title: Policy response, social media and science journalism for the sustainability of the public health system amid the COVID-19 outbreak: The vietnam lessons

text: Having geographical proximity and a high volume of trade with China, the first country to record an outbreak of the new Coronavirus disease (COVID-19), Vietnam was expected to have a high risk of transmission. However, as of 4 April 2020, in comparison to attempts to containing the disease around the world, responses from Vietnam are seen as prompt and effective in protecting the interests of its citizens, with 239 confirmed cases and no fatalities. This study analyzes the situation in terms of Vietnam's policy response, social media and science journalism. A self-made web crawl engine was used to scan and collect official media news related to COVID-19 between the beginning of January and April 4, yielding a comprehensive dataset of 14,952 news items. The findings shed light on how Vietnam-despite being under-resourced-has demonstrated political readiness to combat the emerging pandemic since the earliest days. Timely communication on any developments of the outbreak from the government and the media, combined with up-to-date research on the new virus by the Vietnamese science community, have altogether provided reliable sources of information. By emphasizing the need for immediate and genuine cooperation between government, civil society and private individuals, the case study offers valuable lessons for other nations concerning not only the concurrent fight against the COVID-19 pandemic but also the overall responses to a public health crisis.


Pandemic Communication: A New Challenge for Higher Education


Safety of an immunomodulator Mycobacterium w in COVID-19


title: How to quit confinement? French scenarios face to COVID-19

text: A mathematical model is developed to study the spread of the COVID-19 epidemics in France. Data from French Public Agency of Health are considered to calibrate the model. The spread of the epidemics strongly depends on confinement measures. The aim of the paper is to predict the evolution of the epidemics under various scenarios that could be taken to quit confinement. The spread of the disease and its re-emergence strongly depends on these scenarios.


title: Genetic diversity among SARS-CoV2 strains in South America may impact performance of Molecular detection

text: Since its emergence in Wuhan (China) on December 2019 the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide. After its arrival in South America in February 2020 the virus has expanded throughout the region infecting over 900,000 individuals with approximately 41,000 reported deaths to date. In response to the rapidly growing number of cases, a number of different primer-probe sets have been developed. However, despite being highly specific most of these primer-probe sets are known to exhibit variable sensitivity. Currently, there are more than 700 SARS-CoV2 whole genome sequences deposited in databases from Brazil, Chile, Ecuador, Colombia, Uruguay, Peru and Argentina. To test how regional viral diversity may impact oligo binding sites and affect test performance, we reviewed all available primer-probe sets targeting the E, N and RdRp genes against available South American SARS-CoV-2 genomes checking for nucleotide variations in annealing sites. Results from this in silico analysis showed no nucleotide variations on the E-gene target region, in contrast to the N and RdRp genes which showed massive nucleotide variations within oligo binding sites. In lines with previous data, our results suggest that E-gene stands as the most conserved and reliable target when considering single-gene target testing for molecular diagnosis of SARS-CoV-2 in South America.


title: Social-distancing effectiveness tracking of the COVID-19 hotspot Stockholm

text: Background: The COVID-19 outbreak in Stockholm, Sweden, is characterized by a near-absence of governmental interventions and high fatalities in the care home population. This study analyses the outbreak and the social-distancing effectiveness timeline in the general population and the care homes. Methods: A novel distributed-compartmental, time-variant epidemiological model was designed specifically for COVID-19 transmission characteristics, featuring a/pre/symptomatic transmission, a non-linear hospital model, a weakly-coupled sub-model for the care-home population, and parametrized continuous social-distancing functions. The model parameters and the social-distancing timelines are determined by randomization and Monte-Carlo simulations analysing real-world data. Findings: Despite a high initial reproduction number (3.29) and the near-absence of governmental interventions, the model quantitated that the transmission rate in the general population was suppressed by 73%, and in the care homes by 79%. The measures in the care homes took effect 4.8 days delayed; and if applied 4 or 8 days earlier, the fatalities could have been reduced by 63.2% or 89.9%. The infected population is estimated to 16.2% (June 10). An expected underestimation of population immunity by antibody studies is confirmed. The infection fatality ratio extrapolates to 0.61% (peak: 1.34%). The model indicates a seasonal effect which effectively suppressed a new rise. An analysed large-scale public event had no large influence. The asymptomatic ratio was determined to 35%. Interpretation: The proposed model and methods have proven to analyse a COVID-19 outbreak and to re-construct the social-distancing behaviour with unprecedented accuracy, confirming even minor details indicated by mobility-data analysis, and are applicable to other regions and other emerging infectious diseases of similar transmission characteristics. The self-regulation of the population in Stockholm, influenced by advices by the authorities, was able to suppress a COVID-19 outbreak to a level far beyond that the stringency index of governmental interventions suggests. Proper timing of effective measures in the care homes is important to reduce fatalities.


title: Severe acute respiratory syndrome Pieris MA, Anderson LJ, Osterhaus ADME, Stohr K, Yeun K-Y (Eds.), Blackwell, 2005, 263 pages, ISBN 1-4051-3031-8, £69.50

text: Unknown


title: Possibilities of exponential or Sigmoid growth of Covid19 data in different states of India

text: We have attempted to understand existing covid19 data of India, where growth of total and new cases with time in different states are kept as focal points. Identifying the last trend of exponential growth, mainly noticed in month of March, we have zoomed in its disaster possibilities by straight forward extrapolation of exponential growth. As a hopeful extrapolation, the existing data might be considered low time-axis values of Sigmoid-type function, whose growth might be saturated to values of 10^4 or 10^5. To fulfill this expectation, a turning from increasing to decreasing trend in new case data should be noticed around April-May, which definitely demand extension of present lock-down with additional interventions.


title: Predictors of adherence to public health instructions during the COVID-19 pandemic

text: Importance Identifying risk factors for adherence to public health instructions for the COVID-19 pandemic may be crucial for controlling the rate of transmission and the pandemicprime or minutes health and economic impacts. Objective To determine sociodemographic, health-related, risk-related, and instruction-related factors that predict non-adherence to instructions for the COVID-19 pandemic. Design Crossminussectional survey in Israel collected between March 28 and April 10, 2020. Setting Population-based study. Participants A convenience sample completed an online survey. Exposures Sociodemographic, health-related, risk-related, and instruction-related characteristics of the participants that have been linked to adherence to medical instructions. Main Outcome and Measure Non-adherence to instructions defined by a mean score of less than 4 on a 1 to 5 adherence scale consisting of 19 instruction items. Results Among 654 participants (413 [64.8%] female, age 40.14 [15.23] years), 28.7% were defined as non-adherents. Non-adherence was associated with male gender [adjusted odds ratio (aOR) = 1.54, CI 1.03-2.31], having children [aOR = 1.73, 1.13-2.65], smoking [aOR = 2.27, CI 1.42-3.62], high levels of ADHD symptoms [aOR = 1.55, CI 1.07-.25], high levels of past risk-taking behavior [aOR = 1.41, CI 1.10-1.81], as well as by current high psychological distress [aOR = 1.51, CI 1.14-2.01], low perceived risk of COVID-19 [aOR = 1.52, CI 1.22-1.89], low exposure to the instructions [aOR = 1.45, CI 1.14-1.82], and low perceived efficacy of the instructions [aOR = 1.47, CI 1.16-1.85]. Adjusted OR of age, economic status, physical health status, and exposure to media did not reach the significance level. Conclusions and Relevance People with the above characteristics may have increased risk for non-adherence to public health instructions. There appears to be a need for setting out and communicating instructions to specifically targeted at-risk populations.


