting attainment on the basis of past trends of the health-related Sustainable Development Goals in 188 countries: an analysis from the Global Burden of Disease Study 2016. BACKGROUND The UN's Sustainable Development Goals (SDGs) are grounded in the global ambition of "leaving no one behind". Understanding today's gains and gaps for the health-related SDGs is essential for decision makers as they aim to improve the health of populations. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016), we measured 37 of the 50 health-related SDG indicators over the period 1990-2016 for 188 countries, and then on the basis of these past trends, we projected indicators to 2030. METHODS We used standardised GBD 2016 methods to measure 37 health-related indicators from 1990 to 2016, an increase of four indicators since GBD 2015. We substantially revised the universal health coverage (UHC) measure, which focuses on coverage of essential health services, to also represent personal health-care access and quality for several non-communicable diseases. We transformed each indicator on a scale of 0-100, with 0 as the 2·5th percentile estimated between 1990 and 2030, and 100 as the 97·5th percentile during that time. An index representing all 37 health-related SDG indicators was constructed by taking the geometric mean of scaled indicators by target. On the basis of past trends, we produced projections of indicator values, using a weighted average of the indicator and country-specific annualised rates of change from 1990 to 2016 with weights for each annual rate of change based on out-of-sample validity. 24 of the currently measured health-related SDG indicators have defined SDG targets, against which we assessed attainment. FINDINGS Globally, the median health-related SDG index was 56·7 (IQR 31·9-66·8) in 2016 and country-level performance markedly varied, with Singapore (86·8, 95% uncertainty interval 84·6-88·9), Iceland (86·0, 84·1-87·6), and Sweden (85·6, 81·8-87·8) having the highest levels in 2016 and Afghanistan (10·9, 9·6-11·9), the Central African Republic (11·0, 8·8-13·8), and Somalia (11·3, 9·5-13·1) recording the lowest. Between 2000 and 2016, notable improvements in the UHC index were achieved by several countries, including Cambodia, Rwanda, Equatorial Guinea, Laos, Turkey, and China; however, a number of countries, such as Lesotho and the Central African Republic, but also high-income countries, such as the USA, showed minimal gains. Based on projections of past trends, the median number of SDG targets attained in 2030 was five (IQR 2-8) of the 24 defined targets currently measured. Globally, projected target attainment considerably varied by SDG indicator, ranging from more than 60% of countries projected to reach targets for under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria, to less than 5% of countries projected to achieve targets linked to 11 indicator targets, including those for childhood overweight, tuberculosis, and road injury mortality. For several of the health-related SDGs, meeting defined targets hinges upon substantially faster progress than what most countries have achieved in the past. INTERPRETATION GBD 2016 provides an updated and expanded evidence base on where the world currently stands in terms of the health-related SDGs. Our improved measure of UHC offers a basis to monitor the expansion of health services necessary to meet the SDGs. Based on past rates of progress, many places are facing challenges in meeting defined health-related SDG targets, particularly among countries that are the worst off. In view of the early stages of SDG implementation, however, opportunity remains to take actions to accelerate progress, as shown by the catalytic effects of adopting the Millennium Development Goals after 2000. With the SDGs' broader, bolder development agenda, multisectoral commitments and investments are vital to make the health-related SDGs within reach of all populations. FUNDING Bill & Melinda Gates Foundation.

negative: Traumatization in medical staff helping with COVID-19 control

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: Incidence, mortality, and lethality of hospitalizations for community-acquired pneumonia with comorbid cardiovascular disease in Spain (1997–2015) BACKGROUND: The probability of hospitalization in patients suffering from community-acquired pneumonia (CAP) with an underlying comorbidity, such as a cardiac pathology, is 73-fold higher than that in CAP patients without a comorbidity. Although previous studies have investigated patients with cardiac events and pneumonia, they have not studied the burden of disease in depth at the population level. The objective of this study is to provide population-level data on patients ≥60 years old who were hospitalized with pneumonia with comorbid cardiovascular disease (CVD) in Spain over a period of 19 years (1997–2015). METHODS: This is a retrospective study based on a minimum basic data set (MBDS). The following variables were collected: age, sex, re-admission (yes/no), hospital stay (days), and other diagnoses. Hospitalization rate (per 100,000 inhabitants), mortality rate (per 100,000 inhabitants), and lethality rate (%) were obtained, and the 95% confidence interval of each rate was calculated. Analyses were stratified by age (categorized into 4-year intervals), sex, and year of admission. Differences were assessed for significance with the chi-squared test for proportions and the Poisson model for rates. Logistic regression was run with in-hospital survival as the dependent variable and sex, age, year of admission, and re-admission (yes/no) as the independent variables. The level of significance was p < 0.005. RESULTS: The total number of patients ≥60 years old hospitalized for pneumonia with comorbid CVD was 99,346. The rates of hospitalization, mortality, and lethality increased significantly with age over the 19 years. Men had higher rates of hospitalization and mortality. The probability of a patient with CAP and CVD dying was correlated with male sex, older age, hospital re-admission, and having been hospitalized earlier in the study period. CONCLUSIONS: Community-acquired pneumonia with comorbid cardiovascular disease continues to be a major cause of hospitalization in Spain, especially in the elderly population, making it necessary to develop more preventive strategies for this group of 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: Estimating survival rates in MERS-CoV patients 14 and 45 days after experiencing symptoms and determining the differences in survival rates by demographic data, disease characteristics and regions: a worldwide study Although Middle East respiratory syndrome coronavirus (MERS-CoV) has a recorded 5 years of circulation in 27 countries worldwide, there is no international study to assess whether there is variation in mortality by region. Neither has there been a comprehensive study detailing how the disease characteristics of MERS-CoV influence mortality in patients presenting symptoms. This study aimed to assess how region, patient and disease characteristics influence 14- and 45-day mortality in MERS patients. The author utilised publically available data on MERS-CoV. The study included 883 MERS patients reported between 5 January 2015 and 10 March 2017. Data on patient and disease characteristics were collected. The mean age at MERS-CoV diagnosis was 54.3 years: 69.1% were male, and 86.7% of the cases were reported from Saudi Arabia. About 40% of MERS patients studied were over the age of 60. The study estimated 14- and 45-day survival rates after initial onset of symptoms: 83.67% and 65.9%, respectively. Saudi Arabian MERS patients exhibited 4.1 and 5.0 times higher 14-day (adjusted hazard risk (aHR) = 4.1; 95% confidence interval (CI) 1.012–16.921) and 45-day (aHR = 5.0; 95% CI 1.856–13.581) mortality risk compared with MERS patients in the Republic of Korea or other countries. Similarly, Middle Eastern MERS patients showed 5.3 and 4.1 times higher 14-day (aHR = 5.3; 95% CI 1.070–25.902) and 45-day (aHR = 4.1; 95% CI 1.288–113.076) mortality risk compared with MERS patients in the Republic of Korea or other countries. The results demonstrated a link between mortality and geography, disease and patient factors such as regions, symptoms, source of infections, underlying medical conditions, modes of transmission, non-healthcare workers and those of older age. Educational programmes, access to healthcare and early diagnosis could be implemented as modifiable factors to reduce the higher mortality rates in MERS patients.

negative: Robust estimation of diagnostic rate and real incidence of COVID-19 for European policymakers Policymakers need a clear and fast assessment of the real spread of the epidemic of COVID-19 in each of their respective countries. Standard measures of the situation provided by the governments include reported positive cases and total deaths. While total deaths immediately indicate that countries like Italy and Spain have the worst situation as of mid April 2020, on its own, reported cases do not provide a correct picture of the situation. The reason is that different countries diagnose diversely and present very distinctive reported case fatality rate (CFR). The same levels of reported incidence and mortality might hide a very different underlying picture. Here we present a straightforward and robust estimation of the diagnostic rate in each European country. From that estimation we obtain an uniform unbiased incidence of the epidemic. The method to obtain the diagnostic rate is transparent and empiric. The key assumption of the method is that the real CFR in Europe of COVID-19 is not strongly country-dependent. We show that this number is not expected to be biased due to demography nor the way total deaths are reported. The estimation protocol has a dynamic nature, and it has been giving converging numbers for diagnostic rates in all European countries as of mid April 2020. From this diagnostic rate, policy makers can obtain an Effective Potential Growth (EPG) updated everyday providing an unbiased assessment of the countries with more potential to have an uncontrolled situation. The method developed will be used to track possible improvements on the diagnostic rate in European countries as the epidemic evolves.

negative: Global COVID-19: Warnings and suggestions based on experience of China BACKGROUND: Corona Virus Disease 2019 (COVID-19) is spreading around the world currently, seriously threatening people’s health and global security as an international public health emergency. The objective of this study is to summarize China’s countermeasures and experience in response to the COVID-19 emergence in order to serve as a warning for the global COVID-19 prevention and control, and further provide some suggestions for global fighting to COVID-19. METHODS: Content analysis, expert consultation, and high frequency word analysis were applied in this study. Relevant data and information were collected from official websites, the experience accumulated in China during the fighting to the novel coronavirus, and suggestions from some experts. RESULTS: As of March 29, 2020, China had accumulated 82 419 confirmed diagnoses, and the mortality rate was 4.01%; in the mean time, the global had accumulated 596 042 confirmed diagnoses, and the mortality rate was 4.76%. Although the mortality of COVID-19 was not so high, its harmfulness couldn’t be ignored. Ten facts during COVID-19 epidemic in China were summarized in the study, including: the COVID-19 is highly contagious and can be spread through many channels; although elderly people and people with underlying diseases are susceptible, young people can also be victims; isolation is the most effective way to reduce the risk of COVID-19, and secondary disasters induced by COVID-19 should be emphasized in advance. High frequent words of experts’ suggestions mainly includes: material, prevention and control, pathogeny, propaganda, education, hygiene, technology, medical care, overall planning, policy, panic, etc. The main concerns of experts are from four aspects: publicity and education, various subjects, medical materials and law construction. CONCLUSIONS: COVID-19 is a new infectious disease worldwide, and its infectious source, transmission route, susceptible population, and therapy are not clear. In the face of the COVID-19 epidemic, no country can stand alone to maintain its own safety. People from all over the world should put aside their difference in ideology, religious belief, politics, economy, and culture, and only by global cooperation and globally unified actions, can we successfully overcome COVID-19 in the end.

negative: Pathologies virales émergentes en pneumologie

negative: ANALYSIS OF CLINICAL RECOVERY-PERIOD AND RECOVERY RATE ESTIMATION OF THE FIRST 1000 COVID-19 PATIENTS IN SINGAPORE COVID-19 has been declared as a global pandemic by the World Health Organization (WHO) on March 11, 2020. In this paper, we investigate various aspects of the clinical recovery of the first 1000 COVID-19 patients in Singapore, spanning from January 23 to April 01, 2020. This data consists of 245 clinically recovered patients. The first part of the paper studies the descriptive statistics and the influence of demographic parameters, namely age and gender, in the clinical recovery-period of COVID-19 patients. The second part of the paper is on identifying the distribution of the length of the recovery-period for the patients. We identify a piecewise analysis of three different periods, identified based on trends of both positive confirmation and clinical recovery of COVID-19. As expected, the overall recovery rate has reduced drastically during the exponential increase of incidences. However, our in-depth analysis shows that there is a shift in the age-group of incidences to the younger population, and the recovery-period of the younger population is considerably lower. Here, we have estimated the recovery rate to be 0.125. Overall, the prognosis of COVID-19 indicates an improvement in recovery rate owing to the government-mandated practices of restricted mobility of the older population and aggressive contact tracing.

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

negative: Trends in Infectious Disease Mortality, South Korea, 1983–2015 We used national statistics from 1983–2015 to evaluate trends in mortality caused by infectious diseases in South Korea. Age-standardized mortality from infectious disease decreased from 43.5/100,000 population in 1983 to 16.5/100,000 in 1996, and then increased to 44.6/100,000 in 2015. Tuberculosis was the most common cause of death in 1983 and respiratory tract infections in 2015. We observed a significant decline in infant deaths caused by infectious diseases, but mortality in persons age >65 years increased from 135 deaths/100,000 population in 1996 to 307/100,000 in 2015. The relative inequality indices for respiratory tract infections, sepsis, and tuberculosis tended to increase over time. Although substantial progress has been achieved in terms of infant mortality, death rates from infectious disease has not decreased overall. Elderly populations with lower education levels and subgroups susceptible to respiratory infections and sepsis should be the focus of preventive policies.

negative: Population mortality during the outbreak of Severe Acute Respiratory Syndrome in Toronto BACKGROUND: Extraordinary infection control measures limited access to medical care in the Greater Toronto Area during the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak. The objective of this study was to determine if the period of these infection control measures was associated with changes in overall population mortality due to causes other than SARS. METHODS: Observational study of death registry data, using Poisson regression and interrupted time-series analysis to examine all-cause mortality rates (excluding deaths due to SARS) before, during, and after the SARS outbreak. The population of Ontario was grouped into the Greater Toronto Area (N = 2.9 million) and the rest of Ontario (N = 9.3 million) based upon the level of restrictions on delivery of clinical services during the SARS outbreak. RESULTS: There was no significant change in mortality in the Greater Toronto Area before, during, and after the period of the SARS outbreak in 2003 compared to the corresponding time periods in 2002 and 2001. The rate ratio for all-cause mortality during the SARS outbreak was 0.99 [95% Confidence Interval (CI) 0.93–1.06] compared to 2002 and 0.96 [95% CI 0.90–1.03] compared to 2001. An interrupted time series analysis found no significant change in mortality rates in the Greater Toronto Area associated with the period of the SARS outbreak. CONCLUSION: Limitations on access to medical services during the 2003 SARS outbreak in Toronto had no observable impact on short-term population mortality. Effects on morbidity and long-term mortality were not assessed. Efforts to contain future infectious disease outbreaks due to influenza or other agents must consider effects on access to essential health care services.

negative: Research Communications of the 29th ECVIM‐CA Congress

negative: Rethinking the Gendered Dimensions in the Impacts and Response to COVID-19 Pandemic Abstract The outbreak of the novel coronavirus disease 2019 (COVID-19) has demonstrated the urgency to rethink the health system quality to efficiently support and improve global health. Whilst efforts are now gathering pace in response to the deleterious impacts of COVID-19, gendered analysis of these impacts and response to the pandemic has been far too little. A critical consideration of gendered lenses and the respective brunt of health crises of the pandemic on men and women can improve our understanding and direction of efforts toward building robust and equitable public health response. Strategic plans for preparedness must be fully grounded in strong gender analysis in the remit of gender roles and norms, and strengthen the leadership and resourceful participation of women in the decision-making process toward addressing COVID-19 outbreak.

negative: SARS: screening, disease associations, and response

negative: Transmissible gastroenteritis coronavirus gene 7 is not essential but influences in vivo virus replication and virulence Abstract Transmissible gastroenteritis coronavirus (TGEV) contains eight overlapping genes that are expressed from a 3′-coterminal nested set of leader-containing mRNAs. To facilitate the genetic manipulation of the viral genome, genes were separated by duplication of transcription regulating sequences (TRSs) and introduction of unique restriction endonuclease sites at the 5′ end of each gene using an infectious cDNA clone. The recombinant TGEV (rTGEV) replicated in cell culture with similar efficiency to the wild-type virus and stably maintained the modifications introduced into the genome. In contrast, the rTGEV replication level in the lungs and gut of infected piglets and virulence were significantly reduced. rTGEV in which gene 7 expression was abrogated (rTGEV-Δ7) were recovered from cDNA constructs, indicating that TGEV gene 7 was a nonessential gene for virus replication. Interestingly, in vivo infections with rTGEV-Δ7 showed an additional reduction in virus replication in the lung and gut, and in virulence, indicating that TGEV gene 7 influences virus pathogenesis.

negative: The global burden of premature mortality due to the Middle East respiratory syndrome (MERS) using standard expected years of life lost, 2012 to 2019 BACKGROUND: It has been 8 years since the first case of Middle East respiratory syndrome coronavirus (MERS-CoV) was reported in Saudi Arabia and the disease is still being reported in 27 countries; however, there is no international study to estimate the overall burden related of this emerging infectious disease. The present study was conducted to assess the burden of premature mortality due to Middle East respiratory syndrome (MERS) worldwide. METHODS: In this retrospective analysis, we have utilized publicly available data from the WHO website related to 1789 MERS patients reported between September 23, 2012 and May 17, 2019. To calculate the standard expected years of life lost (SEYLL), life expectancy at birth was set according to the 2000 global burden of disease study on levels 25 and 26 of West model life tables from Coale-Demeny at 82.5 and 80 years for females and males, respectively. RESULTS: Overall, the total SEYLL in males and females was 10,702 and 3817.5 years, respectively. The MERS patients within the age range of 30–59 year-olds had the highest SEYLL (8305.5 years) in comparison to the patients within the age groups 0–29 (SEYLL = 3744.5 years) and ≥ 60 years (SEYLL = 2466.5 years). The total SEYLL in all age groups in 2012, 2013, 2014, 2015, 2016, 2017, 2018, and 2019 were 71.5, 2006.5, 3162, 4425.5, 1809.5, 878, 1257.5 and 909 years, respectively. The most SEYLL related to MERS-CoV infection was in the early four years of the onset of the pandemic (2012 to 2015) and in the last four years of the MERS-CoV pandemic (216 to 2019), a significant reduction was observed in the SEYLL related to MERS-CoV infection in the MERS patients. CONCLUSION: We believe that the findings of this study will shed light about the burden of premature mortality due to MERS infection in the world and the results may provide necessary information for policy-makers to prevent, control, and make a quick response to the outbreak of MERS-CoV disease.

negative: Emerging and Reemerging Infectious Disease Threats

negative: Significant demands on healthcare resources during the COVID crisis

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: A model for COVID-19 prediction in Iran based on China parameters Background: The rapid spread of COVID-19 virus from China to other countries and outbreaks of disease require an epidemiological analysis of the disease in the shortest time and an increased awareness of effective interventions. The purpose of this study was to estimate the COVID-19 epidemic in Iran based on the SIR model. The results of the analysis of the epidemiological data of Iran from January 22 to March 8, 2020 were investigated and the prediction was made until March 29, 2020. Methods: By estimating the three parameters of time-dependent transmission rate, time-dependent recovery rate, and time-dependent mortality rate from Covid-19 outbreak in China, and using the number of Covid-19 infections in Iran, we predicted the number of patients for the next month in Iran. Each of these parameters was estimated using GAM models. All analyses were conducted in R software using the mgcv package. Findings: On average, 925 people with COVID-19 are expected to be infected daily in Iran. The epidemic peaks within one week (15.03.2020 to 03.21.2020) and reaches its highest point on 03.18.2020 with 1126 infected cases. Conclusion: The most important point is to emphasize the timing of the epidemic peak, hospital readiness, government measures and public readiness to reduce social contact.

negative: Antipsychotic treatment effects on cardiovascular, cancer, infection, and intentional self-harm as cause of death in patients with Alzheimer's dementia Abstract Background Alzheimer's disease (AD), the most common disease causing dementia, is linked to increased mortality. However, the effect of antipsychotic use on specific causes of mortality has not yet been investigated thoroughly. Methods Utilizing the Danish nationwide registers, we defined a cohort of patients diagnosed with AD. Utilizing separate Cox regressions for specific causes of mortality, we investigated the effects of cumulative antipsychotic dosage after diagnosis and current antipsychotic exposure in the time period 2000–2011. Results In total, 45,894 patients were followed for 3,803,996 person-years. A total of 6129 cardiovascular related deaths, 2088 cancer related deaths, 1620 infection related deaths, and 28 intentional self-harm related deaths are presented. Current antipsychotic exposure increased mortality rate with HR between 1.92 and 2.31 for cardiovascular, cancer, and infection related death. Cumulative antipsychotic dosages were most commonly associated with increased rates of mortality for cardiovascular and infection as cause of death, whereas the associations were less clear with cancer and intentional self-harm as cause of death. Conclusions We showed that cumulative antipsychotic drug dosages increased mortality rates for cardiovascular and infection as cause of death. These findings highlight the need for further investigations of long-term effects of treatment and of possible sub-groups who could benefit from treatment.

negative: Influenza and Endemic Viral Pneumonia Viruses are a common and important cause of severe community-acquired pneumonia, and may lead to severe respiratory disease and admission to the intensive care unit. Influenza is the most common virus associated with severe viral pneumonia, although other important causes include respiratory syncytial virus, adenovirus, metapneumonia virus, and coronaviruses. Viral pneumonias tend to have a seasonal predilection and are often preceded by a typical viral prodrome. This article focuses on severe influenza pneumonia, including the 2009 H1N1 pandemic, and briefly discusses other causes of severe respiratory disease of viral etiology.

negative: Bacterial and Viral Identification Rate in Acute Exacerbation of Chronic Obstructive Pulmonary Disease in Korea PURPOSE: The most common cause of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is respiratory infection. Most studies of bacterial or viral cause in AECOPD have been conducted in Western countries. We investigated bacterial and viral identification rates in AECOPD in Korea. MATERIALS AND METHODS: We reviewed and analyzed medical records of 736 cases of AECOPD at the Korea University Guro Hospital. We analyzed bacterial and viral identification rates and classified infections according to epidemiological factors, such as Global Initiative for Chronic Obstructive Lung Disease stage, mortality, and seasonal variation. RESULTS: The numbers of AECOPD events involving only bacterial identification, only viral identification, bacterial-viral co-identification, and no identification were 200 (27.2%), 159 (21.6%), 107 (14.5%), and 270 (36.7%), respectively. The most common infectious bacteria identified were Pseudomonas aeruginosa (13.0%), Streptococcus pneumoniae (11.4%), and Haemophilus influenzae (5.3%); the most common viruses identified were influenza virus (12.4%), rhinovirus (9.4%), parainfluenza virus (5.2%), and metapneumovirus (4.9%). The bacterial identification rate tended to be higher at more advanced stages of chronic obstructive pulmonary disease (p=0.020 overall, p=0.011 for P. aeruginosa, p=0.048 for S. pneumoniae). Staphylococcus aureus and Klebsiella pneumoniae were identified more in mortality group (p=0.003 for S. aureus, p=0.009 for K. pneumoniae). All viruses were seasonal (i.e., greater prevalence in a particular season; p<0.050). Influenza virus and rhinovirus were mainly identified in the winter, parainfluenza virus in the summer, and metapneumovirus in the spring. CONCLUSION: This information on the epidemiology of respiratory infections in AECOPD will improve the management of AECOPD using antibiotics and other treatments in Korea.

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

negative: Ontology-Based Approach to Social Data Sentiment Analysis: Detection of Adolescent Depression Signals BACKGROUND: Social networking services (SNSs) contain abundant information about the feelings, thoughts, interests, and patterns of behavior of adolescents that can be obtained by analyzing SNS postings. An ontology that expresses the shared concepts and their relationships in a specific field could be used as a semantic framework for social media data analytics. OBJECTIVE: The aim of this study was to refine an adolescent depression ontology and terminology as a framework for analyzing social media data and to evaluate description logics between classes and the applicability of this ontology to sentiment analysis. METHODS: The domain and scope of the ontology were defined using competency questions. The concepts constituting the ontology and terminology were collected from clinical practice guidelines, the literature, and social media postings on adolescent depression. Class concepts, their hierarchy, and the relationships among class concepts were defined. An internal structure of the ontology was designed using the entity-attribute-value (EAV) triplet data model, and superclasses of the ontology were aligned with the upper ontology. Description logics between classes were evaluated by mapping concepts extracted from the answers to frequently asked questions (FAQs) onto the ontology concepts derived from description logic queries. The applicability of the ontology was validated by examining the representability of 1358 sentiment phrases using the ontology EAV model and conducting sentiment analyses of social media data using ontology class concepts. RESULTS: We developed an adolescent depression ontology that comprised 443 classes and 60 relationships among the classes; the terminology comprised 1682 synonyms of the 443 classes. In the description logics test, no error in relationships between classes was found, and about 89% (55/62) of the concepts cited in the answers to FAQs mapped onto the ontology class. Regarding applicability, the EAV triplet models of the ontology class represented about 91.4% of the sentiment phrases included in the sentiment dictionary. In the sentiment analyses, “academic stresses” and “suicide” contributed negatively to the sentiment of adolescent depression. CONCLUSIONS: The ontology and terminology developed in this study provide a semantic foundation for analyzing social media data on adolescent depression. To be useful in social media data analysis, the ontology, especially the terminology, needs to be updated constantly to reflect rapidly changing terms used by adolescents in social media postings. In addition, more attributes and value sets reflecting depression-related sentiments should be added to the ontology.

negative: The epidemiology of Middle East respiratory syndrome coronavirus in the Kingdom of Saudi Arabia, 2012–2015 Summary Objectives The aim of this study was to review the epidemiology of cases of Middle East respiratory syndrome coronavirus (MERS-CoV) reported in the Kingdom of Saudi Arabia from 2012 when the first MERS-CoV was confirmed up to July 2015. Methods MERS-CoV data were obtained from the Saudi Ministry of Health for the period 2012 to July 2015. Descriptive statistics were used to summarize the results regarding the risk factors and mortality of MERS-CoV infection. Results In this series, the risk factors and outcomes of 939 cases of MERS-CoV occurring in the last 3 years are described. The majority of the affected patients were aged ≥40 years (n =657; 70%). Of the 657 patients aged ≥40 years, 377 (57.3%) died. Conclusions The case-fatality ratio was found to increase significantly with age. It ranged from 12.5% in those aged ≤19 years to 86.2% in those aged ≥80 years. The results confirmed the association between severe MERS-CoV illness and patients with a pre-existing health morbidity. The duration from symptom onset to admission was not statistically associated with the disease outcome.

negative: COVID19-Global: A shiny application to perform a global comparative data visualization for the SARS-CoV-2 epidemic Data visualization is an essential tool for exploring and communicating findings in medical research, especially in epidemiological surveillance. The COVID19-Global online web application systematically produces daily updated data visualization and analysis of the SARS-CoV-2 epidemic on a global scale. It collects automatically daily data on COVID-19 diagnosed cases and mortality worldwide from January 1st, 2020 onwards. We have implemented comparative data visualization between countries for the most common indicators in epidemiological surveillance to follow an epidemic: attack rate, population fatality rate, case fatality rate, and basic reproduction number. The application may help for a better understanding of the SARS-CoV-2 epidemic worldwide.

negative: Redesigning Italy's regional Neurosciences networks in the COVID-19 era: a model for a future healthcare system or skating on thin ice?

negative: Capillary nano-immunoassay for Akt 1/2/3 and 4EBP1 phosphorylation in acute myeloid leukemia. BACKGROUND Overall cure rates in acute myeloid leukemia (AML) continue to range between 60-65% with disease relapse being a major cause of mortality. The PI3K-Akt-mTOR kinase pathway plays a vital role in pro-survival signals within leukemic cells and inhibition of this pathway is being investigated to improve patient outcomes. Tracking activation of multiple signaling proteins simultaneously in patient samples can be challenging especially with limiting cell numbers within rare sub-populations. METHODS The NanoPro 1000 system (ProteinSimple) is built on an automated, capillary-based immunoassay platform and enables a rapid and quantitative analysis of specific proteins and their phosphorylation states. We have utilized this nano-immunoassay to examine activation of Akt 1/2/3 and downstream mTOR target--eukaryotic initiation factor 4E-Binding Protein 1 (4EBP1). RESULTS Assays for Akt 1/2/3 and 4EBP1 were standardized using AML cell lines (MV4-11, MOLM-14, OCI-AML3 and HL-60) prior to testing in patient samples. Target inhibition was studied using mTOR 1/2 inhibitor AZD-8055 and results were corroborated by Western blotting. The assay was able to quantify nanogram amounts of 4EBP1 and Akt 1/2/3 in AML cell lines and primary pediatric AML samples and results were quantifiable, consistent and reproducible. CONCLUSION Our data provides a strong basis for testing this platform on a larger scale and our long term aim is to utilize this nano-immunoassay prospectively in de-novo AML to be able to identify poor responders who might benefit from early introduction of targeted therapy.

negative: Prognostication and Proactive Planning in COVID-19 Abstract Accurate prognostication is challenging in the setting of SARS-CoV-2, the virus responsible for COVID-19, due to rapidly changing data, studies that are not generalizable and lack of morbidity and functional outcomes in survivors. To provide meaningful guidance to patients, existing mortality data must be considered and appropriately applied. While most people infected with SARS-CoV-2 will recover, mortality increases with age and co-morbidity in those who develop severe illness.

negative: 15 Governance, human rights and infectious disease: theoretical, empirical and practical perspectives Publisher Summary This chapter explores the fundamental obligation of governments to protect health. This obligation extends not only to the provision of health care or to the control of infectious disease outbreaks, but also to the cessation of human rights violations that contribute to poor health or disease risk. The relationship between the health status of a population and the behavior of the government under which that population lives is important during war or civil crisis settings, and in the context of chronic health issues such as nutrition, famine, and child mortality. As measured by indicators such as accountability, stability, rule of law, respect for human rights, and the existence of an independent civil society, plays a significant role in health outcomes—a role independent of, and perhaps even superior to, host genetics, insect vectors, or individual behaviors. Famines stem not solely from bad weather or genetics, but also from the failure of governments to protect their populations from civil strife, or to equitably distribute food aid. Despite the widespread acceptance of these findings, the influence of governance on infectious disease spread has received far less attention. Both governance and health can be measured in many different ways, and one factor complicating efforts to measure the association between the two is the difficulty finding accurate, sensitive, and specific enough indicators for either variable. Broad measures of population health—such as life expectancy, and infant and maternal mortality—have been chosen by a number of authors, in part because these indicators capture multiple specific diseases and are broadly distributed across the population.

negative: Risk Analysis Framework Guidance for Wildlife Health Professionals

negative: Abstracts of FIS/HIS 2016 – Poster Presentations

negative: Intensive COVID-19 testing associated with reduced mortality - an ecological analysis of 108 countries Background Intensive screening and testing for COVID-19 could facilitate early detection and isolation of infected persons and thereby control the size of the epidemic. It could also facilitate earlier and more targeted therapy. These factors could plausibly reduce attributable mortality which was the hypothesis tested in this study. Methods Linear regression was used to assess the country-level association between COVID-19 attributable mortality per 100 000 inhabitants (mortality/capita) and COVID-19 tests/capita (number of tests/100 000 inhabitants) controlling for the cumulative number of COVID-19 infections/100 000 inhabitants (cases/capita), the age of the epidemic (number of days between first case reported and 8 April), national health expenditure per capita and WHO world region. Results The COVID-19 mortality rate varied between 0.3 and 3110 deaths/100 000 inhabitants (median 30, IQR 8-105). The intensity of testing per 100 000 also varied considerably (median 21,970, IQR 2,735-89,095) as did the number of COVID-19 cases per 100 000 (median 1,600, IQR 340-4,760 cases/100 000). In the multivariate model, the COVID-19 mortality rate was negatively associated with tests/capita (Coef. -0.036, 95% CI -0.047- -0.025) and positively associated with cases/capita (Coef. 0.093, 95% CI 0.819- 1.034). Conclusions The results are compatible with the hypothesis that intensive testing and isolation could play a role in reducing COVID-10 mortality rates.

negative: Global patterns of mortality in international migrants: a systematic review and meta-analysis. BACKGROUND 258 million people reside outside their country of birth; however, to date no global systematic reviews or meta-analyses of mortality data for these international migrants have been done. We aimed to review and synthesise available mortality data on international migrants. METHODS In this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Library, and Google Scholar databases for observational studies, systematic reviews, and randomised controlled trials published between Jan 1, 2001, and March 31, 2017, without language restrictions. We included studies reporting mortality outcomes for international migrants of any age residing outside their country of birth. Studies that recruited participants exclusively from intensive care or high dependency hospital units, with an existing health condition or status, or a particular health exposure were excluded. We also excluded studies limited to maternal or perinatal outcomes. We screened studies using systematic review software and extracted data from published reports. The main outcomes were all-cause and International Classification of Diseases, tenth revision (ICD-10) cause-specific standardised mortality ratios (SMRs) and absolute mortality rates. We calculated summary estimates using random-effects models. This study is registered with PROSPERO, number CRD42017073608. FINDINGS Of the 12 480 articles identified by our search, 96 studies were eligible for inclusion. The studies were geographically diverse and included data from all global regions and for 92 countries. 5464 mortality estimates for more than 15·2 million migrants were included, of which 5327 (97%) were from high-income countries, 115 (2%) were from middle-income countries, and 22 (<1%) were from low-income countries. Few studies included mortality estimates for refugees (110 estimates), asylum seekers (144 estimates), or labour migrants (six estimates). The summary estimate of all-cause SMR for international migrants was lower than one when compared with the general population in destination countries (0·70 [95% CI 0·65-0·76]; I2=99·8%). All-cause SMR was lower in both male migrants (0·72 [0·63-0·81]; I2=99·8%) and female migrants (0·75 [0·67-0·84]; I2=99·8%) compared with the general population. A mortality advantage was evident for refugees (SMR 0·50 [0·46-0·54]; I2=89·8%), but not for asylum seekers (1·05 [0·89-1·24]; I2=54·4%), although limited data was available on these groups. SMRs for all causes of death were lower in migrants compared with the general populations in the destination country across all 13 ICD-10 categories analysed, with the exception of infectious diseases and external causes. Heterogeneity was high across the majority of analyses. Point estimates of all-cause age-standardised mortality in migrants ranged from 420 to 874 per 100 000 population. INTERPRETATION Our study showed that international migrants have a mortality advantage compared with general populations, and that this advantage persisted across the majority of ICD-10 disease categories. The mortality advantage identified will be representative of international migrants in high-income countries who are studying, working, or have joined family members in these countries. However, our results might not reflect the health outcomes of more marginalised groups in low-income and middle-income countries because little data were available for these groups, highlighting an important gap in existing research. Our results present an opportunity to reframe the public discourse on international migration and health in high-income countries. FUNDING Wellcome Trust, National Institute for Health Research, Medical Research Council, Alliance for Health Policy and Systems Research, Department for International Development, Fogarty International Center, Grand Challenges Canada, International Development Research Centre Canada, Inter-American Institute for Global Change Research, National Cancer Institute, National Heart, Lung and Blood Institute, National Institute of Mental Health, Swiss National Science Foundation, World Diabetes Foundation, UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, and European Society for Clinical Microbiology and Infectious Diseases (ESCMID) Study Group Research Funding for the ESCMID Study Group for Infections in Travellers and Migrants.

negative: COVID-19: Guidelines for Myasthenia Gravis Management and other Neuromuscular Disorders

negative: A Rapid and Low-Cost PCR Thermal Cycler for Infectious Disease Diagnostics The ability to make rapid diagnosis of infectious diseases broadly available in a portable, low-cost format would mark a great step forward in global health. Many molecular diagnostic assays are developed based on using thermal cyclers to carry out polymerase chain reaction (PCR) and reverse-transcription PCR for DNA and RNA amplification and detection, respectively. Unfortunately, most commercial thermal cyclers are expensive and need continuous electrical power supply, so they are not suitable for uses in low-resource settings. We have previously reported a low-cost and simple approach to amplify DNA using vacuum insulated stainless steel thermoses food cans, which we have named it thermos thermal cycler or TTC. Here, we describe the use of an improved set up to enable the detection of viral RNA targets by reverse-transcription PCR (RT-PCR), thus expanding the TTC’s ability to identify highly infectious, RNA virus-based diseases in low resource settings. The TTC was successful in demonstrating high-speed and sensitive detection of DNA or RNA targets of sexually transmitted diseases, HIV/AIDS, Ebola hemorrhagic fever, and dengue fever. Our innovative TTC costs less than $200 to build and has a capacity of at least eight tubes. In terms of speed, the TTC’s performance exceeded that of commercial thermal cyclers tested. When coupled with low-cost endpoint detection technologies such as nucleic acid lateral-flow assay or a cell-phone-based fluorescence detector, the TTC will increase the availability of on-site molecular diagnostics in low-resource settings.

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: Effectiveness and safety of antiviral or antibody treatments for coronavirus: A rapid review Background: To identify safe and effective medical countermeasures (e.g., antivirals/antibodies) to address the current outbreak of a novel coronavirus (COVID-19) Methods: Comprehensive literature searches were developed by an experienced librarian for MEDLINE, EMBASE, the Cochrane Library, and biorxiv.org/medrxiv.org; additional searches for ongoing trials and unpublished studies were conducted in clinicaltrials.gov and the Global Infectious Diseases and Epidemiology Network (GIDEON). Title/abstract and full-text screening, data abstraction, and risk of bias appraisal were carried out by single reviewers. Results: 54 studies were included in the review: three controlled trials, 10 cohort studies, seven retrospective medical record/database studies, and 34 case reports or series. These studies included patients with severe acute respiratory syndrome (SARs, n=33), middle east respiratory syndrome (MERS, n=16), COVID-19 (n=3), and unspecified coronavirus (n=2). The most common treatment was ribavirin (n=41), followed by oseltamivir (n=10) and the combination of lopinavir/ritonavir (n=7). Additional therapies included broad spectrum antibiotics (n=30), steroids (n=39) or various interferons (n=12). No eligible studies examining monoclonal antibodies for COVID-19 were identified. One trial found that ribavirin prophylactic treatment statistically significantly reduced risk of MERS infection in people who had been exposed to the virus. Of the 21 studies reporting rates of ICU admission in hospitalized SARS or MERS patients, none reported statistically significant results in favour of or against antiviral therapies. Of the 40 studies reporting mortality rates in hospitalized SARS or MERS patients, one cohort study (MERS) and one retrospective study (SARS) found a statistically significant increase in the mortality rate for patients treated with ribavirin. Eighteen studies reported potential drug-related adverse effects including gastrointestinal symptoms, anemia, and altered liver function in patients receiving ribavirin. Conclusion: The current evidence for the effectiveness and safety of antiviral therapies for coronavirus is inconclusive and suffers from a lack of well-designed prospective trials or observational studies, preventing any treatment recommendations from being made. However, it is clear that the existing body of evidence is weighted heavily towards ribavirin (41/54 studies), which has not shown conclusive evidence of effectiveness and may cause harmful adverse events so future investigations may consider focusing on other candidates for antiviral therapy.

negative: The Data set for Patient Information Based Algorithm to Predict Mortality Cause by COVID-19 Abstract The data of COVID-19 disease in China and then in South Korea were collected daily from several different official websites. The collected data included 33 death cases in Wuhan city of Hubei province during early outbreak as well as confirmed cases and death toll in some specific regions, which were chosen as representatives from the perspective of the coronavirus outbreak in China. Data were copied and pasted onto Excel spreadsheets to perform data analysis. A new methodology, Patient Information Based Algorithm (PIBA) [1], has been adapted to process the data and used to estimate the death rate of COVID-19 in real-time. Assumption is that the number of days from inpatients to death fall into a pattern of normal distribution and the scores in normal distribution can be obtained by observing 33 death cases and analysing the data [2]. We selected 5 scores in normal distribution of these durations as lagging days, which will be used in the following estimation of death rate. We calculated each death rate on accumulative confirmed cases with each lagging day from the current data and then weighted every death rate with its corresponding possibility to obtain the total death rate on each day. While the trendline of these death rate curves meet the curve of current ratio between accumulative death cases and confirmed cases at some points in the near future, we considered that these intersections are within the range of real death rates. Six tables were presented to illustrate the PIBA method using data from China and South Korea. One figure on estimated rate of infection and patients in serious condition and retrospective estimation of initially occurring time of CORID-19 based on PIBA.

negative: 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: Novel Insights Into Immune Systems of Bats In recent years, viruses similar to those that cause serious disease in humans and other mammals have been detected in apparently healthy bats. These include filoviruses, paramyxoviruses, and coronaviruses that cause severe diseases such as Ebola virus disease, Marburg haemorrhagic fever and severe acute respiratory syndrome (SARS) in humans. The evolution of flight in bats seem to have selected for a unique set of antiviral immune responses that control virus propagation, while limiting self-damaging inflammatory responses. Here, we summarize our current understanding of antiviral immune responses in bats and discuss their ability to co-exist with emerging viruses that cause serious disease in other mammals. We highlight how this knowledge may help us to predict viral spillovers into new hosts and discuss future directions for the field.

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: Are the COVID19 restrictions really worth the cost? A comparison of estimated mortality in Australia from COVID19 and economic recession There has been considerable public debate about whether the economic impact of the current COVID19 restrictions are worth the costs. Although the potential impact of COVID19 has been modelled extensively, very few numbers have been presented in the discussions about potential economic impacts. For a good answer to the question - will the restrictions cause as much harm as COVID19? - credible evidence-based estimates are required, rather than simply rhetoric. Here we provide some preliminary estimates to compare the impact of the current restrictions against the direct impact of the virus. Since most countries are currently taking an approach that reduces the number of COVID19 deaths, the estimates we provide for deaths from COVID19 are deliberately taken from the low end of the estimates of the infection fatality rate, while estimates for deaths from an economic recession are deliberately computed from double the high end of confidence interval for severe economic recessions. This ensures that an adequate challenge to the status quo of the current restrictions is provided. Our analysis shows that strict restrictions to eradicate the virus are likely to lead to at least eight times fewer total deaths than an immediate return to work scenario.

negative: The Burden of COVID-19 in People Living with HIV: A Syndemic Perspective The emergence of the novel coronavirus disease known as COVID-19 creates another health burden for people living with HIV (PLWH) who face multiple morbidities and may be at heightened risk for severe physical health illness from COVID-19. Our abilities to address these morbidities in PLWH must be considered alongside the socially-produced burdens that both place this population at risk for COVID-19 and heighten the likelihood of adverse outcomes. These burdens can affect the physical, emotional, and social well-being of PLWH and interfere with the delivery of effective healthcare and access to HIV treatment. We posit that a syndemic framework can be used to conceptualize the potential impact of COVID-19 among PLWH to inform the development of health programming services.

negative: Trauma complications and in-hospital mortality: failure-to-rescue BACKGROUND: Reducing medical errors and minimizing complications have become the focus of quality improvement in medicine. Failure-to-rescue (FTR) is defined as death after a surgical complication, which is an institution-level surgical safety and quality metric that is an important variable affecting mortality rates in hospitals. This study aims to examine whether complication and FTR are different across low- and high-mortality hospitals for trauma care. METHODS: This was a retrospective cohort study performed at trauma care hospitals registered at Japan Trauma Data Bank (JTDB) from 2004 to 2017. Trauma patients aged ≥ 15 years with injury severity score (ISS) of ≥ 3 and those who survived for > 48 h after hospital admission were included. The hospitals in JTDB were categorized into three groups by standardized mortality rate. We compared trauma complications, FTR, and in-hospital mortality by a standardized mortality rate (divided by the institute-level quartile). RESULTS: Among 184,214 patients that were enrolled, the rate of any complication was 12.7%. The overall mortality rate was 3.7%, and the mortality rate among trauma patients without complications was only 2.8% (non-precedented deaths). However, the mortality rate among trauma patients with any complications was 10.2% (FTR). Hospitals were categorized into high- (40 facilities with 44,773 patients), average- (72 facilities with 102,368 patients), and low- (39 facilities with 37,073 patients) mortality hospitals, using the hospital ranking of a standardized mortality rate. High-mortality hospitals showed lower ISS than low-mortality hospitals [10 (IQR, 9–18) vs. 11 (IQR, 9–20), P < 0.01]. Patients in high-mortality hospitals showed more complications (14.2% vs. 11.2%, P < 0.01), in-hospital mortality (5.1% vs. 2.5%, P < 0.01), FTR (13.6% vs. 7.4%, P < 0.01), and non-precedented deaths (3.6% vs. 1.9%, P < 0.01) than those in low-mortality hospitals. CONCLUSIONS: Unlike reports of elective surgery, complication rates and FTR are associated with in-hospital mortality rates at the center level in trauma care.

negative: Chapter 1 Introduction to Animal Viruses Abstract Viruses are infectious agents that are not cellular in nature. They consist of a nucleic acid genome packaged within a protein shell. Although relatively simple, viruses exhibit significant diversity in terms of size, genome organization, and capsid architecture. All viruses are obligate intracellular parasites as they must obtain energy and building blocks from the cell. They subvert many host cell processes for their own replication, and studying virus replication has provided detailed information about the basic workings of cells. At the cellular level, possible outcomes of infection range from production of virus particles without damage to the cell, to cell death, or occasionally cell transformation. In humans and animals the outcomes of infection range from inapparent (no disease) to considerable disease and death. Some viruses cause acute infections lasting for days or a few weeks while others infect their hosts for a lifetime. Viruses can evolve and rapidly adapt to changing conditions. Some viruses are easily replicated in cultured cells, while others require specific conditions only found in specialized cells within a human or animal. While this text focuses on viruses of humans and other animals, viruses infect organisms of all types, from bacteria to fungi to plants. Viruses are most often classified based on groups of genome and virion characteristics. Genome sequence comparisons provide an unbiased method for grouping and categorizing viruses.

negative: Modeling strict age-targeted mitigation strategies for COVID-19 We use a simple SIR-like epidemic model which integrates known age-contact patterns for the United States to model the effect of age-targeted mitigation strategies for a COVID-19-like epidemic. We find that, among strategies which end with population immunity, strict age-targeted mitigation strategies have the potential to greatly reduce mortalities and ICU utilization for natural parameter choices.

negative: Induction of lactogenic immunity to transmissible gastroneteritis virus of swine using an attenuated coronavirus mutant able to survive in the physicochemical environment of the digestive tract Abstract A trasmissible gastroenteritis (TGE) coronavirus mutant (188-SG), selected as attenuated and resistant to acidity and proteases of the digestive tract of adult pigs, was used as vaccine (“Nouzilly strain”) in sows to protect suckling piglets against a challenge exposure carried out with a higly virulent TGEV strain. The pregnant sows were immunized once (42–49 days before farrowing) or twice (42–49 and 7–15 days before farrowing) by the oral, intramuscular or conjunctival route with the 188-SG strain. Sows exposed to virulent TGEV in the field and experimentally infected sows (two oral inoculations during pregnancy) were used as positive controls leading to high protection. The neutralizing antibody response to vaccination and/or infection was studied in serum and milk. No protection against mortality was observed in the litters of (1) the nine seronegative, susceptible sows, with piglet mortality of 65/70, (2) the seven once orally vaccinated sows, with mortality of 44/54, (3) the seven sows vaccinated twice by the conjunctival route, with mortality of 55/76. Moderate protection was observed in (1) the eight sows vaccinated intramuscularly twice with piglet mortality of 36/90, (2) the seven orally and intramuscularly vaccinated sows with piglet mortality of 31/51. In contrast, improved protection was observed in (1) the 10 sows vaccinated twice orally, with piglet mortality of 23/95, (2) the four naturally infected sows with piglet mortality of 6/41, (3) the six sows experimentally infected with virulent TGEV with piglet mortality of 1/59. No correlation was found between neutralizing antibodies titers in serum and milk and protection rate of the piglets. The results indicate that relative protective lactogenic immunity against TGEV is induced only by repeated ingestion of -SG attenuated 188-SG strain of TGEV.

negative: Infectious diseases in children and adolescents in China: analysis of national surveillance data from 2008 to 2017 OBJECTIVES: To outline which infectious diseases in the pre-covid-19 era persist in children and adolescents in China and to describe recent trends and variations by age, sex, season, and province. DESIGN: National surveillance studies, 2008-17. SETTING: 31 provinces in mainland China. PARTICIPANTS: 4 959 790 Chinese students aged 6 to 22 years with a diagnosis of any of 44 notifiable infectious diseases. The diseases were categorised into seven groups: quarantinable; vaccine preventable; gastrointestinal and enteroviral; vectorborne; zoonotic; bacterial; and sexually transmitted and bloodborne. MAIN OUTCOME MEASURES: Diagnosis of, and deaths from, 44 notifiable infectious diseases. RESULTS: From 2008 to 2017, 44 notifiable infectious diseases were diagnosed in 4 959 790 participants (3 045 905 males, 1 913 885 females) and there were 2532 deaths (1663 males, 869 females). The leading causes of death among infectious diseases shifted from rabies and tuberculosis to HIV/AIDS, particularly in males. Mortality from infectious diseases decreased steadily from 0.21 per 100 000 population in 2008 to 0.07 per 100 000 in 2017. Quarantinable conditions with high mortality have effectively disappeared. The incidence of notifiable infectious diseases in children and adolescents decreased from 280 per 100 000 in 2008 to 162 per 100 000 in 2015, but rose again to 242 per 100 000 in 2017, largely related to mumps and seasonal influenza. Excluding mumps and influenza, the incidence of vaccine preventable diseases fell from 96 per 100 000 in 2008 to 7 per 100 000 in 2017. The incidence of gastrointestinal and enterovirus diseases remained constant, but typhoid, paratyphoid, and dysentery continued to decline. Vectorborne diseases all declined, with a particularly noticeable reduction in malaria. Zoonotic infections remained at low incidence, but there were still unpredictable outbreaks, such as pandemic A/H1N1 2009 influenza. Tuberculosis remained the most common bacterial infection, although cases of scarlet fever doubled between 2008 and 2017. Sexually transmitted diseases and bloodborne infections increased significantly, particularly from 2011 to 2017, among which HIV/AIDS increased fivefold, particularly in males. Difference was noticeable between regions, with children and adolescents in western China continuing to carry a disproportionate burden from infectious diseases. CONCLUSIONS: China’s success in infectious disease control in the pre-covid-19 era was notable, with deaths due to infectious diseases in children and adolescents aged 6-22 years becoming rare. Many challenges remain around reducing regional inequalities, scaling-up of vaccination, prevention of further escalation of HIV/AIDS, renewed efforts for persisting diseases, and undertaking early and effective response to highly transmissible seasonal and unpredictable diseases such as that caused by the novel SARS-CoV-2 virus.

negative: Burden of serious fungal infections in the Netherlands BACKGROUND: Fungal diseases have an ever‐increasing global disease burden, although regional estimates for specific fungal diseases are often unavailable or dispersed. OBJECTIVES: Here, we report the current annual burden of life‐threatening and debilitating fungal diseases in the Netherlands. METHODS: The most recent available epidemiological data, reported incidence and prevalence of fungal diseases were used for calculations. RESULTS: Overall, we estimate that the annual burden of serious invasive fungal infections in the Netherlands totals 3 185 patients, including extrapulmonary or disseminated cryptococcosis (n = 9), pneumocystis pneumonia (n = 740), invasive aspergillosis (n = 1 283), chronic pulmonary aspergillosis (n = 257), invasive Candida infections (n = 684), mucormycosis (n = 15) and Fusarium keratitis (n = 8). Adding the prevalence of recurrent vulvo‐vaginal candidiasis (n = 220 043), allergic bronchopulmonary aspergillosis (n = 13 568) and severe asthma with fungal sensitisation (n = 17 695), the total debilitating burden of fungal disease in the Netherlands is 254 491 patients yearly, approximately 1.5% of the country's population. CONCLUSION: We estimated the annual burden of serious fungal infections in the Netherlands at 1.5% of the population based on previously reported modelling of fungal rates for specific populations at risk. With emerging new risk groups and increasing reports on antifungal resistance, surveillance programmes are warranted to obtain more accurate estimates of fungal disease epidemiology and associated morbidity and mortality.

negative: p38 MAPK inhibition: A promising therapeutic approach for COVID-19 COVID-19, caused by the SARS-CoV-2 virus, is a major source of morbidity and mortality due to its inflammatory effects in the lungs and heart. The p38 MAPK pathway plays a crucial role in the release of pro-inflammatory cytokines such as IL-6 and has been implicated in acute lung injury and myocardial dysfunction. The overwhelming inflammatory response in COVID-19 infection may be caused by disproportionately upregulated p38 activity, explained by two mechanisms. First, angiotensin-converting enzyme 2 (ACE2) activity is lost during SARS-CoV-2 viral entry. ACE2 is highly expressed in the lungs and heart and converts Angiotensin II into Angiotensin 1–7. Angiotensin II signals proinflammatory, pro-vasoconstrictive, pro-thrombotic activity through p38 MAPK activation, which is countered by Angiotensin 1–7 downregulation of p38 activity. Loss of ACE2 upon viral entry may tip the balance towards destructive p38 signaling through Angiotensin II. Second, SARS-CoV was previously shown to directly upregulate p38 activity via a viral protein, similar to other RNA respiratory viruses that may hijack p38 activity to promote replication. Given the homology between SARS-CoV and SARS-CoV-2, the latter may employ a similar mechanism. Thus, SARS-CoV-2 may induce overwhelming inflammation by directly activating p38 and downregulating a key inhibitory pathway, while simultaneously taking advantage of p38 activity to replicate. Therapeutic inhibition of p38 could therefore attenuate COVID-19 infection. Interestingly, a prior preclinical study showed protective effects of p38 inhibition in a SARS-CoV mouse model. A number of p38 inhibitors are in the clinical stage and should be considered for clinical trials in serious COVID-19 infection.

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

negative: Different pattern of viral infections and clinical outcomes in patient with acute exacerbation of chronic obstructive pulmonary disease and chronic obstructive pulmonary disease with pneumonia Respiratory viruses are well‐known causes of acute exacerbation of chronic obstructive pulmonary disease (AE‐COPD) and also important pathogens for concomitant pneumonia in COPD (CP‐COPD). However, the differences in a viral infection pattern and clinical impacts of respiratory viruses between the two groups have not been well investigated. The clinical and microbiological data from COPD patients admitted with AE‐COPD (n = 281) or CP‐COPD (n = 284) between January 2010 and December 2012 were reviewed. After excluding 88 patients (40 with AE‐COPD and 48 with CP‐COPD) who did not undergo a multiplex RT‐PCR test for respiratory viruses, the demographic characteristics, identified viruses, and clinical outcomes of the AE‐COPD and CP‐COPD groups were compared. Respiratory viruses were identified in 41.9% of AE‐COPD group and 33.5% of the CP‐COPD groups. The most common virus was influenza virus in the AE‐COPD group (33.7%) versus human coronavirus (24.1%) in the CP‐COPD group. Influenza virus was significantly more common in the AE‐ACOPD group than in the CP‐COPD group (P < 0.01). In‐hospital mortality of AE‐COPD and CP‐COPD were 1.2% and 12.3%, respectively (P < 0.01). Among CP‐COPD patients, in‐hospital mortality of patients with only viral infection group, only bacterial infection group, and viral‐bacterial co‐infection were 2.6%, 25.8%, and 17.5%, respectively (P = 0.01). Respiratory viruses were commonly identified in both AE‐COPD and CP‐COPD, influenza virus and human coronavirus were the most common viruses identified in AE‐COPD and CP‐COPD patients, respectively. The mortality rates of only viral infection group was significantly lower than only bacterial infection or viral‐bacterial co‐infection group in CP‐COPD patients. J. Med. Virol. 88:2092–2099, 2016. © 2016 Wiley Periodicals, Inc.

negative: Lack of association between HLA‐A, ‐B and ‐DRB1 alleles and the development of SARS: a cohort of 95 SARS‐recovered individuals in a population of Guangdong, southern China Severe acute respiratory syndrome (SARS), caused by infection with a novel coronavirus (SARS‐CoV), was the first major novel infectious disease at the beginning of the 21st century, with China especially affected. SARS was characterized by high infectivity, morbidity and mortality, and the confined pattern of the disease spreading among the countries of South‐East and East Asia suggested the existence of susceptible factor(s) in these populations. Studies in the populations of Hong Kong and Taiwan showed an association of human leucocyte antigen (HLA) polymorphisms with the development and/or severity of SARS, respectively. The aim of the present study was to define the genotypic patterns of HLA‐A, ‐B and ‐DRB1 loci in SARS patients and a co‐resident population of Guangdong province, southern China, where the first SARS case was reported. The samples comprised 95 cases of recovered SARS patients and 403 unrelated healthy controls. HLA ‐A, ‐B and ‐DRB1 alleles were genotyped using polymerase chain reaction with sequence‐specific primers. The severity of the disease was assessed according to the history of lung infiltration, usage of assisted ventilation and occurrence of lymphocytopenia. Although the allelic frequencies of A23, A34, B60, DRB1*12 in the SARS group were slightly higher, and A33, ‐B58 and ‐B61 were lower than in the controls, no statistical significance was found when the Pc value was considered. Similarly, no association of HLA alleles with the severity of the disease was detected. Thus, variations in the major histocompatibility complex are unlikely to have contributed significantly to either the susceptibility or the severity of SARS in the population of Guangdong.

negative: To mask or not to mask: Modeling the potential for face mask use by the general public to curtail the COVID-19 pandemic Face mask use by the general public for limiting the spread of the COVID-19 pandemic is controversial, though increasingly recommended, and the potential of this intervention is not well understood. We develop a compartmental model for assessing the community-wide impact of mask use by the general, asymptomatic public, a portion of which may be asymptomatically infectious. Model simulations, using data relevant to COVID-19 dynamics in the US states of New York and Washington, suggest that broad adoption of even relatively ineffective face masks may meaningfully reduce community transmission of COVID-19 and decrease peak hospitalizations and deaths. Moreover, mask use decreases the effective transmission rate in nearly linear proportion to the product of mask effectiveness (as a fraction of potentially infectious contacts blocked) and coverage rate (as a fraction of the general population), while the impact on epidemiologic outcomes (death, hospitalizations) is highly nonlinear, indicating masks could synergize with other non-pharmaceutical measures. Notably, masks are found to be useful with respect to both preventing illness in healthy persons and preventing asymptomatic transmission. Hypothetical mask adoption scenarios, for Washington and New York state, suggest that immediate near universal (80%) adoption of moderately (50%) effective masks could prevent on the order of 17–45% of projected deaths over two months in New York, while decreasing the peak daily death rate by 34–58%, absent other changes in epidemic dynamics. Even very weak masks (20% effective) can still be useful if the underlying transmission rate is relatively low or decreasing: In Washington, where baseline transmission is much less intense, 80% adoption of such masks could reduce mortality by 24–65% (and peak deaths 15–69%), compared to 2–9% mortality reduction in New York (peak death reduction 9–18%). Our results suggest use of face masks by the general public is potentially of high value in curtailing community transmission and the burden of the pandemic. The community-wide benefits are likely to be greatest when face masks are used in conjunction with other non-pharmaceutical practices (such as social-distancing), and when adoption is nearly universal (nation-wide) and compliance is high.

negative: Outcomes of a Two-Tiered Multifaceted Elderly Suicide Prevention Program in a Hong Kong Chinese Community Objectives 1) To compare the 2-year completed suicide and reattempt rates in a preintervention group of Hong Kong Chinese suicide attempters (aged 65 years and older) who received standard care and a postintervention group enrolled in a regional elderly suicide prevention program (ESPP) that adopts a two-tiered multifaceted care management model and 2) to examine the trend of suicide rates in older adults aged 65 years and older in the pre- and postintervention periods. Design The first part is an observational cohort study with baseline, follow-up, and outcome data being identified from a clinical electronic registry. The second part examines changes in suicide rates from official mortality statistics. Setting A government-funded suicide intervention program serving catchment population (852,796 people aged 65 years and older) in Hong Kong, China. Participants Suicide attempters (aged 65 years and older) presenting to old-age psychiatric service in the pre- and postintervention phases. Measurements 1) Two-year rates of completed suicide and suicide reattempt and 2) changes in population suicide rates in the pre- and postintervention periods. Results The 2-year completed suicide rate was 7.58% in the preintervention group (N = 66) and 1.99$% in the ESPP group (N = 351) χ2 = 6.192; p value: 0.028; df = 1). Reattempt rates were not different. At a population level, suicide rate dropped significantly only in women aged 85 years and older, relative to the preintervention period. Conclusions The ESPP was associated with a reduced rate of completed suicide in old-age suicide attempters and might have contributed to a fall of suicide rate in women aged 85 years and older.

negative: Bovine respiratory disease complex associated mortality and morbidity rates in feedlot cattle from southeastern Brazil. INTRODUCTION A feedlot is an intensive farming system for finishing livestock. Bovine respiratory disease (BRD) is a cause of morbidity and mortality in beef cattle, especially in feedlots. METHODOLOGY This study investigated the morbidity and mortality of BRD in a beef cattle feedlot in southeastern Brazil using: clinical diagnoses, therapy, morbidity, and mortality. Pulmonary fragments were collected from five steers, on feed from 3-32 days, with lesions of pneumonia for identification of BRD infectious agents PCR. RESULTS 188,862 steers were on feed and morbidity was 7.05% (13,315/188,862), mortality 0.64% (1,214/188,862). The causes of morbidity were: BRD (6.13%), lameness (0.29%), trauma (0.21%), clostridiosis (0.13%) and polioencephalomalacia, PEM (0.12%). The causes of mortality were: BRD (0.21%), trauma (0.17%), and clostridiosis (0.13%). When all sick cattle were considered (n=13,315), BRD (86.9%) was the principal cause of morbidity, followed by lameness (4.13%), trauma (3.05%), and clostridiosis (1.82%). The cost of BRD-associated cattle mortality and morbidity was estimated at $14,334.00/10,000 and $16,315.40/10,000 respectively. It was projected that the economic effects due to BRD-associated morbidity in Brazil were $6.31 million/annum, while losses due to mortality were $5.54 million, resulting in an annual loss of $11.85 million. Coinfections in cattle with pneumonia due to Mannheimia haemolytica and Pasteurella multocida were identified in 4/5 steers tested. CONCLUSIONS This is the first longitudinal study that investigated the incidence of BRD in feedlot cattle from Brazil, and the results herein described indicate that BRD contributed significantly to the development of mortality and morbidity of cattle on feed.

negative: A genetic analysis of macrophage activation and specific antibodies in relation to the resistance of heterogeneous mouse populations to MHV3 infection The genetically selected high antibody responder mice (H(III)) are susceptible and the low antibody responder mice (L(III)) are resistant to the experimental infection with Mouse Hepatitis Virus 3 (MHV3). The mortality rates of the F(1) hybrids and of the F(2) segregants showed the codominance of the susceptible and resistant characters. The direct individual intrapopulation correlation between the induction of antiviral state in macrophages activated by IFN gamma and the resistance to the virus infection, showed that an antiviral state could be induced in resistant mouse macrophages, whereas in susceptible mouse macrophages no restriction of virus replication could be observed. A direct inter- and intrapopulation correlation of pre-existing antibody titres against MHV3 with the mortality and a direct interpopulation correlation of those titres with the mean survival time of susceptible animals was shown. The data indicate, among the mechanisms of resistance against the virus infection, a role of IFN gamma macrophage-activation and of antibodies against MHV3 which may delay the mean survival time in susceptible animals.

negative: Predicting the epidemic trend of COVID-19 in China and across the world using the machine learning approach Background: Although COVID-19 has been well controlled in China, it is rapidly spreading outside the country and may have catastrophic results globally without implementation of necessary mitigation measures. Because the COVID-19 outbreak has made comprehensive and profound impacts on the world, an accurate prediction of its epidemic trend is significant. Although many studies have predicted the COVID-19 epidemic trend, most have used early-stage data and focused on Chinese cases. Methods: We first built models to predict daily numbers of cumulative confirmed cases (CCCs), new cases (NCs), and death cases (DCs) of COVID-19 in China based on data from January 20, 2020, to March 1, 2020. Based on these models, we built models to predict the epidemic trend across the world (outside China). We also built models to predict the epidemic trend in Italy, Spain, Germany, France, UK, and USA where COVID-19 is rapidly spreading. Findings: The COVID-19 outbreak will have peaked on February 22, 2020, in China and will peak on May 22, 2020, across the world. It will be basically under control in early April 2020 in China and end-August 2020 across the world. The total number of COVID-19 cases will reach around 89,000 in China and 6,126,000 across the world during the epidemic. Around 4,000 and 290,000 people will die of COVID-19 in China and across the world, respectively. The COVID-19 outbreak will have peaked recently in Italy and will peak in Spain, Germany, France, UK, and USA within two weeks. Interpretation: The COVID-19 outbreak is controllable in the foreseeable future if comprehensive and stringent control measures are taken.

negative: What are the risks of COVID-19 infection in pregnant women?

negative: The novel coronavirus outbreak: what can be learned from China in public reporting? The new coronavirus outbreak gets everyone’s attention. China’s national actions against the outbreak have contributed great contributions to the world. China has been learning from practice for better reporting and is fast to adapt itself. In this article we discuss China’s practice in public reporting and its implications to global health. Confirmed cases, dynamic suspected cases, recovered cases, and deaths have been reported both in accumulative numbers and their daily updates. Some ratio indictors reporting (fatality rate, recovery rate, etc.), trend reporting, and global surveillance have been applied as well. Some improvements can still be made. It is necessary to further explore the influential factors behind the indicators for interventions. Recommendations are made to the World Health Organization and other countries for better public reporting and surveillance.

negative: Liver diseases in the Asia-Pacific region: a Lancet Gastroenterology & Hepatology Commission The Asia-Pacific region is home to more than half of the global population and accounted for 62·6% of global deaths due to liver diseases in 2015. 54·3% of global deaths due to cirrhosis, 72·7% of global deaths due to hepatocellular carcinoma, and more than two-thirds of the global burden of acute viral hepatitis occurred in this region in 2015. Chronic hepatitis B virus (HBV) infection caused more than half of the deaths due to cirrhosis in the region, followed by alcohol consumption (20·8%), non-alcoholic fatty liver disease (NAFLD; 12·1%), and chronic infection with hepatitis C virus (HCV; 15·7%). In 2015, HBV accounted for about half the cases of hepatocellular carcinoma in the region. Preventive strategies for viral hepatitis-related liver disease include increasing access to clean drinking water and sanitation. HBV vaccination programmes for neonates have been implemented by all countries, although birth-dose coverage is extremely suboptimal in some. Availability of screening tests for blood and tissue, donor recall policies, and harm reduction strategies are in their initial stages in most countries. Many governments have put HBV and HCV drugs on their essential medicines lists and the availability of generic versions of these drugs has reduced costs. Efforts to eliminate viral hepatitis as a public health threat, together with the rapid increase in per-capita alcohol consumption in countries and the epidemic of obesity, are expected to change the spectrum of liver diseases in the Asia-Pacific region in the near future. The increasing burden of alcohol-related liver diseases can be contained through government policies to limit consumption and promote less harmful patterns of alcohol use, which are in place in some countries but need to be enforced more strictly. Steps are needed to control obesity and NAFLD, including policies to promote healthy lifestyles and regulate the food industry. Inadequate infrastructure and insufficient health-care personnel trained in liver diseases are issues that also need to be addressed in the Asia-Pacific region. The policy response of most governments to liver diseases has thus far been inadequate and poorly funded. There must be a renewed focus on prevention, early detection, timely referral, and research into the best means to introduce and improve health interventions to reduce the burden of liver diseases in the Asia-Pacific region.

negative: An international physical activity and public health research agenda to inform COVID-19 policies and practices

negative: Porcine epidemic diarrhea: A retrospect from Europe and matters of debate Abstract A retrospect is given on the emergence of porcine epidemic diarrhea (PED) during the early seventies in Europe. While, at first, it appeared as a disease affecting feeder pigs, fattening- and adult swine, it later also became pathogenic for neonatal and suckling pigs hereby drastically increasing its economic impact. Isolation of the causative virus revealed a new porcine coronavirus, the origin of which has never been clarified. Pathogenesis studies with the prototype strain CV777 showed severe villous atrophy in neonatal pigs and the virus-animal interactions showed many similarities with transmissible gastro-enteritis virus (TGEV), another porcine coronavirus. Disease patterns in field outbreaks showed muchvariation but, while farm related factors played a role, possible genetic variations of virus strains in Europe have not been examined and are thus unknown. CV777 in experimental pigs caused diarrheal disease and mortality rates similar to those later encountered in Asia and more recently with the “original” US strains even though genomic typing of the prototype European strain have shown that it belongs to the S-INDEL strains. In Europe, PED has become endemic during the eighties and nineties and subsequently regressed so that, after 2000, swine populations in many countries have largely become seronegative. Sporadic outbreaks have recently reappeared showing a large variety of clinical outcomes.

negative: Estimating the burden of influenza‐associated hospitalization and deaths in Oman (2012‐2015) BACKGROUND: Influenza is a serious vaccine‐preventable disease with high incidence, hospitalization, and mortality in high‐risk groups. The epidemiology, seasonality, and risk factors for influenza are well defined in most of the temperate countries, but estimating influenza burden in the World Health Organization (WHO) Region for the Eastern Mediterranean is scarce. In Oman, despite the advancements in influenza surveillance, the clinical burden and seasonality of influenza remain not fully understood. OBJECTIVES: To estimate the incidence of influenza‐associated hospitalizations and in‐hospital death in Oman. PATIENTS AND METHODS: Influenza‐associated hospitalizations and in‐hospital deaths were estimated using hospital discharge records based on ICD‐10 codes (J09‐J18), results of virological analysis and population census for the period between 2012 and 2015. RESULTS: During 2012 and 2015, we identified a total of 19 405 influenza‐associated hospitalization and 847 deaths. Influenza positivity percentage ranged from 6.4% in 2013 to 20.6% in 2015. Influenza‐associated hospitalization incidence rate was 7.3 (95% CI: 6.4‐8.1) per 100 000 in 2013 and 27.5 (95% CI: 25.9‐29.1) per 100 000 in 2015 with an overall rate of 20.6 (95% CI: 19.9‐21.3) per 100 000. The highest incidence of influenza‐associated death was among those aged ≥65 years and ranged between 39.5 (95% CI: 27.3‐51.8) per 100 000 in 2014 and 11.3 (95% CI: 7.5‐15.1) in 2015. CONCLUSIONS: Influenza causes a substantial number of hospitalizations and deaths in Oman. Hospitalization rates were highest among children, and adults ≥65 years showed the highest death rate. The potential value of using seasonal influenza vaccine in these groups should be considered.

negative: Healthcare impact of COVID-19 epidemic in India: A stochastic mathematical model Abstract Background In India, the SARS-CoV-2 COVID-19 epidemic has grown to 1251 cases and 32 deaths as on 30 Mar 2020. The healthcare impact of the epidemic in India was studied using a stochastic mathematical model. Methods A compartmental SEIR model was developed, in which the flow of individuals through compartments is modeled using a set of differential equations. Different scenarios were modeled with 1000 runs of Monte Carlo simulation each using MATLAB. Hospitalization, intensive care unit (ICU) requirements, and deaths were modeled on SimVoi software. The impact of nonpharmacological interventions (NPIs) including social distancing and lockdown on checking the epidemic was estimated. Results Uninterrupted epidemic in India would have resulted in more than 364 million cases and 1.56 million deaths with peak by mid-July. As per the model, at current growth rate of 1.15, India is likely to reach approximately 3 million cases by 25 May, implying 125,455 (±18,034) hospitalizations, 26,130 (±3298) ICU admissions, and 13,447 (±1819) deaths. This would overwhelm India's healthcare system. The model shows that with immediate institution of NPIs, the epidemic might still be checked by mid-April 2020. It would then result in 241,974 (±33,735) total infections, 10,214 (±1649) hospitalizations, 2121 (±334) ICU admissions, and 1081 (±169) deaths. Conclusion At the current growth rate of epidemic, India's healthcare resources will be overwhelmed by the end of May. With the immediate institution of NPIs, total cases, hospitalizations, ICU requirements, and deaths can be reduced by almost 90%.

negative: Can early and high intravenous dose of vitamin C prevent and treat coronavirus disease 2019 (COVID-19)?

negative: Comprehensive Analysis of Severe Viral Infections of Respiratory Tract admitted to PICUs during the Winter Season in Turkey OBJECTIVES: To analyze the course of seasonal viral infections of respiratory tract in patients hospitalized in pediatric intensive care units (PICU) of 16 centers in Turkey. MATERIALS AND METHODS: It is a retrospective, observational, and multicenter study conducted in 16 tertiary PICUs in Turkey includes a total of 302 children with viral cause in the nasal swab which required PICU admission with no interventions. RESULTS: Median age of patients was 12 months. Respiratory syncytial virus (RSV) was more common in patients over one year of age whereas influenza, human Bocavirus in patients above a year of age was more common (p <0.05). Clinical presentations influencing mortality were neurologic symptoms, tachycardia, hypoxia, hypotension, elevated lactate, and acidosis. The critical pH value related with mortality was ≤7.10, and critical PCO(2) ≥60 mm Hg. CONCLUSION: Our findings demonstrate that patients with neurological symptoms, tachycardia, hypoxia, hypotension, acidosis, impaired liver, and renal function at the time of admission exhibit more severe mortal progressions. Presence of acidosis and multiorgan failure was found to be predictor for mortality. Knowledge of clinical presentation and age-related variations among seasonal viruses may give a clue about severe course and prognosis. By presenting the analyzed data of 302 PICU admissions, current study reveals severity of viral respiratory tract infections and release tips for handling them. HOW TO CITE THIS ARTICLE: Kockuzu E, Bayrakcı B, Kesici S, Cıtak A, Karapınar K, Emeksiz S, et al. Comprehensive Analysis of Severe Viral Infections of Respiratory Tract admitted to PICUs During the Winter Season in Turkey. Indian J Crit Care Med 2019;23(6):263–269.

negative: The effect of regionalization on outcome in pulmonary lobectomy: A Canadian national study Objective To examine the effect of regionalization of thoracic surgery services in Canada by evaluating change over time in hospital volumes of pulmonary lobectomy and its impact on length of stay and in-hospital mortality. Methods Data on pulmonary lobectomy between 1999 and 2007 were abstracted from the Canadian Institute for Health Information Discharge Abstract Database. In-hospital mortality was analyzed by logistic regression, and log-transformed length of stay was analyzed by linear regression. Cross-sectional analysis of hospital volume, in-hospital mortality, and length of stay was performed, controlling for clustering. Within-hospital changes in annual volume on outcome was analyzed using multivariable logistic regression, controlling for Charlson comorbidity index and other confounders. Results Of 19,732 patients, 10, 281 (52%) were male, with an average age of 63.3 years. There was a 45% (95% confidence interval, 21–61; P = .001) relative risk reduction in in-hospital mortality with a 19% reduction in length of stay (95% confidence interval, 12–25; P < .0001). On comparison of volume between hospitals, an increase of 20 cases was associated with a 15% relative risk reduction (95% confidence interval, 9–19; P < .0001) in in-hospital mortality and a 5% relative decrease (95% confidence interval, 3–7; P < .001) in length of stay. Within hospitals there was a nonsignificant relationship between volume and in-hospital mortality. Conclusions In-hospital mortality and length of stay for lobectomies have decreased in Canada. In multivariate analysis, volume was associated with improved in-hospital mortality, but there was no reduction in mortality when volume was increased within a given hospital. However, the proportion of patients treated in high-volume centers has increased over time, inferring the importance of high-volume centers in improved outcomes. This supports regionalization policies for pulmonary lobectomy.

negative: Emerging and re-emerging coronaviruses in pigs Porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome-coronavirus (SADS-CoV) are emerging/reemerging coronaviruses (CoVs). They cause acute gastroenteritis in neonatal piglets. Sequence analyses suggest that PEDV and SADS-CoV may have originated from bat CoVs and PDCoV from a sparrow CoV, reaffirming the interspecies transmission of CoVs. The clinical signs and pathogenesis of the three viruses are similar. Necrosis of infected intestinal epithelial cells occurs, causing villous atrophy that results in malabsorptive diarrhea. The severe diarrhea and vomiting may lead to dehydration and death of piglets. Natural infection induces protective immunity, but there is no cross-protection among the three viruses. Besides strict biosecurity measures, individual vaccines are needed for each virus for disease prevention and control.

negative: Emerging Viruses Emerging viruses are viruses that appear suddenly in the human population. These are viruses to which man has no history of exposure and thus no or limited immunity; they are not new evolutionary creations, but are viruses than man meets due to environmental changes, such as deforestation, entering into new habitats, or viruses that are transmitted from one species of animal to humans. Most of these viruses are terrifying, and cause hemorrhagic fever, a complete destruction of the circulation system; they include Lassa fever, Nipah virus, Ebola, HIV, Severe acute respiratory syndrome (SARS), and, recently, Middle East respiratory syndrome (MERS), which is the latest in a series of “new” respiratory viruses infecting man. It is possible that unknown emerging viruses are the cause of death, often listed as “death due to an unknown cause,” as in the retrospective cases of HIV. Emerging viruses might also include poliovirus and influenza, since their introduction into the human population is (was) often sudden and due to changes in the environment or due to contact with other animal species. For examples, polio was a result of changes in sanitation in the countries of North America and Western Europe, and influenza is constantly jumping from aquatic birds to man and other animal species where genomic reassortment occurs.

negative: Upheaval in cancer care during the COVID-19 outbreak On Monday, 23 March 2020, Nigeria recorded its first mortality from the novel global COVID-19 outbreak. Before this, the country reported 36 confirmed cases (at the time of writing) and has discharged home two cases after weeks of care at a government-approved isolation centre in Lagos State. This first mortality was that of a 67-year-old man with a history of multiple myeloma, a type of blood cancer. He was undergoing chemotherapy and had just returned to Nigeria following medical treatment in the United Kingdom. The novel COVID-19 pandemic has grounded several global activities including the provision of health care services to people with chronic conditions such as cancer. Evidence from China suggests that cancer patients with COVID-19 infection are a vulnerable group, with a higher risk of severe illness resulting in intensive care unit admissions or death, particularly if they received chemotherapy or surgery. This letter is an attempt to suggest practicable interventions such as the use of existing digital health platforms to limit patients’ and oncology professionals’ physical interactions as a way of reducing the risk of COVID-19 infection transmission amongst cancer patients and oncologists, as well as outlining effective strategies to ensure that cancer care is not completely disrupted during the outbreak.