title: Forecasting the Wuhan coronavirus (2019-nCoV) epidemics using a simple (simplistic) model - update (Feb. 8, 2020)

text: Confirmed infection cases in mainland China were analyzed using the data up to January 28, 2020 (first 13 days of reliable confirmed cases). For the first period the cumulative number of cases followed an exponential function. However, from January 28, we discerned a downward deviation from the exponential growth. This slower-than-exponential growth was also confirmed by a steady decline of the effective reproduction number. A backtrend analysis suggested the original basic reproduction number R0 to be about 2.4 to 2.5. As data become available, we subsequently analyzed them during three consecutive periods obtaining a sequence of model predictions. All available data up were processed the same way. We used a simple logistic growth model that fitted very well with all data. Using this model and the three sets of data, we estimated maximum cases as about 21,000, 28,000 and 35,000 cases refining these predictions in near-real time. With slightly different approach (linearization in time) the estimate of maximum cases was even higher (about 65,000). Although the estimates of maximum cases increase as more data were reported all models show reaching a peak in mid-February in contrast to the unconfined exponential growth. These predictions do not account for any possible other secondary sources of infection.


docid: lxzmiehr

title: Outbreak of Kawasaki disease in children during COVID-19 pandemic: a prospective observational study in Paris, France

text: Background: Acute clinical manifestations of SARS-CoV-2 infection are less frequent and less severe in children than in adults. However, recent observations raised concerns about potential post-viral severe inflammatory reactions in children infected with SARS-CoV-2. Methods: We describe an outbreak of cases of Kawasaki disease (KD) admitted between April 27 and May 7, 2020, in the general paediatrics department of a university hospital in Paris, France. All children prospectively underwent nasopharyngeal swabs for SARS-CoV-2 RT-PCR, SARS-CoV-2 IgG serology testing, and echocardiography. The number of admissions for KD during the study period was compared to that observed since January 1, 2018, based on discharge codes, using Poisson regression. Results: A total of 17 children were admitted for KD over an 11-day period, in contrast with a mean of 1.0 case per 2-week period over 2018-2019 (Poisson incidence rate ratio: 13.2 [95% confidence interval: 7.3-24.1], p <0.001). Their median age was 7.5 (range, 3.7-16.6) years, and 59% of patients originated from sub-Saharan Africa or Caribbean islands. Eleven patients presented with KD shock syndrome (KDSS) requiring intensive care support, and 12 had myocarditis. All children had marked gastrointestinal symptoms at the early stage of illness and high levels of inflammatory markers. Fourteen patients (82%) had evidence of recent SARS-CoV-2 infection (positive RT-PCR 7/17, positive IgG antibody detection 14/16). All patients received immunoglobulins and some received corticosteroids (5/17). The clinical outcome was favourable in all patients. Moderate coronary artery dilations were detected in 5 cases (29%) during hospitalisation. Conclusions: The ongoing outbreak of KD in the Paris might be related to SARS-CoV2, and shows an unusually high proportion of children with gastrointestinal involvement, KDSS and African ancestry.


title: Higher risk of COVID-19 hospitalization for unemployed: an analysis of 1,298,416 health insured individuals in Germany

text: Background: Previous research on infectious disease has revealed that infection risk as well as the severity of diseases is related to income and poverty. In this study we investigate if unemployed persons have a higher risk to become hospitalized with a COVID-19 diagnosis compared with employed persons. Methods: We used routine data on hospitalizations in a study population of 1,298,416persons between the ages 18 and 65 who were enrolled in a German health insurance and who were active on the labour market (either employed or unemployed). Hospital diagnosis of COVID-19 (ICD-10-GM U07.1 and U07.2) were reported on a daily basis from 01.01.2020 to 04.06.2020. We studied if the rate of persons hospitalized with a COVID-19 diagnoses differed by employment situation. Logistic regression models comparing employed with short- and long-term unemployed were calculated adjusting for age and sex. Results: In total, we observed 1,311 persons who were hospitalized, corresponding to a rate of 100.98 cases per 100.000 in our study population. Rates varied between the groups in different employment situations with lowest rates for employed and highest for long-term unemployed. Odds ratio for a hospitalization was 1.84 (1.64 - 2.07) for long-term and 1.18 (0.75 - 1.85) for short-term unemployed compared with employed persons. Conclusion: The results are in line with earlier (mainly ecological) studies from the USA and Great Britain which found social inequalities in hospitalization risk. The fact that differences exist in Germany, a country with a universal health care system, indicates socioeconomic differences in the COVID-19 pandemic exists across countries.


title: Computational Simulation to Assess Patient Safety of Uncompensated COVID-19 Two-patient Ventilator Sharing Using the Pulse Physiology Engine

text: Background: The COVID-19 pandemic is stretching medical resources internationally, including creating ventilator shortages that complicate clinical and ethical situations. The possibility of needing to ventilate multiple patients with a single ventilator raises patient health and safety concerns. This simulation study explores patient compatibility and ventilator settings during multi-patient ventilation without the use of flow compensating resistances. Methods: A whole-body computational physiology model was used to simulate each patient on a ventilator. The primary model of a single patient with a dedicated ventilator was augmented to model two patients sharing a single ventilator. A range of ventilator settings and patient characteristics were simulated for paired patients. In addition to mechanical ventilation parameters, the full physiological simulation provides estimates of additional values for oxyhemoglobin saturation, arterial oxygen tension, and other patient parameters. Findings: These simulations show patient outcome during multi-patient ventilation is most closely correlated to lung compliance, oxygenation index, oxygen saturation index, and endtidal carbon dioxide of individual patients. The simulated patient outcome metrics were satisfactory when the lung compliance difference between two patients was less than 12 cmH2O/mL, and the oxygen saturation index difference was less than 2 mmHg. Interpretation: In resource-limited regions of the world, the COVID-19 pandemic will result in equipment shortages. While single-patient ventilation is preferable, if unavailable, these simulations provide a conceptual framework for clinical patient selection guidelines if ventilator sharing is the only available alternative.


title: Remdesivir but not famotidine inhibits SARS-CoV-2 replication in human pluripotent stem cell-derived intestinal organoids

text: Gastrointestinal symptoms in COVID-19 are associated with prolonged symptoms and increased severity. We employed human intestinal organoids derived from pluripotent stem cells (PSC-HIOs) to analyze SARS-CoV-2 pathogenesis and to validate efficacy of specific drugs in the gut. Certain, but not all cell types in PSC-HIOs express SARS-CoV-2 entry factors ACE2 and TMPRSS2, rendering them susceptible to SARS-CoV-2 infection. Remdesivir, a promising drug to treat COVID-19, effectively suppressed SARS-CoV-2 infection of PSC-HIOs. In contrast, the histamine-2-blocker famotidine showed no effect. Thus, PSC-HIOs provide an interesting platform to study SARS-CoV-2 infection and to identify or validate drugs.


title: Influence of blood pressure on pneumonia risk: Epidemiological association and Mendelian randomisation in the UK Biobank

text: Objectives: To determine whether elevated blood pressure influences risk for respiratory infection. Design: Prospective, population-based epidemiological and Mendelian randomisation studies. Setting: UK Biobank. Participants: 377,143 self-identified British descent (54% women; median age 58 years) participants in the UK Biobank. Main outcome measures: First incident pneumonia over an average of 8 follow-up years. Results: 107,310 (30%) participants had hypertension at UK Biobank enrolment, and 9,969 (3%) developed a pneumonia during follow-up. Prevalent hypertension at baseline was significantly associated with increased risk for incident respiratory disease including pneumonia (hazard ratio 1.36 (95% confidence interval 1.29 to 1.43), P<0.001), acute respiratory distress syndrome or respiratory failure (1.43 (1.29 to 1.59), P<0.001), and chronic lower respiratory disease (1.30 (1.25 to 1.36), P<0.001), independent of age, age2, sex, smoking status, BMI, prevalent diabetes mellitus, prevalent coronary artery disease, and principal components of ancestry. Mendelian randomisation analyses indicated that genetic predisposition to a 5 mmHg increase in blood pressure was associated with increased risk of incident pneumonia for SBP (1.08, (1.04 to 1.13), P<0.001) and DBP (1.11 (1.03 to 1.20), P=0.005). Additionally, consistent with epidemiologic associations, increase in blood pressure genetic risk was significantly associated with reduced forced expiratory volume in the first second, forced vital capacity, and the ratio of the two (P<0.001 for all). Conclusions: These results strongly suggest that elevated blood pressure independently increases risk for pneumonia and reduces pulmonary function. Maintaining adequate blood pressure control, in addition to other measures, may reduce risk for pneumonia. Whether the present findings are generalizable to novel coronavirus disease 2019 (COVID-19) require further study.


docid: kqetjqys

title: Perspectives on the death investigation during the COVID-19 pandemic

text: Abstract The pandemic of COVID-19 caused by 2019-nCoV outbreaks in most of the countries, which has subsequently spread rapidly and become a pandemic worldwide. Due to the strong infectivity of COVID-19 and lack of experience of performing an autopsy to infectious disease-induced death, the pandemic created some challenges for forensic practitioners. In this article, we summarize the experience of how we handle the confirmed or suspected infectious cases, and give some perspectives for the future.


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


title: Modelling the Occurrence of the Novel Pandemic COVID-19 Outbreak; A Box and Jenkins Approach

text: The corona virus disease 2019 (COVID-19) is a novel pandemic disease that spreads very fast and causes severe respiratory problem to its carrier and thereby results to death in some cases. In this research, we studied the trend, model Nigeria daily COVID-19 cases and forecast for the future occurrences in the country at large. We adopt the Box and Jenkins approach. The time plot showed that the cases of COVID-19 rises rapidly in recent time. KPSS test confirms the non-stationarity of the process (p < 0.05) before differencing. The test also confirmed the stationarity of the process (p > 0.05) after differencing. Various ARIMA (p,d,q) were examined with their respective AICs and Log-likelihood. ARIMA (1, 2, 1) was selected as the best model due to its least AIC (559.74) and highest log likelihood (-276.87). Both Shapiro-Wilk test and Box test performed confirm the fitness of the model (p > 0.05) for the series. Forecast for 30 days was then made for COVID-19 cases in Nigeria. Conclusively, the model obtained in this research can be used to model, monitor and forecast the daily occurrence of COVID-19 cases in Nigeria.


title: Neurological features of COVID-19 and their treatment: a review

text: Severe acute respiratory syndrome–correlated new coronavirus (SARS-Cov-2) infection may result in neurological signs and symptoms through different mechanisms. Although direct infection of the central nervous system is uncertain or very rare and the para-infectious complications (e.g. inflammatory neuropathies) are rare, delirium and septic encephalopathy are common in severely ill patients. Smell dysfunction and headache are very common in mild cases, especially in younger people and females. Muscle pain is common in both mild and severe cases, and in the most compromised patients, it is accompanied by increased creatine kinase levels and by a likely true myopathic damage. Ischemic stroke has been reported as a possible complication of the hypercoagulability associated with severe SARS-Cov-2 infection, but further studies are needed. Most of the neurological manifestations may occur early in the illness. Therefore, during the pandemic period, neurologists need to be involved, alert, and prepared. Neurological practice will not be the same until a vaccine is available.


title: Epidemiological and clinical characteristics of COVID-19 in adolescents and young adults

text: Background: Adolescents and young adults might play a key role in the worldwide spread of Coronavirus Disease 2019 (COVID-19), because they are more involved in overseas studying, business, working, and travelling. However, the epidemiological and clinical characteristics of them are still unknown. Methods: We collected data of 46 confirmed COVID-19 patients aged 10 to 35 years from the study hospital. The demographics, epidemiological, and clinical data were collected. Several key epidemiological parameters, the asymptomatic cases and transmission to their family members and the clinical characteristics at admission, and during treatment were summarized. RESULTS: Of 46 confirmed patients, 14 patients (47.3%) were aged from 10 to 24 years, and 24 (52.7%) patients were male. The mean incubation period for symptomatic cases was 6.6 days (95% confidence interval (CI) 4.4 - 9.6). The median serial interval was 1.9 days (95% CI 0.4 - 6.2). Three of asymptomatic cases showed the transmission to their family members. Only 1 patient was identified as severe cases at admission. The common symptoms at admission were dry cough (34, 91.0%), and fever (29, 69.0%). Nearly 60% of the patients had showed ground-glass opacity by chest CT findings. Three patients developed acute kidney injury during treatment. Majority of patients (78.3%) were discharged by the end of the follow-up. Conclusions: The adolescent and young adult patients of COVID-19 had a long incubation period, and a short serial interval. The transmission to their family contactors occurred in asymptomatic cases. Few of the study patients have developed complications during treatment.