negative: Herpes Simplex Virus-1 Fine-Tunes Host’s Autophagic Response to Infection: A Comprehensive Analysis in Productive Infection Models Herpes simplex virus-1 (HSV-1) infection causes severe conditions, with serious complications, including corneal blindness from uncontrolled ocular infections. An important cellular defense mechanism against HSV-1 infection is autophagy. The autophagic response of the host cell was suggested to be regulated by HSV-1. In this study, we performed a detailed analysis of autophagy in multiple HSV-1-targeted cell types, and under various infection conditions that recapitulate a productive infection model. We found that autophagy was slightly inhibited in one cell type, while in other cell types autophagy maintained its basal levels mostly unchanged during productive infection. This study refines the concept of HSV-1-mediated autophagy regulation to imply either inhibition, or prevention of activation, of the innate immune pathway.

negative: Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis Acute respiratory distress syndrome (ARDS) is immune-driven pathologies that are observed in severe cases of severe acute respiratory syndrome coronavirus (SARS-CoV) infection. SARS-CoV emerged in 2002 to 2003 and led to a global outbreak of SARS. As with the outcome of human infection, intranasal infection of C57BL/6J mice with mouse-adapted SARS-CoV results in high-titer virus replication within the lung, induction of inflammatory cytokines and chemokines, and immune cell infiltration within the lung. Using this model, we investigated the role of the complement system during SARS-CoV infection. We observed activation of the complement cascade in the lung as early as day 1 following SARS-CoV infection. To test whether this activation contributed to protective or pathologic outcomes, we utilized mice deficient in C3 (C3(–/–)), the central component of the complement system. Relative to C57BL/6J control mice, SARS-CoV-infected C3(–/–) mice exhibited significantly less weight loss and less respiratory dysfunction despite equivalent viral loads in the lung. Significantly fewer neutrophils and inflammatory monocytes were present in the lungs of C3(–/–) mice than in C56BL/6J controls, and subsequent studies revealed reduced lung pathology and lower cytokine and chemokine levels in both the lungs and the sera of C3(–/–) mice than in controls. These studies identify the complement system as an important host mediator of SARS-CoV-induced disease and suggest that complement activation regulates a systemic proinflammatory response to SARS-CoV infection. Furthermore, these data suggest that SARS-CoV-mediated disease is largely immune driven and that inhibiting complement signaling after SARS-CoV infection might function as an effective immune therapeutic.

negative: COVID-19 and dialysis: why we should be worried

negative: Viruses of the Serengeti: patterns of infection and mortality in African lions 1. We present data on the temporal dynamics of six viruses that infect lions (Panthera leo) in the Serengeti National Park and Ngorongoro Crater, Tanzania. These populations have been studied continuously for the past 30 years, and previous research has documented their seroprevalence for feline herpesvirus, feline immunodeficiency virus (FIV), feline calicivirus, feline parvovirus, feline coronavirus and canine distemper virus (CDV). A seventh virus, feline leukaemia virus (FeLV), was absent from these animals. 2. Comprehensive analysis reveals that feline herpesvirus and FIV were consistently prevalent at high levels, indicating that they were endemic in the host populations. Feline calici‐, parvo‐ and coronavirus, and CDV repeatedly showed a pattern of seroprevalence that was indicative of discrete disease epidemics: a brief period of high exposure for each virus was followed by declining seroprevalence. 3. The timing of viral invasion suggests that different epidemic viruses are associated with different minimum threshold densities of susceptible hosts. Furthermore, the proportion of susceptibles that became infected during disease outbreaks was positively correlated with the number of susceptible hosts at the beginning of each outbreak. 4. Examination of the relationship between disease outbreaks and host fitness suggest that these viruses do not affect birth and death rates in lions, with the exception of the 1994 outbreak of canine distemper virus. Although the endemic viruses (FHV and FIV) were too prevalent to measure precise health effects, there was no evidence that FIV infection reduced host longevity.

negative: A Stratified Model to Quantify the Effects of Containment Policies on the Spread of COVID-19 The SARS-Cov-2 virus is spreading fast all over the world and has already imposed a significant social and economic cost in many countries. Different countries have utilised a variety of containment policies with an emphasis on social distancing as a strategy to stop the spread of COVID-19. Quantifying the effects of such policies in different time-scales and comparing the efficacy of various available policies is of utmost importance for policy-makers in different countries. That is even more important when the policy-makers want to plan for long-term strategies and to weigh each option based on its epidemiological effects and socio-economic costs. In the absence of detailed knowledge of the interactions between individuals in a population and the characteristics of the SARS-Cov-2 virus, quantifying the effects of these policies is very difficult. Hence, there is an immediate need for models that can predict the spread of COVID-19 in a population, without the need for such detailed information. In this manuscript, a method is presented that can be used to predict the spread of COVID-19 in any country and under any containment policy imposed separately on different groups in the population. The method tunes the parameters of a known stratified model based on the available data on the spread of COVID-19. The model includes a set of nonlinear ordinary differential equations and is easy to simulate and easy to understand. As it is presented in this manuscript, the population is divided into age-groups. But given the availability of the data, there is no reason to limit the stratification into only age-groups and we can consider any relevant groups. To estimate the parameters of the model such that it reflects the characteristics of the spread of COVID-19 in a population, the method relies on an optimisation scheme. More specifically, the optimisation scheme estimates the contact rates between different age groups in the population. But a very important and useful feature of the model is that the estimated parameters for one population can be translated and used for any other population with a known age-structure, which in this day and age, includes almost any country or city in the world. Also, it is shown that the method is quite insensitive to the underlying assumptions in the optimisation scheme and also to deliberate or non-deliberate errors that might have occurred in collecting the data. The capabilities of the model are demonstrated using a case study under different containment policies, from an uncontained population to mitigation and suppression policies. Also, we can use the model to quantify the effects of strategies which include switching between different containment policies at pre-determined points in time. The model allows us to quantify the effects of each of these policies on the spread of the disease in a population, in particular, the instantaneous and total numbers of infectious individuals in a population which are important parameters for policy-makers. The simulation results, as explained in the following, provide some insight into various policies and some of the results are possibly counter-intuitive for many people. For example, the model predicts that closing down schools and universities without any other containment policy imposed on older age-groups has almost no impact on the number of patients that might need support-care in hospitals. The method provides an easy-to-use tool to use the information collected on the spread of COVID-19 in a country or region and then use that information in another population which might not have been as widely affected by the disease yet.

negative: A new pandemic out of China: the Wuhan 2019-nCoV coronavirus syndrome

negative: Ventilation Techniques and Risk for Transmission of Coronavirus Disease, Including COVID-19: A Living Systematic Review of Multiple Streams of Evidence BACKGROUND: Mechanical ventilation is used to treat respiratory failure in coronavirus disease 2019 (COVID-19). PURPOSE: To review multiple streams of evidence regarding the benefits and harms of ventilation techniques for coronavirus infections, including that causing COVID-19. (PROSPERO registration: CRD42020178187). DATA SOURCES: 21 standard, World Health Organization-specific and COVID-19-specific databases, without language restrictions, until 1 May 2020. STUDY SELECTION: Studies of any design and language comparing different oxygenation approaches in patients with coronavirus infections, including severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS), or with hypoxemic respiratory failure. Animal, mechanistic, laboratory, and preclinical evidence was gathered regarding aerosol dispersion of coronavirus. Studies evaluating risk for virus transmission to health care workers from aerosol-generating procedures (AGPs) were included. DATA EXTRACTION: Independent and duplicate screening, data abstraction, and risk of bias assessment (GRADE for certainty of evidence and AMSTAR 2 for included systematic reviews). DATA SYNTHESIS: 123 studies were eligible (45 on COVID-19, 70 on SARS, 8 on MERS), but only 5 studies (1 on COVID-19, 3 on SARS, 1 on MERS) adjusted for important confounders. A study in hospitalized patients with COVID-19 reported slightly higher mortality with noninvasive ventilation (NIV) than with invasive mechanical ventilation (IMV), but 2 opposing studies, 1 in patients with MERS and 1 in patients with SARS, suggest a reduction in mortality with NIV (very low-certainty evidence). Two studies in patients with SARS report a reduction in mortality with NIV compared with no mechanical ventilation (low-certainty evidence). Two systematic reviews suggest a large reduction in mortality with NIV compared with conventional oxygen therapy. Other included studies suggest increased odds of transmission from AGPs. LIMITATION: Direct studies in COVID-19 are limited and poorly reported. CONCLUSION: Indirect and low-certainty evidence suggests that use of NIV, similar to IMV, probably reduces mortality but may increase the risk for transmission of COVID-19 to health care workers. PRIMARY FUNDING SOURCE: World Health Organization.

negative: Childhood Infectious Diseases: Overview Of the annual burden of 10 million deaths among children under 5 years, a large proportion is associated with infectious diseases. These include 36% of the 4 million newborn deaths due to sepsis, pneumonia, diarrhea, and tetanus. Among the postneonatal deaths due to infections, estimates and uncertainty bounds include: 22% of deaths attributed to diarrhea (14–30%), 21% to pneumonia (14–24%), 9% to malaria (6–13%), and 1% to measles (1–9%). Some 42 countries alone account for almost 90% of the global burden of child mortality. There is now sufficient evidence available on evidence-based interventions that can make a difference. It is estimated that almost two-thirds of these deaths are potentially preventable if interventions can be delivered at scale. Newborn infections and related mortality can be reduced by maternal tetanus toxoid vaccination, clean delivery, cord hygiene, exclusive and early breast-feeding, and prompt diagnosis and therapy. Diarrheal deaths can be prevented by adequate attention to breast-feeding, hand-washing and sanitation strategies, rota virus vaccine, adequate treatment including oral rehydration, appropriate dietary therapy, and oral zinc administration. Similarly, the global burden of pneumonia deaths can be reduced by vaccination strategies for measles, Hib, and pneumococcal disease, timely case detection, and treatment with appropriate antibiotics.

negative: Mortality of people with intellectual disabilities during the 2017/2018 influenza epidemic in the Netherlands: potential implications for the COVID‐19 pandemic BACKGROUND: Data on the development of Covid‐19 among people with intellectual disabilities (IDs) are scarce and it is uncertain to what extent general population data applies to people with ID. To give an indication of possible implications, this study investigated excess mortality patterns during a previous influenza epidemic. METHODS: Using Dutch population and mortality registers, a historical cohort study was designed to compare mortality during the 2017–2018 influenza epidemic with mortality in the same period in the three previous years. People with ID were identified by entitlements to residential ID‐care services as retrieved from a national database. RESULTS: Data covered the entire adult Dutch population (12.6 million; GenPop), of which 91 064 individuals were identified with an ID. During the influenza epidemic, mortality among people with ID increased almost three times as much than in the GenPop (15.2% vs. 5.4%), and more among male individuals with ID (+19.5%) than among female individuals with ID (+10.6%), as compared with baseline. In both cohorts, comparable increases in mortality within older age groups and due to respiratory causes were seen. Particularly in the ID‐cohort, excess deaths also occurred in younger age groups, due to endocrine diseases and ID‐specific causes. CONCLUSIONS: During the 2017–2018 influenza epidemic, excess mortality among people with ID was three times higher than in the general Dutch population, appeared more often at young age and with a broader range of underlying causes. These findings suggest that a pandemic may disproportionally affect people with ID while population data may not immediately raise warnings. Early detection of diverging patterns and faster implementation of tailored strategies therefore require collection of good quality data.

negative: Managing healthcare delivery system to fight the COVID-19 epidemic: experience in Japan Amid the global pandemic of a novel Coronavirus Disease 2019 (COVID-19), healthcare delivery system is being stretched. In Japan, rapid spread of the epidemic brings hospitals to the brink of exhaustion. This commentary aims to briefly review related policies of Japan in managing healthcare delivery system. Among the relevant actions, strengthening the hospitalized care is emphasized to save lives. Despite of limitations, the policies show a success in preventing a collapse of healthcare delivery system and skyrocketing mortality from happening so far. On the other hand, huge concerns remain if the infections continue to rapidly increase. The experience in Japan indicates the urgency of planning of healthcare delivery system, mobilizing all relevant social sectors by consensus, and guiding people with calm manner based on the best shared knowledge and evidences.

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: Lessons from Severe Acute Respiratory Syndrome (SARS): Implications for Infection Control Severe acute respiratory syndrome (SARS), the first global epidemic in the 21st century, affected over 8500 people in approximately 30 countries (1–7). With a crude mortality of 9%, its cause was quickly identified as a novel coronavirus that jumped species from animals to man. The SARS coronavirus epidemic, which began in the Fall of 2002, was related to the exotic food industry in southern China, initially involving disproportionate numbers of animal handlers, chefs, and caterers. Subsequently, person-to-person transmission spawned the outbreak. What distinguished this illness clinically was the fact that approximately half of the victims were health care workers (8), infected while caring for recognized or unrecognized patients with SARS. There are many curiosities and uncertainties surrounding the epidemic of SARS with lessons that may be useful to the community of infectious diseases physicians, especially when looking ahead to the next epidemic. Herein we relate our perspectives on useful lessons derived from a review of the SARS epidemic.

negative: Real time estimation of the risk of death from novel coronavirus (2019-nCoV) infection: Inference using exported cases The exported cases of 2019 novel coronavirus (2019-nCoV) infection who were confirmed in other countries provide a chance to estimate the cumulative incidence and confirmed case fatality risk (cCFR) in China. Knowledge of the cCFR is critical to characterize the severity and understand pandemic potential of 2019-nCoV in the early stage of epidemic. Using the exponential growth rate of the incidence, the present study statistically estimated the cCFR and the basic reproduction number, i.e., the average number of secondary cases generated by a single primary case in a naive population. As of 24 January 2020, with 23 exported cases, and estimating the growth rate from 8 December 2019 (scenario 1) and using the data since growth of exported cases (scenario 2), the cumulative incidence in China was estimated at 5433 cases (95% confidence interval (CI): 3883, 7160) and 17780 cases (95% CI: 9646, 28724), respectively. The latest estimates of the cCFR were 4.6% (95% CI: 3.1-6.6) for scenario 1 and 7.7% (95% CI: 4.9-11.3%) for scenario 2, respectively. The basic reproduction number was estimated to be 2.2 (95% CI: 2.1, 2.3) and 3.7 (95% CI: 3.1, 4.3) for scenarios 1 and 2, respectively. Based on the results, we note that current 2019-nCoV epidemic has a substation potential to cause a pandemic. The proposed approach can provide insights into early risk assessment using only publicly available data.

negative: Epidemiological, socio-demographic and clinical features of the early phase of the COVID-19 epidemic in Ecuador Abstract Background: The SARS-CoV-2 virus has spread all over the world infecting more than 3,585,936 people from over 210 countries and caused more than 245,803 deaths worldwide. We report the first epidemiological, socio-demographic, and clinical findings for the first 9,468 confirmed COVID-19 cases in Ecuador. Methods: We conducted a descriptive cross-sectional analysis of 9,468 COVID-19 confirmed cases in Ecuador from 27 February to 18 April 2020. The overall incidence, mortality, and case fatality rate was computed according to the entire population at risk living in a canton or a province. Disability adjusted life years, attack and crude mortality rates as well as relative risk and odds ratios were computed as an outcome. Results: Since the first case reported in Ecuador on 27 Feb 2020, at least 9,468 positive COVID-19 cases of which 474 deaths were officially registered over a 54-day period. Men accounted for 55.40% (n = 5, 247) of the overall cases with an incidence rate of 60.5 per 100,000 while women accounted for 44.60 % (n = 4, 221) representing 47.2 per 100,000. The mortality rate per canton showed that cantons with a lower attack rate had higher mortality rates. Coastal cantons have a lower attack rate than the highlands and living above >2,500 m seems to be linked with a lower risk of dying (RR: 0.63 [CI 95% 0.50 - 0.79]). Fatigue was reported in 53.2% of the patients, followed by headache (43%), dry cough (41.7%), ageusia (37.1%) and anosmia (36.1%). Conclusion: This study is the first of its kind in Ecuador. The results of this analysis show that men are at higher risk of dying from COVID-19 than women, which increases as with age and the presence of comorbidities. Areas with better testing capabilities reported lower CFR% and mortality, additionally cantons located above 2,500 m have lower attack and mortality rates although the risk of dying is greater among highlanders. Keywords: COVID-19; SARS-CoV-2; Ecuador; Epidemiology; Latin America

negative: Viral Replication in the Nasopharynx Is Associated with Diarrhea in Patients with Severe Acute Respiratory Syndrome The role of severe acute respiratory syndrome (SARS) coronavirus as an enteric pathogen was investigated in a cohort of 142 patients with SARS who were treated with a standard treatment protocol. Data from daily hematological, biochemical, radiological, and microbiological investigations were prospectively collected, and the correlation of these findings with diarrhea was retrospectively analyzed. Sixty-nine patients (48.6%) developed diarrhea at a mean (± standard deviation [SD]) of 7.6 ± 2.6 days after the onset of symptoms. The diarrhea was most severe at a mean (±SD) of 8.8 ± 2.4 days after onset, with a maximum frequency of 24 episodes per day (median, 5 episodes; range, 3–24 episodes). A higher mean virus load in nasopharyngeal specimens obtained on day 10 after the onset of symptoms was significantly associated with the occurrence of diarrhea (3.1 log(10) vs. 1.8 log(10) copies/mL; P = .01) and mortality (6.2 vs. 1.7 log(10) copies/mL; P < .01). However, diarrhea was not associated with mortality. The lung and the gastrointestinal tract may react differently to SARS coronavirus infection. Additional investigation of the role of SARS coronavirus in the pathogenesis of diarrhea in patients with SARS should be conducted.

negative: Effects of latency and age structure on the dynamics and containment of COVID-19 In this paper we develop an SEIR-type model of COVID-19, with account for two particular aspects: non-exponential distribution of incubation and recovery periods, as well as age structure of the population. For the mean-field model, which does not distinguish between different age groups, we demonstrate that including a more realistic Gamma distribution of incubation and recovery periods may not have an effect on the total number of deaths and the overall size of an epidemic, but it has a major effect in terms of increasing the peak numbers of infected and critical care cases, as well as on changing the timescales of an epidemic, both in terms of time to reach the peak, and the overall duration of an outbreak. In order to obtain more accurate estimates of disease progression and investigate different strategies for introducing and lifting the lockdown, we have also considered an age-structured version of the model, which has allowed us to include more accurate data on age-specific rates of hospitalisation and COVID-19 related mortality. Applying this model to three comparable neighbouring regions in the UK has delivered some fascinating insights regarding the effect of quarantine in regions with different population structure. We have discovered that for a fixed quarantine duration, the timing of its start is very important in the sense that the second epidemic wave after lifting the quarantine can be significantly smaller or larger depending on the specific population structure. Also, the later the fixed-duration quarantine is introduced, the smaller is the resulting final number of deaths at the end of the outbreak. When the quarantine is introduced simultaneously for all regions, increasing quarantine duration postpones and slightly reduces the epidemic peak, though without noticeable differences in peak magnitude between different quarantine durations.

negative: 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: Coronavirus (COVID-19) Outbreak: What the Department of Radiology Should Know Abstract In December 2019, a novel coronavirus (COVID-19) pneumonia emerged in Wuhan, China. Since then, this highly contagious COVID-19 has been spreading worldwide, with a rapid rise in the number of deaths. Novel COVID-19–infected pneumonia (NCIP) is characterized by fever, fatigue, dry cough, and dyspnea. A variety of chest imaging features have been reported, similar to those found in other types of coronavirus syndromes. The purpose of the present review is to briefly discuss the known epidemiology and the imaging findings of coronavirus syndromes, with a focus on the reported imaging findings of NCIP. Moreover, the authors review precautions and safety measures for radiology department personnel to manage patients with known or suspected NCIP. Implementation of a robust plan in the radiology department is required to prevent further transmission of the virus to patients and department staff members.

negative: Comparative Epidemiology of Human Fatal Infections with Novel, High (H5N6 and H5N1) and Low (H7N9 and H9N2) Pathogenicity Avian Influenza A Viruses This study aimed to assess the mortality risks for human infection with high (HPAI) and low (LPAI) pathogenicity avian influenza viruses. The HPAI case fatality rate (CFR) was far higher than the LPAI CFR [66.0% (293/444) vs. 68.75% (11/16) vs. 40.4% (265/656) vs. 0.0% (0/18) in the cases with H5N1, H5N6, H7N9, and H9N2 viruses, respectively; p < 0.001]. Similarly, the CFR of the index cases was greater than the secondary cases with H5N1 [100% (43/43) vs. 43.3% (42/97), p < 0.001]. Old age [22.5 vs. 17 years for H5N1, p = 0.018; 61 vs. 49 years for H7H9, p < 0.001], concurrent diseases [18.8% (15/80) vs. 8.33% (9/108) for H5N1, p = 0.046; 58.6% (156/266) vs. 34.8% (135/388) for H7H9, p < 0.001], delayed confirmation [13 vs. 6 days for H5N1, p < 0.001; 10 vs. 8 days for H7N9, p = 0.011] in the fatalities and survivors, were risk factors for deaths. With regard to the H5N1 clusters, exposure to poultry [67.4% (29/43) vs. 45.2% (19/42), p = 0.039] was the higher risk for the primary than the secondary deaths. In conclusion, old age, comorbidities, delayed confirmation, along with poultry exposure are the major risks contributing to fatal outcomes in human HPAI and LPAI infections.

negative: ESTIMATION OF COVID-19 CASES IN FRANCE AND IN DIFFERENT COUNTRIES: HOMOGENEISATION BASED ON MORTALITY Every day the authorities of different countries provide an estimate of the number of persons affected by Covid-19 and a count of fatality. We propose to use the fatality reported in each country to provide a better estimate (Ct0-estimated) of the number of cases at a given time t0. Ct0-estimated = (Ft0 / Fr-est) * (1+ [C(est-d) / C(est-3d)])6 With Ft0: number of actual fatalities reported in a country at time t0; Fr-est: estimated fatality rate; C(est-d): estimated fatalities 18 days before t0; C(est-3d): estimated fatalities 21 days before t0. Based on Ct0-estimated calculated using a fatality rate of 2%, we assessed the number of cases April 10th, 2020 in Belgium, China, France, Germany, Iran, Italy, South Korea, Netherlands, Spain, United Kingdom and USA. This number reached 2,872,097 in France and 924,892 persons in Germany. The proposed formulas also make it possible to evaluate the impact of policies to prevent the spread of epidemic on the appearance of new cases.

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: 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: Does Coronavirus Disease 2019 Disprove the Obesity Paradox in Acute Respiratory Distress Syndrome? Obesity is associated with a decrease in mortality in patients with Adult Respiratory Distress Syndrome (ARDS) and is referred to as the obesity paradox.1 ARDS is a type of respiratory failure characterised by rapid onset of widespread inflammation in the lungs and is usually the result of infectious or chemical injury. The obesity paradox in ARDS patients has been investigated by Ni et al,1 who conclude that obesity and morbid obesity were associated with a lower mortality rate in patients with ARDS.

negative: Disease burden of the most commonly detected respiratory viruses in hospitalized patients calculated using the disability adjusted life year (DALY) model Abstract Background The most common acute infections occur in the respiratory tract. Recent discoveries of several novel viruses have markedly increased the repertoire of agents understood to cause presentations of acute respiratory disease. Objectives Further understanding is needed of the relative importance of newly discovered pathogens in the clinical setting to provide clinicians with an indication of appropriate diagnostic and therapeutic targets. To address this, quantification of the disease burden of respiratory viruses in hospitalized patients was undertaken. Study design Disease burden caused by respiratory viruses in hospitalized patients was quantified using the World Health Organization endorsed DALY model. Diagnostic testing results from samples collected over three years for adenovirus (AdV), influenzas A and B, parainfluenza viruses 1, 2 and 3 (PIV-1, -2 and -3), respiratory syncytial virus (HRSV), and previously published retrospective screening for human metapneumovirus, rhinoviruses, and four respiratory coronaviruses were applied to the DALY model. Disability weights were calculated per 1000 hospitalized patients in age banded groups. Results Strikingly different disease burden profiles were observed in children and adults. Adenoviruses were among the leading cause of respiratory presentations in children but not adults. HRSV and influenza A were consistently one of the greatest causes of disease regardless of sampled population. Rhinoviruses and PIV-3 were significant pathogens in all groups except those aged 16–64 years. In immunocompromised patients rhinoviruses were the leading viral cause of disease. Conclusions These analyses provide a framework which can be used to identify where finite resources should be directed in respiratory therapeutics and vaccine development.

negative: Influenza and Pneumonia in Pregnancy Influenza is a significant cause of morbidity and mortality from febrile respiratory illness worldwide. Influenza in pregnant women has historically been associated with a higher rate of morbidity and mortality. Pneumonia is the sixth leading cause of death in the United States, and it is the number one cause of death from an infectious disease. Although pregnant women do not get pneumonia more often than nonpregnant women, it can result in greater morbidity and mortality because of the physiologic adaptations of pregnancy. Pregnant patients who have either of these conditions require a higher level of surveillance and intervention.

negative: Establishing an ICD-10 code based SARI-surveillance in Germany – description of the system and first results from five recent influenza seasons BACKGROUND: Syndromic surveillance of severe acute respiratory infections (SARI) is important to assess seriousness of disease as recommended by WHO for influenza. In 2015 the Robert Koch Institute (RKI) started to collaborate with a private hospital network to develop a SARI surveillance system using case-based data on ICD-10 codes. This first-time description of the system shows its application to the analysis of five influenza seasons. METHODS: Since week 40/2015, weekly updated anonymized data on discharged patients overall and on patients with respiratory illness including ICD-10 codes of primary and secondary diagnoses are transferred from the network data center to RKI. Retrospective datasets were also provided. Our descriptive analysis is based on data of 47 sentinel hospitals collected between weeks 1/2012 to 20/2016. We applied three different SARI case definitions (CD) based on ICD-10 codes for discharge diagnoses of respiratory tract infections (J09 - J22): basic CD (BCD), using only primary diagnoses; sensitive CD (SCD), using primary and secondary diagnoses; timely CD (TCD), using only primary diagnoses of patients hospitalized up to one week. We compared the CD with regard to severity, age distribution and timeliness and with results from the national primary care sentinel system. RESULTS: The 47 sentinel hospitals covered 3.6% of patients discharged from all German hospitals in 2013. The SCD comprised 2.2 times patients as the BCD, and 3.6 times as many as the TCD. Time course of SARI cases corresponded well to results from primary care surveillance and influenza virus circulation. The patients fulfilling the TCD had been completely reported after 3 weeks, which was fastest among the CD. The proportion of SARI cases among patients was highest in the youngest age group of below 5-year-olds. However, the age group 60 years and above contributed most SARI cases. This was irrespective of the CD used. CONCLUSIONS: In general, available data and the implemented reporting system are appropriate to provide timely and reliable information on SARI in inpatients in Germany. Our ICD-10-based approach proved to be useful for fulfilling requirements for SARI surveillance. The exploratory approach gave valuable insights in data structure and emphasized the advantages of different CD.

negative: This journal issue contains abstracts that have been accepted for presentation as the 8th Annual Conference of the International Society for Quality of Life Research (ISOQOL)

negative: Age-specific and sex-specific morbidity and mortality from avian influenza A(H7N9) Abstract We used data on age and sex for 136 laboratory confirmed human A(H7N9) cases reported as of 11 August 2013 to compare age-specific and sex-specific patterns of morbidity and mortality from the avian influenza A(H7N9) virus with those of the avian influenza A(H5N1) virus. Human A(H7N9) cases exhibit high degrees of age and sex bias: mortality is heavily biased toward males >50 years, no deaths have been reported among individuals <25 years old, and relatively few cases documented among children or adolescents. The proportion of fatal cases (PFC) for human A(H7N9) cases as of 11 August 2013 was 32%, compared to a cumulative PFC for A(H5N1) of 83% in Indonesia and 36% in Egypt. Approximately 75% of cases of all A(H7N9) cases occurred among individuals >45 years old. Morbidity and mortality from A(H7N9) are lowest among individuals between 10 and 29 years, the age group which exhibits the highest cumulative morbidity and case fatality rates from A(H5N1). Although individuals <20 years old comprise nearly 50% of all human A(H5N1) cases, only 7% of all reported A(H7N9) cases and no deaths have been reported among individuals in this age group. Only 4% of A(H7N9) cases occurred among children<5 years old, and only one case from the 10 to 20 year age group. Age- and sex-related differences in morbidity and mortality from emerging zoonotic diseases can provide insights into ecological, economic, and cultural factors that may contribute to the emergence and proliferation of novel zoonotic diseases in human populations.

negative: Risk perception in Northeast Asia Multi-country surveys of the public’s perception of risk using the same questionnaire were sequentially implemented from April to December 2006 in Japan, China, and South Korea. Statistical analyses, such as traditional mean tests, rank order tests, two-step cluster analysis, and principal component analysis were used to analyze the survey data. The results revealed that Chinese tend to be more tolerant of risk than Japanese and South Koreans. In all three countries, the threats of global warming, cancer, traffic accidents, and fire were perceived as higher-order risks, while infectious diseases and threats from high technology were perceived as lower-order risks. Looking across the entire multi-country sample, we found that Chinese participants perceived greater risk in typhoons, SARS, and drugs; Japanese saw greater risk from gas explosions and potential threats coming over the Internet; while people in all three countries identified earthquakes as a primary risk. These differences in risk perception reflect the natural and socioeconomic conditions in the three countries. Although the study did not emphasize differences in risk perception within countries based on demographic factors such as education, age, and gender, we found that differences based on education and age tended to be greater in China and South Korea than in Japan. We also found that men perceived greater risks than women in China and South Korea, while in Japan it was the opposite with women perceiving greater risks. A comparison of these results with previous studies reveals a bias in past studies toward student samples and indicates the need for more representative samples in multi-country surveys.

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: Genetic diversity and phylogenetic analysis of Feline Coronavirus sequences from Portugal Abstract The distribution of FCoV Types I and II in a Portuguese cat population was studied by a RT-PCR assay targeting the 3′-end of the viral RNA. For a period of 3 years, 120 samples were collected and 57 were found positive for FCoV RNA. Within the positive samples the presence of FCoV Type I was found in 79%. Type II was only detected in 3.5% in animals with Feline Infectious Peritonitis. The remaining 17.5% could not be differentiated. These viral sequences, comprising a region within gene S were further subjected to a heteroduplex mobility assay (HMA) detecting the presence of viral quasispecies in 17% of the samples. Phylogenetic analysis for FCoV Type I revealed high genetic diversity between the Portuguese sequences and other previously characterized strains, while Type II tree showed a higher genetic homogeneity. This study confirmed the presence of FCoV Types I and II circulating in Portugal and detected high genetic diversity between circulating strains suggesting that the virus persists within the host as mixed viral populations.

negative: The effect of uncontrolled travelers and social distancing on the spread of novel coronavirus disease (COVID-19) in Colombia

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

negative: Lockdown exit strategies and risk of a second epidemic peak: a stochastic agent-based model of SARS-CoV-2 epidemic in France Most European countries have responded to the COVID-19 threat by nationwide implementation of barrier measures and lockdown. However, assuming that population immunity will build up through the epidemic, it is likely to rebound once these measures are relaxed, possibly leading to a second or multiple repeated lockdowns. In this report, we present results of epidemiological modelling that has helped inform policy making in France. We used a stochastic agent-based microsimulation model of the COVID-19 epidemic in France, and examined the potential impact of post-quarantine measures, including social distancing, mask-wearing, and shielding of the population the most vulnerable to severe COVID-19 infection, on the disease's cumulative incidence and mortality, and on ICU-bed occupancy. The model calibrated well and variation of model parameter values had little impact on outcome estimates. While quarantine is effective in containing the viral spread, it would be unlikely to prevent a rebound of the epidemic once lifted, regardless of its duration. Both social distancing and mask-wearing, although effective in slowing the epidemic and in reducing mortality, would also be ineffective in ultimately preventing the overwhelming of ICUs and a second lockdown. However, these measures coupled with shielding of vulnerable people would be associated with better outcomes, including lower cumulative incidence, mortality, and maintaining an adequate number of ICU beds to prevent a second lockdown. Benefits would nonetheless be markedly reduced if these measures were not applied by most people or not maintained for a sufficiently long period, as herd immunity progressively establishes in the less vulnerable population.

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: Data-Based Analysis, Modelling and Forecasting of the COVID-19 outbreak Since the first suspected case of coronavirus disease-2019 (COVID-19) on December 1st, 2019, in Wuhan, Hubei Province, China, a total of 40,235 confirmed cases and 909 deaths have been reported in China up to February 10, 2020, evoking fear locally and internationally. Here, based on the publicly available epidemiological data for Hubei, China from January 11 to February 10, 2020, we provide estimates of the main epidemiological parameters. In particular, we provide an estimation of the case fatality and case recovery ratios, along with their 90% confidence intervals as the outbreak evolves. On the basis of a Susceptible-Infected-Recovered-Dead (SIDR) model, we provide estimations of the basic reproduction number (R0), and the per day infection mortality and recovery rates. By calibrating the parameters of the SIRD model to the reported data, we also attempt to forecast the evolution of the of the outbreak at the epicenter three weeks ahead, i.e. until February 29. As the number of infected individuals, especially of those with asymptomatic or mild courses, is suspected to be much higher than the official numbers, which can be considered only as a subset of the actual numbers of infected and recovered cases in the total population, we have repeated the calculations under a second scenario that considers twenty times the number of confirmed infected cases and forty times the number of recovered, leaving the number of deaths unchanged. Based on the reported data, the expected value of R0 as computed considering the period from the 11th of January until the 18th of January, using the official counts of confirmed cases was found to be ~4.6, while the one computed under the second scenario was found to be ~3.2. Thus, based on the SIRD simulations, the estimated average value of R0 was found to be ~2.6 based on confirmed cases and ~2 based on the second scenario. Our forecasting flashes a note of caution for the presently unfolding outbreak in China. Based on the official counts for confirmed cases, the simulations suggest that the cumulative number of infected could reach 180,000 (with lower bound of 45,000) by February 29. Regarding the number of deaths, simulations forecast that on the basis of the up to the 10th of February reported data, the death toll might exceed 2,700 (as a lower bound) by February 29. Our analysis further reveals a significant decline of the case fatality ratio from January 26 to which various factors may have contributed, such as the severe control measures taken in Hubei, China (e.g. quarantine and hospitalization of infected individuals), but mainly because of the fact that the actual cumulative numbers of infected and recovered cases in the population most likely are much higher than the reported ones. Thus, in a scenario where we have taken twenty times the confirmed number of infected and forty times the confirmed number of recovered cases, the case fatality ratio is around 0.15% in the total population. Importantly, based on this scenario, simulations suggest a slow down of the outbreak in Hubei at the end of February.

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

negative: Current status of treatment for 2019 novel coronavirus pneumonia/ 中华微生物学和免疫学杂志 2019 novel coronavirus (2019-nCoV) is a new member of coronavirus family that can cause serious respiratory diseases after the emergence of severe acute respiratory syndrome-coronavirus (SARS-CoV) and middle east respiratory syndrome-coronavirus (MERS-CoV). At present, there is no specific antiviral drug targeting 2019-nCoV. In facing of the increasingly serious epidemic of 2019 novel coronavirus pneumonia and the urgent needs in drug treatment strategies, this paper reviewed the current research situation and progress in antiviral treatment for the newly identified disease.

negative: Treatment outcomes for patients with Middle Eastern Respiratory Syndrome Coronavirus (MERS CoV) infection at a coronavirus referral center in the Kingdom of Saudi Arabia BACKGROUND: Middle Eastern Respiratory Syndrome coronavirus (MERS-CoV) is a poorly understood disease with no known treatments. We describe the clinical features and treatment outcomes of patients with laboratory confirmed MERS-CoV at a regional referral center in the Kingdom of Saudi Arabia. METHODS: In 2014, a retrospective chart review was performed on patients with a laboratory confirmed diagnosis of MERS-CoV to determine clinical and treatment characteristics associated with death. Confounding was evaluated and a multivariate logistic regression was performed to assess the independent effect of treatments administered. RESULTS: Fifty-one patients had an overall mortality of 37 %. Most patients were male (78 %) with a mean age of 54 years. Almost a quarter of the patients were healthcare workers (23.5 %) and 41 % had a known exposure to another person with MERS-CoV. Survival was associated with male gender, working as a healthcare worker, history of hypertension, vomiting on admission, elevated respiratory rate, abnormal lung exam, elevated alanine transaminase (ALT), clearance of MERS-CoV on repeat PCR polymerase chain reaction (PCR) testing, and mycophenolate mofetil treatment. Survival was reduced in the presence of coronary artery disease, hypotension, hypoxemia, CXR (chest X-ray) abnormalities, leukocytosis, creatinine >1 · 5 mg/dL, thrombocytopenia, anemia, and renal failure. In a multivariate analysis of treatments administered, severity of illness was the greatest predictor of reduced survival. CONCLUSIONS: Care for patients with MERS-CoV remains a challenge. In this retrospective cohort, interferon beta and mycophenolate mofetil treatment were predictors of increased survival in the univariate analysis. Severity of illness was the greatest predictor of reduced survival in the multivariate analysis. Larger randomized trials are needed to better evaluate the efficacy of these treatment regimens for MERS-CoV.

negative: Influenza-associated Deaths in Tropical Singapore We used a regression model to examine the impact of influenza on death rates in tropical Singapore for the period 1996–2003. Influenza A (H3N2) was the predominant circulating influenza virus subtype, with consistently significant and robust effect on mortality rates. Influenza was associated with an annual death rate from all causes, from underlying pneumonia and influenza, and from underlying circulatory and respiratory conditions of 14.8 (95% confidence interval 9.8–19.8), 2.9 (1.0–5.0), and 11.9 (8.3–15.7) per 100,000 person-years, respectively. These results are comparable with observations in the United States and subtropical Hong Kong. An estimated 6.5% of underlying pneumonia and influenza deaths were attributable to influenza. The proportion of influenza-associated deaths was 11.3 times higher in persons age >65 years than in the general population. Our findings support the need for influenza surveillance and annual influenza vaccination for at-risk populations in tropical countries.

negative: Clinical Significance of Human Coronavirus in Bronchoalveolar Lavage Samples From Hematopoietic Cell Transplantation Recipients and Hematologic Malignancy Patients

negative: Crazy-paving sign in high-resolution computed tomography in parainfluenza virus pneumonia Abstract The crazy-paving sign is the appearance of a smooth linear pattern superimposed on an area of ground-glass opacity on thin-section computed tomography (CT). A 69-year-old woman was admitted to our hospital for treatment of pneumonia. Thoracic CT showed a crazy-paving sign in the right lung field on admission. She received ceftriaxone and clarithromycin, and the symptoms and infiltration shadow promptly disappeared. Serologic testing revealed a greater than 4-fold increase in the IgG titer for parainfluenza virus I. To our knowledge, there is no previous report of the crazy-paving sign in associated with viral pneumonia in a non-immunocompromised host or with parainfluenza pneumonia.

negative: Comparative survey of canine parvovirus, canine distemper virus and canine enteric coronavirus infection in free-ranging wolves of central Italy and south-eastern France Diseases likely affect large carnivore demography and can hinder conservation efforts. We considered three highly contagious viruses that infect a wide range of domestic and wild mammals: canine parvovirus type 2 (CPV-2), canine distemper virus (CDV) and canine enteric coronaviruses (CECoV). Infection by either one of these viruses can affect populations through increased mortality and/or decreased general health. We investigated infection in the wolf populations of Abruzzo, Lazio e Molise National Park (PNALM), Italy, and of Mercantour National Park (PNM), France. Faecal samples were collected during one winter, from October to March, from four packs in PNALM (n = 79) and from four packs in PNM (n = 66). We screened samples for specific sequences of viral nucleic acids. To our knowledge, our study is the first documented report of CECoV infection in wolves outside Alaska, and of the large-scale occurrence of CPV-2 in European wolf populations. The results suggest that CPV-2 is enzootic in the population of PNALM, but not in PNM and that CECoV is episodic in both areas. We did not detect CDV. Our findings suggest that density and spatial distribution of susceptible hosts, in particular free-ranging dogs, can be important factors influencing infections in wolves. This comparative study is an important step in evaluating the nature of possible disease threats in the studied wolf populations. Recent emergence of new viral strains in Europe additionally strengthens the need for proactive monitoring of wolves and other susceptible sympatric species for viral threats and other impairing infections.

negative: Abstract Presentations from the AABB Annual Meeting San Diego, CA ctober 7‐10, 2017

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

negative: Use of airway clearance therapy in children hospitalised with acute lower respiratory tract infections in a South African paediatric hospital BACKGROUND: Little is known about the prescription, frequency and nature of airway clearance therapy (ACT) in children hospitalised with lower respiratory tract infections (LRTIs). OBJECTIVES: To describe the characteristics and outcomes of children hospitalised with LRTIs at a tertiary paediatric hospital in South Africa and to investigate the role and impact of ACT in these children. METHOD: A retrospective folder review of children hospitalised with LRTI between January and June 2015 was conducted, extracting data on demographic characteristics, health condition, ACT interventions and patient outcomes. RESULTS: A total of 1208 individual cases (median [IQR] age 7.6 (2.8–19.0) months), in 1440 hospitalisations, were included. The majority of children were hospitalised primarily for the management of bronchiolitis. Comorbidities were present in 52.6% of patients during at least one of their hospitalisations. Airway clearance therapy was administered in 5.9% (n = 85) of admissions, most commonly conventional (manual) ACT. Transient oxyhaemoglobin desaturation was reported in six children, and one child developed lobar collapse an hour post-treatment. No other adverse events were reported. The median (IQR) duration of hospitalisation was 2.3 (1.5–5.0) days, and the overall mortality rate was 0.7%. Children hospitalised for presumed nosocomial infections and pneumonia had the longest length of stay, were more likely to receive ACT and had the highest mortality rate. CONCLUSION: Airway clearance therapy was infrequently used in this population and was more commonly applied in those with nosocomial LRTI and pneumonia. CLINICAL IMPLICATIONS: Although ACT was generally well tolerated, safety has not been ascertained, and oxygen saturation should be carefully monitored during therapy.

negative: Tracking and Predicting COVID-19 Epidemic in China Mainland By proposing a varying coefficient Susceptible-Infected-Removal model (vSIR), we track the epidemic of COVID-19 in 30 provinces in China and 15 cities in Hubei province, the epicenter of the outbreak. It is found that the spread of COVID-19 has been significantly slowing down within the two weeks from January 27 to February 10th with 87.0% and 84.3% reductions in the reproduction number R0 among the 30 provinces and 15 Hubei cities, respectively. This suggests the extreme control measures implemented since January 23, which include cutting off Wuhan and many other cities and towns, a great public awareness and high level of self isolation at home, have contributed to a substantial decline in the reproductivity of the COVID-19 in China. We predict that Hubei province will reach its peak between February 20 and 22, 2020, and if the removal rate can be increased to 0.1, the epidemic outside Hubei province will end in May 2020, and inside Hubei in early June.

negative: Prediction of the number of deaths in India due to SARS-CoV-2 at 5–6 weeks Abstract Introduction and Aims: No valid treatment or preventative strategy has evolved till date to counter the SARS CoV 2 (Novel Coronavirus) epidemic that originated in China in late 2019 and have since wrought havoc on millions across the world with illness, socioeconomic recession and death. This analysis was aimed at tracing a trend related to death counts expected at the 5th and 6th week of the COVID-19 in India. Material and methods Validated database was used to procure global and Indian data related to coronavirus and related outcomes. Multiple regression and linear regression analyses were used interchangeably. Since the week 6 death count data was not correlated significantly with any of the chosen inputs, an auto-regression technique was employed to improve the predictive ability of the regression model. Results A linear regression analysis predicted average week 5 death count to be 211 with a 95% CI: 1.31–2.60). Similarly, week 6 death count, in spite of a strong correlation with input variables, did not pass the test of statistical significance. Using auto-regression technique and using week 5 death count as input the linear regression model predicted week 6 death count in India to be 467, while keeping at the back of our mind the risk of over-estimation by most of the risk-based models. Conclusion According to our analysis, if situation continue in present state; projected death rate (n) is 211 and467 at the end of the 5th and 6th week from now, respectively.

negative: COVID-19: what has been learned and to be learned about the novel coronavirus disease The outbreak of Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), has thus far killed over 3,000 people and infected over 80,000 in China and elsewhere in the world, resulting in catastrophe for humans. Similar to its homologous virus, SARS-CoV, which caused SARS in thousands of people in 2003, SARS-CoV-2 might also be transmitted from the bats and causes similar symptoms through a similar mechanism. However, COVID-19 has lower severity and mortality than SARS but is much more transmissive and affects more elderly individuals than youth and more men than women. In response to the rapidly increasing number of publications on the emerging disease, this article attempts to provide a timely and comprehensive review of the swiftly developing research subject. We will cover the basics about the epidemiology, etiology, virology, diagnosis, treatment, prognosis, and prevention of the disease. Although many questions still require answers, we hope that this review helps in the understanding and eradication of the threatening disease.

negative: Dairy calf management, morbidity and mortality in Ontario Holstein herds. I. The data Heifer calf management practices and clinical outcomes were studied on 104 randomly selected Holstein dairy farms in southwestern Ontario between October 1980 and July 1983. Data were collected at both the farm level (all farms) and the individual calf level (1968 calves, 35 farms). Farm-level management data were collected by means of questionnaires and farm visits. Calf-level management data were recorded by farmers on forms provided. Treatments for disease and mortality data were recorded by the farmers on the calves up to the age of weaning, the age at which calves were no longer fed milk or milk substitutes on a regular basis. Farm size ranged from 23 to 154 calvings per year. Farm-level mortality rates per six-month season (winter/summer) were skewed, with a mean of about 6%, a median of zero, and a range of 67%. Morbidity rates were similarly skewed. Four percent of liveborn heifer calves died, 20% were treated for scours, and 15% were treated for pneumonia before the age of weaning. Stated farm policies on calf rearing were implemented to varying degrees on different farms, as estimated from individual calf data. This posed particular problems for interpreting farm-level data, since the danger of committing an ecologic fallacy was high. The data set described in this paper formed the basis for an observational study of the interlationships of heifer calf management and clinical outcomes.

negative: Role of the atmospheric pollution in the Covid-19 outbreak risk in Italy Background: After the initial outbreak in China, the diffusion in Italy of SARS-CoV-2 is exhibiting a clear regional trend with Northern areas being the most affected in terms of both frequency and severity of cases. Among multiple factors possibly involved in such geographical differences, a role has been hypothesized for atmospheric pollution. Objectives: We provide additional evidence on the possible influence of air quality, particularly in terms of chronicity of exposure on the spread viral infection in Italian regions. Methods: Actual data on to COVID-19 outbreak in Italian provinces and corresponding long-term air quality evaluations, were obtained from Italian and European agencies, elaborated and tested for possible interactions. Discussion: Our elaborations reveal that, beside concentrations, the chronicity of exposure may influence the anomalous variability of SARS-CoV-2 in Italy. Data on distribution of atmospheric pollutants (NO2, O3, PM2.5 and PM10) in Italian regions during the last 4 years, days exceeding regulatory limits, and years of the last decade (2010-2019) in which the limits have been exceeded for at least 35 days, confirmed that Northern Italy has been constantly exposed to chronic air pollution. Long-term air-quality data significantly correlated with cases of Covid-19 in up to 71 Italian provinces (updated 6 April) providing further evidence that chronic exposure to atmospheric contamination may represent a favourable context for the spread of the virus. Pro-inflammatory responses and high incidence of respiratory and cardiac affections are well known, while the capability of this coronavirus to bind particulate matters remains to be established. Atmospheric and environmental pollution should be considered as part of an integrated approach for sustainable development, human health protection and prevention of epidemic spreads.

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: 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: Covid-19 in China: ten critical issues for intensive care medicine

negative: Excess of Mortality in Adults and Elderly and Circulation of Subtypes of Influenza Virus in Southern Brazil PURPOSE: In the elderly population, the influenza infection and its clinical complications are important causes of hospitalization and death, particularly, in longer-lived age. The objective of this study is to analyze the impact of influenza virus circulation on mortality in the elderly and adults, in years with different predominant virus strains. METHODS: We performed a time trend study to evaluated excess of mortality for pneumonia and influenza, respiratory disease, and all-causes in southern region of Brazil, from 2002 to 2015. After considering other models, we opted for Serfling regression. Excess of death rates per 100,000 inhabitants were analyzed in specific age groups (24–59, 60–69, 70–79, ≥80 years) and by year of occurrence. Mortality information were taken from Brazilian Mortality Information System and etiological data were accessed in Sentinel Virological Surveillance database, getting the weekly positivity of the immunofluorescence tests for influenza A (H1N1, H3N2), and B. RESULTS: In southern Brazil, there is an evident seasonal pattern of all death outcomes among different age groups in the dry and cold season (April–September). The highest excess mortality rates occurs among older, particularly in years of circulation of influenza AH3N2, especially among people ≥80 years, in 2003 and 2007—years of great severity of influenza activity. After 2009, with the introduction of the pandemic influenza AH1N1, we observed a lower impact on the mortality of the elderly compared to <60 years. DISCUSSION: A cross reactivity antibody response from past exposure probably provided protection against disease in the elderly. Despite not controlling for comorbidities, climate, and vaccination, for the >70 years, ratio of respiratory diseases excess mortality rates between AH1N1 (2009) and severe year of H3N2 (2007) shows protection in the pandemic year and great vulnerability during AH3N2 virus predominance. CONCLUSION: The reduced immune response to infection, and to vaccination, and presence of comorbidities recommend a special attention to this age group in Brazil. Besides medical assistance, the timeliness of vaccine campaigns, its composition, and etiological surveillance of respiratory diseases are some of the preventive and public health measures.

negative: Why are pregnant women susceptible to COVID-19? An immunological viewpoint Abstract The 2019 novel coronavirus disease (COVID-19) was first detected in December 2019 and became epidemic in Wuhan, Hubei Province, China. COVID-19 has been rapidly spreading out in China and all over the world. The virus causing COVID-19, SARS-CoV-2 has been known to be genetically similar to severe acute respiratory syndrome coronavirus (SARS-CoV) but distinct from it. Clinical manifestation of COVID-19 can be characterized by mild upper respiratory tract infection, lower respiratory tract infection involving non-life threatening pneumonia, and life-threatening pneumonia with acute respiratory distress syndrome. It affects all age groups, including newborns, to the elders. Particularly, pregnant women may be more susceptible to COVID-19 since pregnant women, in general, are vulnerable to respiratory infection. In pregnant women with COVID-19, there is no evidence for vertical transmission of the virus, but an increased prevalence of preterm deliveries has been noticed. The COVID-19 may alter immune responses at the maternal-fetal interface, and affect the well-being of mothers and infants. In this review, we focused on the reason why pregnant women are more susceptible to COVID-19 and the potential maternal and fetal complications from an immunological viewpoint.

negative: A Flood of Health Functional Foods: What Is to Be Recommended? Health functional food is referred to a food prepared or processed from specific components or ingredients for functionality beneficial to the body through extraction, concentration, purification, blending and other methods. The demand for health functional foods is steadily increasing, and red ginseng is the most demanded food among women in the 50s, followed by multivitamin, omega-3, glucosamine and aloe. To date, there is insufficient evidence on the effect of red ginseng on exercise capacity, somatic symptom and cognitive performance in healthy individuals. Moreover, evidence is insufficient that a nutritional dose of vitamin or mineral reduces the incidence of cardiovascular disease and cancer, or mortality rate. A steady intake of oily fish is recommended to prevent the incidence of cardiovascular disease for postmenopausal women. Consumption of omega-3 fatty acids is expected to prevent cardiovascular disease in postmenopausal women with almost no intake of oily fish and those not taking statins. It still remains controversial whether glucosamine is effective in the treatment of osteoarthritis. Hence, physicians should fully inform patients with all controversial information about the effectiveness of glucosamine when prescribing glucosamine for patients with osteoarthritis.

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: Monitoring the COVID-19 epidemic in the context of widespread local transmission

negative: Effects of air temperature and relative humidity on coronavirus survival on surfaces. Assessment of the risks posed by severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) on surfaces requires data on survival of this virus on environmental surfaces and on how survival is affected by environmental variables, such as air temperature (AT) and relative humidity (RH). The use of surrogate viruses has the potential to overcome the challenges of working with SARS-CoV and to increase the available data on coronavirus survival on surfaces. Two potential surrogates were evaluated in this study; transmissible gastroenteritis virus (TGEV) and mouse hepatitis virus (MHV) were used to determine effects of AT and RH on the survival of coronaviruses on stainless steel. At 4 degrees C, infectious virus persisted for as long as 28 days, and the lowest level of inactivation occurred at 20% RH. Inactivation was more rapid at 20 degrees C than at 4 degrees C at all humidity levels; the viruses persisted for 5 to 28 days, and the slowest inactivation occurred at low RH. Both viruses were inactivated more rapidly at 40 degrees C than at 20 degrees C. The relationship between inactivation and RH was not monotonic, and there was greater survival or a greater protective effect at low RH (20%) and high RH (80%) than at moderate RH (50%). There was also evidence of an interaction between AT and RH. The results show that when high numbers of viruses are deposited, TGEV and MHV may survive for days on surfaces at ATs and RHs typical of indoor environments. TGEV and MHV could serve as conservative surrogates for modeling exposure, the risk of transmission, and control measures for pathogenic enveloped viruses, such as SARS-CoV and influenza virus, on health care surfaces.

negative: Acute respiratory distress syndrome secondary to human metapneumovirus infection in a young healthy adult

negative: Impact of Middle East Respiratory Syndrome coronavirus (MERS‐CoV) on pregnancy and perinatal outcome BACKGROUND: Middle East Respiratory Syndrome coronavirus (MERS-CoV) is a viral respiratory disease. Most people infected with MERS-CoV develop severe acute respiratory illness. It was first reported in Saudi Arabia in 2012 and has since spread to several other countries. We report the clinical course of MERS-CoV infection in a pregnant woman who acquired the infection during the last trimester. CASE PRESENTATION: The patient is a 33-year-old female working as a critical care nurse. She was 32 weeks pregnant when she presented with respiratory symptoms after direct contact with a MERS-COV patient. Although the patient was in respiratory failure, necessitated mechanical ventilation, and intensive care (ICU) admission, a healthy infant was delivered. The mother recovered. To the best of our knowledge, this is the first reported case of a laboratory-confirmed Middle East Respiratory Syndrome Coronavirus in a pregnant woman. CONCLUSIONS: Middle East Respiratory Syndrome coronavirus (MERS-CoV) known to cause severe acute respiratory illness associated with a high risk of mortality Various factors may have contributed to the successful outcome of this patient such as young age, presentation during the last stages of pregnancy, and possible differences in immune response.

negative: CHAPTER 2 Infections, Inflammogens, and Drugs Publisher Summary This chapter examines environmental inflammatory factors in vascular disease and dementia with a focus on infections, environmental inflammogens, and drugs that modulate both vascular disease and dementia. Infections and blood levels of inflammatory proteins are risk factors for future coronary events and possibly for dementia. When early age mortality is high, the survivors carry long-term infections that impair growth and accelerate mortality at later ages (“cohort morbidity phenotype”). Chronic infections, which are endured by most of the world's human and animal populations, cause energy reallocation for host defense. Infections and inflammation may impair stem cell generation, with consequences to arterial and brain aging. Diet may introduce glycotoxins that stimulate inflammation. Some anti-inflammatory and anti-coagulant drugs may protect against coronary artery disease and certain cancers, and possibly also for Alzheimer disease. These “pharmacopleiotropies” implicate shared mechanisms in diverse diseases of aging.

negative: 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.

negative: Comparing SARS-CoV-2 with SARS-CoV and influenza pandemics The objective of this Personal View is to compare transmissibility, hospitalisation, and mortality rates for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with those of other epidemic coronaviruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), and pandemic influenza viruses. The basic reproductive rate (R(0)) for SARS-CoV-2 is estimated to be 2·5 (range 1·8–3·6) compared with 2·0–3·0 for SARS-CoV and the 1918 influenza pandemic, 0·9 for MERS-CoV, and 1·5 for the 2009 influenza pandemic. SARS-CoV-2 causes mild or asymptomatic disease in most cases; however, severe to critical illness occurs in a small proportion of infected individuals, with the highest rate seen in people older than 70 years. The measured case fatality rate varies between countries, probably because of differences in testing strategies. Population-based mortality estimates vary widely across Europe, ranging from zero to high. Numbers from the first affected region in Italy, Lombardy, show an all age mortality rate of 154 per 100 000 population. Differences are most likely due to varying demographic structures, among other factors. However, this new virus has a focal dissemination; therefore, some areas have a higher disease burden and are affected more than others for reasons that are still not understood. Nevertheless, early introduction of strict physical distancing and hygiene measures have proven effective in sharply reducing R(0) and associated mortality and could in part explain the geographical differences.

negative: Endocrine changes in SARS-CoV-2 patients and lessons from SARS-CoV Coronavirus infection outbreaks have occurred frequently in the last two decades and have led to significant mortality. Despite the focus on reducing mortality by preventing the spread of the virus, patients have died due to several other complications of the illness. The understanding of pathological mechanisms and their implications is continuously evolving. A number of symptoms occur in these patients due to the involvement of various endocrine glands. These clinical presentations went largely unnoticed during the first outbreak of severe acute respiratory syndrome (SARS) in 2002–2003. A few of these derangements continued during the convalescence phase and sometimes occurred after recovery. Similar pathological and biochemical changes are being reported with the novel coronavirus disease outbreak in 2020. In this review, we focus on these endocrine changes that have been reported in both SARS coronavirus and SARS coronavirus-2. As we battle the pandemic, it becomes imperative to address these underlying endocrine disturbances that are contributing towards or predicting mortality of these patients.

negative: 2019-nCoV epidemic: address mental health care to empower society

negative: Epidemiology of the 2020 Pandemic of COVID-19 in the State of Texas: The First Month of Community Spread The pandemic of novel Coronavirus (SARS-CoV-2) is currently spreading rapidly across the United States. We provide a comprehensive overview of COVID-19 epidemiology across the state of Texas, which includes vast rural & vulnerable communities that may be disproportionately impacted by the spread of this new disease. All 254 Texas counties were included in this study. We examined the geographic variation of COVID-19 from March 1 through April 8, 2020 by extracting data on incidence and case fatality from various national and state datasets. We contrasted incidence and case fatality rates by county-level demographic and healthcare resource factors. Counties which are part of metropolitan regions, such as Harris and Dallas, experienced the highest total number of confirmed cases. However, the highest incidence rates per 100,000 population were in found in counties of Donley (353.5), Castro (136.4), Matagorda (114.4) and Galveston (93.4). Among counties with greater than 10 cases, the highest CFR were observed in counties of Comal (10.3%), Hockley (10%), Hood (10%), and Castro (9.1%). Counties with the highest CFR (> 10%) had a higher proportion of non-Hispanic Black residents, adults aged 65 and older, and adults smoking, but lower number of ICU beds per 100,000 population, and number of primary care physicians per 1000 population. Although the urban areas of Texas account for the majority of COVID-19 cases, the higher case-fatality rates and low health care capacity in rural areas need attention.

negative: Inferring the number of COVID-19 cases from recently reported deaths We estimate the number of COVID-19 cases from newly reported deaths in a population without previous reports. Our results suggest that by the time a single death occurs, hundreds to thousands of cases are likely to be present in that population. This suggests containment via contact tracing will be challenging at this point, and other response strategies should be considered. Our approach is implemented in a publicly available, user-friendly, online tool.

negative: What does the COVID-19 pandemic mean for HIV, tuberculosis, and malaria control? Despite its current relatively low global share of cases and deaths in Africa compared to other regions, coronavirus disease 2019 (COVID-19) has the potential to trigger other larger crises in the region. This is due to the vulnerability of health and economic systems, coupled with the high burden of human immunodeficiency virus (HIV), tuberculosis (TB), and malaria. Here we examine the potential implications of COVID-19 on the control of these major epidemic diseases in Africa. We use current evidence on disease burden of HIV, TB, and malaria, and epidemic dynamics of COVID-19 in Africa, retrieved from the literature. Our analysis shows that the current measures to control COVID-19 neglect important and complex context-specific epidemiological, social, and economic realities in Africa. There is a similarity of clinical features of TB and malaria, with those used to track COVID-19 cases. This coupled with institutional mistrust and misinformation might result in many patients with clinical features similar to those of COVID-19 being hesitant to voluntarily seek care in a formal health facility. Furthermore, most people in productive age in Africa work in the informal sector, and most of those in the formal sector are underemployed. With the current measures to control COVID-19, these populations might face unprecedented difficulties to access essential services, mainly due to reduced ability of patients to support direct and indirect medical costs, and unavailability of transportation means to reach health facilities. Therefore, if not accompanied with appropriate economic and epidemiological considerations, we anticipate that these measures might result in unprecedented difficulties among vulnerable segments of society to access essential services, including antiretroviral and prophylactic drugs among people living with HIV and Acquired Immune Deficiency Syndrome, anti-tuberculosis drugs, and curative and preventive treatments for malaria among pregnant women and children. This might increase the propensity of patients taking substandard doses and/or medicines, which has the potential to compromise drug efficacy, and worsen health inequalities in the region. COVID-19 responses at country level should include measures to protect vulnerable and under-served segments of society.

negative: Continuous Invasion by Respiratory Viruses Observed in Rural Households During a Respiratory Syncytial Virus Seasonal Outbreak in Coastal Kenya BACKGROUND: Households are high-intensity close-contact environments favorable for transmission of respiratory viruses, yet little is known for low-income settings. METHODS: Active surveillance was completed on 47 households in rural coastal Kenya over 6 months during a respiratory syncytial virus (RSV) season. Nasopharyngeal swabs (NPSs) were taken from 483 household members twice weekly irrespective of symptoms. Using molecular diagnostics, NPSs from 6 households were screened for 15 respiratory viruses and the remainder of households only for the most frequent viruses observed: rhinovirus (RV), human coronavirus (HCoV; comprising strains 229E, OC43, and NL63), adenovirus (AdV), and RSV (A and B). RESULTS: Of 16928 NPSs tested for the common viruses, 4259 (25.2%) were positive for ≥1 target; 596 (13.8%) had coinfections. Detection frequencies were 10.5% RV (1780), 7.5% HCoV (1274), 7.3% AdV (1232), and 3.2% RSV (537). On average, each household and individual had 6 and 3 different viruses detected over the study period, respectively. Rhinovirus and HCoV were detected in all the 47 households while AdV and RSV were detected in 45 (95.7%) and 40 (85.1%) households, respectively. The individual risk of infection over the 6-month period was 93.4%, 80.1%, 71.6%, 61.5%, and 37.1% for any virus, RV, HCoV, AdV, and RSV, respectively. NPSs collected during symptomatic days and from younger age groups had higher prevalence of virus detection relative to respective counterparts. RSV was underrepresented in households relative to hospital admission data. CONCLUSIONS: In this household setting, respiratory virus infections and associated illness are ubiquitous. Future studies should address the health and economic implications of these observations.

negative: Coronavirus disease 2019 and obstructive sleep apnea syndrome

negative: How Should the Rehabilitation Community Prepare for 2019-nCoV? Abstract With the 2019-nCoV pandemic spreading quickly in USA and the world, it is urgent that the rehabilitation community quickly understands the epidemiology of the virus and what we can and must do to face this microbial adversary at the early stages of this likely long global pandemic. The 2019-nCoV is a novel virus so the majority of world’s population does not have prior immunity to it. It is more infectious and fatal than seasonal influenza, and definitive treatment and a vaccine are months away. Our arsenal against it are currently mainly social distancing and infection control measures.

negative: Community responses during early phase of the COVID-19 epidemic: a cross-sectional study Community responses are important for outbreak management during the early phase when preventive interventions are the major options. Therefore, this study aims to examine the behavioral responses of the community during the early phase of the COVID-19 epidemic in the Razavi Khorasan Province of Iran. A cross-sectional online survey was proceeded after confirmed COVID-19 in Iran. The population of the study was 500 residents of Razavi Khorasan areas were randomly surveyed. The research tool was demographic and risk perception questionnaire and Anxiety was assessed using the 7item GAD Scale. The data analyzed using the SPSS statistical version (V.20). The means of age participants was 31.9 11.9. The mean GAD-7 scores were 6.4 5.2 and 92.4% had moderate or severe anxiety (GAD-7 score ≥10). Many respondents reported their health status were very good or good (62.2 %; 311/500). About a quarter of them had respiratory symptoms in the past 14 days and experienced 20% of them travelled outside the Razavi Khorasan Province in the previous. Risk perception toward COVID-19 in the community of the Razavi Khorasan Province was moderate. Most participants are alert to disease progression. This study suggested timely behavioral assessment of the community is beneficial and effective to inform next intervention, and risk communication strategies in epidemic disease.

negative: Impact of population mask wearing on Covid-19 post lockdown COVID-19, caused by SARS-CoV2 is a rapidly spreading global pandemic. Although precise transmission routes and dynamics are unknown, SARS-CoV2 is thought primarily to spread via contagious respiratory droplets. Unlike with SARS-CoV, maximal viral shedding occurs in the early phase of illness, and this is supported by models that suggest 40-80% of transmission events occur from pre- and asymptomatic individuals. One widely-discussed strategy to limit transmission of SARS-CoV2, particularly from presymptomatic individuals, has been population-level wearing of masks. Modelling for pandemic influenza suggests some benefit in reducing total numbers infected with even 50% mask-use. COVID-19 has a higher hospitalization and mortality rate than influenza, and the impacts on these parameters, and critically, at what point in the pandemic trajectory mask-use might exert maximal benefit are completely unknown. We derived a simplified SIR model to investigate the effects of near-universal mask-use on COVID-19 assuming 8 or 16% mask efficacy. We decided to model, in particular, the impact of masks on numbers of critically-ill patients and cumulative mortality, since these are parameters that are likely to have the most severe consequences in the COVID-19 pandemic. Whereas mask use had a relatively minor benefit on critical-care and mortality rates when transmissibility (Reff) was high, the reduction on deaths was dramatic as the effective R approached 1, as might be expected after aggressive social-distancing measures such as wide-spread lockdowns. One major concern with COVID-19 is its potential to overwhelm healthcare infrastructures, even in resource-rich settings, with one third of hospitalized patients requiring critical-care. We incorporated this into our model, increasing death rates for when critical-care resources have been exhausted. Our simple model shows that modest efficacy of masks could avert substantial mortality in this scenario. Importantly, the effects on mortality became hyper-sensitive to mask-wearing as the effective R approaches 1, i.e. near the tipping point of when the infection trajectory is expected to revert to exponential growth, as would be expected after effective lockdown. Our model suggests that mask-wearing might exert maximal benefit as nations plan their post-lockdown strategies and suggests that mask-wearing should be included in further more sophisticated models of the current pandemic.

negative: COVID-19: Learning from Lessons To Guide Treatment and Prevention Interventions Coronavirus disease 2019 (COVID-19) is caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and first emerged in December 2019 in Wuhan, Hubei province, China. Since then, the virus has rapidly spread to many countries. While the outbreak in China appears to be in decline, the disease has spread across the world, with a daily increase in the number of confirmed cases and infection-related deaths. Here, we highlight (i) the lessons that have been learnt so far and how they will benefit reducing the impact of COVID-19 disease and (ii) an update on the status of drug treatment and vaccine development to prevent COVID-19 and potential future related pandemics. Although the mortality rate is clearly higher than for influenza, the rate does seem to vary from country to country, possibly reflecting differences in how rapidly local health authorities respond to isolate and effectively care for the affected population. Drugs are urgently needed for both prophylaxis and the treatment of severely ill patients; however, no proven effective therapies for SARS-CoV-2 currently exist. A number of drugs that have been approved for other diseases are being tested for the treatment of COVID-19 patients, but there is an absence of data from appropriately designed clinical trials showing that these drugs, either alone or in combination, will prove effective. There is also a global urgency to develop a vaccine against COVID-19, but development and appropriate testing will take at least a year before such a vaccine will be globally available. This review summarizes the lessons learnt so far from the COVID-19 pandemic, examines the evidence regarding the drugs that are being tested for the treatment of COVID19, and describes the progress made in efforts to develop an effective vaccine.

negative: The effect of BCG vaccination on COVID-19 examined by a statistical approach: no positive results from the Diamond Princess and cross-national differences previously reported by world-wide comparisons are flawed in several ways Recently, the controversial hypothesis that BCG (Bacillus Calmette-Guerin) vaccination reduces infection or severity of COVID-19 has been proposed. The present study examined this hypothesis using statistical approaches based on the public data. Three approaches were utilized: 1) comparing the infection and mortality ratio of people on the cruise ship Diamond Princess, 2) comparing the number of mortalities among nations, and 3) comparing the maximum daily increase rate of total mortalities among nations. The result of 1) showed that there is no significant difference in infection per person onboard and mortality-infection between Japanese citizens vs. other nationalities and BCG obligatory nations vs. non-BCG obligatory nations on the Diamond Princess. The result of 2) showed that the number of mortalities among nations is similar to the previous studies, but this analysis also considered the timing of COVID-19 arrival in each nation. After correcting for arrival time, previously reported effect of BCG vaccination on decreasing total mortality disappeared. This is because nations that lack BCG vaccination are concentrated in Western Europe, which is near an epicenter of COVID-19. Therefore some previous reports are now considered to be affected by this artifact; the result may have been flawed by on-land dispersal from an epicenter. However, some results showed weakly significant differences in the number of deaths at a particular time among BCG obligatory and non-BCG nations (especially the use of Japanese BCG strain Tokyo 172). However, these results are affected by the results of three countries and the effect of BCG vaccination remains inconclusive. The result of 3) showed that the maximum daily increasing rate in death among nations showed no significant difference among BCG vaccination policies. In the present study, although some results showed statistically significant differences among BCG vaccination policies, they may be affected by the impact of various other factors, such as national infection-control policies, social distancing, behavioral changes of people, possible previous local epidemics of closely related viruses, or inter-population differences in ACE2 or other genetic polymorphism. Further research is needed to better understand the underlying cause of the observed differences in infection and mortality of the disease among nations. Nevertheless, our results show that the effect of BCG vaccination, if any, can be masked by many other factors. Therefore, the possible effect might be relatively small. In fact, in Japan, where almost all citizens have been vaccinated, COVID-19 cases are constantly increasing. Given the importance of peoples behavior in preventing viral propagation, the spread of optimism triggered by this hypothesis would be harmful to BCG vaccination nations.

negative: Is Global BCG Vaccination Coverage Relevant To The Progression Of SARS-CoV-2 Pandemic? Abstract The lower than expected number of SARS-CoV-2 cases in countries with fragile health systems is puzzling. Herein, we hypothesize that BCG vaccination policies adopted by different countries might influence the SARS-CoV-2 transmission patterns and/or COVID-19 associated morbidity and mortality through the vaccine’s capacity to confer heterologous protection. We also postulate that until a specific vaccine is developed, SARS-CoV-2 vulnerable populations could be immunized with BCG vaccines to attain heterologous nonspecific protection from the new coronavirus.

negative: A multisite, randomized field trial to evaluate the influence of lactoferrin on the morbidity and mortality of dairy calves with diarrhea ABSTRACT Diarrhea is one of the most common causes of antimicrobial use and mortality in young calves. To reduce antimicrobial use and resistance on dairy farms, research on alternative therapies for calf diarrhea is necessary. Our laboratory previously conducted a randomized clinical trial investigating the effectiveness of lactoferrin, an iron-binding protein found in colostrum, as a treatment for calf diarrhea. The trial showed significantly reduced calf mortality in diarrheic calves that were administered lactoferrin. Thus, the objective of this study was to corroborate the results of our prior clinical trial across multiple farms and to investigate the effect of lactoferrin on the morbidity and mortality of preweaned calves with naturally occurring cases of diarrhea. This randomized field trial was conducted on 5 commercial dairy farms in Ohio. In total, 485 calves (≤21 d of age) were enrolled at first diarrhea diagnosis (fecal score ≥2 defined as loose to watery) and randomly assigned to receive an oral dose of lactoferrin (3 g of lactoferrin powder dissolved in 30 mL of water) or 30 mL of water (control) once daily for 3 consecutive days. Health assessments were conducted on the day of diarrhea diagnosis (d 0) and 1, 2, 3, 7, 14, 21, 28, and 35 d following diagnosis. Producer records of disease treatment and mortality were collected 120 d following diagnosis. A Poisson regression model was used to test differences between treatments in disease frequency through 35 d post-diarrhea diagnosis and the incidence risk of treatment and mortality risk 120 d post-diarrhea diagnosis; the model controlled for calf age at enrollment, farm, and treatment. Median calf age at enrollment was 11 d and ranged from 1 to 26 d of age. At study enrollment, 51.3% (123/240) and 52.2% (128/245) of calves in the control and lactoferrin treatment groups, respectively, were diagnosed with severe diarrhea (fecal score = 3). The frequency of disease (diarrhea, dehydration, depression, signs of respiratory disease) through 35 d following diarrhea diagnosis was not significantly different for calves in the lactoferrin and control groups. Overall mortality risk for enrolled calves was 9.9%, and 10.7% (22/243) and 9.1% (26/242) of calves in the lactoferrin and control groups, respectively, died or were culled in the 120 d following diarrhea diagnosis. The relative risk of death or culling did not differ between treatment groups, however. Therefore, as performed in this study, lactoferrin as a treatment for calf diarrhea was not beneficial.

negative: Covid‐19: biotechnologists make their contribution

negative: Abstract of 29th Regional Congress of the ISBT

negative: Data-based analysis, modelling and forecasting of the COVID-19 outbreak Since the first suspected case of coronavirus disease-2019 (COVID-19) on December 1st, 2019, in Wuhan, Hubei Province, China, a total of 40,235 confirmed cases and 909 deaths have been reported in China up to February 10, 2020, evoking fear locally and internationally. Here, based on the publicly available epidemiological data for Hubei, China from January 11 to February 10, 2020, we provide estimates of the main epidemiological parameters. In particular, we provide an estimation of the case fatality and case recovery ratios, along with their 90% confidence intervals as the outbreak evolves. On the basis of a Susceptible-Infectious-Recovered-Dead (SIDR) model, we provide estimations of the basic reproduction number (R(0)), and the per day infection mortality and recovery rates. By calibrating the parameters of the SIRD model to the reported data, we also attempt to forecast the evolution of the outbreak at the epicenter three weeks ahead, i.e. until February 29. As the number of infected individuals, especially of those with asymptomatic or mild courses, is suspected to be much higher than the official numbers, which can be considered only as a subset of the actual numbers of infected and recovered cases in the total population, we have repeated the calculations under a second scenario that considers twenty times the number of confirmed infected cases and forty times the number of recovered, leaving the number of deaths unchanged. Based on the reported data, the expected value of R(0) as computed considering the period from the 11th of January until the 18th of January, using the official counts of confirmed cases was found to be ∼4.6, while the one computed under the second scenario was found to be ∼3.2. Thus, based on the SIRD simulations, the estimated average value of R(0) was found to be ∼2.6 based on confirmed cases and ∼2 based on the second scenario. Our forecasting flashes a note of caution for the presently unfolding outbreak in China. Based on the official counts for confirmed cases, the simulations suggest that the cumulative number of infected could reach 180,000 (with a lower bound of 45,000) by February 29. Regarding the number of deaths, simulations forecast that on the basis of the up to the 10th of February reported data, the death toll might exceed 2,700 (as a lower bound) by February 29. Our analysis further reveals a significant decline of the case fatality ratio from January 26 to which various factors may have contributed, such as the severe control measures taken in Hubei, China (e.g. quarantine and hospitalization of infected individuals), but mainly because of the fact that the actual cumulative numbers of infected and recovered cases in the population most likely are much higher than the reported ones. Thus, in a scenario where we have taken twenty times the confirmed number of infected and forty times the confirmed number of recovered cases, the case fatality ratio is around ∼0.15% in the total population. Importantly, based on this scenario, simulations suggest a slow down of the outbreak in Hubei at the end of February.

negative: Structure and immune recognition of the porcine epidemic diarrhea virus spike protein Porcine epidemic diarrhea virus is an alphacoronavirus responsible for significant morbidity and mortality in pigs. A key determinant of viral tropism and entry, the PEDV spike protein is a key target for the host antibody response and a good candidate for a protein-based vaccine immunogen. We used electron microscopy to evaluate the PEDV spike structure, as well as pig polyclonal antibody responses to viral infection. The structure of the PEDV spike reveals a configuration similar to that of HuCoV-NL63. Several PEDV protein-protein interfaces are mediated by non-protein components including a glycan at Asn264 and two bound palmitoleic acid molecules. The polyclonal antibody response to PEDV infection shows a dominance of epitopes in the S1 region. This structural and immune characterization provides new insights into coronavirus spike stability determinants and explores the immune landscape of viral spike proteins.

negative: Age effects in monetary valuation of reduced mortality risks: the relevance of age-specific hazard rates This paper highlights the relevance of age-specific hazard rates in explaining the age variation in “value of statistical life” (VSL) figures. The analysis—which refers to a stated preference framework—contributes to the ongoing discussion of whether benefits resulting from reduced mortality risk should be valued differently depending on the age of the beneficiaries. By focussing on a life-threatening environmental phenomenon I show that the consideration of the individual’s age-specific hazard rate is important. If a particular risk affects all individuals regardless of their age so that their hazard rate is age-independent, VSL is rather constant for people at different age; if hazard rate varies with age, VSL estimates are sensitive to age. The results provide an explanation for the mixed outcomes in empirical studies and illustrate in which cases an adjustment to age may or may not be justified. Efficient provision of live-saving measures requires that such differences to be taken into account.

negative: ASSESSMENT OF WORKERS PERSONAL VULNERABILITY TO COVID-19 USING COVID-AGE Decisions on fitness for employment that entails a risk of contracting Covid-19 require an assessment of the workers personal vulnerability should infection occur. Using recently published UK data, we have developed a risk model that provides estimates of personal vulnerability to Covid-19 according to sex, age, ethnicity, and various comorbidities. Vulnerability from each risk factor is quantified in terms of its equivalence to added years of age. Addition of the impact from each risk factor to an individuals true age generates their Covid-age, a summary measure representing the age of a healthy UK white male with equivalent vulnerability. We discuss important limitations of the model, including current scientific uncertainties and limitations on generalisability beyond the UK setting and its use beyond informing assessments of individual vulnerability in the workplace. As new evidence becomes available, some of these limitations can be addressed. The model does not remove the need for clinical judgement or for other important considerations when managing occupational risks from Covid-19.

negative: The impact on neonatal mortality of shifting childbirth services among levels of hospitals: Taiwan's experience BACKGROUND: There is considerable discussion surrounding whether advanced hospitals provide better childbirth care than local community hospitals. This study examines the effect of shifting childbirth services from advanced hospitals (i.e., medical centers and regional hospitals) to local community hospitals (i.e., clinics and district hospitals). The sample population was tracked over a seven-year period, which includes the four months of the 2003 severe acute respiratory syndrome (SARS) epidemic in Taiwan. During the SARS epidemic, pregnant women avoided using maternity services in advanced hospitals. Concerns have been raised about maintaining the quality of maternity care with increased demands on childbirth services in local community hospitals. In this study, we analyzed the impact of shifting maternity services among hospitals of different levels on neonatal mortality and maternal deaths. METHODS: A population-based study was conducted using data from Taiwan's National Health Insurance annual statistics of monthly county neonatal morality rates. Based on a pre-SARS sample from January 1998 to December 2002, we estimated a linear regression model which included "trend," a continuous variable representing the effect of yearly changes, and two binary variables, "month" and "county," controlling for seasonal and county-specific effects. With the estimated coefficients, we obtained predicted neonatal mortality rates for each county-month. We compared the differences between observed mortality rates of the SARS period and predicted rates to examine whether the shifting in maternity services during the SARS epidemic significantly affected neonatal mortality rates. RESULTS: With an analysis of a total of 1,848 observations between 1998 and 2004, an insignificantly negative mean of standardized predicted errors during the SARS period was found. The result of a sub-sample containing areas with advanced hospitals showed a significant negative mean of standardized predicted errors during the SARS period. These findings indicate that despite increased use of local community hospitals, neonatal mortality during the SARS epidemic did not increase, and even decreased in areas with advanced hospitals. CONCLUSION: An increased use of maternity services in local community hospitals occurred during the SARS epidemic in Taiwan. However, we observed no increase in neonatal and maternity mortality associated with these increased demands on local community hospitals.