title: Utilize State Transition Matrix Model to Predict the Novel Corona Virus Infection Peak and Patient Distribution

text: Background: Since December 2019, a pneumonia caused by the 2019 novel coronavirus (2019-nCoV) has broken out in Wuhan, Hubei province, China. The continuous rising of infected cases has imposed overwhelming pressure on public health decision and medical resource allocation in China. We managed to forecast the infection peak time in Hubei province and the severe and critical case distribution. Methods: We used data resource according to cases reported by the National Health Commission of the People's Republic of China (Jan 25, 2019, to Feb 28, 2020) as the training set to deduce the arrival of the peak infection time and the number of severe and critical cases in Wuhan on subsequent days. Medical observation, discharge, infected, non-Severe, infected and severe, cure and death data were collected and analyzed. Using this state transition matrix model, we will be able predict when the inflection peak time (the maximum open infection cases) in Hubei Province will occur. Also, we can use this model to predict the patient distribution (severe, non-severe) to better allocate medical resource. Under relative pessimistic scenario, the inflection peak time is April 6-April 14. The numbers of critically ill and critically ill patients will lie between 8300-9800 and 2200-2700, respectively. Results: In very optimistic scenarios (daily NCC decay rate of -10%), the peak time of open inflection cases will arrive around February 23-February 26. At the same time, there will be a peak in the numbers of severely ill and critically ill patients, between 6800-7200 and 1800-2000, respectively. In a relative optimistic scenario (daily NCC decay rate of -5%), the inflection case peak time will arrive around February 28-March 2. The numbers of critically ill and critically ill patients will lie between 7100-7800 and 1900-2200, respectively. In a relatively pessimistic scenario (daily NCC decay rate of -1%), the inflection peak time does not arrive around the end of March. Estimated time is April 6-April 14. The numbers of critically ill and critically ill patients will lie between 8300-9800 and 2200-2700, respectively. We are using the diagnosis rate, mortality rate, cure rate as the 2/8 data. There should be room for improvement, if these metrics continue to improve. In that case, the peak time will arrive earlier than our estimation. Also, the severe and critical case ratios are likely to decline as the virus becomes less toxic and medical conditions improve. If that happens, the peak numbers will be lower than predicted above. Conclusion: We can infer that we are still not close to the end of this outbreak and the number of critically ill patients is still climbing. Assisting critical care resources in Hubei province requires the government to consider further tilt, and it is vital to make reasonable management of doctors and medical assistance systems to curb the transmission trend.


title: Population genomics insights into the recent evolution of SARS-CoV-2

text: The current coronavirus disease 2019 (COVID-19) pandemic is caused by the SARS-CoV-2 virus and is still spreading rapidly worldwide. Full-genome-sequence computational analysis of the SARS-CoV-2 genome will allow us to understand the recent evolutionary events and adaptability mechanisms more accurately, as there is still neither effective therapeutic nor prophylactic strategy. In this study, we used population genetics analysis to infer the mutation rate and plausible recombination events that may have contributed to the evolution of the SARS-CoV-2 virus. Furthermore, we localized targets of recent and strong positive selection. The genomic regions that appear to be under positive selection are largely co-localized with regions in which recombination from non-human hosts appeared to have taken place in the past. Our results suggest that the pangolin coronavirus genome may have contributed to the SARS-CoV-2 genome by recombination with the bat coronavirus genome. However, we find evidence for additional recombination events that involve coronavirus genomes from other hosts, i.e., Hedgehog and Sparrow. Even though recombination events within human hosts cannot be directly assessed, due to the high similarity of SARS-CoV-2 genomes, we infer that recombinations may have recently occurred within human hosts using a linkage disequilibrium analysis. In addition, we employed an Approximate Bayesian Computation approach to estimate the parameters of a demographic scenario involving an exponential growth of the size of the SARS-CoV-2 populations that have infected European, Asian and Northern American cohorts, and we demonstrated that a rapid exponential growth in population size can support the observed polymorphism patterns in SARS-CoV-2 genomes.


title: Coronavirus Disease: A Review of a New Threat to Public Health

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


title: COVID-19 severity is predicted by earlier evidence of accelerated aging

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


title: REMBRANDT: A high-throughput barcoded sequencing approach for COVID-19 screening

text: The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), also known as 2019 novel coronavirus (2019-nCoV), is a highly infectious RNA virus. A still-debated percentage of patients develop coronavirus disease 2019 (COVID-19) after infection, whose symptoms include fever, cough, shortness of breath and fatigue. Acute and life-threatening respiratory symptoms are experienced by 10-20% of symptomatic patients, particularly those with underlying medical conditions that includes diabetes, COPD and pregnancy. One of the main challenges in the containment of COVID-19 is the identification and isolation of asymptomatic/pre-symptomatic individuals. As communities re-open, large numbers of people will need to be tested and contact-tracing of positive patients will be required to prevent additional waves of infections and enable the continuous monitoring of the viral loads COVID-19 positive patients. A number of molecular assays are currently in clinical use to detect SARS-CoV-2. Many of them can accurately test hundreds or even thousands of patients every day. However, there are presently no testing platforms that enable more than 10,000 tests per day. Here, we describe the foundation for the REcombinase Mediated BaRcoding and AmplificatioN Diagnostic Tool (REMBRANDT), a high-throughput Next Generation Sequencing-based approach for the simultaneous screening of over 100,000 samples per day. The REMBRANDT protocol includes direct two-barcoded amplification of SARS-CoV-2 and control amplicons using an isothermal reaction, and the downstream library preparation for Illumina sequencing and bioinformatics analysis. This protocol represents a potentially powerful approach for community screening, a major bottleneck for testing samples from a large patient population for COVID-19.


title: Überlegungen zur Lockerung des Lockdowns

text: The fight against the coronavirus pandemic has led to an insulation of social and economic life and will have considerable economic consequences. Important areas of the industry and service sectors were partially or completely shutdown. A resumption of activity should happen as soon as possible, once the medical pre-conditions have been established and are met. This requires a clear exit strategy and following several steps to return to previous welfare and growth data levels. After securing survival during this crisis via various liquidity lines and bridging loans, the economy’s restart requires the relaunch of public infrastructure, especially of schools and kindergartens. To facilitate a coordinated and synchronised restart of complex industrial value chains, we need clear signals on a planned schedule. A tax policy driven departure signal and a demand side focused growth programme could make an important contribution to a new economic dynamic after the crisis.


title: Single-cell screening of SARS-CoV-2 target cells in pets, livestock, poultry and wildlife

text: A few animals have been suspected to be intermediate hosts of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, a large-scale single-cell screening of SARS-CoV-2 target cells on a wide variety of animals is missing. Here, we constructed the single-cell atlas for 11 representative species in pets, livestock, poultry, and wildlife. Notably, the proportion of SARS-CoV-2 target cells in cat was found considerably higher than other species we investigated and SARS-CoV-2 target cells were detected in multiple cell types of domestic pig, implying the necessity to carefully evaluate the risk of cats during the current COVID-19 pandemic and keep pigs under surveillance for the possibility of becoming intermediate hosts in future coronavirus outbreak. Furthermore, we screened the expression patterns of receptors for 144 viruses, resulting in a comprehensive atlas of virus target cells. Taken together, our work provides a novel and fundamental strategy to screen virus target cells and susceptible species, based on single-cell transcriptomes we generated for domesticated animals and wildlife, which could function as a valuable resource for controlling current pandemics and serve as an early warning system for coping with future infectious disease threats.