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: Epidemiological shift and geographical heterogeneity in the burden of leptospirosis in China BACKGROUND: Leptospirosis morbidity and mortality rates in China have decreased since the 2000s. Further analyses of the spatiotemporal and demographic changes occurring in the last decade and its implication on estimates of disease burden are required to inform intervention strategies. In this study, we quantified the epidemiological shift and geographical heterogeneity in the burden of leptospirosis during 2005–2015 in China. METHODS: We used reported leptospirosis case data from 1st January 2005 to 31st of December 2015 that routinely collected by the China Information System for Disease Control and Prevention (CISDCP) to analyze the epidemiological trend and estimate the burden in terms of disability-adjusted life-years (DALYs) over space, time, and demographical groups. RESULTS: A total of 7763 cases were reported during 2005–2015. Of which, 2403 (31%) cases were the laboratory-confirmed case. Since 2005, the notified incidence rate was gradually decreased (P < 0.05) and it was relatively stable during 2011–2015 (P > 0.05). During 2005–2015, we estimated a total of 10 313 DALYs were lost due to leptospirosis comprising a total of 1804 years-lived with disability (YLDs) and 8509 years-life lost (YLLs). Males had the highest burden of disease (7149 DALYs) compared to females (3164 DALYs). The highest burden estimate was attributed to younger individuals aged 10–19 years who lived in southern provinces of China. During 2005–2015, this age group contributed to approximately 3078 DALYs corresponding to 30% of the total DALYs lost in China. Yet, our analysis indicated a declining trend in burden estimates (P < 0.001) since 2005 and remained relatively low during 2011–2015. Low burden estimates have been identified in the endemic regions where infections principally distributed. Most of the changes in DALY estimates were driven by changes in YLLs. CONCLUSIONS: In the last 11-years, the burden estimates of leptospirosis have shown a declining trend across the country; however, leptospirosis should not be neglected as it remains an important zoonotic disease and potentially affecting the young and productive population in economically less-developed provinces in southern of China. In addition, while in the last five years the incidence has been reported at very low-level, this might not reflect the true incidence of leptospirosis. Strengthened surveillance in the endemic regions is, hence, substantially required to capture the actual prevalence to better control leptospirosis in China. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40249-018-0435-2) contains supplementary material, which is available to authorized users.

negative: Identifying a Kidney Transplant Recipient COVID Phenotype to Aid Test Utilization in the Setting of Limited Testing Availability - Does One Exist? Abstract: The high morbidity and mortality of COVID-19 in immunocompetent patients raises significant concern for immunosuppressed kidney transplant recipients (KTRs). This level of concern, both on the part of the KTRs and transplant professionals, is heightened by a lack of prior knowledge on how SARS-CoV-2 may manifest differently in immunosuppressed patients. Characterizing how KTRs may present differently than the general population would allow for more targeted and timely evaluation and treatment of KTRs with COVID-19 infection. Methods Without prior knowledge of how this virus would affect our transplant center’s delivery of care to KTRs who are SARS-CoV-2 positive or Patients Under Investigation (PUIs), and in the setting of limited testing availability, we initiated a Quality Assurance and Improvement Project (QAPI) to track KTRs followed at our transplant center through the SARS-CoV-2 testing process. Results Of the 53 symptomatic patients, 20 (38%) tested positive for SARS-CoV-2 either on presentation to the emergency department, or referral to a designated outpatient testing center. In addition, 16 (80%) of the 20 patients who tested positive required inpatient treatment. Intriguingly, patients with a history of polyoma BK viremia (BKV) had a higher incidence of testing positive for SARS-CoV-2 compared to patients without history of BKV (80% and 28%, respectively; p= 0.002). The Positive Predictive Value and Likelihood ratio was 80% and 6.6 for this association, respectively. Among our KTRs tested, those receiving belatacept had a lower likelihood of testing positive for SARS-CoV-2. This finding approached, but did not achieve, statistical significance (p=0.06).

negative: Infection in the critically ill—questions we should be asking Best practice in infection control and management in the critically ill continues to generate considerable debate. The wide variation in current practice is witness to this continuing uncertainty. In large part this is due to the lack of a decent evidence base and to an over-reliance on deep-set dogma. Data that go against the grain are often conveniently overlooked and political imperatives frequently supervene. This article highlights some of these discrepancies and argues for a more balanced, scientific approach. In this time of financial restraint, we need to identify true priorities from both health and economic perspectives, and to see what practices can safely and effectively be modified or abandoned.

negative: Infections in Hematology Patients Infections are major causes of morbidity and mortality in hematology patients especially those having undergone allogeneic hematopoietic stem cell transplantation. The management relies on early diagnosis and rapid introduction of appropriate antimicrobial drugs frequently before the infectious agent has been identified. The use of broad-spectrum antibacterial drugs has reduced the mortality in febrile neutropenia. However, the increase of multiresistant strains has in several countries become a major threat, and the development of new antibacterial drugs is urgently needed. Infection control strategies are also very important to limit the spread of multiresistant bacteria. Early diagnosis with imaging and tests for antigen or DNA is important for the management of fungal infections. High-risk patients should also receive prophylaxis. Viral infections are important causes of severe disease in patients having undergone allogeneic stem cell transplantation but do occur also in non-transplanted patients. Early diagnosis usually with tests for viral nucleic acids is the key for appropriate management. Prevention and treatment with antiviral drugs are available for some viruses especially herpesviruses.

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: Immune modulation to improve survival of respiratory virus infections in mice Viral pneumonia remains a global health threat requiring novel treatment strategies, as strikingly exemplified in the SARS-CoV-2 pandemic of 2019-2020. We have reported that mice treated with a combination of inhaled Toll-like receptor (TLR) 2/6 and TLR 9 agonists (Pam2-ODN) to stimulate innate immunity are broadly protected against respiratory pathogens, but the mechanisms underlying this protection remain incompletely elucidated. Here, we show in a lethal paramyxovirus model that Pam2-ODN-enhanced survival is associated with robust virus inactivation by reactive oxygen species (ROS), which occurs prior to internalization by lung epithelial cells. However, we also found that mortality in sham-treated mice temporally corresponded with CD8+ T cell-enriched lung inflammation that peaks on days 11-12 after viral challenge, when the viral burden has waned to a scarcely detectable level. Pam2-ODN treatment blocked this injurious inflammation by reducing the viral burden, and alternatively, depleting CD8+ T cells 8 days after viral challenge also decreased mortality. These findings reveal opportunities for targeted immunomodulation to protect susceptible individuals against the morbidity and mortality of respiratory viral infections.

negative: Noninvasive ventilation in acute respiratory failure due to H1N1 influenza: A word of caution

negative: Inactivating influenza viruses on surfaces using hydrogen peroxide or triethylene glycol at low vapor concentrations BACKGROUND: Surfaces in congregate settings, such as vehicles used for mass transportation, can become contaminated with infectious microorganisms and facilitate disease transmission. We disinfected surfaces contaminated with H1N1 influenza viruses using hydrogen peroxide (HP) vapor at concentrations below 100 ppm and triethylene glycol (TEG)-saturated air containing 2 ppm of TEG at 25°C. METHODS: Influenza viruses in aqueous suspensions were deposited on stainless-steel coupons, allowed to dry at ambient conditions, and then exposed for up to 15 minutes to 10 to 90 ppm of HP vapor or TEG-saturated air. Virus assays were done on the solution used to wash the viruses from these coupons and from coupons treated similarly but without exposure to HP or TEG vapor. RESULTS: After 2.5 minutes, exposure to 10-ppm HP vapor resulted in 99% inactivation. For air saturated with TEG at 25 to 29°C, the disinfection rate was about 1.3 log(10) reductions per hour, about 16 times faster than the measured natural inactivation rate under ambient conditions. CONCLUSIONS: Vapor concentrations of 10 ppm HP or 2 ppm TEG can provide effective surface disinfection. At these low concentrations, the potential for damage to even the avionics of an airplane would be expected to be minimal. At a TEG vapor concentration of 2 ppm, there are essentially no health risks to people.

negative: Performance Characteristics of the Abbott Architect SARS-CoV-2 IgG Assay and Seroprevalence in Boise, Idaho. Coronavirus disease-19 (COVID19), the novel respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with severe morbidity and mortality. The rollout of diagnostic testing in the United States was slow, leading to numerous cases that were not tested for SARS-CoV-2 in February and March 2020, necessitating the use of serological testing to determine past infections. Here, we evaluated the Abbott SARS-CoV-2 IgG test for detection of anti-SARS-CoV-2 IgG antibodies by testing 3 distinct patient populations. We tested 1,020 serum specimens collected prior to SARS-CoV-2 circulation in the United States and found one false positive, indicating a specificity of 99.90%. We tested 125 patients who tested RT-PCR positive for SARS-CoV-2 for which 689 excess serum specimens were available and found sensitivity reached 100% at day 17 after symptom onset and day 13 after PCR positivity. Alternative index value thresholds for positivity resulted in 100% sensitivity and 100% specificity in this cohort. We tested 4,856 individuals from Boise, Idaho collected over one week in April 2020 as part of the Crush the Curve initiative and detected 87 positives for a positivity rate of 1.79%. These data demonstrate excellent analytical performance of the Abbott SARS-CoV-2 IgG test as well as the limited circulation of the virus in the western United States. We expect the availability of high-quality serological testing will be a key tool in the fight against SARS-CoV-2.

negative: Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID‐19) implicate special control measures By 27 February 2020, the outbreak of coronavirus disease 2019 (COVID‐19) caused 82 623 confirmed cases and 2858 deaths globally, more than severe acute respiratory syndrome (SARS) (8273 cases, 775 deaths) and Middle East respiratory syndrome (MERS) (1139 cases, 431 deaths) caused in 2003 and 2013, respectively. COVID‐19 has spread to 46 countries internationally. Total fatality rate of COVID‐19 is estimated at 3.46% by far based on published data from the Chinese Center for Disease Control and Prevention (China CDC). Average incubation period of COVID‐19 is around 6.4 days, ranges from 0 to 24 days. The basic reproductive number (R(0)) of COVID‐19 ranges from 2 to 3.5 at the early phase regardless of different prediction models, which is higher than SARS and MERS. A study from China CDC showed majority of patients (80.9%) were considered asymptomatic or mild pneumonia but released large amounts of viruses at the early phase of infection, which posed enormous challenges for containing the spread of COVID‐19. Nosocomial transmission was another severe problem. A total of 3019 health workers were infected by 12 February 2020, which accounted for 3.83% of total number of infections, and extremely burdened the health system, especially in Wuhan. Limited epidemiological and clinical data suggest that the disease spectrum of COVID‐19 may differ from SARS or MERS. We summarize latest literatures on genetic, epidemiological, and clinical features of COVID‐19 in comparison to SARS and MERS and emphasize special measures on diagnosis and potential interventions. This review will improve our understanding of the unique features of COVID‐19 and enhance our control measures in the future.

negative: Comparative community burden and severity of seasonal and pandemic influenza: results of the Flu Watch cohort study BACKGROUND: Assessment of the effect of influenza on populations, including risk of infection, illness if infected, illness severity, and consultation rates, is essential to inform future control and prevention. We aimed to compare the community burden and severity of seasonal and pandemic influenza across different age groups and study years and gain insight into the extent to which traditional surveillance underestimates this burden. METHODS: Using preseason and postseason serology, weekly illness reporting, and RT-PCR identification of influenza from nasal swabs, we tracked the course of seasonal and pandemic influenza over five successive cohorts (England 2006–11; 5448 person-seasons' follow-up). We compared burden and severity of seasonal and pandemic strains. We weighted analyses to the age and regional structure of England to give nationally representative estimates. We compared symptom profiles over the first week of illness for different strains of PCR-confirmed influenza and non-influenza viruses using ordinal logistic regression with symptom severity grade as the outcome variable. FINDINGS: Based on four-fold titre rises in strain-specific serology, on average influenza infected 18% (95% CI 16–22) of unvaccinated people each winter. Of those infected there were 69 respiratory illnesses per 100 person-influenza-seasons compared with 44 per 100 in those not infected with influenza. The age-adjusted attributable rate of illness if infected was 23 illnesses per 100 person-seasons (13–34), suggesting most influenza infections are asymptomatic. 25% (18–35) of all people with serologically confirmed infections had PCR-confirmed disease. 17% (10–26) of people with PCR-confirmed influenza had medically attended illness. These figures did not differ significantly when comparing pandemic with seasonal influenza. Of PCR-confirmed cases, people infected with the 2009 pandemic strain had markedly less severe symptoms than those infected with seasonal H3N2. INTERPRETATION: Seasonal influenza and the 2009 pandemic strain were characterised by similar high rates of mainly asymptomatic infection with most symptomatic cases self-managing without medical consultation. In the community the 2009 pandemic strain caused milder symptoms than seasonal H3N2. FUNDING: Medical Research Council and the Wellcome Trust.

negative: Do Men Have a Higher Case Fatality Rate of Severe Acute Respiratory Syndrome than Women Do? Severe acute respiratory syndrome (SARS) has been reported in 30 countries and regions, with a cumulative total of 8,099 probable cases and 774 deaths as of July 31, 2003, according to the World Health Organization. In Hong Kong, People’s Republic of China, 1,755 SARS cases and 299 deaths had occurred as of September 22, 2003. The authors analyzed data from the Department of Health, Hong Kong SAR. The data series includes details regarding sex, age, and chronic disease history. Using data from early March to September 22, 2003, the authors found that males had a significantly (p < 0.0001) higher case fatality rate than females did, 21.9% versus 13.2%; the relative risk was 1.66 (95% confidence interval (CI): 1.35, 2.05), and it was 1.62 (95% CI: 1.21, 2.16) after adjustment for age. Subgroup analysis was conducted by excluding health care workers (n = 386) from the analysis. The overall crude relative risk of mortality was 1.41 (95% CI: 1.15, 1.74), and the adjusted relative risk was 1.48 (95% CI: 1.10, 2.00). Thus, among SARS patients, males may be more severely affected by the disease than females are. This finding could be related to a nonuniform case definition of SARS disease, a different treatment regimen, a past smoking history, work-environment factors, or gender-specific immune-defense factors, for instance.

negative: Signals of T(h)2 immune response from COVID-19 patients requiring intensive care

negative: Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study BACKGROUND: Pneumonia is the leading cause of death among children younger than 5 years. In this study, we estimated causes of pneumonia in young African and Asian children, using novel analytical methods applied to clinical and microbiological findings. METHODS: We did a multi-site, international case-control study in nine study sites in seven countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. All sites enrolled in the study for 24 months. Cases were children aged 1–59 months admitted to hospital with severe pneumonia. Controls were age-group-matched children randomly selected from communities surrounding study sites. Nasopharyngeal and oropharyngeal (NP-OP), urine, blood, induced sputum, lung aspirate, pleural fluid, and gastric aspirates were tested with cultures, multiplex PCR, or both. Primary analyses were restricted to cases without HIV infection and with abnormal chest x-rays and to controls without HIV infection. We applied a Bayesian, partial latent class analysis to estimate probabilities of aetiological agents at the individual and population level, incorporating case and control data. FINDINGS: Between Aug 15, 2011, and Jan 30, 2014, we enrolled 4232 cases and 5119 community controls. The primary analysis group was comprised of 1769 (41·8% of 4232) cases without HIV infection and with positive chest x-rays and 5102 (99·7% of 5119) community controls without HIV infection. Wheezing was present in 555 (31·7%) of 1752 cases (range by site 10·6–97·3%). 30-day case-fatality ratio was 6·4% (114 of 1769 cases). Blood cultures were positive in 56 (3·2%) of 1749 cases, and Streptococcus pneumoniae was the most common bacteria isolated (19 [33·9%] of 56). Almost all cases (98·9%) and controls (98·0%) had at least one pathogen detected by PCR in the NP-OP specimen. The detection of respiratory syncytial virus (RSV), parainfluenza virus, human metapneumovirus, influenza virus, S pneumoniae, Haemophilus influenzae type b (Hib), H influenzae non-type b, and Pneumocystis jirovecii in NP-OP specimens was associated with case status. The aetiology analysis estimated that viruses accounted for 61·4% (95% credible interval [CrI] 57·3–65·6) of causes, whereas bacteria accounted for 27·3% (23·3–31·6) and Mycobacterium tuberculosis for 5·9% (3·9–8·3). Viruses were less common (54·5%, 95% CrI 47·4–61·5 vs 68·0%, 62·7–72·7) and bacteria more common (33·7%, 27·2–40·8 vs 22·8%, 18·3–27·6) in very severe pneumonia cases than in severe cases. RSV had the greatest aetiological fraction (31·1%, 95% CrI 28·4–34·2) of all pathogens. Human rhinovirus, human metapneumovirus A or B, human parainfluenza virus, S pneumoniae, M tuberculosis, and H influenzae each accounted for 5% or more of the aetiological distribution. We observed differences in aetiological fraction by age for Bordetella pertussis, parainfluenza types 1 and 3, parechovirus–enterovirus, P jirovecii, RSV, rhinovirus, Staphylococcus aureus, and S pneumoniae, and differences by severity for RSV, S aureus, S pneumoniae, and parainfluenza type 3. The leading ten pathogens of each site accounted for 79% or more of the site's aetiological fraction. INTERPRETATION: In our study, a small set of pathogens accounted for most cases of pneumonia requiring hospital admission. Preventing and treating a subset of pathogens could substantially affect childhood pneumonia outcomes. FUNDING: Bill & Melinda Gates Foundation.

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

negative: Update to the Latin American Thoracic Society (ALAT) Recommendations on Community-Acquired Pneumonia

negative: Older people and COVID-19: Isolation, risk and ageism. Internationally, health authorities and governments are warning older people that they are at a higher risk of more serious and possible fatal illness associated with COVID-19. Mortality data from Oxford COVID-19 Evidence Service (25/3/20) indicates a risk of mortality of 3.6% for people in their 60s, which increases to 8.0% and 14.8% for people in their 70s and over 80s. Therefore, the global recommendation for older populations includes social isolation, which involves staying at home and avoiding contact with other people, possibly for an extended period of time, currently estimated to be between three and four months. Older populations in this current context, refers to people over 70 years, and 50 years in some particularly vulnerable Indigenous populations.

negative: Pandemic preparedness: perceptions of vulnerable migrants in Thailand towards WHO-recommended non-pharmaceutical interventions: a cross-sectional study BACKGROUND: Non-pharmaceutical interventions (NPIs) constituted the principal public health response to the previous influenza A (H1N1) 2009 pandemic and are one key area of ongoing preparation for future pandemics. Thailand is an important point of focus in terms of global pandemic preparedness and response due to its role as the major transportation hub for Southeast Asia, the endemic presence of multiple types of influenza, and its role as a major receiving country for migrants. Our aim was to collect information about vulnerable migrants’ perceptions of and ability to implement NPIs proposed by the WHO. We hope that this information will help us to gauge the capacity of this population to engage in pandemic preparedness and response efforts, and to identify potential barriers to NPI effectiveness. METHODS: A cross-sectional survey was performed. The study was conducted during the influenza H1N1 2009 pandemic and included 801 migrant participants living in border areas thought to be high risk by the Thailand Ministry of Public Health. Data were collected by Migrant Community Health Workers using a 201-item interviewer-assisted questionnaire. Univariate descriptive analyses were conducted. RESULTS: With the exception of border measures, to which nearly all participants reported they would be adherent, attitudes towards recommended NPIs were generally negative or uncertain. Other potential barriers to NPI implementation include limited experience applying these interventions (e.g., using a thermometer, wearing a face mask) and inadequate hand washing and household disinfection practices. CONCLUSIONS: Negative or ambivalent attitudes towards NPIs combined with other barriers identified suggest that vulnerable migrants in Thailand have a limited capacity to participate in pandemic preparedness efforts. This limited capacity likely puts migrants at risk of propagating the spread of a pandemic virus. Coordinated risk communication and public education are potential strategies that may reduce barriers to individual NPI implementation.

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: Prevalence of human respiratory viruses in adults with acute respiratory tract infections in Beijing, 2005–2007 To determine the aetiological role and epidemiological profile of common respiratory viruses in adults with acute respiratory tract infections (ARTIs), a 2-year study was conducted in Beijing, China, from May 2005 to July 2007. Nose and throat swab samples from 5808 ARTI patients were analysed by PCR methods for common respiratory viruses, including influenza viruses (IFVs) A, B, and C, parainfluenza viruses (PIVs) 1–4, enteroviruses (EVs), human rhinoviruses (HRVs), respiratory syncytial virus (RSV), human metapneumovirus (HMPV), human coronaviruses (HCoVs) OC43, 229E, NL63, and HKU1, and adenoviruses (ADVs). Viral pathogens were detected in 34.6% of patient samples, and 1.6% of the patients tested positive for more than one virus. IFVs (19.3%) were the dominant agents detected, followed by HRVs (6.5%), PIVs (4.3%), EVs (3.2%), and HCoVs (1.1%). ADVs, RSV and HMPV were also detected (<1%). The viral detection rates differed significantly between infections of the lower and upper respiratory tracts in the sample population: PIVs, the second most commonly detected viral agents in lower acute respiratory tract infections (LRTIs), were more prevalent than in upper acute respiratory tract infections, indicating that the pathogenic role of PIVs in LRTIs should be investigated. Currently, this study is the largest-scale investigation of respiratory virus infections in China with multiple agent detection, providing baseline data for further studies of respiratory virus infections in adults with ARTIs.

negative: The UK Coronavirus Cancer Monitoring Project: protecting patients with cancer in the era of COVID-19

negative: Ferret Coronavirus-Associated Diseases A novel coronavirus of ferrets was first described in 1993. This coronavirus caused an enteric disease called epizootic catarrhal enteritis (ECE). Recently, a ferret systemic coronavirus (FRSCV)-associated disease was discovered. This new systemic disease resembles the dry form of feline infectious peritonitis (FIP) and has been reported in the United States and Europe. This article addresses the clinical signs, pathology, pathogenesis, diagnosis, treatment, and prevention of this ferret FIP-like disease.

negative: A demographic scaling model for estimating the total number of COVID-19 infections Understanding how widely COVID-19 has spread is critical for examining the pandemic's progression. Despite efforts to carefully monitor the pandemic, the number of confirmed cases may underestimate the total number of infections. We introduce a demographic scaling model to estimate COVID-19 infections using an broadly applicable approach that is based on minimal data requirements: COVID-19 related deaths, infection fatality rates (IFRs), and life tables. As many countries lack reliable estimates of age-specific IFRs, we scale IFRs between countries using remaining life expectancy as a marker to account for differences in age structures, health conditions, and medical services. Across 10 countries with most COVID-19 deaths as of May 13, 2020, the number of infections is estimated to be four [95% prediction interval: 2-11] times higher than the number of confirmed cases. Cross-country variation is high. The estimated number of infections is 1.4 million (six times the number of confirmed cases) for Italy; 3.1 million (2.2 times the number of confirmed cases) for the U.S.; and 1.8 times the number of confirmed cases for Germany, where testing has been comparatively extensive. Our prevalence estimates, however, are markedly lower than most others based on local seroprevalence studies. We introduce formulas for quantifying the bias that is required in our data on deaths in order to reproduce estimates published elsewhere. This bias analysis shows that either COVID-19 deaths are severely underestimated, by a factor of two or more; or alternatively, the seroprevalence based results are overestimates and not representative for the total population.

negative: Chemical disinfection of non-porous inanimate surfaces experimentally contaminated with four human pathogenic viruses. The chemical disinfection of virus-contaminated non-porous inanimate surfaces was investigated using coxsackievirus B3, adenovirus type 5, parainfluenza virus type 3 and coronavirus 229E as representatives of important nosocomial viral pathogens. A 10 microliter amount of the test virus, suspended in either faeces or mucin, was placed onto each stainless steel disk (about 1 cm in diameter) and the inoculum allowed to dry for 1 h under ambient conditions. Sixteen disinfectant formulations were selected for this study based on the findings of an earlier investigation with a human rotavirus. After 1 min exposure to 20 microliters of the disinfectant, the virus from the disks was immediately eluted into tryptose phosphate broth and plaque assayed. Using an efficacy criterion of a 3 log10 or greater reduction in virus infectivity titre and irrespective of the virus suspending medium, only the following five disinfectants proved to be effective against all the four viruses tested: (1) 2% glutaraldehyde normally used as an instrument soak, (2) a strongly alkaline mixture of 0.5% sodium o-benzyl-p-chlorophenate and 0.6% sodium lauryl sulphate, generally used as a domestic disinfectant cleaner for hard surfaces, (3) a 0.04% solution of a quaternary ammonium compound containing 7% hydrochloric acid, which is the basis of many toilet bowl cleaners, (4) chloramine T at a minimum free chlorine level of 3000 p.p.m. and (5) sodium hypochlorite at a minimum free chlorine concentration of 5000 p.p.m. Of those chemicals suitable for use as topical antiseptics, 70% ethanol alone or products containing at least 70% ethanol were ineffective only against coxsackievirus B3. These results emphasize the care needed in selecting chemical disinfectants for routine use in infection control.

negative: A Simple Early Warning Signal for COVID-19 The paper provides some initial evidence that daily mortality rates (for any cause) by municipality or province can be used as a statistically reliable predictor of looming COVID-19 crises. Using recently published deaths figures for 1,689 Italian municipalities, we estimate the growth in daily mortality rates between the period 2015-2019 and 2020 by province. All provinces that experienced a major COVID-19 shock in mid-March 2020 had increases in mortality rates of 100% or above already in early February 2020. This increase was particularly strong for males and older people, two recognizable features of COVID-19. Using a panel fixed effect model, we show that the association between these early increases in mortality for any cause and the March 2020 COVID-19 shock is strong and significant. We conclude that the growth in mortality rates can be used as a statistically reliable predictor of COVID-19 crises.

negative: A mechanistic population balance model to evaluate the impact of interventions on infectious disease outbreaks: Case for COVID19 Infectious diseases, especially when new and highly contagious, could be devastating producing epidemic outbreaks and pandemics. Predicting the outcomes of such events in relation to possible interventions is crucial for societal and healthcare planning and forecasting of resource needs. Deterministic and mechanistic models can capture the main known phenomena of epidemics while also allowing for a meaningful interpretation of results. In this work a deterministic mechanistic population balance model was developed. The model describes individuals in a population by infection stage and age group. The population is treated as in a close well mixed community with no migrations. Infection rates and clinical and epidemiological information govern the transitions between stages of the disease. The present model provides a steppingstone to build upon and its current low complexity retains accessibility to non experts and policy makers to comprehend the variables and phenomena at play. The impact of specific interventions on the outbreak time course, number of cases and outcome of fatalities were evaluated including that of available critical care. Data available from the COVID19 outbreak as of early April 2020 was used. Key findings in our results indicate that (i) universal social isolation measures appear effective in reducing total fatalities only if they are strict and the number of daily social interactions is reduced to very low numbers; (ii) selective isolation of only the elderly (at higher fatality risk) appears almost as effective in reducing total fatalities but at a much lower economic damage; (iii) an increase in the number of critical care beds could save up to eight lives per extra bed in a million population with the current parameters used; (iv) the use of protective equipment (PPE) appears effective to dramatically reduce total fatalities when implemented extensively and in a high degree; (v) infection recognition through random testing of the population, accompanied by subsequent (self) isolation of infected aware individuals, can dramatically reduce the total fatalities but only if conducted extensively to almost the entire population and sustained over time; (vi) ending isolation measures while R0 values remain above 1.0 (with a safety factor) renders the isolation measures useless and total fatality numbers return to values as if nothing was ever done; (vii) ending the isolation measures for only the population under 60 y/o at R0 values still above 1.0 increases total fatalities but only around half as much as if isolation ends for everyone; (viii) a threshold value, equivalent to that for R0, appears to exist for the daily fatality rate at which to end isolation measures, this is significant as the fatality rate is (unlike R0) very accurately known. Any interpretation of these results for the COVID19 outbreak predictions and interventions should be considered only qualitatively at this stage due to the low confidence (lack of complete and valid data) on the parameter values available at the time of writing. Any quantitative interpretation of the results must be accompanied with a critical discussion in terms of the model limitations and its frame of application.

negative: Are Community Acquired Respiratory Viral Infections an Underestimated Burden in Hematology Patients? Despite a plethora of studies demonstrating significant morbidity and mortality due to community-acquired respiratory viral (CRV) infections in intensively treated hematology patients, and despite the availability of evidence-based guidelines for the diagnosis and management of respiratory viral infections in this setting, there is no uniform inclusion of respiratory viral infection management in the clinical hematology routine. Nevertheless, timely diagnosis and systematic management of CRV infections in intensively treated hematology patients has a demonstrated potential to significantly improve outcome. We have briefly summarized the recently published data on CRV infection epidemiology, as well as guidelines on the diagnosis and management of CRV infections in patients intensively treated for hematological malignancies. We have also assessed available treatment options, as well as mentioned novel agents currently in development.

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: When half of the population died: the epidemic of hemorrhagic fevers of 1576 in Mexico During the 16th century, Mexico suffered a demographic catastrophe with few parallels in world's history. In 1519, the year of the arrival of the Spaniards, the population in Mexico was estimated to be between 15 and 30 million inhabitants. Eighty-one years later, in 1600, only two million remained. Epidemics (smallpox, measles, mumps), together with war, and famine have been considered to be the main causes of this enormous population loss. However, re-evaluation of historical data suggests that approximately 60–70% of the death toll was caused by a series of epidemics of hemorrhagic fevers of unknown origin. In order to estimate the impact of the 1576 epidemic of hemorrhagic fevers on the population we analyzed the historical record and data from the 1570 and 1580 censuses of 157 districts. The results identified several remarkable aspects of this epidemic: First, overall, the population loss for these 157 districts was 51.36%. Second, there was a clear ethnic preference of the disease, the Spanish population was minimally affected whereas native population had high mortality rate. Third, the outbreak originated in the valleys of central Mexico whence it evolved as an expansive wave. Fourth, a positive correlation between altitude and mortality in central Mexico was found. Fifth, a specific climatic sequence of events was associated with the initiation and dissemination of the hemorrhagic fevers. Although the last epidemic of hemorrhagic fevers in Mexico ended in 1815, many questions remain to be answered. Perhaps the most relevant ones are whether there is a possible reemergence of the hemorrhagic fevers and how vulnerable we are to the disease.

negative: Single-cell Transcriptome Analysis Indicates New Potential Regulation Mechanism of ACE2 and NPs signaling among heart failure patients infected with SARS-CoV-2 BACKGROUND: COVID-19 patients with comorbidities such as hypertension or heart failure (HF) are associated with poor clinical outcomes. Angiotensin-converting enzyme 2 (ACE2), the critical enzyme for SARS-CoV-2 infection, is broadly expressed in many organs including heart. However, the cellular distribution of ACE2 in the human heart, particularly the failing heart is unknown. METHODS: We analyzed single-cell RNA sequencing (scRNA-seq) data in both normal and failing hearts, and characterized the ACE2 gene expression profile in various cell subsets, especially in cardiomyocyte subsets, as well as its interaction with gene networks relating to various defense and immune responses at the single cell level. RESULTS: The results demonstrated that ACE2 is present in cardiomyocytes (CMs), endothelial cells, fibroblasts and smooth muscle cells in the heart, while the number of ACE2-postive (ACE2+) CMs and ACE2 gene expression in these CMs are significantly increased in the failing hearts. Interestingly, both brain natriuretic peptides (BNP) and atrial natriuretic peptide (ANP) are significantly up-regulated in the ACE2+ CMs. Further analysis shows that ANP, BNP and ACE2 may form a negative feedback loop with a group of genes associated with the development of heart failure. To our surprise, we found that genes related to virus entry, virus replication and suppression of interferon-gamma（IFN-γ）signaling are all up-regulated in CMs in failing hearts, and the increases were significantly higher in ACE2+ CMs as compared with ACE2 negative (ACE2−) CMs, suggesting that these ACE2+ CMs may be more vulnerable to virus infection. Since ACE2 expression is correlated with BNP expression, we further performed retrospective analysis of the plasma BNP levels and clinic outcome of 91 COVID-19 patients from a single-center. Patients with higher plasma BNP were associated with significantly higher mortality rate and expression levels of inflammatory and infective markers such as procalcitonin and C-reactive protein. CONCLUSION: In the failing heart, the upregulation of ACE2 and virus infection associated genes, as well as the increased expression of ANP and BNP could facilitate SARS-CoV-2 virus entry and replication in these vulnerable cardiomyocyte subsets. These findings may advance our understanding of the underlying molecular mechanisms of myocarditis associated with COVID-19.

negative: Coronavirus Epidemic and Extracorporeal Therapies in Intensive Care: si vis pacem para bellum

negative: Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations Summary As coronavirus disease 2019 (COVID-19) spreads across the world, the intensive care unit (ICU) community must prepare for the challenges associated with this pandemic. Streamlining of workflows for rapid diagnosis and isolation, clinical management, and infection prevention will matter not only to patients with COVID-19, but also to health-care workers and other patients who are at risk from nosocomial transmission. Management of acute respiratory failure and haemodynamics is key. ICU practitioners, hospital administrators, governments, and policy makers must prepare for a substantial increase in critical care bed capacity, with a focus not just on infrastructure and supplies, but also on staff management. Critical care triage to allow the rationing of scarce ICU resources might be needed. Researchers must address unanswered questions, including the role of repurposed and experimental therapies. Collaboration at the local, regional, national, and international level offers the best chance of survival for the critically ill.