title: COVID-19 in Africa -- outbreak despite interventions?

text: In Africa, while most countries report some COVID-19 cases, the fraction of reported patients is low, with about 20,000 cases compared to the more than 2.3 million cases reported globally as of April 18, 2020. Few African countries have reported case numbers above one thousand, with South Africa reporting 3,034 cases being hit hardest in Sub-Saharan Africa. Several African countries, especially South Africa, have already taken strong non-pharmaceutical interventions that include physical distancing, restricted economic, educational and leisure activities and reduced human mobility options. The required strengths and overall effectiveness of such interventions, however, are debated because of simultaneous but opposing interests in most African countries: strongly limited health care capacities and testing capabilities largely conflict with pressured national economies and socio-economic hardships on the individual level, limiting compliance to intervention targets. Here we investigate implications of interventions on the COVID-19 outbreak dynamics, focusing on South Africa before and after the national lockdown enacted on March 27, 2020. Our analysis shows that initial exponential growth of existing case numbers is consistent with doubling times of about 2.5 days. After lockdown, the growth remains exponential, now with doubling times of 18 days, but still in contrast to subexponential growth reported for Hubei/China after lockdown. Moreover, a scenario analysis of a computational data-driven agent based mobility model for the Nelson Mandela Bay Municipality (with 1.14 million inhabitants) hints that keeping current levels of intervention measures and compliance until the end of April is of insufficient length and still too weak, too unspecific or too inconsistently complied with to not overload local intensive care capacity. Yet, enduring, slightly stronger, more specific interventions combined with sufficient compliance may constitute a viable option for interventions for regions in South Africa and potentially for large parts of the African continent and the Global South.


title: A phased lift of control: a practical strategy to achieve herd immunity against Covid-19 at the country level

text: Most countries are affected by the Covid-19 pandemic and experience rapidly increasing numbers of cases and deaths. Many have implemented nationwide stringent control to avoid overburdening the health care system. This paralyzes economic and social activities until the availability of a vaccine, which may take years. We propose an alternative exit strategy to develop herd immunity in a predictable and controllable way: a phased lift of control. This means that successive parts of the country (e.g. provinces) stop stringent control, and Covid-19-related IC admissions are distributed over the country as the whole. Importantly, vulnerable individuals need to be shielded until herd immunity has developed in their area. We explore the characteristics and duration of this strategy using a novel individual-based model for geographically stratified transmission of Covid-19 in a country. The model predicts that individuals will have to experience stringent control for about 14 months on average, but this duration may be significantly shortened by future developments (more IC beds, better drugs). Clearly, the strategy will have a profound impact on individuals and society, and should therefore be considered carefully by various other disciplines (e.g. health systems, ethics, economics) before actual implementation.


title: Characteristics of patients presenting, and not presenting, to the emergency department during the early days of COVID-19

text: Objective: Societal responses to the COVID-19 pandemic have had a substantial effect upon the number of patients seeking healthcare. An initial step in estimating the impact of these changes is characterizing the patients, visits, and diagnoses for whom care is being delayed or deferred. Methods: We conducted an observational study, examining demographics and diagnoses for all patient visits to the ED of an urban Level-1 trauma center before and after the state declaration and compared them to visits from a similar period in 2019. We estimated the ratios of the before and after periods using Poisson regression, calculated the percent change with respect to 2019 for total ED visits, patient characteristics, and diagnoses, and then evaluated the interactions between each factor and the overall change in ED visits. Results: There was a significant 35.2% drop in overall ED visits after the state declaration. Disproportionate declines were seen in visits by pediatric and older patients, women, and Medicare recipients as well as for presentations of syncope, cerebrovascular accidents, urolithiasis, abdominal and back pain. Significantly disproportionate increases were seen in ED visits for potential symptoms of COVID-19, including URIs, shortness of breath, and chest pain. Conclusions: Patient concerns about health care settings and public health have significantly altered care-seeking during the COVID-19 pandemic. Overall and differential declines in ED visits for certain demographic groups and disease processes should prompt efforts to encourage care-seeking and research to monitor for the morbidity and mortality that is likely to result from delayed or deferred care.


Neonatologists’ Challenges During COVID-19 Pandemic


title: Work with emotions in remote psychotherapy in the time of Covid-19: a clinical experience

text: Objective: Face-to-face experiential work with emotions is effective, but it remains unclear what the feasibility of teletherapeutic work with emotions is. The current Covid-19 worldwide situation represents an opportunity for psychotherapists to test new ways of working with clients, including from an emotion-focused and emotionally focused perspective. Methods: The present brief report describes a clinical experience based on 6 weeks, so far, of telepsychotherapeutic work focused on emotions via online tools, during the Covid-19 partial confinement in Switzerland. Results: We found a certain feasibility of remote work with emotions in psychotherapy, for individual clients, and for couples. Specific challenges represent relationship and contextual factors (clear communication, using tone of voice, regular check ins, setting up a clear frame, technical aspects of communication, the Self of the therapist), accessing and deepening emotions and managing dysregulated experience and interpersonal escalation. Discussion: Based on this initial clinical experience, we propose that integrative experiential practice partially delivered via a computer screen be studied in controlled settings by psychotherapy research in the future.


docid: znepggin

title: anti-IL-6 versus anti-IL-6R Blocking Antibodies to Treat Acute Ebola Infection in BALB/c Mice with Potential Implications for Treating Patients Presenting with COVID-19

text: Cytokine release syndrome (CRS) is known to be a factor in morbidity and mortality associated with acute viral infections including those caused by filoviruses and coronaviruses. IL-6 has been implicated as a cytokine negatively associated with survival after filovirus infection. However, IL-6 has also been shown to be an important mediator of innate immunity, important for the host response to an acute viral infection. Clinical studies are now being conducted by various researchers to evaluate the possible role of IL-6 blockers to improve outcomes in critically ill patients with SARS-CoV-2 infection. Most of these studies involve the use of anti-IL-6R monoclonal antibodies (mAbs). We present data showing that direct neutralization of IL-6 with an anti-IL-6 mAb in a BALB/c Ebolavirus (EBOV) challenge model produced a statistically significant improvement in outcome compared with controls when administered within the first 24 hours of challenge and repeated every 72 hours. A similar effect was seen in mice treated with the same dose of anti-IL-6R mAb when the treatment was delayed 48 hrs post-challenge. These data suggest that direct neutralization of IL-6, early during the course of infection, may provide additional clinical benefits to IL-6 receptor blockade alone during treatment of patients with virus-induced CRS. These results may have implications for selecting and managing IL-6 blockade therapy for patients with COVID-19.


title: Regression Analysis of COVID-19 Spread in India and its Different States

text: Linear and polynomial regression model has been used to investigate the COVID-19 outbreak in India and its different states using time series epidemiological data up to 26th May 2020. The data driven analysis shows that the case fatality rate (CFR) for India (3.14% with 95% confidence interval of 3.12% to 3.16%) is half of the global fatality rate, while higher than the CFR of the immediate neighbors i.e. Bangladesh, Pakistan and Sri Lanka. Among Indian states, CFR of West Bengal (8.70%, CI: 8.21-9.18%) and Gujrat (6.05%, CI: 4.90-7.19%) is estimated to be higher than national rate, whereas CFR of Bihar, Odisha and Tamil Nadu is less than 1%. The polynomial regression model for India and its different states is trained with data from 21st March 2020 to 19th May 2020 (60 days). The performance of the model is estimated using test data of 7 days from 20th May 2020 to 26th May 2020 by calculating RMSE and % error. The model is then used to predict number of patients in India and its different states up to 16th June 2020 (21 days). Based on the polynomial regression analysis, Maharashtra, Gujrat, Delhi and Tamil Nadu are continue to remain most affected states in India.


title: The dynamics and interactions of respiratory pathogen carriage among French pilgrims during the 2018 Hajj

text: Respiratory tract infections are frequent among Hajj pilgrims. We conducted this study to describe the dynamics of the acquisition of respiratory pathogens, their potential interactions and risk factors for possible lower respiratory tract infection symptoms (LRTI) among French pilgrims during the 2018 Hajj. Pilgrims from Marseille who were participating in the Hajj were recruited. Each participant underwent four successive systematic nasopharyngeal swabs before and during their stay in Saudi Arabia. Carriage of the main respiratory pathogens was assessed by PCR. 121 pilgrims were included and 93.4% reported respiratory symptoms during the study period. Polymicrobial carriage was observed in 73.8% samples. The acquisition of rhinovirus, coronaviruses and Staphylococcus aureus occurred soon after arrival in Saudi Arabia and rates decreased gradually after days 5 and 6. In contrast, Streptococcus pneumoniae and Klebsiella pneumoniae carriage increased progressively until the end of the stay in Saudi Arabia. Haemophilus influenzae and Moraxella catarrhalis carriage increased starting around days 12 and 13, following an initial clearance. Influenza viruses were rarely isolated. We observed an independent positive mutual association between S. aureus and rhinovirus carriage and between H. influenzae and M. catarrhalis carriage. Dual carriage of H. influenzae and M. catarrhalis was strongly associated with S. pneumoniae carriage (OR = 6.22, 95%CI [2.04-19.01]). Finally, our model showed that M. catarrhalis carriage was negatively associated with K. pneumoniae carriage. Chronic respiratory disease was associated with symptoms of LRTI. K. pneumoniae, M. catarrhalis-S. aureus and H. influenzae-rhinovirus dual carriage was associated with LRTI symptoms. Our data suggest that RTIs at the Hajj are a result of complex interactions between a number of respiratory viruses and bacteria. Author summary Despite the recommendation to take individual preventive measures to prevent respiratory tract infections, these infections remain common among Hajj pilgrims. Respiratory pathogens acquired during the Hajj are usually studied individually, although in their natural environment they often compete or coexist with multiple microbial species. A better understanding of polymicrobial interactions in the nasopharynx among Hajj pilgrims is important. Our study describes the dynamics of the acquisition of respiratory pathogens and their potential interactions among pilgrims during the Hajj. We found that polymicrobial carriage was observed in most individuals and that some pathogens associated positively while other did not. Some pathogen associations correlated with symptoms of lower respiratory tract infections.


Mendelian Inheritance in Man and Its Online Version, OMIM


Social Distancing—What Would It Mean for It to Work?


title: Rapid estimation of excess mortality in times of COVID-19 in Portugal - Beyond reported deaths

text: 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.


title: Inhibition of the replication of SARS-CoV-2 in human cells by the FDA-approved drug chlorpromazine

text: Urgent action is needed to fight the ongoing COVID-19 pandemic by reducing the number of infected people along with the infection contagiousness and severity. Chlorpromazine (CPZ), the prototype of typical antipsychotics from the phenothiazine group, is known to inhibit clathrin-mediated endocytosis and acts as an antiviral, in particular against SARS-CoV-1 and MERS-CoV. In this study, we describe the in vitro testing of CPZ against a SARS-CoV-2 isolate in monkey and human cells. We evidenced an antiviral activity against SARS-CoV-2 with an IC50 of ∼10μM. Because of its high biodistribution in lung, saliva and brain, such IC50 measured in vitro may translate to CPZ dosage used in clinical routine. This extrapolation is in line with our observations of a higher prevalence of symptomatic and severe forms of COVID-19 infections among health care professionals compared to patients in psychiatric wards. These preclinical findings support the repurposing of CPZ, a largely used drug with mild side effects, in COVID-19 treatment.


title: Wirtschaftliche Implikationen der Corona-Krise und wirtschaftspolitische Maßnahmen

text: The corona crisis started in China and had great consequences for public health and the economy. In the meantime, high and rapidly growing numbers of cases of infections with SARS-CoV-2 have also been recorded in Japan, Korea, Italy, Germany, Great Britain, France, Spain and above all in the USA. Forecasts of economic growth have been massively revised downwards and governments around the world are struggling to find the right economic policy response. This article describes basic short-term options for the German government to react to the corona shock and briefl y assesses the package of measures “Schutzschirm für Beschäftigte und Unternehmen” presented on 13 March 2020 by the German Finance Minister Olaf Scholz and the German Economics Minister Peter Altmaier.


title: A novel comprehensive metric to assess COVID-19 testing outcomes: Effects of geography, government, and policy response

text: Testing and case identification are key strategies in controlling the COVID-19 pandemic. Contact tracing and isolation are only possible if cases have been identified. The effectiveness of testing must be tracked, but a single comprehensive metric is not available to assess testing effectiveness, and no timely estimates of case detection rate are available globally, making inter-country comparisons difficult. The purpose of this paper was to propose a single, comprehensive metric, called the COVID-19 Testing Index (CovTI) scaled from 0 to 100, that incorporated several testing metrics. The index was based on case-fatality rate, test positivity rate, active cases, and an estimate of the detection rate. It used parsimonious modeling to estimate the true total number of COVID-19 cases based on deaths, testing, health system capacity, and government transparency. Publicly reported data from 188 countries and territories were included in the index. Estimates of detection rates aligned with previous estimates in literature (R2=0.97). As of June 3, 2020, the states with the highest CovTI included Iceland, Australia, New Zealand, Hong Kong, and Thailand, and some island nations. Globally, CovTI increased from April 20 ([x]=43.2) to June 3 ([x]=52.2) but declined in ca. 10% of countries. Bivariate analyses showed the average in countries with open public testing policies (59.7, 95% CI 55.6-63.8) were significantly higher than countries with no testing policy (30.2, 95% CI 18.1-42.3) (p<0.0001). A multiple linear regression model assessed the association of independent grouping variables with CovTI. Open public testing and extensive contact tracing were shown to significantly increase CovTI, after adjusting for extrinsic factors, including geographic isolation and centralized forms of government. This tool may be useful for policymakers to assess testing effectiveness, inform decisions, and identify model countries. It may also serve as a tool for researchers in analyses by combining it with other databases.