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

negative: Seeding COVID-19 across sub-Saharan Africa: an analysis of reported importation events across 40 countries Background: The first case of COVID-19 in sub-Saharan Africa (SSA) was reported by Nigeria on February 27, 2020. While case counts in the entire region remain considerably less than those being reported by individual countries in Europe, Asia, and the Americas, SSA countries remain vulnerable to significant COVID morbidity and mortality due to systemic healthcare weaknesses, less financial resources and infrastructure to address the new crisis, and untreated comorbidities. Variation in preparedness and response capacity as well as in data availability has raised concerns about undetected transmission events. Methods: Confirmed cases reported by SSA countries were line-listed to capture epidemiological details related to early transmission events into and within countries. Data were retrieved from publicly available sources, including institutional websites, situation reports, press releases, and social media accounts, with supplementary details obtained from news articles. A data availability score was calculated for each imported case in terms of how many indicators (sex, age, travel history, date of arrival in country, reporting date of confirmation, and how detected) could be identified. We assessed the relationship between time to first importation and overall Global Health Security Index (GHSI) using Cox regression. K-means clustering grouped countries according to healthcare capacity and health and demographic risk factors. Results: A total of 2417 confirmed cases of COVID-19 were reported by 40 countries in sub-Saharan Africa during the 30 days after the first known introduction to the region. Out of the 876 cases for which information was publicly available, 677 (77.3%) were considered importation events. At the regional level, imported cases tended to be male (67.3%), were a median 43.0 years old (Range: 6 weeks - 88 years), and most frequently had recent travel history from Europe (43.3%). The median time to reporting an introduction was 19 days; a country's time to report its first importation was not related to GHSI. Mean data availability scores were lowest for countries that had, on average, the highest case fatality rates, lowest healthcare capacity, and highest probability of premature death due to non-communicable diseases. Conclusion: Countries with systemic, demographic, and pre-existing health vulnerabilities to severe COVID-related morbidity and mortality are less likely to report any cases or are reporting with limited public availability of information. Reporting of information on COVID detection and response efforts, as well as on trends in non-COVID illness and care-seeking behavior, is critical to assessing direct and indirect consequences and capacity needs in resource-constrained settings. Such assessments aid in the ability to make data-driven decisions about interventions, country priorities, and risk assessment.

negative: Trends in Tuberculosis in Taiwan, 2002–2008 Background/Purpose Tuberculosis (TB) remains an important infectious disease in Taiwan. To control TB effectively, the Taiwan Centers for Disease Control implemented the National Tuberculosis Program (NTP) in 2006, modeled on the World Health Organization global TB control program. The goal of the program was to reduce the number of TB cases by half within a decade. This study was designed to describe the epidemiology of TB in Taiwan, and to evaluate the preliminary effectiveness of the NTP. Methods We conducted a retrospective study of data from the National Tuberculosis Registry System collected between 2002 and 2008. Demographics, geographic distribution of disease, and change in rates of TB incidence and mortality were analyzed. Results From 2002 to 2008, new TB cases declined from 16,758 to 14,265, and incidence decreased from 75 per 100,000 population to 62 per 100,000 population. More than 50% of new cases occurred among elderly adults. Over the study period, TB mortality decreased from 5.7 per 100,000 population to 3.3 per 100,000 population, with over half of TB deaths occurring among patients aged ≥ 65 years. Since the NTP was implemented, from 2005 to 2008, TB incidence and mortality declined by 14% and 23%, respectively. Conclusion TB-associated incidence and mortality decreased over the course of the study. Nevertheless, there continue to be high-incidence areas that show the opposite trend; these areas should strive to improve case management and consultation. In the most populous districts, rigorous surveillance is necessary to track incidence and mortality rate fluctuations.

negative: Palliative Care Utilization among Patients with COVID-19 in an Underserved Population: A Single-Center Retrospective Study BACKGROUND: As healthcare institutions mobilize resources to address the coronavirus disease 2019 (COVID-19) pandemic, palliative care may potentially be underutilized. It is important to assess the use of palliative care in response to the COVID-19 pandemic. METHODS: This is a retrospective single center study of patients with COVID-19 diagnosed via reverse transcriptase–polymerase chain reaction assay (RT-PCR) admitted between 3/1/2020 and 4/24/2020. An analysis of the utilization of palliative care in accordance with patient comorbidities and other characteristics was performed while considering clinical outcomes. Chi square test was used to determine associations between categorical variables while T tests were used to compare continuous variables. RESULTS: The overall mortality rate was 21.5% (n=52) and in 48% (n=25) of these patients, palliative care was not involved. Fifty nine percent (n=24) of those who had palliative consults eventually elected for comfort measures and transitioned to hospice care. Among those classified as having severe COVID-19, only 40% (n=31) had palliative care involvement. Of these patients with severe COVID-19, 68% (n=52) died. Patients who got palliative care consults were of older age, had higher rates of intubation, need for vasopressors, and death. CONCLUSION: There was a low utilization rate of palliative care in patients with COVID-19. Conscious utilization of palliative care is needed at the time of COVID-19.

negative: Clinical trials on drug repositioning for COVID-19 treatment The World Health Organization (WHO) was informed on December 2019 about a coronavirus pneumonia outbreak in Wuhan, Hubei province (China). Subsequently, on March 12, 2020, 125,048 cases and 4,614 deaths were reported. Coronavirus is an enveloped RNA virus, from the genus Betacoronavirus, that is distributed in birds, humans, and other mammals. WHO has named the novel coronavirus disease as COVID-19. More than 80 clinical trials have been launched to test coronavirus treatment, including some drug repurposing or repositioning for COVID-19. Hence, we performed a search in March 2020 of the clinicaltrials.gov database. The eligibility criteria for the retrieved studies were: contain a clinicaltrials.gov base identifier number; describe the number of participants and the period for the study; describe the participants’ clinical conditions; and utilize interventions with medicines already studied or approved for any other disease in patients infected with the novel coronavirus SARS-CoV-2 (2019-nCoV). It is essential to emphasize that this article only captured trials listed in the clinicaltrials.gov database. We identified 24 clinical trials, involving more than 20 medicines, such as human immunoglobulin, interferons, chloroquine, hydroxychloroquine, arbidol, remdesivir, favipiravir, lopinavir, ritonavir, oseltamivir, methylprednisolone, bevacizumab, and traditional Chinese medicines (TCM). Although drug repurposing has some limitations, repositioning clinical trials may represent an attractive strategy because they facilitate the discovery of new classes of medicines; they have lower costs and take less time to reach the market; and there are existing pharmaceutical supply chains for formulation and distribution.

negative: How will this continue? Modelling interactions between the COVID-19 pandemic and policy responses Much of the uncertainty about the progression of the COVID-19 pandemic stems from questions about when and how non-pharmaceutical interventions (NPI) by governments, in particular social distancing measures, are implemented, to what extent the population complies with these measures, and how compliance changes through time. Further uncertainty comes from a lack of knowledge of the potential effects of removing interventions once the epidemic is declining. By combining an epidemiological model of COVID-19 for the United Kingdom with simple sub-models for these societal processes, this study aims to shed light on the conceivable trajectories that the pandemic might follow over the next 1.5 years. We show strong improvements in outcomes if governments review NPI more frequently whereas, in comparison, the stability of compliance has surprisingly small effects on cumulative mortality. Assuming that mortality does considerably increase once a country's hospital capacity is breached, we show that the inherent randomness of societal processes can lead to a wide range of possible outcomes, both in terms of disease dynamics and mortality, even when the principles according to which policy and population operate are identical.. Our model is easily modified to take other aspects of the socio-pandemic interaction into account.

negative: The risk factors associated with MERS-CoV patient fatality: A global survey Abstract Risk factors associated with Middle East respiratory syndrome coronavirus (MERS-CoV) infection outcome were established by analyses of WHO data from September 23, 2012 to 18 June 2018. Of the 2220 reported cases, 1408 cases, including 451 MERS-CoV deaths, were analyzed. The case fatality rate was 32% (95% CI: 29.4–34.5). Compared to MERS patients ≤30 years old, those with >30 years had the adjusted odds ratio estimate for death of 2.38 [95% CI: 1.75–3.22]. This index was 1.43 [95% CI: 1.06–1.92] for Saudi patients in comparison to non-Saudi; 1.76 [95% CI: 1.39–2.22] for patient with comorbidity in comparison to those without comorbidity; 0.58 [95% CI: 0.44–0.75] for those who had close contact to a camel in the past 14 days and 0.42 [95% CI: 0.31–0.57] for patients with >14 days with onset of signs and hospital admission compared to patients with ≤14 days.

negative: Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity Despite the ongoing spread of MERS, there is limited knowledge of the factors affecting its severity and outcomes. We analyzed clinical data and specimens from fourteen MERS patients treated in a hospital who collectively represent a wide spectrum of disease severity, ranging from mild febrile illness to fatal pneumonia, and classified the patients into four groups based on severity and mortality. Comparative and kinetic analyses revealed that high viral loads, weak antibody responses, and lymphopenia accompanying thrombocytopenia were associated with disease mortality, whereas persistent and gradual increases in lymphocyte responses might be required for effective immunity against MERS-CoV infection. Leukocytosis, primarily due to increased neutrophils and monocytes, was generally observed in more severe and fatal cases. The blood levels of cytokines such as IL-10, IL-15, TGF-β, and EGF were either positively or negatively correlated with disease mortality. Robust induction of various chemokines with differential kinetics was more prominent in patients that recovered from pneumonia than in patients with mild febrile illness or deceased patients. The correlation of the virological and immunological responses with disease severity and mortality, as well as their responses to current antiviral therapy, may have prognostic significance during the early phase of MERS.

negative: Age, gender and COVID-19 infections Data for ten European countries which provide detailed distribution of COVID-19 cases by sex and age show that among people of working age, women diagnosed with COVID-19 substantially outnumber infected men. This pattern reverses around retirement: infection rates among women fall at age 60-69, resulting in a cross-over with infection rates among men. The relative disadvantage of women peaks at ages 20-29, whereas the male disadvantage in infection rates peaks at ages 70-79. The elevated infection rates among women of working age are likely tied to their higher share in health- and care-related occupations. Our examination also suggests a link between women's employment profiles and infection rates in prime working ages. The same factors that determine women's higher life expectancy account for their lower fatality and higher male disadvantage at older ages.

negative: Harveian Oration 2017: Triumphs and challenges in a world shaped by medicine.

negative: The role of corticosteroids in the management of critically ill patients with coronavirus disease 2019 (COVID-19): A meta-analysis Objective: There are no controlled studies on the role of systemic corticosteroids (CS) in patients with coronavirus disease 2019 (COVID-19). In the absence of high-quality evidence, understandably the recommendations from various organizations are cautious. Several randomized controlled trials are underway but shall take time to conclude. We therefore undertook a meta-analysis to ascertain the role of CS in the management of critically ill patients with COVID-19. Data Sources: Electronic databases, including Pubmed, Cochrane library and Embase, were searched, using the keywords of interest and the PICO search technique, from inception to 12th April 2020. Study Selection: Studies highlighting the use of CS in coronavirus infection with severe acute respiratory syndrome (SARS), Middle East Respiratory Syndrome (MERS) and COVID-19 were selected based on pre-determined inclusion criteria. Data extraction: Data was extracted into an excel sheet and transferred to comprehensive meta-analysis software version 3, Biostat Inc., Englewood, NJ, USA, for analysis. Data synthesis: Five studies with SARS-CoV-2 infection were included in the meta-analysis. The rate ratio (RR) for mortality in patients with SARS-CoV-2 infection was 1.26 (95% CI: 0.96-1.65, I2: 74.46), indicating lack of benefit of CS therapy on mortality in critically ill patients with COVID-19. The RR for mortality on analysis of the three studies that particularly reported on patients with significant pulmonary compromise secondary to SARS-CoV-2 infection was neutral (RR: 0.91, 95% CI: 0.63-1.33, I2: 63.38). Conclusions: The use of CS in critically ill patients with COVID-19 did not improve or worsen mortality. Pending further information from controlled studies, CS can be used in critically ill patients with COVID-19 with critical illness related corticosteroid insufficiency and moderate to severe ARDS without the risk of increased mortality.

negative: Evaluation of "stratify and shield" as a policy option for ending the COVID-19 lockdown in the UK Although population-wide lockdowns have been successful in slowing the COVID-19 epidemic, there is a consensus among disease modellers that keeping the load on critical care services within manageable limits will require an adaptive social distancing strategy, alternating cycles of relaxation and re-imposition until a vaccine is available. An alternative strategy that has been tentatively proposed is to shield the elderly and others at high risk of severe disease, while allowing immunity to build up in those at low risk until the entire population is protected. We examine the performance required from a classifier that uses information from medical records to assign risk status for a such a stratify-and-shield policy to be effective in limiting mortality when social distancing is relaxed. We show that under plausible assumptions about the level of immunity required for population-level immunity, the proportion shielded is constrained to be no more than 15% of the population. Under varying assumptions about the infection fatality ratio (from 0.1% to 0.4%) and the performance of the classifier (3 to 4.5 bits of information for discrimination), we calculate the expected number of deaths in the unshielded group. We show that with likely values of the performance of a classifier that uses information from age, sex and medical records, at least 80% of those who would die if unshielded would be allocated to the high-risk shielded group comprising 15% of the population. Although the proportion of deaths that would be prevented by effective shielding does not vary much with the infection fatality ratio, the absolute number of deaths in the unshielded varies from less than 10,000 if the infection fatality rate is 0.1% to more than 50,000 if the infection fatality rate is as high as 0.4%. For projecting the effect of an optimally applied stratify-and-shield policy, studies now under way should help to resolve key uncertainties: the extent to which infection confers immunity, the prevalence of immunity, the infection fatality ratio, and the performance of a classifier constructed using information from medical records. It is time to give serious consideration to a stratify-and-shield policy that could bring the COVID-19 epidemic to an end in a matter of months while restoring economic activity, avoiding overload of critical care services and limiting mortality.

negative: Incidence and Outcomes of Acute Respiratory Distress Syndrome: A Nationwide Registry-Based Study in Taiwan, 1997 to 2011 Most epidemiological studies of acute respiratory distress syndrome (ARDS) have been conducted in western countries, and studies in Asia are limited. The aim of our study was to evaluate the incidence, in-hospital mortality, and 1-year mortality of ARDS in Taiwan. We conducted a nationwide inpatient cohort study based on the Taiwan National Health Insurance Research Database between 1997 and 2011. A total of 40,876 ARDS patients (68% male; mean age 66 years) were identified by International Classification of Diseases, 9th edition coding and further analyzed for clinical characteristics, medical costs, and mortality. The overall crude incidence of ARDS was 15.74 per 100,000 person-years, and increased from 2.53 to 19.26 per 100,000 person-years during the study period. The age-adjusted incidence of ARDS was 15.19 per 100,000 person-years. The overall in-hospital mortality was 57.8%. In-hospital mortality decreased from 59.7% in 1997 to 47.5% in 2011 (P < 0.001). The in-hospital mortality rate was lowest (33.5%) in the youngest patients (age 18–29 years) and highest (68.2%) in the oldest patients (>80 years, P < 0.001). The overall 1-year mortality rate was 72.1%, and decreased from 75.8% to 54.7% during the study period. Patients who died during hospitalization were older (69 ± 17 versus 62 ± 19, P < 0.001) and predominantly male (69.8% versus 65.3%, P < 0.001). In addition, patients who died during hospitalization had significantly higher medical costs (6421 versus 5825 US Dollars, P < 0.001) and shorter lengths of stay (13 versus 19 days, P < 0.001) than patients who survived. We provide the first large-scale epidemiological analysis of ARDS incidence and outcomes in Asia. Although the overall incidence was lower than has been reported in a prospective US study, this may reflect underdiagnosis by International Classification of Diseases, 9th edition code and identification of only patients with more severe ARDS in this analysis. Overall, there has been a decreasing trend in in-hospital and 1-year mortality rates in recent years, likely because of the implementation of lung-protective ventilation.

negative: Descriptive epidemiology of morbidity and mortality in Minnesota dairy heifer calves Abstract A prospective study was carried out on 845 heifer calves born during 1991 on 30 Holstein dairy farms in southeast Minnesota. The objectives of the study were to describe the epidemiology of morbidity and mortality in dairy calves from birth to 16 weeks of age (with an emphasis on respiratory disease), to examine individual calf and herd management practices as risk factors for calf morbidity and mortality, and to validate producer diagnosis of mortality. Incidence rates for all morbidity, enteritis, and pneumonia were 0.20, 0.15, and 0.10 cases per 100 calf-days at risk for the period of the study. Risk of enteritis was highest in the first 3 weeks of life, with pneumonia risk highest at 10 weeks of age. Case fatality rates averaged 11.8%, 17.9%, and 9.4% for all diagnoses, enteritis, and pneumonia, respectively. Average daily rates of gain from birth to 16 weeks of age differed between farms that had inadequate calf housing (0.8 kg day−1) versus those with adequate calf housing (1.0 kg day−1). Approximately half of the calves in the cohort (418) had blood samples taken monthly from birth until 16 weeks of age. Of the calves sampled, only 19 calves showed a four-fold rise in serum titers to respiratory viruses. Sixteen calves seroconverted to BVDV, two calves to IBRV, and one calf to PI3 virus. Of 98 calves less than 10 days of age tested for adequacy of passive transfer, 35 (35.7%) had serum immunoglobulin levels of less than 800 mg dl−1. There were no significant differences in mortality or morbidity between calves that had adequate passive transfer and those that did not. The incidence of mortality was 0.08 deaths per 100 calf-days at risk; 64 calves died during the 16 months of the study. The risk of death was highest at 2 weeks of age. Enteritis was the most common cause of death (28 deaths, 44% of all deaths) followed by pneumonia (19 deaths, 30% of all deaths). Comparing producer diagnosis of mortality with necropsy results yielded sensitivities of 58.3% and 56% and specificities of 93% and 100% for producer diagnoses of enteritis and pneumonia, respectively. The kappa statistic comparing producer diagnosis with necropsy result was 0.47. The most common pathogens isolated from calves that died of enteritis were rotavirus (five calves), and Escherichia coli (four calves). Pathogens isolated from pneumonic lungs included Pasteurella multocida (three calves), Haemophilus somnus (three calves), and Pasteurella haemolytica (one calf).

negative: Do not violate the International Health Regulations during the COVID-19 outbreak

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: COVID-19; Systematic and literature review of transmission, case definitions, clinical management and clinical trials. Background: SARS-CoV-2, the viral agent responsible for coronavirus disease 2019 (COVID-19) was identified in Wuhan, China at the end of December 2019. It rapidly spread to the rest of the world, and was declared a Public Health Emergency of International Concern on the 30th of January 2020. Our understanding of the virus, it is clinical manifestations and treatment options continues to evolve at an unparalleled pace. Objective: This review sought to summarise the key literature regarding transmission, case definitions, clinical management and trials, and performed a systematic review of reported clinical data on COVID-19. Synthesis methods: Two reviewers selected all the literature independently, and extracted information according to pre-defined topics. Results: COVID-19 is pandemic with ~4 million cases and 270,000 deaths in 210 countries as of 8 May 2020. Our review of reports showed that SARS-CoV-2 was mainly transmitted via inhalation of respiratory droplets containing the virus and had an incubation period of four to six days. The commonly reported symptoms were fever (80%) and cough (60%) across the spectrum of clinical disease - mild, moderate, severe and critical. Categorization of these cases for home care or hospital management need to be well defined considering the age of the patient and the presence of underlying co-morbidities. The case definitions we reviewed varied among affected countries, which could have contributed to the differences observed in the mean case fatality rates among continents: Oceania (1%), Asia (3%), Africa (4%), South America (5%), North America (6%) and Europe (10%). Asymptomatic cases, which constituted an estimated 80% of COVID-19 cases are a huge threat to control efforts. Conclusion: The presence of fever and cough may be sufficient to warrant a COVID-19 testing but using these symptoms in isolation will miss a proportion of cases. A clear definition of a COVID-19 case is important for managing, treating and tracking clinical illness. While several treatments are in development or in clinical trials for COVID-19, home care of mild/moderate cases and hospital care for severe and critical cases remain the recommended management for the disease. Quarantine measures and social distancing can help control the spread of SARS-CoV-2.

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: Injecting epidemiology into population viability analysis: avian cholera transmission dynamics at an arctic seabird colony. Infectious diseases have the potential to spread rapidly and cause high mortality within populations of immunologically naïve hosts. The recent appearance of avian cholera, a highly virulent disease of birds caused by the bacterium Pasteurella multocida, at remote Arctic seabird colonies is an emerging conservation concern. Determining disease risk to population viability requires a quantitative understanding of transmission potential and the factors that regulate epidemic persistence. Estimates of the basic (R0 ) and real-time (Rt ) reproductive number are critical in this regard - enumerating the number of secondary infections caused by each primary infection in a newly invaded host population and the decline in transmission rate as susceptible individuals are removed via mortality or immunized recovery. Here, we use data collected at a closely monitored common eider (Somateria mollissima) breeding colony located in the Canadian Arctic to examine transmission and host population dynamics. Specifically, we infer epidemic curves from daily mortality observations and use a likelihood-based procedure to estimate changes in the reproductive number over a series of annual outbreaks. These data are interpreted in relation to concurrent changes in host numbers to assess local extinction risk. Consistent with expectations for a novel pathogen invasion, case incidence increased exponentially during the initial wave of exposure (R0 = 2·5; generation time = 6·5 days ± 1·1 SD). Disease conditions gradually abated, but only after several years of smouldering infection (Rt ≈ 1). In total, 6194 eider deaths were recorded during outbreaks spanning eight consecutive breeding seasons. Breeding pair abundance declined by 56% from the pre-outbreak peak; however, a robust population of >4000 pairs remained intact upon epidemic fade-out. Overall, outbreak patterns were consistent with herd immunity acting as a mitigating factor governing in the extent and duration of mortality. Disease mortality is frequently modelled as a form of stochastic catastrophe in wildlife population assessments, whereas our approach gives shape to the functional response between transmission and host population dynamics. We conclude that increased emphasis on integrating epidemiological and population processes is essential to predicting the conservation impact of emerging infectious diseases in wildlife.

negative: Severe Acute Respiratory Syndrome: Pertinent Clinical Characteristics and Therapy Severe acute respiratory syndrome (SARS) is a newly emerged infection that is caused by a previously unrecognized virus–a novel coronavirus designated as SARS-associated coronavirus (SARS-CoV). From November 2002 to July 2003 the cumulative number of worldwide cases was >8000, with a mortality rate of close to 10%. The mortality has been higher in older patients and those with co-morbidities. SARS has been defined using clinical and epidemiological criteria and cases are considered laboratory-confirmed if SARS coronavirus is isolated, if antibody to SARS coronavirus is detected, or a polymerase chain reaction test by appropriate criteria is positive. At the time of writing (24 May 2004), no specific therapy has been recommended. A variety of treatments have been attempted, but there are no controlled data. Most patients have been treated throughout the illness with broad-spectrum antimicrobials, supplemental oxygen, intravenous fluids, and other supportive measures. Transmission of SARS is facilitated by close contact with patients with symptomatic infection. The majority of cases have been reported among healthcare providers and family members of SARS patients. Since SARS-CoV is contagious, measures for prevention center on avoidance of exposure, and infection control strategies for suspected cases and contacts. This includes standard precautions (hand hygiene), contact precautions (gowns, goggles, gloves) and airborne precautions (negative pressure rooms and high efficiency masks). In light of reports of new cases identified during the winter of 2003–4 in China, it seems possible that SARS will be an important cause of pneumonia in the future, and the screening of outpatients at risk for SARS may become part of the pneumonia evaluation.

negative: Age groups and spread of influenza: implications for vaccination strategy BACKGROUND: The unpredictable nature of the potentially devastating impact of 2009 pH1N1 influenza pandemic highlights the need for pandemic preparedness planning, where modeling studies could be most useful for simulations of possible future scenarios. METHODS: A compartmental model with pre-symptomatic and asymptomatic influenza infections is proposed which incorporates age groups as well as intervention measures such as age-specific vaccination, in order to study spread of influenza in a community. RESULTS: We derive the basic reproduction number and other effective reproduction numbers under various intervention measures. For illustration, we make use of the Pneumonia and Influenza (P&I) mortality data and vaccination data of the very young (age 0-2) and the very old (age >64) during 2004-2005 Taiwan winter influenza season to fit our model and to compute the relevant reproduction numbers. The reproduction number for this winter flu season is estimated to be slightly above one (~1.0001). CONCLUSIONS: Comparatively large errors in fitting the P&I mortality data of the elderly (>64) were observed shortly after winter school closings in January, which may indicate the impact of younger, more active age groups transmitting influenza to other age groups outside of the school settings; in particular, to the elderly in the households. Pre-symptomatic infections seemed to have little effect on the model fit, while asymptomatic infection by asymptomatic infectives has a more pronounced impact on the model fit for the elderly mortality, perhaps indicating a larger role in disease transmission by asymptomatic infection. Simulations indicate that the impact of vaccination on the disease incidence might not be fully revealed in the change (or the lack thereof) in the effective reproduction number with interventions, but could still be substantial. The estimated per contact transmission probability for susceptible elderly is significantly higher than that of any other age group, perhaps highlighting the vulnerability of the elderly due to close contacts with their caretakers from other age groups. The relative impact of targeting the very young and the very old for vaccination was weakened by their relative inactivity, thus giving evidence of the lack of impact of vaccinating these two groups on the overall transmissibility of the disease in the community. This further underscores the need for morbidity-based strategy to prevent elderly mortality.

negative: Changes in cold-related mortalities between 1995 and 2016 in South East England Abstract Objective The aim of the study was to examine trends in cold-related mortalities between 1995 and 2016. Study design This is a longitudinal mortality study. Methods For men and women aged 65–74 years or those older than 85 years in South East England, the relationship between daily mortality (deaths per million population) and outdoor temperatures below 18 °C, with allowance for influenza epidemics, was assessed by linear regression on an annual basis. The regression coefficients were expressed as a percentage of the mortality at 18 °C to adjust for changes in mortality through health care. Trends in ‘specific’ cold-related mortalities were then examined over two periods, 1977–1994 and 1995–2016. Results In contrast to the early period, annual trends in cold-related specific mortalities showed no decline between 1995 and 2016. ‘Specific’ cold-related mortality of women, but not men, in the age group older than 85 years showed a significant increase over the 1995–2016 period, which was different from the trend over the earlier period (P < 0.01). Conclusion Despite state-funded benefits to help alleviate fuel poverty and public health advice, very elderly women appear to be at increasing risk of cold-related mortality—greater help may be necessary.

negative: Reply to Nepomuceno et al.: A renewed call for detailed social and demographic COVID-19 data from all countries

negative: Corticosteroids as Adjunctive Therapy in Severe Community-Acquired Pneumonia Mortality in community acquired pneumonia (CAP) has not decreased in the intensive care unit (ICU), despite progress in antimicrobial therapy [1, 2]. Approximately 10% of patients hospitalized with CAP are admitted to the ICU [3]. In a multicenter study by Mongardon et al. in patients with severe pneumococcal CAP admitted to the ICU, the mortality rate was 29%, with high proportions of patients in septic shock and needing mechanical ventilation [4]. Severe CAP is a progressive disease and patients may die despite early and adequate antibiotic treatment. The host local and systemic inflammatory immune response in patients with severe CAP is exacerbated and disproportionate and this is probably the main cause for the high mortality in this specific population, as it contributes to impaired alveolar gas exchange, sepsis and end-organ dysfunction [5]. In this specific population of patients with severe CAP, adjuvant treatments, such as corticosteroids, may be beneficial.

negative: Diarrhea Diarrheal diseases continue to contribute significant morbidity and mortality to pediatric populations in developed and developing countries around the world. The prevalence of diarrheal illness across cultures is inversely proportional to the availability of public sanitation, clean water supply, and adequate medical care. As such, it is not surprising that the incidence of diarrheal disease is much higher in developing societies and can approach 10 episodes per child per year in children under 5 years of age. In these areas, aggregate mortality can reach 3–5 million deaths per year. In the US and other developed nations, both the incidence (1–2 episodes per year) and mortality (approximately 400–500 deaths annually) are considerably decreased. Nonetheless, the burdens placed on Western healthcare systems by pediatric diarrheal disease are considerable and approximately 20% of all pediatric ambulatory visits and 10% of all inpatient hospital admissions in children under 3 years of age are for the evaluation and treatment of these disorders and their complications.

negative: Quantifying risks and interventions that have affected the burden of lower respiratory infections among children younger than 5 years: an analysis for the Global Burden of Disease Study 2017 BACKGROUND: Despite large reductions in under-5 lower respiratory infection (LRI) mortality in many locations, the pace of progress for LRIs has generally lagged behind that of other childhood infectious diseases. To better inform programmes and policies focused on preventing and treating LRIs, we assessed the contributions and patterns of risk factor attribution, intervention coverage, and sociodemographic development in 195 countries and territories by drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) LRI estimates. METHODS: We used four strategies to model LRI burden: the mortality due to LRIs was modelled using vital registration data, demographic surveillance data, and verbal autopsy data in a predictive ensemble modelling tool; the incidence of LRIs was modelled using population representative surveys, health-care utilisation data, and scientific literature in a compartmental meta-regression tool; the attribution of risk factors for LRI mortality was modelled in a counterfactual framework; and trends in LRI mortality were analysed applying changes in exposure to risk factors over time. In GBD, infectious disease mortality, including that due to LRI, is among HIV-negative individuals. We categorised locations based on their burden in 1990 to make comparisons in the changing burden between 1990 and 2017 and evaluate the relative percent change in mortality rate, incidence, and risk factor exposure to explain differences in the health loss associated with LRIs among children younger than 5 years. FINDINGS: In 2017, LRIs caused 808 920 deaths (95% uncertainty interval 747 286–873 591) in children younger than 5 years. Since 1990, there has been a substantial decrease in the number of deaths (from 2 337 538 to 808 920 deaths; 65·4% decrease, 61·5–68·5) and in mortality rate (from 362·7 deaths [330·1–392·0] per 100 000 children to 118·9 deaths [109·8–128·3] per 100 000 children; 67·2% decrease, 63·5–70·1). LRI incidence declined globally (32·4% decrease, 27·2–37·5). The percent change in under-5 mortality rate and incidence has varied across locations. Among the risk factors assessed in this study, those responsible for the greatest decrease in under-5 LRI mortality between 1990 and 2017 were increased coverage of vaccination against Haemophilus influenza type b (11·4% decrease, 0·0–24·5), increased pneumococcal vaccine coverage (6·3% decrease, 6·1–6·3), and reductions in household air pollution (8·4%, 6·8–9·2). INTERPRETATION: Our findings show that there have been substantial but uneven declines in LRI mortality among countries between 1990 and 2017. Although improvements in indicators of sociodemographic development could explain some of these trends, changes in exposure to modifiable risk factors are related to the rates of decline in LRI mortality. No single intervention would universally accelerate reductions in health loss associated with LRIs in all settings, but emphasising the most dominant risk factors, particularly in countries with high case fatality, can contribute to the reduction of preventable deaths. FUNDING: Bill & Melinda Gates Foundation.

negative: Coronavirus infections reported by ProMED, February 2000–January 2020 Abstract Introduction Sources describing the global burden of emerging diseases accurately are still limited. We reviewed coronavirus infections reported by ProMED and assessed the reliability of the data retrieved compared to published reports. We evaluated the effectiveness of ProMED as a source of epidemiological data on coronavirus. Methods Using the keyword “coronavirus” in the ProMED search engine, we reviewed all the information from the reports and collected data using a structured form, including year, country, gender, occupation, the number of infected individuals, and the number of fatal cases. Results We identified 109 entries reported between February 29, 2000 and January 22, 2020. A total of 966 cases were reported, with death reported in 188 cases, suggesting an overall case fatality rate (CFR) of 19.5%. Of 70 cases for which the gender was reported, 47 (67.1%) were male. Most of the cases were reported from China, the United Arab Emirates, and Saudi Arabia, with reports from other countries, including imported cases in Europe and North America. Conclusions Internet-based reporting systems such as ProMED are useful to gather information and synthesize knowledge on emerging infections. Although certain areas need to be improved, ProMED provided useful information about coronaviruses especially during outbreaks.

negative: Ribavirin and Interferon Therapy for Critically Ill Patients With Middle East Respiratory Syndrome: A Multicenter Observational Study BACKGROUND: The objective of this study was to evaluate the effect of ribavirin and recombinant interferon (RBV/rIFN) therapy on the outcomes of critically ill patients with Middle East respiratory syndrome (MERS), accounting for time-varying confounders. METHODS: This is a retrospective cohort study of critically ill patients with laboratory-confirmed MERS from 14 hospitals in Saudi Arabia diagnosed between September 2012 and January 2018. We evaluated the association of RBV/rIFN with 90-day mortality and MERS coronavirus (MERS-CoV) RNA clearance using marginal structural modeling to account for baseline and time-varying confounders. RESULTS: Of 349 MERS patients, 144 (41.3%) patients received RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a; none received rIFN-β1b). RBV/rIFN was initiated at a median of 2 days (Q1, Q3: 1, 3 days) from intensive care unit admission. Crude 90-day mortality was higher in patients with RBV/rIFN compared to no RBV/rIFN (106/144 [73.6%] vs 126/205 [61.5%]; P = .02]. After adjusting for baseline and time-varying confounders using a marginal structural model, RBV/rIFN was not associated with changes in 90-day mortality (adjusted odds ratio, 1.03 [95% confidence interval {CI}, .73–1.44]; P = .87) or with more rapid MERS-CoV RNA clearance (adjusted hazard ratio, 0.65 [95% CI, .30–1.44]; P = .29). CONCLUSIONS: In this observational study, RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a) therapy was commonly used in critically ill MERS patients but was not associated with reduction in 90-day mortality or in faster MERS-CoV RNA clearance.

negative: Characteristics of patients with COVID-19 during epidemic ongoing outbreak in Wuhan, China Background Since Dec 2019, SARS-CoV-2 has caused about fifty thousand patients and over two thousand deaths in Wuhan, China. We reported characteristics of patients with COVID-19 during epidemic ongoing outbreak in Wuhan. Methods Data of COVID-19 patients with clinical outcome in a designated hospital in Wuhan, were retrospectively collected from electronic medical records. Characteristics were compared between patients who died or recovered, and between patients with different disease severity. Results By Feb 25, 2020, 403 patients were enrolled, 100 died and 303 recovered. Most of non-survivors tended to be males, old aged, or with chronic diseases. Duration from illness onset to admission was 9 (7-12) days. Patients with severe or critical illness had more days from onset to admission compared to those with ordinary illness. Lymphopenia, anemia, hypoproteinemia, and abnormal serum sodium were presented in 52.6%, 54.6%, 69.8%, and 21.8% cases, respectively. Patients who died or with severe/critical illness showed increased white blood cell and neutrophil count, serum total bilirubin, creatinine, hypersensitive troponin I, D-dimer, procalcitonin, and C-reactive protein, and decreased red blood cell, lymphocyte, platelet count, and serum albumin on admission compared to those who recovered or with ordinary illness. Complications of acute organ injury and secondary infection were common in patients with COVID-19, especially in non-survivors. Conclusions Multiple homeostasis disturbances were common in patients with severe or critical illness at admission. Early support should be provided, especially for old men with chronic disease, which is vital to control disease progression and reduce mortality of COVID-19 during epidemic ongoing outbreak.

negative: Cyberbiosecurity Challenges of Pathogen Genome Databases Pathogen detection, identification, and tracking is shifting from non-molecular methods, DNA fingerprinting methods, and single gene methods to methods relying on whole genomes. Viral Ebola and influenza genome data are being used for real-time tracking, while food-borne bacterial pathogen outbreaks and hospital outbreaks are investigated using whole genomes in the UK, Canada, the USA and the other countries. Also, plant pathogen genomes are starting to be used to investigate plant disease epidemics such as the wheat blast outbreak in Bangladesh. While these genome-based approaches provide never-seen advantages over all previous approaches with regard to public health and biosecurity, they also come with new vulnerabilities and risks with regard to cybersecurity. The more we rely on genome databases, the more likely these databases will become targets for cyber-attacks to interfere with public health and biosecurity systems by compromising their integrity, taking them hostage, or manipulating the data they contain. Also, while there is the potential to collect pathogen genomic data from infected individuals or agricultural and food products during disease outbreaks to improve disease modeling and forecast, how to protect the privacy of individuals, growers, and retailers is another major cyberbiosecurity challenge. As data become linkable to other data sources, individuals and groups become identifiable and potential malicious activities targeting those identified become feasible. Here, we define a number of potential cybersecurity weaknesses in today's pathogen genome databases to raise awareness, and we provide potential solutions to strengthen cyberbiosecurity during the development of the next generation of pathogen genome databases.

negative: Síndrome respiratorio agudo grave. Una nueva enfermedad infecciosa emergente

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: 11 Social, cultural, and other diversity issues in the traumatic stress field This chapter describes how the impact of psychological trauma and posttraumatic stress disorder (PTSD) differ, depending on individual differences and the social and cultural context and culture-specific teachings and resources available to individuals, families, and communities. A social-ecological framework is used to differentiate the impact of exposure to traumatic stressors and the development of (or resistance to) PTSD, based on the individual’s or group’s (i) personal, unique physical characteristics, including skin color, racial background, gender, and sexual orientation; and (ii) family, ethnocultural, and community membership, including majority or minority group status, religious beliefs and practices, socioeconomic resources, and political and civic affiliations. While personal, familial, social, and cultural factors can be a positive resource contributing to safety and well-being, they also can be a basis for placing the person, group, or entire community or population in harm’s way or at heightened risk of developing PTSD.

negative: Situation analysis and an insight into assessment of pandemic COVID-19

negative: Late mortality in survivors of autologous hematopoietic-cell transplantation: report from the Bone Marrow Transplant Survivor Study. We assessed late mortality in 854 individuals who had survived 2 or more years after autologous hematopoietic cell transplantation (HCT) for hematologic malignancies. Median age at HCT was 36.5 years, and median length of follow-up was 7.6 years. Overall survival was 68.8% +/- 1.8% at 10 years, and the cohort was at a 13-fold increased risk for late death (standardized mortality ratio [SMR] = 13.0) when compared with the general population. Mortality rates approached those of the general population after 10 years among patients at standard risk for relapse at HCT (SMR = 1.1) and in patients undergoing transplantation for acute myeloid leukemia (AML; SMR = 0.9). Relapse of primary disease (56%) and subsequent malignancies (25%) were leading causes of late death. Relapse-related mortality was increased among patients with Hodgkin disease (HD; relative risk [RR] = 3.6), non-Hodgkin lymphoma (NHL; RR = 2.1), and acute lymphoblastic leukemia (ALL; RR = 6.5). Total body irradiation (RR = 0.6) provided a protective effect. Nonrelapse-related mortality was increased after carmustine (RR = 2.3) and with use of peripheral blood stem cells (RR = 2.4). Survivors were more likely to report difficulty in holding jobs (RR = 9.4) and in obtaining health (RR = 7.7) or life insurance (RR = 8.4) when compared with siblings. Although mortality rates approach that of the general population after 10 years in certain subgroups, long-term survivors of autologous HCT continue to face challenges affecting their health and well-being.

negative: Response strategies for COVID-19 epidemics in African settings: a mathematical modelling study Background The health impact of COVID-19 may differ in African settings as compared to countries in Europe or China due to demographic, epidemiological, environmental and socio-economic factors. We evaluated strategies to reduce SARS-CoV-2 burden in African countries, so as to support decisions that balance minimising mortality, protecting health services and safeguarding livelihoods. Methods We used a Susceptible-Exposed-Infectious-Recovered mathematical model, stratified by age, to predict the evolution of COVID-19 epidemics in three countries representing a range of age distributions in Africa (from oldest to youngest average age: Mauritius, Nigeria and Niger), under various effectiveness assumptions for combinations of different non-pharmaceutical interventions: self-isolation of symptomatic people, physical distancing, and shielding (physical isolation) of the high-risk population. We adapted model parameters to better represent uncertainty about what might be expected in African populations, in particular by shifting the distribution of severity risk towards younger ages and increasing the case-fatality ratio. Results We predicted median clinical attack rates over the first 12 months of 17% (Niger) to 39% (Mauritius), peaking at 2-4 months, if epidemics were unmitigated. Self-isolation while symptomatic had a maximum impact of about 30% on reducing severe cases, while the impact of physical distancing varied widely depending on percent contact reduction and R 0 . The effect of shielding high-risk people, e.g. by rehousing them in physical isolation, was sensitive mainly to residual contact with low-risk people, and to a lesser extent to contact among shielded individuals. Response strategies incorporating self-isolation of symptomatic individuals, moderate physical distancing and high uptake of shielding reduced predicted peak bed demand by 46% to 54% and mortality by 60% to 75%. Lockdowns delayed epidemics by about 3 months. Estimates were sensitive to differences in age-specific social mixing patterns, as published in the literature. Discussion In African settings, as elsewhere, current evidence suggests large COVID-19 epidemics are expected. However, African countries have fewer means to suppress transmission and manage cases. We found that self-isolation of symptomatic persons and general physical distancing are unlikely to avert very large epidemics, unless distancing takes the form of stringent lockdown measures. However, both interventions help to mitigate the epidemic. Shielding of high-risk individuals can reduce health service demand and, even more markedly, mortality if it features high uptake and low contact of shielded and unshielded people, with no increase in contact among shielded people. Strategies combining self-isolation, moderate physical distancing and shielding will probably achieve substantial reductions in mortality in African countries. Temporary lockdowns, where socioeconomically acceptable, can help gain crucial time for planning and expanding health service capacity.

negative: From SARS-CoV to SARS-CoV-2: safety and broad-spectrum are important for coronavirus vaccine development The global pandemic of COVID-19 caused by SARS-CoV-2 (also known as 2019-nCoV and HCoV-19) has posed serious threats to public health and economic stability worldwide, thus calling for development of vaccines against SARS-CoV-2 and other emerging and reemerging coronaviruses. Since SARS-CoV-2 and SARS-CoV have high similarity of their genomic sequences and share the same cellular receptor (ACE2), it is essential to learn the lessons and experiences from the development of SARS-CoV vaccines for the development of SARS-CoV-2 vaccines. In this review, we summarized the current knowledge on the advantages and disadvantages of the SARS-CoV vaccine candidates and prospected the strategies for the development of safe, effective and broad-spectrum coronavirus vaccines for prevention of infection by currently circulating SARS-CoV-2 and other emerging and reemerging coronaviruses that may cause future epidemics or pandemics.

negative: Influenza viruses and the evolution of avian influenza virus H5N1 Summary Although small in size and simple in structure, influenza viruses are sophisticated organisms with highly mutagenic genomes and wide antigenic diversity. They are species-specific organisms. Mutation and reassortment have resulted in newer viruses such as H5N1, with new resistance against anti-viral medications, and this might lead to the emergence of a fully transmissible strain, as occurred in the 1957 and 1968 pandemics. Influenza viruses are no longer just a cause of self-limited upper respiratory tract infections; the H5N1 avian influenza virus can cause severe human infection with a mortality rate exceeding 50%. The case death rate of H5N1 avian influenza infection is 20 times higher than that of the 1918 infection (50% versus 2.5%), which killed 675000 people in the USA and almost 40 million people worldwide. While the clock is still ticking towards what seems to be inevitable pandemic influenza, on April 17, 2007 the U.S. Food and Drug Administration (FDA) approved the first vaccine against the avian influenza virus H5N1 for humans at high risk. However, more research is needed to develop a more effective and affordable vaccine that can be given at lower doses.

negative: Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension The dysfunction of the renin-angiotensin system (RAS) has been observed in coronavirus infection disease (COVID-19) patients, but whether RAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs), are associated with clinical outcomes remains unknown. COVID-19 patients with hypertension were enrolled to evaluate the effect of RAS inhibitors. We observed that patients receiving ACEI or ARB therapy had a lower rate of severe diseases and a trend toward a lower level of IL-6 in peripheral blood. In addition, ACEI or ARB therapy increased CD3 and CD8 T cell counts in peripheral blood and decreased the peak viral load compared to other antihypertensive drugs. This evidence supports the benefit of using ACEIs or ARBs to potentially contribute to the improvement of clinical outcomes of COVID-19 patients with hypertension.

negative: Traumatic Spinal Cord Injury: An Overview of Pathophysiology, Models and Acute Injury Mechanisms Traumatic spinal cord injury (SCI) is a life changing neurological condition with substantial socioeconomic implications for patients and their care-givers. Recent advances in medical management of SCI has significantly improved diagnosis, stabilization, survival rate and well-being of SCI patients. However, there has been small progress on treatment options for improving the neurological outcomes of SCI patients. This incremental success mainly reflects the complexity of SCI pathophysiology and the diverse biochemical and physiological changes that occur in the injured spinal cord. Therefore, in the past few decades, considerable efforts have been made by SCI researchers to elucidate the pathophysiology of SCI and unravel the underlying cellular and molecular mechanisms of tissue degeneration and repair in the injured spinal cord. To this end, a number of preclinical animal and injury models have been developed to more closely recapitulate the primary and secondary injury processes of SCI. In this review, we will provide a comprehensive overview of the recent advances in our understanding of the pathophysiology of SCI. We will also discuss the neurological outcomes of human SCI and the available experimental model systems that have been employed to identify SCI mechanisms and develop therapeutic strategies for this condition.

negative: Proportional morbidity rates of enteropathogens among diarrheic dairy calves in central Spain Abstract Faecal samples from 218 diarrheic dairy calves in 65 dairy herds, selected by convenience, were screened for the presence of rotavirus, coronavirus, Cryptosporidium spp., F5+ Escherichia coli and Salmonella spp. Animals surveyed were from 1 to 30 days old. Cryptosporidium and rotavirus were the most commonly detected agents (52.3% and 42.7% of the samples positive, respectively). F5+ E. coli was detected in the faeces of 11.9% of the calves and bovine coronavirus was detected in the faeces of 7.3% of the calves. Salmonella spp. was only found in the faeces of two calves (0.9%). Mixed infections with two or more agents occurred in 28% of the calves. Concurrent infection of rotavirus and Cryptosporidium was found in 21.6% of the calves. Two tests were used for the detection of rotavirus (a commercial ELISA and PAGE), F5+ E. coli (ELISA and bacterial culture) and Cryptosporidium (ELISA and microscopy). The validity of the commercial ELISA for the detection of rotavirus, F5+ E. coli and Cryptosporidium in faeces from diarrheic calves was evaluated using PAGE, bacterial culture and microscopy as gold standard, respectively. The ELISA showed a very low sensitivity (28.6%) for the detection of F5+ E. coli compared to bacterial culture.

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: Facing the COVID-19 epidemic in NYC: a stochastic agent-based model of various intervention strategies Global spread of coronavirus disease 2019 (COVID-19) has created an unprecedented infectious disease crisis worldwide. Despite uncertainties about COVID-19, model-based forecasting of competing mitigation measures on its course is urgently needed to inform mitigation policy. We used a stochastic agent-based microsimulation model of the COVID-19 epidemic in New York City and evaluated the potential impact of quarantine duration (from 4 to 16 weeks), quarantine lifting type (1-step lifting for all individuals versus a 2-step lifting according to age), post-quarantine screening, and use of a hypothetical effective treatment against COVID-19 on the disease's cumulative incidence and mortality, and on ICU-bed occupancy. The source code of the model has been deposited in a public source code repository. The model calibrated well and variation of model parameter values had little impact on outcome estimates. While quarantine is efficient to contain the viral spread, it is unlikely to prevent a rebound of the epidemic once lifted. We projected that lifting quarantine in a single step for the full population would be unlikely to substantially lower the cumulative mortality, regardless of quarantine duration. By contrast, a two-step quarantine lifting according to age was associated with a substantially lower cumulative mortality and incidence, up to 71% and 23%, respectively, as well as lower ICU-bed occupancy. Although post-quarantine screening was associated with diminished epidemic rebound, this strategy may not prevent ICUs from being overcrowded. It may even become deleterious after a 2-step quarantine lifting according to age if the herd immunity effect does not had sufficient time to become established in the younger population when the quarantine is lifted for the older population. An effective treatment against COVID-19 would considerably reduce the consequences of the epidemic, even more so if ICU capacity is not exceeded.

negative: Outbreak Trends of Coronavirus Disease–2019 in India: A Prediction OBJECTIVE: The objective of this paper is to prepare the government and citizens of India to take or implement the control measures proactively to reduce the impact of coronavirus disease 2019 (COVID-19). METHOD: In this work, the COVID-19 outbreak in India has been predicted based on the pattern of China using a machine learning approach. The model is built to predict the number of confirmed cases, recovered cases, and death cases based on the data available between January 22, 2020, and April 3, 2020. The time series forecasting method is used for prediction models. RESULTS: The COVID-19 effects are predicted to be at peak between the third and fourth weeks of April 2020 in India. This outbreak is predicted to be controlled around the end of May 2020. The total number of predicted confirmed cases of COVID-19 might reach around 68 978, and the number of deaths due to COVID-19 are predicted to be 1557 around April 25, 2020, in India. If this outbreak is not controlled by the end of May 2020, then India will face a severe shortage of hospitals, and it will make this outbreak even worse. CONCLUSION: The COVID-19 pandemic may be controlled if the Government of India takes proactive steps to aggressively implement a lockdown in the country and extend it further. This presented epidemiological model is an effort to predict the future forecast of COVID-19 spread, based on the present scenario, so that the government can frame policy decisions, and necessary actions can be initiated.

negative: SARS-CoV-2 epidemiology and control, different scenarios for Turkey Background/aim: Coronavirus Infectious Disease 2019 (COVID-19) is now a pandemic spreading in most countries including Turkey. Materials and methods: The current knowledge of COVID-19 and the virus causing it, SARS-CoV-2, was reviewed. The epidemiology and control in different countries was compared and the differences discussed. Results: The population attack rates and case fatality rates vary from country to country with Lombardy in northern Italy reporting an attack rate in the general population of 0.37% compared to 0.004% in Hong Kong. The differences are caused by different testing strategies and reporting systems. Conclusion: Turkey is early in the outbreak. Different control strategies are available with South Korea, Hong Kong and Singapore being models to follow.

negative: COVID-19, Modern Pandemic: A Systematic Review From Front-Line Health Care Providers’ Perspective Coronavirus disease 2019 (COVID-19) caused infection in 168,000 cases worldwide in about 148 countries and killed more than 6,610 people around the world as of March 16, 2020, as per the World Health Organization (WHO). Compared to severe acute respiratory syndrome and Middle East respiratory syndrome, there is the rapid transmission, long incubation period, and disease containment is becoming extremely difficult. The main aim of this systematic review is to provide a comprehensive clinical summary of all the available data from high-quality research articles relevant to the epidemiology, demographics, trends in hospitalization and outcomes, clinical signs and symptoms, diagnostic methods and treatment methods of COVID-19, thus increasing awareness in health care providers. We also discussed various preventive measures to combat COVID-19 effectively. A systematic and protocol-driven approach is needed to contain this disease, which was declared as a global pandemic on March 11, 2020, by the WHO.

negative: Impact of sex and gender on COVID-19 outcomes in Europe BACKGROUND: Emerging evidence from China suggests that coronavirus disease 2019 (COVID-19) is deadlier for infected men than women with a 2.8% fatality rate being reported in Chinese men versus 1.7% in women. Further, sex-disaggregated data for COVID-19 in several European countries show a similar number of cases between the sexes, but more severe outcomes in aged men. Case fatality is highest in men with pre-existing cardiovascular conditions. The mechanisms accounting for the reduced case fatality rate in women are currently unclear but may offer potential to develop novel risk stratification tools and therapeutic options for women and men. CONTENT: The present review summarizes latest clinical and epidemiological evidence for gender and sex differences in COVID-19 from Europe and China. We discuss potential sex-specific mechanisms modulating the course of disease, such as hormone-regulated expression of genes encoding for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) entry receptors angiotensin converting enzyme (ACE) 2 receptor and TMPRSS2 as well as sex hormone-driven innate and adaptive immune responses and immunoaging. Finally, we elucidate the impact of gender-specific lifestyle, health behavior, psychological stress, and socioeconomic conditions on COVID-19 and discuss sex specific aspects of antiviral therapies. CONCLUSION: The sex and gender disparities observed in COVID-19 vulnerability emphasize the need to better understand the impact of sex and gender on incidence and case fatality of the disease and to tailor treatment according to sex and gender. The ongoing and planned prophylactic and therapeutic treatment studies must include prospective sex- and gender-sensitive analyses.

negative: Evaluating the virucidal efficacy of hydrogen peroxide vapour Summary Background Surface contamination has been implicated in the transmission of certain viruses, and surface disinfection can be an effective measure to interrupt the spread of these agents. Aim To evaluate the in-vitro efficacy of hydrogen peroxide vapour (HPV), a vapour-phase disinfection method, for the inactivation of a number of structurally distinct viruses of importance in the healthcare, veterinary and public sectors. The viruses studied were: feline calicivirus (FCV, a norovirus surrogate); human adenovirus type 1; transmissible gastroenteritis coronavirus of pigs (TGEV, a severe acute respiratory syndrome coronavirus [SARS-CoV] surrogate); avian influenza virus (AIV); and swine influenza virus (SwIV). Methods The viruses were dried on stainless steel discs in 20- or 40-μL aliquots and exposed to HPV produced by a Clarus L generator (Bioquell, Horsham, PA, USA) in a 0.2-m3 environmental chamber. Three vaporized volumes of hydrogen peroxide were tested in triplicate for each virus: 25, 27 and 33mL. Findings No viable viruses were identified after HPV exposure at any of the vaporized volumes tested. HPV was virucidal (>4-log reduction) against FCV, adenovirus, TGEV and AIV at the lowest vaporized volume tested (25mL). For SwIV, due to low virus titre on the control discs, >3.8-log reduction was shown for the 25-mL vaporized volume and >4-log reduction was shown for the 27-mL and 33-mL vaporized volumes. Conclusion HPV was virucidal for structurally distinct viruses dried on surfaces, suggesting that HPV can be considered for the disinfection of virus-contaminated surfaces.

negative: Pandemic Flu: Clinical management of patients with an influenza-like illness during an influenza pandemic

negative: Determining the spatial effects of COVID-19 using the spatial panel data model Abstract This study investigates the propagation power and effects of the coronavirus disease 2019 (COVID-19) in light of published data. We examine the factors affecting COVID-19 together with the spatial effects, and use spatial panel data models to determine the relationship among the variables including their spatial effects. Using spatial panel models, we analyse the relationship between confirmed cases of COVID-19, deaths thereof, and recovered cases due to treatment. We accordingly determine and include the spatial effects in this examination after establishing the appropriate model for COVID-19. The most efficient and consistent model is interpreted with direct and indirect spatial effects.

negative: Human monoclonal antibody as prophylaxis for SARS coronavirus infection in ferrets Summary SARS coronavirus continues to cause sporadic cases of severe acute respiratory syndrome (SARS) in China. No active or passive immunoprophylaxis for disease induced by SARS coronavirus is available. We investigated prophylaxis of SARS coronavirus infection with a neutralising human monoclonal antibody in ferrets, which can be readily infected with the virus. Prophylactic administration of the monoclonal antibody at 10 mg/kg reduced replication of SARS coronavirus in the lungs of infected ferrets by 3·3 logs (95% Cl 2·6–4·0 logs; p<0·001), completely prevented the development of SARS coronavirus-induced macroscopic lung pathology (p=0·013), and abolished shedding of virus in pharyngeal secretions. The data generated in this animal model show that administration of a human monoclonal antibody might offer a feasible and effective prophylaxis for the control of human SARS coronavirus infection.

negative: Case-based reported mortality associated with laboratory-confirmed influenza A(H1N1) 2009 virus infection in the Netherlands: the 2009-2010 pandemic season versus the 2010-2011 influenza season BACKGROUND: In contrast to seasonal influenza epidemics, where the majority of deaths occur amongst elderly, a considerable part of the 2009 pandemic influenza related deaths concerned relatively young people. In the Netherlands, all deaths associated with laboratory-confirmed influenza A(H1N1) 2009 virus infection had to be notified, both during the 2009-2010 pandemic season and the 2010-2011 influenza season. To assess whether and to what extent pandemic mortality patterns were reverting back to seasonal patterns, a retrospective analyses of all notified fatal cases associated with laboratory-confirmed influenza A(H1N1) 2009 virus infection was performed. METHODS: The notification database, including detailed information about the clinical characteristics of all notified deaths, was used to perform a comprehensive analysis of all deceased patients with a laboratory-confirmed influenza A(H1N1) 2009 virus infection. Characteristics of the fatalities with respect to age and underlying medical conditions were analysed, comparing the 2009-2010 pandemic and the 2010-2011 influenza season. RESULTS: A total of 65 fatalities with a laboratory-confirmed influenza A(H1N1) 2009 virus infection were notified in 2009-2010 and 38 in 2010-2011. During the pandemic season, the population mortality rates peaked in persons aged 0-15 and 55-64 years. In the 2010-2011 influenza season, peaks in mortality were seen in persons aged 0-15 and 75-84 years. During the 2010-2011 influenza season, the height of first peak was lower compared to that during the pandemic season. Underlying immunological disorders were more common in the pandemic season compared to the 2010-2011 season (p = 0.02), and cardiovascular disorders were more common in the 2010-2011 season (p = 0.005). CONCLUSIONS: The mortality pattern in the 2010-2011 influenza season still resembled the 2009-2010 pandemic season with a peak in relatively young age groups, but concurrently a clear shift toward seasonal patterns was seen, with a peak in mortality in the elderly, i.e. ≥ 75 years of age.

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: 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: A deductive approach to modeling the spread of COVID-19 Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), previously known as 2019-nCoV, is responsible for the atypical pneumonia pandemic designated as Coronavirus Disease 2019 (COVID-19). The confirmed number of cases continues to grow exponentially reaching 492,000 people in 175 countries as of March 25, 2020. 22,169 people (~4.5%) infected with SARS-COV-2 virus have died. We have developed an exponential regression model using the COVID-19 case data (Jan 22 - Mar 22, 2020). Our primary model uses designated Phase 1 countries, who exceed 2500 cases on Mar 22. The model is then applied to Phase 2 countries: those that escaped the initial Phase 1 global expansion of COVID-19. With the exception of stabilizing countries (South Korea, Japan, and Iran) all Phase 1 countries are growing exponentially, as per I2500(t)=120.4 × e0.238t, with a rate, r = 0.238 ± 0.068. Excluding China, the BRICS developing nations and Australia are in Phase 2. Case data from Phase 2 countries are following the model derived from Phase 1 countries. In the absence of measures employed to flatten the curve including social distancing, quarantine, and healthcare expansion, our model projects over 274,000 cases and 12,300 deaths in the US by Mar 31. India can expect 123,000 cases by April 16. By flattening the curve to the growth rate of stabilizing countries (r = 0.044 ± 0.062), the US would prevent 8,500 deaths by Mar 31, and India would prevent 5,500 deaths by April 16.

negative: Proceedings of Réanimation 2019, the French Intensive Care Society International Congress

negative: Pulmonary infections in the returned traveller Pulmonary infections in the returned traveller are a common presentation. A wide variety of infections may present with pulmonary symptoms. It is important for clinicians to differentiate the cause of these symptoms. The risk of contracting certain travel-related pulmonary diseases depends on travel destination, length of stay, activities undertaken and co-morbidities. Some pathogens are found worldwide, whilst others are related to specific locations. This review article will discuss the approach to diagnosing and treating pulmonary infections in the returned traveller.

negative: Preparing for the Perpetual Challenges of Pandemics of Coronavirus Infections with Special Focus on SARS-CoV-2 COVID-19, arising from novel, zoonotic coronavirus-2, has gripped the world in a pandemic. The present chapter discusses the current internationally implemented pandemic preparedness strategies succeeding/recommended to curb the COVID-19 threat to humankind. The updated phase-wise categorization of a pandemic as recommended by the WHO is described, and associated innovations in surveillance, response, and medical measures/advisory in practice across the globe are elaborated. From a bird’s eye view, the COVID-19 pandemic management relies on revolutionizing the disease surveillance by incorporating artificial intelligence and data analytics, boosting the response strategies—extensive testing, case isolation, contact tracing, and social distancing—and promoting awareness and access to pharmaceutical and non-pharmaceutical interventions, which are discussed in the present chapter. We also preview the economic bearing of the COVID-19 pandemic.

negative: Epidemiology of the 2020 pandemic of COVID‐19 in the state of Georgia: Inadequate critical care resources and impact after 7 weeks of community spread OBJECTIVES: Novel coronavirus (COVID‐19) is a global pandemic currently spreading rapidly across the United States. We provide a comprehensive look at COVID‐19 epidemiology across the state of Georgia, which includes vast rural communities that may be disproportionately impacted by the spread of this infectious disease. METHODS: All 159 Georgia counties were included in this study. We examined the geographic variation of COVID‐19 in Georgia from March 3 through April 24, 2020 by extracting data on incidence and mortality from various national and state datasets. We contrasted county‐level mortality rates per 100,000 population (MRs) by county‐level factors. RESULTS: Metropolitan Atlanta had the overall highest number of confirmed cases; however, the southwestern rural parts of Georgia, surrounding the city of Albany, had the highest bi‐weekly increases in incidence rate. Among counties with >10 cases, MRs were highest in the rural counties of Randolph (233.2), Terrell (182.5), Early (136.3), and Dougherty (114.2). Counties with the highest MRs (22.5–2332 per 100,000) had a higher proportion of: non‐Hispanic Blacks residents, adults aged 60+, adults earning <$20,000 annually, and residents living in rural communities when compared with counties with lower MRs. These counties also had a lower proportion of the population with a college education, lower number of ICU beds per 100,000 population, and lower number of primary care physicians per 10,000 population. CONCLUSIONS: While urban centers in Georgia account for the bulk of COVID‐19 cases, high mortality rates and low critical care capacity in rural Georgia are also of critical concern.

negative: The socio-economic determinants of the coronavirus disease (COVID-19) pandemic The magnitude of the coronavirus disease (COVID-19) pandemic has an enormous impact on the social life and the economic activities in almost every country in the world. Besides the biological and epidemiological factors, a multitude of social and economic criteria also govern the extent of the coronavirus disease spread in the population. Consequently, there is an active debate regarding the critical socio-economic determinants that contribute to the resulting pandemic. In this paper, we contribute towards the resolution of the debate by leveraging Bayesian model averaging techniques and country level data to investigate the potential of 29 determinants, describing a diverse set of socio-economic characteristics, in explaining the coronavirus pandemic outcome. We show that the true empirical model behind the coronavirus outcome is constituted only of few determinants, but the extent to which each determinant is able to provide a credible explanation varies between countries due to their heterogeneous socio-economic characteristics. To understand the relationship between the potential determinants in the specification of the true model, we develop the coronavirus determinants Jointness space. In this space, two determinants are connected with each other if they are able to jointly explain the coronavirus outcome. As constructed, the obtained map acts as a bridge between theoretical investigations and empirical observations, and offers an alternate view for the joint importance of the socio-economic determinants when used for developing policies aimed at preventing future epidemic crises.

negative: Year in review in Intensive Care Medicine 2014: III. Severe infections, septic shock, healthcare-associated infections, highly resistant bacteria, invasive fungal infections, severe viral infections, Ebola virus disease and paediatrics

negative: Identification of a super-spreading chain of transmission associated with COVID-19 Background: Super-spreading events were associated with the outbreaks of SARS and MERS, but their association with the outbreak of COVID-19 remains unknown. Here, we report a super-spreading transmission chain of SARS-CoV-2 involving an index patient, seven cancer patients, 40 health care workers and four family members. Methods: We conducted a retrospective study to identify the index patient and the exposed individuals linked to a chain of transmission associated with COVID-19. We collected and analyzed the data on demographic features, exposure history, clinical presentation, laboratory investigation, radiological examination, and disease outcome of these patients. Results: We identified the index patient and another presumptive super-spreader, who initiated and amplified a super-spreading transmission chain associated with COVID-19, respectively. There were 31 female and 21 male patients in this cohort, and the median age was 37 years (range: 22-79 years). Each of them had an exposure history with the index patient or his close contacts. Approximately 87% (45/52) of the patients had fever or other symptoms, 96% (50/52) had abnormal chest CT-scan findings, 86% of the tested patients (39/45) were positive for SARS-CoV-2 in the nasopharyngeal or throat swab specimen, 85% of the tested patients (29/34) were positive for SARS-CoV-2-specific IgM and/or IgG, 15% of the RT-PCR positive patients were tested negative for the specific IgM and/or IgG at the convalescent phase, and 15% of the RT-PCR negative patients were tested positive for the specific IgM and/or IgG. The severe patients experienced a significant decrease in oximetry saturation, lymphocyte, and platelet counts, along with a significant increase in C-reactive protein, D-dimer, and lactate dehydrogenase. All six fatal cases had comorbidities and five of the seven cancer patients (71%) died within 2-20 days of the disease onset. Conclusions: The super-spreading events were associated with the outbreak of COVID-19 in Wuhan and its impact on disease transmission warrants further investigation. Cancer patients appeared highly vulnerable to COVID-19. The finding that a significant portion of SARS-CoV-2 infected patients were tested negative for the serum specific IgM and IgG at the convalescent phase should be addressed by additional studies.

negative: Mathematical assessment of the impact of non-pharmaceutical interventions on curtailing the 2019 novel Coronavirus A pandemic of a novel Coronavirus emerged in December of 2019 (COVID-19), causing devastating public health impact across the world. In the absence of a safe and effective vaccine or antivirals, strategies for con- trolling and mitigating the burden of the pandemic are focused on non-pharmaceutical interventions, such as social-distancing, contact-tracing, quarantine, isolation and the use of face-masks in public. We develop a new mathematical model for assessing the population-level impact of the aforementioned control and mitigation strategies. Rigorous analysis of the model shows that the disease-free equilibrium is locally-asymptotically stable if a certain epidemiological threshold, known as the reproduction number (denoted by Rc), is less than unity. This equilibrium is globally-asymptotically stable, for a special case of the model where quarantined-susceptible individuals do not acquire COVID-19 infection during quarantine, when Rc is less than unity. The epidemiological consequence of this theoretical result is that, the community-wide implementation of control interventions that can bring (and maintain) Rc to a value less than unity will lead to the effective control (or elimination) of COVID-19 in the community. Simulations of the model, using data relevant to COVID-19 transmission dynamics in the US state of New York and the entire US, show that the pandemic burden will peak in mid and late April, respectively. The worst-case scenario projections for cumulative mortality (based on baseline levels of interventions) are 105, 100 for New York state and 164, 000 for the entire US by the end of the pandemic. These numbers dramatically decreased by 80% and 64%, respectively, if adherence to strict social-distancing measures is improved and maintained until the end of May or June. The duration and timing of the relaxation or termination of the strict social-distancing measures are crucially important in determining the future trajectory of the COVID-19 pandemic. This study shows that early termination of the strict social-distancing measures could trigger a devastating second wave with burden similar to those projected before the onset of the strict social-distance measures were implemented. The use of efficacious face-masks (such as surgical masks, with estimated efficacy ≥ 70%) in public could lead to the elimination of the pandemic if at least 70% of the residents of New York state use such masks in public consistently (nationwide, a compliance of at least 80% will be required using such masks). The use of low efficacy masks, such as cloth masks (of estimated efficacy less than 30%), could also lead to significant reduction of COVID-19 burden (albeit, they are not able to lead to elimination). Combining low efficacy masks with improved levels of the other anti-COVID-19 intervention strategies can lead to the elimination of the pandemic. This study emphasizes the important role social-distancing plays in curtailing the burden of COVID-19. Increases in the adherence level of social-distancing protocols result in dramatic reduction of the burden of the pandemic, and the timely implementation of social-distancing measures in numerous states of the US may have averted a catastrophic outcome with respect to the burden of COVID-19. Using face-masks in public (including the low efficacy cloth masks) is very useful in minimizing community transmission and burden of COVID-19, provided their coverage level is high. The masks coverage needed to eliminate COVID-19 decreases if the masks-based intervention is combined with the strict social-distancing strategy.

negative: Inactivation of surrogate coronaviruses on hard surfaces by health care germicides BACKGROUND: In the 2003 severe acute respiratory syndrome outbreak, finding viral nucleic acids on hospital surfaces suggested surfaces could play a role in spread in health care environments. Surface disinfection may interrupt transmission, but few data exist on the effectiveness of health care germicides against coronaviruses on surfaces. METHODS: The efficacy of health care germicides against 2 surrogate coronaviruses, mouse hepatitis virus (MHV) and transmissible gastroenteritis virus (TGEV), was tested using the quantitative carrier method on stainless steel surfaces. Germicides were o-phenylphenol/p-tertiary amylphenol) (a phenolic), 70% ethanol, 1:100 sodium hypochlorite, ortho-phthalaldehyde (OPA), instant hand sanitizer (62% ethanol), and hand sanitizing spray (71% ethanol). RESULTS: After 1-minute contact time, for TGEV, there was a log(10) reduction factor of 3.2 for 70% ethanol, 2.0 for phenolic, 2.3 for OPA, 0.35 for 1:100 hypochlorite, 4.0 for 62% ethanol, and 3.5 for 71% ethanol. For MHV, log(10) reduction factors were 3.9 for 70% ethanol, 1.3 for phenolic, 1.7 for OPA, 0.62 for 1:100 hypochlorite, 2.7 for 62% ethanol, and 2.0 for 71% ethanol. CONCLUSION: Only ethanol reduced infectivity of the 2 coronaviruses by >3-log(10) after 1 minute. Germicides must be chosen carefully to ensure they are effective against viruses such as severe acute respiratory syndrome coronavirus.

negative: 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: Chest X-ray severity index as a predictor of in-hospital mortality in coronavirus disease 2019: A study of 302 patients from Italy Abstract Objectives This study aimed to assess the usefulness of a new chest X-ray scoring system, the Brixia score, to predict the risk of in-hospital mortality in hospitalized patients with coronavirus disease 2019 (COVID-19) Methods Between March 4, 2020 and March 24, 2020, all CXR reports containing the Brixia score were retrieved. We enrolled only hospitalized Caucasian patients with COVID-19 for whom the final outcome was available. For each patient, age, sex, underlying comorbidities, immunosuppressive therapies and the CXR report containing the highest score were considered for the analysis. These independent variables were analyzed using a multivariable logistic regression model to extract the predictive factors for in-hospital mortality. Results 302 Caucasian patients who were hospitalized for COVID-19 were enrolled. In the multivariable logistic regression model, only Brixia score, patient age, and conditions that induced immunosuppression were the significant predictive factors for in-hospital mortality. On receiver operating characteristic curve analyses, the optimal cutoff values for Brixia score and patient age were 8 points and 71 years, respectively. Three different models that included the Brixia score showed excellent predictive power. Conclusions Patients with high Brixia score and at least one other predictive factor had the highest risk of in-hospital death.

negative: Incidence and Mortality Rates of Disasters and Mass Casualty Incidents in Korea: A Population-Based Cross-Sectional Study, 2000-2009 The objective of study was to evaluate the incidence and mortality rates of disasters and mass casualty incidents (MCIs) over the past 10 yr in the administrative system of Korea administrative system and to examine their relationship with population characteristics. This was a population-based cross-sectional study. We calculated the nationwide incidence, as well as the crude mortality and injury incidence rates, of disasters and MCIs. The data were collected from the administrative database of the National Emergency Management Agency (NEMA) and from provincial fire departments from January 2000 to December 2009. A total of 47,169 events were collected from the NEMA administrative database. Of these events, 115 and 3,079 cases were defined as disasters and MCIs that occurred in Korea, respectively. The incidence of technical disasters/MCIs was approximately 12.7 times greater than that of natural disasters/MCIs. Over the past 10 yr, the crude mortality rates for disasters and MCIs were 2.36 deaths per 100,000 persons and 6.78 deaths per 100,000 persons, respectively. The crude injury incidence rates for disasters and MCIs were 25.47 injuries per 100,000 persons and 152 injuries per 100,000 persons, respectively. The incidence and mortality of disasters/MCIs in Korea seem to be low compared to that of trend around the world.

negative: Impact of Comorbidity on Fatality Rate of Patients with Middle East Respiratory Syndrome To date, 1841 cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection have been reported worldwide, with 652 deaths. We used a publically available case line list to explore the effect of relevant factors, notably underlying comorbidities, on fatal outcome of Middle East respiratory syndrome (MERS) cases up to the end of October 2016. A Bayesian Weibull proportional hazards regression model was used to assess the effect of comorbidity, age, epidemic period and sex on the fatality rate of MERS cases and its variation across countries. The crude fatality rate of MERS cases was 32.1% (95% credibility interval (CI): 29.9%, 34.3%). Notably, the incremental change of daily death rate was most prominent during the first week since disease onset with an average increase of 13%, but then stabilized in the remaining two weeks when it only increased 3% on average. Neither sex, nor country of infection were found to have a significant impact on fatality rates after taking into account the age and comorbidity status of patients. After adjusting for age, epidemic period, MERS patients with comorbidity had around 4 times the risk for fatal infection than those without (adjusted hazard ratio of 3.74 (95% CI: 2.57, 5.67)).

negative: A comprehensive germline variant and expression analyses of ACE2, TMPRSS2 and SARS-CoV-2 activator FURIN genes from the Middle East: Combating SARS-CoV-2 with precision medicine The severity of the new COVID-19 pandemic caused by the SARS-CoV-2 virus is strikingly variable in different global populations. SARS-CoV-2 uses ACE2 as a cell receptor, TMPRSS2 protease, and FURIN peptidase to invade human cells. Here, we investigated 1,378 whole-exome sequences of individuals from the Middle Eastern populations (Kuwait, Qatar, and Iran) to explore natural variations in the ACE2, TMPRSS2, and FURIN genes. We identified two activating variants (K26R and N720D) in the ACE2 gene that are more common in Europeans than in the Middle Eastern, East Asian, and African populations. We postulate that K26R can activate ACE2 and facilitate binding to S-protein RBD while N720D enhances TMPRSS2 cutting and, ultimately, viral entry. We also detected deleterious variants in FURIN that are frequent in the Middle Eastern but not in the European populations. This study highlights specific genetic variations in the ACE2 and FURIN genes that may explain SARS-CoV-2 clinical disparity. We showed structural evidence of the functionality of these activating variants that increase the SARS-CoV-2 aggressiveness. Finally, our data illustrate a significant correlation between ACE2 variants identified in people from Middle Eastern origins that can be further explored to explain the variation in COVID-19 infection and mortality rates globally.

negative: Forecasting influenza epidemics by integrating internet search queries and traditional surveillance data with the support vector machine regression model in Liaoning, from 2011 to 2015 BACKGROUND: Influenza epidemics pose significant social and economic challenges in China. Internet search query data have been identified as a valuable source for the detection of emerging influenza epidemics. However, the selection of the search queries and the adoption of prediction methods are crucial challenges when it comes to improving predictions. The purpose of this study was to explore the application of the Support Vector Machine (SVM) regression model in merging search engine query data and traditional influenza data. METHODS: The official monthly reported number of influenza cases in Liaoning province in China was acquired from the China National Scientific Data Center for Public Health from January 2011 to December 2015. Based on Baidu Index, a publicly available search engine database, search queries potentially related to influenza over the corresponding period were identified. An SVM regression model was built to be used for predictions, and the choice of three parameters (C, γ, ε) in the SVM regression model was determined by leave-one-out cross-validation (LOOCV) during the model construction process. The model’s performance was evaluated by the evaluation metrics including Root Mean Square Error, Root Mean Square Percentage Error and Mean Absolute Percentage Error. RESULTS: In total, 17 search queries related to influenza were generated through the initial query selection approach and were adopted to construct the SVM regression model, including nine queries in the same month, three queries at a lag of one month, one query at a lag of two months and four queries at a lag of three months. The SVM model performed well when with the parameters (C = 2, γ = 0.005, ɛ = 0.0001), based on the ensemble data integrating the influenza surveillance data and Baidu search query data. CONCLUSIONS: The results demonstrated the feasibility of using internet search engine query data as the complementary data source for influenza surveillance and the efficiency of SVM regression model in tracking the influenza epidemics in Liaoning.

negative: Clinical Efficacy of Intravenous Immunoglobulin Therapy in Critical Patients with COVID-19: A multicenter retrospective cohort study Summary Background Coronavirus disease 2019 (COVID-19) has spread all over the world, causing more than 1.5 million infections and over ten thousands of deaths in a short period of time. However, little is known about its pathological mechanism, and there are still no clinical study reports on specific treatment. The purpose of this study is to determine the clinical efficacy of intravenous immunoglobulin (IVIG) therapy on COVID-19. Methods In this multicenter retrospective cohort study, adult critical COVID-19 patients (including severe type and critical type, according to the clinical classification defined by National Health Commission of China) in 8 government designated treatment center in China from Dec 23, 2019 to Mar 31, 2020 were enrolled. Demographic, clinical, treatment, and laboratory data, prognosis were extracted from electronic medical records, and IVIG was exposure factor. Primary outcomes were the 28 days and 60 days mortality, and secondary outcomes were the total length of in-hospital and the total duration of the disease. Meanwhile, the parameters of inflammation response and organ function were detected. The risk factors were determined by COX proportional hazards model. The subgroup analysis was carried out according to clinical classification of COVID-19, IVIG dosage and timing. Findings 325patients were included in this study, of whom 222 (68%) were severe type, 103 (32%) were critical type. 42 (13%) died in 28 days within hospitalization, total 54 (17%) died in 60 days, and 6 (3%) died in severe type, 48 (47%) died in critical type. 174 cases were used IVIG, and 151 cases were not. Compared with the baseline characteristics between two groups, the results showed that the patients in IVIG group had higher Acute Physiology and Chronic Health Evaluation (APACHII) score, Sequential Organ Failure Assessment (SOFA) score, IL-6 and lactate level, lower lymphocyte count and oxygenation index (all P<0.05). The 28 day and 60 day mortality did not improve with IVIG in overall patients. The in-hospital stay and the total duration of disease were longer in IVIG group (p<0.001). Risk factors were clinical classification (hazards ratio 0.126, 95% confidence interval 0.039-0.413, P=0.001), and using IVIG (hazards ratio 0.252, 95% confidence interval 0.107-0.591, P=0.002) with COX regression. Subgroup analysis showed that only in patients with critical type, IVIG could significantly reduce the 28 day mortality, decrease the inflammatory response and improve some organ functions (all p<0.05), and 60-day mortality reduced significantly by using IVIG in the early stage (admission[≤]7 days) and with high dose (>15 g/d). Interpretation Early and high dose of IVIG therapy may improve the prognosis of COVID-19 patients only in critical type, which provides the clinical basis for the choice of treatment population and method of IVIG therapy for the SARS-CoV-2 infection. Keywords: SARS-COV-2, COVID-19, IVIG, clinical efficacy, mortality

negative: 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: Outcomes of hydroxychloroquine usage in United States veterans hospitalized with COVID-19 Abstract Background Despite limited and conflicting evidence, hydroxychloroquine, alone or in combination with azithromycin, is widely used in COVID-19 therapy. Methods We performed a retrospective study of electronic health records of patients hospitalized with confirmed SARS-CoV-2 infection in United States Veterans Health Administration medical centers between March 9, 2020 and April 29, 2020. Patients hospitalized within 24 hours of diagnosis were classified based on their exposure to hydroxychloroquine alone (HC) or with azithromycin (HC+AZ) or no HC as treatments. The primary outcomes were mortality and use of mechanical ventilation. Findings A total of 807 patients were evaluated. Compared to the no HC group, after propensity score adjustment for clinical characteristics, the risk of death from any cause was higher in the HC group (adjusted hazard ratio (aHR), 1.83; 95% CI, 1.16 to 2.89; P=0.009) but not in the HC+AZ group (aHR, 1.31; 95% CI, 0.80 to 2.15; P=0.28). Both the propensity score-adjusted risks of mechanical ventilation and death after mechanical ventilation were not significantly different in the HC group (aHR, 1.19; 95% CI, 0.78 to 1.82; P=0.42 and aHR, 2.11; 95% CI, 0.96 to 4.62; P=0.06, respectively) or in the HC+AZ group (aHR, 1.09; 95% CI, 0.72 to 1.66; P=0.69 and aHR, 1.25; 95% CI, 0.59 to 2.68; P=0.56, respectively), compared to the no HC group. Conclusions Among patients hospitalized with COVID-19, this retrospective study did not identify any significant reduction in mortality or in the need for mechanical ventilation with hydroxychloroquine treatment with or without azithromycin. Funding University of Virginia Strategic Investment Fund.