title: COVID-19 related concerns of people with long-term respiratory conditions: A qualitative study

text: BACKGROUND The COVID-19 pandemic is having profound psychological impacts on populations globally, with increasing levels of stress, anxiety, and depression being reported, especially in people with pre-existing medical conditions who appear to be particularly vulnerable. There are limited data on the specific concerns people have about COVID-19 and what these are based on. METHODS The aim of this study was to identify and explore the concerns of people with long-term respiratory conditions in the UK regarding the impact of the COVID-19 pandemic and how these concerns were affecting them. We conducted a thematic analysis of free text responses to the question 'What are your main concerns about getting coronavirus?', which was included in the British Lung Foundation/Asthma UK (BLF-AUK) partnership COVID-19 survey, conducted between the 1st and 8th of April. This was during the 3rd week of the UK's initial social distancing measures. RESULTS 7,039 responses were analysed, with respondents from a wide range of ages, gender, and all UK nations. Respondents reported having asthma (85%), COPD (9%), bronchiectasis (4%), interstitial lung disease (2%), or 'other' lung diseases (e.g. lung cancer) (1%). Four main themes were identified: 1) vulnerability to COVID-19; 2) anticipated experience of contracting COVID-19; 3) wide-reaching uncertainty; and 4) inadequate national response. CONCLUSIONS The COVID-19 pandemic is having profound psychological impacts. The concerns we identified largely reflect objective, as well as subjective, aspects of the current situation. Hence, key approaches to reducing these concerns require changes to the reality of their situation, and are likely to include i) helping people optimise their health, limit risk of infection, and access necessities; ii) minimising the negative experience of disease where possible, iii) providing up-to-date, accurate and consistent information, iv) improving the government and healthcare response.


title: Global Ranking of COVID-19-Related Mortality by Country using a Novel Pandemic Efficiency Index (PEI)

text: The world is currently witnessing a dramatic disruption of everyday life owing to the rapid progression of the coronavirus disease 2019 (COVID-19) pandemic. As the pandemic evolves, there is an urgent need to better understand its epidemiology, characterize its potential impact, and identify mitigatory strategies to avert pandemic-related mortality. There is a need for a tool or algorithm to evaluate the extent to which public health policy and/or economic preparedness measures are effectively averting COVID-19 related mortality. We present a simple and yet practical epidemiological tool, the Pandemic Efficiency Index (PEI), that can be utilized globally to test the relative efficiency of measures put in place to avert death resulting from COVID-19 infection. Using the PEI and current COVID-19-related mortality, we determined that so far Germany demonstrates the highest PEI (5.1) among countries with more than 5,000 recorded cases of the infection, indicating high quality measures instituted by the country to avert death during the pandemic. Italy and France currently have the lowest COVID-19-related PEIs. Epidemics and pandemics come and go, but local, national, and global abilities to determine the efficiency of their efforts in averting deaths is critical.


title: The curvilinear relationship between the age of adults and their mental health in Iran after its peak of COVID-19 cases

text: The emerging body of research on the predictors of mental health in the COVID-19 pandemic has revealed contradictory findings, which prevent effective psychiatry screening for mental health assistance. This study aims to identify the predictors of nonsomatic pain, depression, anxiety, and distress, especially focusing on age as a nonlinear predictor. We conducted a survey of 474 adults in Iran during April 1-10, 2020, when Iran had just passed its first peak of the COVID-19 pandemic with new confirmed cases. We found that Age had a curvilinear relationship with nonsomatic pain, depression, and anxiety. Age was associated with pain, depression, and anxiety disorders negatively among adults younger than 45 years, but positively among seniors older than 70 years. Adults who were female, unsure about their chronic diseases, and exercised less per day were more likely to have mental health issues. This study advances the use of age as an effective predictor by uncovering a curvilinear relationship between individuals' age and mental health issues by using a sample of adults across a wide spectrum of ages. We hope future research on mental health during COVID-19 pays more attention to nonlinear predictors.


Randomized Re-Opening of Training Facilities during the COVID-19 pandemic


docid: peirjejf

title: Spatial modeling cannot currently differentiate SARS-CoV-2 coronavirus and human distributions on the basis of climate in the United States

text: The SARS-CoV-2 coronavirus is wreaking havoc globally, yet knowledge of its biology is limited. Climate and seasonality influence the distributions of many diseases, and studies suggest a link between SARS-CoV-2 and cool weather. One such study, building species distribution models (SDMs), predicted SARS-CoV-2 risk may remain concentrated in the Northern Hemisphere, shifting northward in summer months. Others have highlighted issues with SARS-CoV-2 SDMs, notably: the primary niche of the virus is the host it infects, climate may be a weak distributional predictor, global prevalence data have issues, and the virus is not in a population equilibrium. While these issues should be considered, climate still may be important for predicting the future distribution of SARS-CoV-2. To further examine if there is a link, we model with raw cases and population scaled cases for SARS-CoV-2 county-level data from the United States. We show that SDMs built from population scaled cases data cannot be distinguished from control models built from raw human population data, while SDMs built on raw data fail to predict the current known distribution of cases in the US. The population scaled analyses indicate that climate may not play a central role in current US viral distribution and that human population density is likely a primary driver. Still, we do find slightly more population scaled viral cases in cooler areas. This coupled with our geographically constrained focus make it so we cannot rule out climate as a partial driver of the US SARS-CoV-2 distribution. Climate's role on SARS-CoV-2 should continue to be cautiously examined, but at this time we should assume that SARS-CoV-2 can spread anywhere in the US.