negative: Human Coronavirus NL63 Molecular Epidemiology and Evolutionary Patterns in Rural Coastal Kenya BACKGROUND: Human coronavirus NL63 (HCoV-NL63) is a globally endemic pathogen causing mild and severe respiratory tract infections with reinfections occurring repeatedly throughout a lifetime. METHODS: Nasal samples were collected in coastal Kenya through community-based and hospital-based surveillance. HCoV-NL63 was detected with multiplex real-time reverse transcription PCR, and positive samples were targeted for nucleotide sequencing of the spike (S) protein. Additionally, paired samples from 25 individuals with evidence of repeat HCoV-NL63 infection were selected for whole-genome virus sequencing. RESULTS: HCoV-NL63 was detected in 1.3% (75/5573) of child pneumonia admissions. Two HCoV-NL63 genotypes circulated in Kilifi between 2008 and 2014. Full genome sequences formed a monophyletic clade closely related to contemporary HCoV-NL63 from other global locations. An unexpected pattern of repeat infections was observed with some individuals showing higher viral titers during their second infection. Similar patterns for 2 other endemic coronaviruses, HCoV-229E and HCoV-OC43, were observed. Repeat infections by HCoV-NL63 were not accompanied by detectable genotype switching. CONCLUSIONS: In this coastal Kenya setting, HCoV-NL63 exhibited low prevalence in hospital pediatric pneumonia admissions. Clade persistence with low genetic diversity suggest limited immune selection, and absence of detectable clade switching in reinfections indicates initial exposure was insufficient to elicit a protective immune response.

negative: Emerging Influenza and Psychosis: An Important Story in Psychological Medicine

negative: Viral Pneumonias Other Than Cytomegalovirus in Transplant Recipients Community-acquired respiratory viruses (CARVs) are frequent causes of upper and lower respiratory tract infections in tranplant recipients. In most series, respiratory syncytial virus and parainfluenza are the most common CARVs, followed by influenza and adenovirus. Significant morbidity and mortality are associated with these infections, particularly when they progress to pneumonia or when they are associated with bacterial or fungal coinfections. Outcomes are also poor with adenovirus, frequently reflecting disseminated infection. Efforts to prevent morbidity and mortality from CARV infection should focus on prevention, because treatment options are limited with inconclusive data to support their efficacy.

negative: Clinical Significance of Human Coronavirus in Bronchoalveolar Lavage Samples From Hematopoietic Cell Transplant Recipients and Patients With Hematologic Malignancies BACKGROUND. The possible role of human coronavirus (HCoV) in lower respiratory tract disease (LRTD) in hematopoietic cell transplant (HCT) recipients and patients with hematologic malignancies (HM) has not been well studied. METHODS. We conducted a retrospective review of HCT/HM patients with HCoV detected in bronchoalveolar lavage (BAL). HCoV strains were identified in BAL samples using strain-specific polymerase chain reaction. Mortality rates were compared among HCT recipients with LRTD caused by HCoV, respiratory syncytial virus (RSV), influenza virus, or parainfluenza virus (PIV) by multivariable Cox regression analysis. RESULTS. We identified 35 patients (37 episodes) with HCoV LRTD. Among 23 available BAL samples, 48% were strain OC43, 22% were NL63, 17% were 229E, and 13% were HKU1. Overall, 21 patients (60%) required oxygen therapy at diagnosis and 19 (54%) died within 90 days of diagnosis. Respiratory copathogens were detected in 21 episodes (57%), including viruses (n = 12), fungi (n = 10), and bacteria (n = 8). Mortality rates were not different between patients with and without copathogens (P = .65). In multivariable models, mortality associated with HCoV LRTD was similar to that seen with RSV, influenza, and PIV LRTD in HCT recipients (adjusted hazard ratio, 1.34 [95% confidence interval, .66–2.71], P = .41 vs RSV, adjusted for cell source, cytopenia, copathogens, oxygen use, and steroid use). CONCLUSIONS. HCoV LRTD in patients with HCT or HM is associated with high rates of oxygen use and mortality. Mortality associated with HCoV LRTD in HCT recipients appears to be similar to that seen with RSV, influenza virus, and PIV.

negative: Environments, Behaviors, and Inequalities: Reflecting on the Impacts of the Influenza and Coronavirus Pandemics in the United States In the past century, dramatic shifts in demographics, globalization and urbanization have facilitated the rapid spread and transmission of infectious diseases across continents and countries. In a matter of weeks, the 2019 coronavirus pandemic devastated communities worldwide and reinforced the human perception of frailty and mortality. Even though the end of this pandemic story has yet to unfold, there is one parallel that is undeniable when a comparison is drawn between the 2019 coronavirus and the 1918 influenza pandemics. The public health response to disease outbreaks has remained nearly unchanged in the last 101 years. Furthermore, the role of environments and human behaviors on the effect and response to the coronavirus pandemic has brought to light many of the historic and contemporaneous inequalities and injustices that plague the United States. Through a reflection of these pandemic experiences, the American burden of disparity and disproportionality on morbidity, mortality and overall social determinants of health has been examined. Finally, a reimagination of a post-coronavirus existence has also been presented along with a discussion of possible solutions and considerations for moving forward to a new and better normal.

negative: Early and massive testing saves lives: COVID-19 related infections and deaths in the United States during March of 2020 To optimize epidemiologic interventions, predictors of mortality should be identified. The US COVID-19 epidemic data, reported up to 31 March 2020, were analyzed using kernel regularized least squares regression. Six potential predictors of mortality were investigated: (i) the number of diagnostic tests performed in testing week I; (ii) the proportion of all tests conducted during week I of testing; (iii) the cumulative number of (test-positive) cases through 3-31-2020, (iv) the number of tests performed/million citizens; (v) the cumulative number of citizens tested; and (vi) the apparent prevalence rate, defined as the number of cases/million citizens. Two metrics estimated mortality: the number of deaths and the number of deaths/million citizens. While both expressions of mortality were predicted by the case count and the apparent prevalence rate, the number of deaths/million citizens was {approx}3.5 times better predicted by the apparent prevalence rate than the number of cases. In eighteen states, early testing/million citizens/population density was inversely associated with the cumulative mortality reported by 31 March, 2020. Findings support the hypothesis that early and massive testing saves lives. Other factors --e.g., population density-- may also influence outcomes. To optimize national and local policies, the creation and dissemination of high resolution geo-referenced, epidemic data is recommended.

negative: Positive rate of RT-PCR detection of SARS-CoV-2 infection in 4880 cases from one hospital in Wuhan, China, from Jan to Feb 2020 Abstract Background There’s an outbreak of a novel coronavirus (SARS-CoV-2) infection since December 2019, first in China, and currently with more than 80 thousand confirmed infection globally in 29 countries till March 2, 2020. Identification, isolation and caring for patients early are essential to limit human-to-human transmission including reducing secondary infections among close contacts and health care workers, preventing transmission amplification events. The RT-PCR detection of viral nucleic acid test (NAT) was one of the most quickly established laboratory diagnosis method in a novel viral pandemic, just as in this COVID-19 outbreak. Methods 4880 cases that had respiratory infection symptoms or close contact with COVID-19 patients in hospital in Wuhan, China, were tested for SARS-CoV-2 infection by use of quantitative RT-PCR (qRT-PCR) on samples from the respiratory tract. Positive rates were calculated in groups divided by genders or ages. Results The positive rate was about 38% for the total 4880 specimens. Male and older population had a significant higher positive rates. However, 57% was positive among the specimens from the Fever Clinics. Binary logistic regression analysis showed that age, not gender, was the risk factor for SARS-CoV-2 infection in fever clinics. Conclusions Therefore, we concluded that viral NAT played an important role in identifying SARS-CoV-2 infection.

negative: Global COVID-19: Warnings and suggestions based on experience of China Background: Corona Virus Disease 2019 (COVID-19) is spreading around the world currently, seriously threatening people's health and global security as an international public health emergency. The objective of this study is to summarize China's countermeasures and experience in response to the COVID-19 emergence in order to serve as a warning for the global COVID-19 prevention and control, and further provide some suggestions for global fighting to COVID-19. Methods: Content analysis, expert consultation, and high frequency word analysis were applied in this study. Relevant data and information were collected from official websites, the experience accumulated in China during the fighting to the novel coronavirus, and suggestions from some experts. Results: As of March 29, 2020, China had accumulated 82 419 confirmed diagnoses, and the mortality rate was 4.01%; in the mean time, the global had accumulated 596 042 confirmed diagnoses, and the mortality rate was 4.76%. Although the mortality of COVID-19 was not so high, its harmfulness couldn't be ignored. Ten facts during COVID-19 epidemic in China were summarized in the study, including: the COVID-19 is highly contagious and can be spread through many channels; although elderly people and people with underlying diseases are susceptible, young people can also be victims; isolation is the most effective way to reduce the risk of COVID-19, and secondary disasters induced by COVID-19 should be emphasized in advance. High frequent words of experts' suggestions mainly includes: material, prevention and control, pathogeny, propaganda, education, hygiene, technology, medical care, overall planning, policy, panic, etc. The main concerns of experts are from four aspects: publicity and education, various subjects, medical materials and law construction. Conclusions: COVID-19 is a new infectious disease worldwide, and its infectious source, transmission route, susceptible population, and therapy are not clear. In the face of the COVID-19 epidemic, no country can stand alone to maintain its own safety. People from all over the world should put aside their difference in ideology, religious belief, politics, economy, and culture, and only by global cooperation and globally unified actions, can we successfully overcome COVID-19 in the end.

negative: Long-term trends in seasonality of mortality in urban Madagascar: the role of the epidemiological transition Background: Seasonal patterns of mortality have been identified in Sub-Saharan Africa but their changes over time are not well documented. Objective: Based on death notification data from Antananarivo, the capital city of Madagascar, this study assesses seasonal patterns of all-cause and cause-specific mortality by age groups and evaluates how these patterns changed over the period 1976–2015. Methods: Monthly numbers of deaths by cause were obtained from death registers maintained by the Municipal Hygiene Office in charge of verifying deaths before the issuance of burial permits. Generalized Additive Mixed regression models (GAMM) were used to test for seasonality in mortality and its changes over the last four decades, controlling for long-term trends in mortality. Results: Among children, risks of dying were the highest during the hot and rainy season, but seasonality in child mortality has significantly declined since the mid-1970s, as a result of declines in the burden of infectious diseases and nutritional deficiencies. In adults aged 60 and above, all-cause mortality rates are the highest in the dry and cold season, due to peaks in cardiovascular diseases, with little change over time. Overall, changes in the seasonality of all-cause mortality have been driven by shifts in the hierarchy of causes of death, while changes in the seasonality within broad categories of causes of death have been modest. Conclusion: Shifts in disease patterns brought about by the epidemiological transition, rather than changes in seasonal variation in cause-specific mortality, are the main drivers of trends in the seasonality of all-cause mortality.

negative: The Role of the Global Health Development/Eastern Mediterranean Public Health Network and the Eastern Mediterranean Field Epidemiology Training Programs in Preparedness for COVID-19 The World Health Organization (WHO) declared the current COVID-19 a public health emergency of international concern on January 30, 2020. Countries in the Eastern Mediterranean Region (EMR) have a high vulnerability and variable capacity to respond to outbreaks. Many of these countries addressed the need for increasing capacity in the areas of surveillance and rapid response to public health threats. Moreover, countries addressed the need for communication strategies that direct the public to actions for self- and community protection. This viewpoint article aims to highlight the contribution of the Global Health Development (GHD)/Eastern Mediterranean Public Health Network (EMPHNET) and the EMR’s Field Epidemiology Training Program (FETPs) to prepare for and respond to the current COVID-19 threat. GHD/EMPHNET has the scientific expertise to contribute to elevating the level of country alert and preparedness in the EMR and to provide technical support through health promotion, training and training materials, guidelines, coordination, and communication. The FETPs are currently actively participating in surveillance and screening at the ports of entry, development of communication materials and guidelines, and sharing information to health professionals and the public. However, some countries remain ill-equipped, have poor diagnostic capacity, and are in need of further capacity development in response to public health threats. It is essential that GHD/EMPHNET and FETPs continue building the capacity to respond to COVID-19 and intensify support for preparedness and response to public health emergencies.

negative: Comparing the impact of various interventions to control the spread of COVID-19 in 12 countries

negative: Centring sexual and reproductive health and justice in the global COVID-19 response

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

negative: Common Pitfalls in the Interpretation of COVID-19 Data and Statistics Policymakers, experts and the general public heavily rely on the data that are being reported in the context of the coronavirus pandemic. Daily data releases on confirmed COVID-19 cases and deaths provide information on the course of the pandemic.

negative: Flattening the curves: on-off lock-down strategies for COVID-19 with an application to Brazi The current COVID-19 pandemic is affecting different countries in different ways. The assortment of reporting techniques alongside other issues, such as underreporting and budgetary constraints, makes predicting the spread and lethality of the virus a challenging task. This work attempts to gain a better understanding of how COVID-19 will affect one of the least studied countries, namely Brazil. Currently, several Brazilian states are in a state of lock-down. However, there is political pressure for this type of measures to be lifted. This work considers the impact that such a termination would have on how the virus evolves locally. This was done by extending the SEIR model with an on / off strategy. Given the simplicity of SEIR we also attempted to gain more insight by developing a neural regressor. We chose to employ features that current clinical studies have pinpointed has having a connection to the lethality of COVID-19. We discuss how this data can be processed in order to obtain a robust assessment.

negative: Does susceptibility to novel coronavirus (COVID-19) infection differ by age?: Insights from mathematical modelling Among Italy, Spain, and Japan, the age distributions of novel coronavirus (COVID-19) mortality show only small variation even though the number of deaths per country shows large variation. To understand the determinant for this situation, we constructed a mathematical model describing the transmission dynamics and natural history of COVID-19 and analyzed the dataset of fatal cases of COVID-19 in Italy, Spain, and Japan. We estimated the parameter which describes the age-dependency of susceptibility by fitting the model to reported data, taking into account the effect of change in contact patterns during the outbreak of COVID-19, and the fraction of symptomatic COVID-19 infections. Our modelling study revealed that if the mortality rate or the fraction of symptomatic infections among all COVID-19 cases does not depend on age, then unrealistically different age-dependencies of susceptibilities against COVID-19 infections between Italy, Japan, and Spain are required to explain the similar age distribution of mortality but different basic reproduction numbers (R0). Variation of susceptibility by age itself cannot explain the robust age distribution in mortality by COVID-19 in those three countries, however it does suggest that the age-dependencies of i) the mortality rate and ii) the fraction of symptomatic infections among all COVID-19 cases determine the age distribution of mortality by COVID-19.

negative: Pandemic Risk Modelling This chapter will explore the nature of communicable diseases, a brief history of pandemics, and will introduce the mathematical models used to evaluate the risk pandemics pose to human populations. Such modelling is used in a public health context, where modelling past and current events provides insight in how to respond most effectively to a new outbreak. It is also used in the context of risk mutualisation and transfer. As recently as 2013, a survey of 30,000 insurance executives placed global pandemic as the biggest extreme risk facing insurers (Towers Watson. 2013. Insurers Rate Global Pandemic as the Major Extreme Risk. 3 December). The chapter will introduce the principles used to model these events in the insurance industry and will conclude with a review of the way these models are applied in an unconventional risk transfer context.

negative: Optimization of Microbiological Laboratory Detection Strategy for Patients in A Designated Hospital Treating Novel Coronavirus Pneumonia in Anhui Province Novel coronavirus pneumonia (NCP) is an emerging, highly contagious community acquired pneumonia (CAP) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Highly efficient and accurate microbiological laboratory assay is essential to confirm the SARS-CoV-2 infection, rule out other pathogens that can cause CAP, and monitor secondary infections. Here, we enrolled and provide microbiological analysis for 129 suspected and 52 transferred confirmed NCP patients hospitalized in the First Affiliated Hospital of University of Science and Technology of China (USTC) from Jan 21 to Feb 29, 2020. By analyzing the dual swab samples (sputum and pharyngeal) from 129 suspected patients with realtime RT-PCR, we confirmed 33 SARS-CoV-2 infections, with two co-infection cases with adenovirus or rhinovirus. We also used multiplex PCR to detect 13 common respiratory tract pathogens in 96 non-NCP patients, and found that 30 patients (31.25%) were infected with at least one respiratory tract pathogen that may cause CAP. Further, we performed bacterial and fungal cultures as well as fungal serologic tests and found that there is no secondary bacterial/fungal infections in confirmed NCP patients. Our studies suggest that, during the epidemic of NCP in Anhui province, there was a certain proportion of infection and co-infection of other common pathogens of CAP, and the secondary bacterial and fungal infection is not detectable in NCP patients. In comparison with SARS-CoV-2 detection alone, this optimized strategy combining multiple pathogen detection for identification of NCP and other CAP patients as well as cultures and serologic tests for confirmed patients increases the diagnosis efficiency and facilitates the personalized medication.

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

negative: Risk factors associated with mortality after Roux-en-Y gastric bypass surgery. OBJECTIVE We sought to identify the major risk factors associated with mortality in Roux-en-Y gastric bypass (RYGB) surgery. BACKGROUND Bariatric surgery has become an established treatment for extreme obesity. Bariatric surgery mortality has steadily declined with current rates of less than 0.5%. However, significant variation in the mortality rates has been reported for specific patient cohorts and among bariatric centers. METHODS Clinical outcome data from 185,315 bariatric surgery patients from the Bariatric Outcome Longitudinal Database were reviewed. Of these, 157,559 patients had either documented 30 or more day follow-up data, including mortality. Multiple demographic, socioeconomic, and clinical factors were analyzed by univariate analysis for their association with 30-day mortality after gastric bypass. Variables found to be significant were entered into a multiple logistic regression model to identify factors independently associated with 30-day mortality. On the basis of these results, a RYGB mortality risk score was developed. RESULTS The overall 30-day mortality rate for the entire bariatric surgery cohort was 0.1%. Of the 81,751 RYGB patients, the mortality rate was 0.15%. Factors significantly associated with 30-day gastric bypass mortality included increasing body mass index (BMI) (P<0.0001), increasing age (P<0.005), male gender (P<0.001), pulmonary hypertension (P<0.0001), congestive heart failure (P=0.0008), and liver disease (P=0.038). When the RYGB risk score was applied, a significant trend (P<0.0001) between increasing risk score and mortality rate is found. CONCLUSIONS Increasing BMI, increasing age, male gender, pulmonary hypertension, congestive heart failure, and liver disease are risk factors for 30-day mortality after RYGB. The RYGB risk score can be used to determine patients at greater risk for mortality after RYGB surgery.

negative: Prediction of High Incidence of Dengue in the Philippines BACKGROUND: Accurate prediction of dengue incidence levels weeks in advance of an outbreak may reduce the morbidity and mortality associated with this neglected disease. Therefore, models were developed to predict high and low dengue incidence in order to provide timely forewarnings in the Philippines. METHODS: Model inputs were chosen based on studies indicating variables that may impact dengue incidence. The method first uses Fuzzy Association Rule Mining techniques to extract association rules from these historical epidemiological, environmental, and socio-economic data, as well as climate data indicating future weather patterns. Selection criteria were used to choose a subset of these rules for a classifier, thereby generating a Prediction Model. The models predicted high or low incidence of dengue in a Philippines province four weeks in advance. The threshold between high and low was determined relative to historical incidence data. PRINCIPAL FINDINGS: Model accuracy is described by Positive Predictive Value (PPV), Negative Predictive Value (NPV), Sensitivity, and Specificity computed on test data not previously used to develop the model. Selecting a model using the F(0.5) measure, which gives PPV more importance than Sensitivity, gave these results: PPV = 0.780, NPV = 0.938, Sensitivity = 0.547, Specificity = 0.978. Using the F(3) measure, which gives Sensitivity more importance than PPV, the selected model had PPV = 0.778, NPV = 0.948, Sensitivity = 0.627, Specificity = 0.974. The decision as to which model has greater utility depends on how the predictions will be used in a particular situation. CONCLUSIONS: This method builds prediction models for future dengue incidence in the Philippines and is capable of being modified for use in different situations; for diseases other than dengue; and for regions beyond the Philippines. The Philippines dengue prediction models predicted high or low incidence of dengue four weeks in advance of an outbreak with high accuracy, as measured by PPV, NPV, Sensitivity, and Specificity.

negative: Geriatric infections: Decreased immunity or evolved opportunists? In host–parasite co-evolution, parasites are assumed to have an advantage owing to their shorter generation time. Evolution of pathogens within the lifetime of a host individual is implicated as a strong selective force in the evolution of sex and aging in the host. However, this assumption or its testable predictions have not been examined empirically. We classified infectious bacteria and viruses into those that can have continued long-term existence on the host body (group 1) versus those that have only a short-term interaction during an active infection (group 2). We surveyed the literature for age-specific incidence data about infections from both the groups. The age trends of the two groups show contrasting patterns. The incidence of infections by all group 1 pathogens showed a 2.28- to 28-fold increase in older ages. In group 2, 6 out of the 9 pathogens showed a significant declining trend in incidence with age. In both groups, there was greater mortality or morbidity among the infected in the old-age classes. These patterns are better explained by pathogen evolution than by age-related decline in immunity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12038-020-0025-x) contains supplementary material, which is available to authorized users.

negative: COVID-19: Knowns, Unknowns, and Questions The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the Hubei province in China in late 2019 demonstrates the epidemic potential of coronaviruses. The rapid spread of this virus across the world in only 2 months highlights the transmissibility of this family of viruses and the significant morbidity and mortality that they can cause. We highlight the current state of knowledge of coronavirus biology while answering questions concerning the current outbreak of SARS-CoV-2.

negative: Basic reproduction number of 2019 Novel Coronavirus Disease in Major Endemic Areas of China: A latent profile analysis Objective: The aim of the study is to analyze the latent class of basic reproduction number (R0) trend of 2019 novel coronavirus disease (COVID−19) in major endemic areas of China. Methods The provinces that reported more than 500 cases of COVID−19 till February 18, 2020 were selected as the major endemic area. The Verhulst model was used to fit the growth rate of cumulative confirmed cases. The R0 of COVID−19 was calculated using the parameters of severe acute respiratory syndrome (SARS) and COVID−19, respectively. The latent class of R0 was analyzed using a latent profile analysis model. Results The median R0 calculated from SARS and COVID−19 parameters were 1.84 − 3.18 and 1.74 − 2.91, respectively. The R0 calculated from the SARS parameters was greater than that of calculated from the COVID−19 parameters (Z = −4.782 − −4.623, P < 0.01). Both R0 can be divided into three latent classes. The initial value of R0 in class 1 (Shandong Province, Sichuan Province and Chongqing Municipality) was relatively low and decreases slowly. The initial value of R0 in class 2 (Anhui Province, Hunan Province, Jiangxi Province, Henan Province, Zhejiang Province, Guangdong Province and Jiangsu Province) was relatively high and decreases rapidly. Moreover, the initial value of R0 of class 3 (Hubei Province) was between that of class 1 and class 2, but the higher level of R0 lasts longer and decreases slowly. Conclusion The results indicated that overall trend of R0 has been falling with the strengthening of China's comprehensive prevention and control measures for COVID−19, however, presents regional differences.

negative: Longitudinal study on morbidity and mortality in white veal calves in Belgium BACKGROUND: Mortality and morbidity are hardly documented in the white veal industry, despite high levels of antimicrobial drug use and resistance. The objective of the present study was to determine the causes and epidemiology of morbidity and mortality in dairy, beef and crossbred white veal production. A total of 5853 calves, housed in 15 production cohorts, were followed during one production cycle. Causes of mortality were determined by necropsy. Morbidity was daily recorded by the producers. RESULTS: The total mortality risk was 5,3% and was significantly higher in beef veal production compared to dairy or crossbreds. The main causes of mortality were pneumonia (1.3% of the calves at risk), ruminal disorders (0.7%), idiopathic peritonitis (0.5%), enterotoxaemia (0.5%) and enteritis (0.4%). Belgian Blue beef calves were more likely to die from pneumonia, enterotoxaemia and arthritis. Detection of bovine viral diarrhea virus at necropsy was associated with chronic pneumonia and pleuritis. Of the calves, 25.4% was treated individually and the morbidity rate was 1.66 cases per 1000 calf days at risk. The incidence rate of respiratory disease, diarrhea, arthritis and otitis was 0.95, 0.30, 0.11 and 0.07 cases per 1000 calf days at risk respectively. Morbidity peaked in the first three weeks after arrival and gradually declined towards the end of the production cycle. CONCLUSIONS: The present study provided insights into the causes and epidemiology of morbidity and mortality in white veal calves in Belgium, housed in the most frequent housing system in Europe. The necropsy findings, identified risk periods and differences between production systems can guide both veterinarians and producers towards the most profitable and ethical preventive and therapeutic protocols.

negative: Middle East respiratory syndrome (MERS): A new zoonotic viral pneumonia Coronaviruses have traditionally been associated with mild upper respiratory tract infections throughout the world. In the fall of 2002, a new coronavirus emerged in in Asia causing severe viral pneumonia, i.e., severe acute respiratory syndrome (SARS). Nearly a decade following the SARS epidemic, a new coronavirus causing severe viral pneumonia has emerged, i.e., middle east respiratory syndrome (MERS). Since the initial case of MERS-CoV occurred in June of 2012 in Saudi Arabia there have been 688 confirmed cases and 282 deaths in 20 countries. Although both SARS and MERS are caused by coronaviruses, SARS was characterized by efficient human transmission and relatively low mortality rate. In contrast, MERS is relatively inefficiently transmitted to humans but has a high mortality rate. Given the potential overlap in presentation and manifestation, it is important to understand the clinical and epidemiologic differences between MERS, SARS and influenza.

negative: The Impact of the COVID-19 Outbreak on the Medical Treatment of Chinese Children with Chronic Kidney Disease (CKD)：A Multicenter Cross-section Study in the Context of a Public Health Emergency of International Concern Objective: To investigate the impact of the COVID-19 outbreak on the medical advice seeking of Chinese children with chronic kidney disease (CKD). Materials and Methods: An anonymous online questionnaire survey was conducted in 17 pediatric nephropathy diagnosis and treatment centers in China. The questions collected basic information on the patients and their parents and data on changes in the approach to medical treatment and their needs in the context of the outbreak etc. This is a Multicenter Cross-section Study. Results: A total of 735 valid questionnaires were collected. 555 patients (75.5%) and their parents said that the outbreak had a significant influence on their medical treatment: 264 patients (47.6%) said that it would be delayed by 2 to 4 weeks and 199 patients (35.9%) by 4 to 8 weeks. 510 patients (84.16%) hoped to get in touch with specialists through online consultation, and 528 patients (84.5%) hoped that online consultation could be implemented and that medication could be delivered to them.. A total of 458 patients (62.3%) said that their greatest concern was that the CKD would be aggravated or that they would experience a relapse; only 203 patients were infected by 2019-nCoV. A total of 313 patients (42.5%) experienced anxiety and thus required the intervention of psychologists. Conclusion: The COVID-19 outbreak has affected the medical treatment of children with CKD. Online consultation, medication delivery and psychological counselling are the greatest needs reported by patients and their families and could especially provide solutions for the management of low income children with CKD in remote rural areas in the context of the COVID-19 epidemic.

negative: Serology-informed estimates of SARS-COV-2 infection fatality risk in Geneva, Switzerland The infection fatality risk (IFR) is the average number of deaths per infection by a pathogen and is key to characterizing the severity of infection across the population and for specific demographic groups. To date, there are few empirical estimates of IFR published due to challenges in measuring infection rates. Outside of closed, closely surveilled populations where infection rates can be monitored through viral surveillance, we must rely on indirect measures of infection, like specific antibodies. Representative seroprevalence studies provide an important avenue for estimating the number of infections in a community, and when combined with death counts can lead to robust estimates of the IFR. We estimated overall and age-specific IFR for the canton of Geneva, Switzerland using age-stratified daily case and death incidence reports combined with five weekly population-based seroprevalence estimates. From February 24th to June 2nd there were 5'039 confirmed cases and 286 reported deaths within Geneva (population of 506'765). We inferred age-stratified (5-9, 10-19, 20-49, 50-65 and 65+) IFRs by linking the observed number of deaths to the estimated number of infected individuals from each serosurvey. We account for the delays between infection and seroconversion as well as between infection and death. Inference is drawn in a Bayesian framework that incorporates uncertainty in seroprevalence estimates (supplement). Of the 286 reported deaths caused by SARS-CoV-2, the youngest person to die was 31 years old. Infected individuals younger than 50 years experienced statistically similar IFRs (range 0.00032-0.0016%), which increases to 0.14% (95% CrI 0.096-0.19) for those 50-64 years old to 5.6% (95% CrI 4.3-7.4) for those 65 years and older (supplement). After accounting for demography and age-specific seroprevalence, we estimate a population-wide IFR of 0.64% (95% CrI 0.38-0.98). Our results are subject to two notable limitations. Among the 65+ age group that died of COVID-19 within Geneva, 50% were reported among residents of assisted care facilities, where around 0.8% of the Geneva population resides. While the serosurvey protocol did not explicitly exclude these individuals, they are likely to have been under-represented. This would lead to an overestimation of the IFR in the 65+ age group if seroprevalence in this institutionalized population was higher than in the general population (supplement). Further, our IFR estimates are based on current evidence regarding post-infection antibody kinetics, which may differ between severe and mild infections. If mild infections have significantly lower and short-lived antibody responses, our estimates of IFR may be biased upwards. Estimates of IFR are key for understanding the true pandemic burden and for weighing different risk reduction strategies. The IFR is not solely determined by host and pathogen biology, but also by the capacity of health systems to treat severe cases. Despite having among the highest per capita incidence in Switzerland, Geneva's health system accommodated the influx of cases needing intensive care (peak of 80/110 ICU-beds including surge capacity) while maintaining care quality standards. As such, our IFR estimates can be seen as a best-case scenario with respect to health system capacity. Our results reveal that population-wide estimates of IFR mask great heterogeneity by age and point towards the importance of age-targeted interventions to reduce exposures among those at highest risk of death.

negative: Countrywide quarantine only mildly increased anxiety level during COVID-19 outbreak in China In the recent outbreak of COVID-19, many countries have taken various kinds of quarantine measures to slow down the explosive spreading of COVID-19. Although these measures were proven to be successful in stopping the outbreak in China, the potential adverse effects of countrywide quarantine have not been thoroughly investigated. In this study, we performed an online survey to evaluate the psychological effects of quarantine in China using Zung Self-rating Anxiety Scale in February 2020 when the outbreak was nearly peaked in China. Along with the anxiety scores, limited personal information such as age, gender, region, education, occupation and specifically, the type and duration of quarantine were collected for analysis. For a total number of 992 valid questionnaires, clinical significance of anxiety symptoms was observed in 9.58% respondents according to clinical diagnostic standards in China. Statistical results showed population with different age, education level, health status and personnel category responded differently. Other characteristics such as gender, marital status, region, and acquaintance with suspected or confirmed cases of COVID-19 did not affect anxiety levels significantly. Respondents experienced different forms of quarantine showed different anxiety levels. Unexpectedly, longer durations of quarantine did not lead to significant increase of anxiety level. Our results suggest a rather mild negative psychological influence caused by the countrywide quarantine during COVID-19 outbreak in China and provided reference for other countries and regions to battle COVID-19.

negative: A Review of Pediatric Critical Care in Resource-Limited Settings: A Look at Past, Present, and Future Directions Fifteen years ago, United Nations world leaders defined millenium development goal 4 (MDG 4): to reduce under-5-year mortality rates by two-thirds by the year 2015. Unfortunately, only 27 of 138 developing countries are expected to achieve MDG 4. The majority of childhood deaths in these settings result from reversible causes, and developing effective pediatric emergency and critical care services could substantially reduce this mortality. The Ebola outbreak highlighted the fragility of health care systems in resource-limited settings and emphasized the urgent need for a paradigm shift in the global approach to healthcare delivery related to critical illness. This review provides an overview of pediatric critical care in resource-limited settings and outlines strategies to address challenges specific to these areas. Implementation of these tools has the potential to move us toward delivery of an adequate standard of critical care for all children globally, and ultimately decrease global child mortality in resource-limited settings.

negative: Particularités épidémiologiques et prévention des infections nosocomiales virales Résumé Objectifs Décrire les caractéristiques épidémiologiques des infections nosocomiales virales (INV) et les principes de leur prévention. Épidémiologie De nombreux facteurs concourent à une sous-évaluation des INV : l’intrication des infections communautaires et nosocomiales pour les viroses saisonnières, la durée d’incubation entraînant une manifestation après la sortie du patient, les difficultés diagnostiques. Les populations les plus à risques d’INV sont les enfants, les personnes âgées et tous les immunodéprimés. Chez ces derniers, le risque de formes cliniques graves et/ou chroniques est important. Le réservoir principal des virus responsables d’INV est constitué des sujets infectés, symptomatiques ou non. Les porteurs asymptomatiques, notamment le personnel de soins, représentent un risque élevé de transmission. Les principales voies de transmission sont les voies digestive, respiratoire, cutanéomuqueuse et l’exposition au sang et produits biologiques. Une revue des principaux virus impliqués en fonction des modes de transmission est présentée. Prévention Les mesures préventives des INV sont capitales. Au premier plan, figure l’application rigoureuse des précautions standard d’hygiène et, dans certaines situations, des précautions d’isolement septique. En cas d’épidémie de grande ampleur, le regroupement des patients infectés pourra être instauré. La prévention spécifique repose principalement sur la vaccination, la chimioprophylaxie (varicelle-zona, herpès, grippe, accident d’exposition au sang) et la sélection clinique et biologique des donneurs de sang, d’organes, de tissus et de cellules. Summary Objectives To describe epidemiological features of viral nosocomial infections (VNI) and their prevention principles. Epidemiology Many factors lead to underestimate VNI: difficulty to distinguish between community-acquired and nosocomial infections for seasonal viral diseases, incubation time leading to symptoms after patient discharge, difficulty for diagnosis. Population at high risks of VNI are the children, the elderly and the immunocompromized patients. The risk of severe diseases is high in this last population. The main reservoir of virus is infected symptomatic or asymptomatic individuals. Asymptomatic carriers, especially health care workers, are a major source of transmission. Main routes of transmission are the fecal–oral route, the respiratory route, cutaneous or mucous contact and blood and body fluids exposure. A review of the main virus involved in VNI is presented. Prevention Preventive measures, such as strict adherence to standard precautions and, in some instances, to isolation procedures, are critical to control VNI. In a major outbreak situation, it may be necessary to consider cohort isolation. Specific control measures rely on immunization, antiviral drug prophylaxis (varicella–zooster, herpes, influenza, exposure to blood) and clinical and biological screening of organ, blood, tissue and cell donors.

negative: Assessing Ebola-related web search behaviour: insights and implications from an analytical study of Google Trends-based query volumes BACKGROUND: The 2014 Ebola epidemic in West Africa has attracted public interest worldwide, leading to millions of Ebola-related Internet searches being performed during the period of the epidemic. This study aimed to evaluate and interpret Google search queries for terms related to the Ebola outbreak both at the global level and in all countries where primary cases of Ebola occurred. The study also endeavoured to look at the correlation between the number of overall and weekly web searches and the number of overall and weekly new cases of Ebola. METHODS: Google Trends (GT) was used to explore Internet activity related to Ebola. The study period was from 29 December 2013 to 14 June 2015. Pearson’s correlation was performed to correlate Ebola-related relative search volumes (RSVs) with the number of weekly and overall Ebola cases. Multivariate regression was performed using Ebola-related RSV as a dependent variable, and the overall number of Ebola cases and the Human Development Index were used as predictor variables. RESULTS: The greatest RSV was registered in the three West African countries mainly affected by the Ebola epidemic. The queries varied in the different countries. Both quantitative and qualitative differences between the affected African countries and other Western countries with primary cases were noted, in relation to the different flux volumes and different time courses. In the affected African countries, web query search volumes were mostly concentrated in the capital areas. However, in Western countries, web queries were uniformly distributed over the national territory. In terms of the three countries mainly affected by the Ebola epidemic, the correlation between the number of new weekly cases of Ebola and the weekly GT index varied from weak to moderate. The correlation between the number of Ebola cases registered in all countries during the study period and the GT index was very high. CONCLUSION: Google Trends showed a coarse-grained nature, strongly correlating with global epidemiological data, but was weaker at country level, as it was prone to distortions induced by unbalanced media coverage and the digital divide. Global and local health agencies could usefully exploit GT data to identify disease-related information needs and plan proper communication strategies, particularly in the case of health-threatening events. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-015-0090-9) contains supplementary material, which is available to authorized users.

negative: The battle against SARS and MERS coronaviruses: Reservoirs and Animal Models In humans, infection with the coronavirus, especially the severe acute respiratory syndrome coronavirus (SARS‐CoV) and the emerging Middle East respiratory syndrome coronavirus (MERS‐CoV), induces acute respiratory failure, resulting in high mortality. Irregular coronavirus related epidemics indicate that the evolutionary origins of these two pathogens need to be identified urgently and there are still questions related to suitable laboratory animal models. Thus, in this review we aim to highlight key discoveries concerning the animal origin of the virus and summarize and compare current animal models.