title: Knowledge and attitude toward COVID-19 among healthcare workers at District 2 Hospital, Ho Chi Minh City

text: Objective: To assess the knowledge and attitude toward coronavirus disease-2019 (COVID-19) among healthcare workers at District 2 Hospital in Ho Chi Minh City (HCMC) Methods: A cross-sectional study was performed between January 2020 and February 2020 at District 2 Hospital A systematic random sampling strategy was carried out and the data was collected through a self-administered questionnaire of the knowledge and attitude of healthcare workers regarding COVID-19 Descriptive analysis was reported to describe the demographic, mean knowledge and attitude score of healthcare workers Inferential statistics including t-test, ANOVA and Spearman's correlation were used to evaluate the relationship between study variables Results: A total of 327 eligible healthcare workers had a mean score of knowledge and attitude of 8 17 +/- 1 3 (range 4-10) and 1 86 +/- 0 43 (range 1-5), respectively They showed good knowledge and a positive attitude However, approximately two thirds of the participants knew the mode of transmission, the isolation period and treatment (67 0%, 65 8%, and 58 4%, respectively), and 82 3% and 79 8%, respectively, held positive attitude regarding the risk of personal and family members getting illness There was a negative correlation between knowledge scores and attitude scores (r=-0 21, P<0 001) Additionally, healthcare workerspredominately used social media to inform themselves about COVID-19 (91 1%) Conclusions: The majority of healthcare workers had good knowledge and positive attitude toward COVID-19 However, the level of some knowledge and attitude lower than that expected for their position level towards the virus Additional education interventions and campaigns are required for healthcare workers


title: Appendix A Infectious Disease Rule-Outs for Medical Problems*

text: Unknown


title: Random time transformation analysis of Covid19 2020

text: The SIR epidemiological equations model new affected and removed cases as roughly proportional to the current number of infected cases. The present report adopts an alternative that has been considered in the literature, in which the number of new affected cases is proportional to the [≤] 1 power of the number of infected cases. After arguing that = 1 models exponential growth while < 1 models polynomial growth, a simple method for parameter estimation in differential equations subject to noise, the random-time transformation RTT of Bassan, Meilijson, Marcus and Talpaz 1997, will be reviewed and applied in an attempt to settle the question as to the nature of Covid19.


title: COVID-19 transmission risk factors

text: We analyze risk factors correlated with the initial transmission growth rate of the recent COVID-19 pandemic in different countries. The number of cases follows in its early stages an almost exponential expansion; we chose as a starting point in each country the first day with 30 cases and we used 12 days, capturing thus the early exponential growth. We looked then for linear correlations of the exponents with other variables, for a sample of 126 countries. We find a positive correlation, faster spread of COVID-19 , with high confidence level with the following variables, with respective p-value: low Temperature (4x10 -7), high ratio of old vs. working-age people (3x10 -6), life expectancy (8x10 -6), number of international tourists (1x10 -5), earlier epidemic starting date (2x10 -5), high level of physical contact in greeting habits (6x10 -5), lung cancer prevalence (6x10 -5), obesity in males (1x10 -4), share of population in urban areas (2x10 -4), cancer prevalence (3x10 -4), alcohol consumption (0.0019), daily smoking prevalence (0.0036), UV index (0.004, smaller sample, 73 countries), low Vitamin D serum levels (0.002-0.006, smaller sample, 50 countries). There is highly significant correlation also with blood type: positive correlation with types RH- (2x10 -5) and A+ (2x10 -3), negative correlation with B+ (2x10 -4). We also find positive correlation with moderate confidence level (p-value of 0.02-0.03) with: CO2/SO emissions, type-1 diabetes in children, low vaccination coverage for Tuberculosis (BCG). Several of the above variables are correlated with each other and so they are likely to have common interpretations. Other variables are found to have a counterintuitive negative correlation, which may be explained due their strong negative correlation with life expectancy: slower spread of COVID-19 is correlated with high death-rate due to pollution, prevalence of anemia and hepatitis B, high blood pressure in females. We also analyzed the possible existence of a bias: countries with low GDP-per capita, typically located in warm regions, might have less intense testing and we discuss correlation with the above variables.


title: Prevalence and risk factors for mortality related to COVID-19 in a severely affected area of Madrid, Spain

text: 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.


title: Testing, tracing and isolation in compartmental models

text: Existing compartmental mathematical modelling methods for epidemics, such as SEIR models, cannot accurately represent effects of testing, contact tracing and isolation. This makes them inappropriate for evaluating testing and contact tracing strategies to contain an outbreak. An alternative used in practice is the application of agent- or individual-based models (ABM). However ABMs are complex, less well-understood and much more computationally expensive. This paper presents a new method for accurately including the effects of Testing, contact-Tracing and Isolation (TTI) strategies in standard compartmental models. We derive our method using a careful probabilistic argument to show how contact tracing at the individual level is reflected in aggregate on the population level. We show that the resultant SEIR-TTI model accurately approximates the behaviour of a mechanistic agent-based model at far less computational cost. The computationally efficiency is such that it be easily and cheaply used for exploratory modelling to quantify the required levels of testing and tracing, alone and with other interventions, to assist adaptive planning for managing disease outbreaks.


title: The dramatic impact of coronavirus outbreak on air quality: Has it saved as much as it has killed so far?

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


title: The COVID-19 pandemic and its implications for rural economies

text: This paper presents a rapid assessment of current and likely future impacts of the COVID-19 outbreak on rural economies given their socio-economic characteristics. Drawing principally on current evidence for the UK, as well as lessons from the 2001 Foot and Mouth Disease outbreak and the 2007/8 financial crises, it outlines the likely key demand and supply effects, paying attention to the situation for agriculture as well as discussing the implications for rural communities. A distinction is made between the effects on businesses offering goods and services for out-of-home as opposed to in-home consumption. Gendered dimensions are also noted as likely business and household strategies for coping and adaptation. The paper concludes with a brief mapping of a research agenda for studying the longer-term effects of COVID-19 on rural economies.


title: Patient-collected tongue, nasal, and mid-turbinate swabs for SARS-CoV-2 yield equivalent sensitivity to health care worker collected nasopharyngeal swabs

text: Background: Current testing for SARS-CoV-2 requires health care workers to collect a nasopharyngeal (NP) sample from a patient. NP sampling requires the use of personal protective equipment that are in limited supply, is uncomfortable for the patient, and reduces clinical efficiency. This study explored the equivalency of patient-collected tongue, anterior nares (nasal), and mid-turbinate (MT) samples to health care worker-collected NP samples for detecting SARS-CoV-2. Methods: Patients presenting to five urgent care facilities with symptoms indicative of an upper respiratory infection provided self-collected samples from three anatomic sites along with a health care worker-collected NP sample. Using NP as the comparator, sensitivities and one-sided 95% confidence intervals for the tongue, nasal, and MT samples for detection of SARS-CoV-2 were calculated. Results: The sensitivity for detecting SARS-CoV-2 in patient-collected tongue, nasal, and mid-turbinate samples was 89.8% (95% CI: 80.2 -100.0), 94.0 (95% CI: 84.6-100.0) and 96.2 (95% CI: 87.7-100.0), respectively. Among samples yielding positive results, cycle threshold (Ct) values (a measure of viral load) had correlation coefficients of 0.48, 0.78, and 0.86 between the NP samples and the tongue, nasal, and MT samples, respectively. Conclusions: Patient-collected nasal and MT samples demonstrated high sensitivity for SARS-CoV-2 detection using health care worker-collected NP samples as the comparator. Among patients testing positive with NP samples, nasal and MT Ct values demonstrated high correlations with those Ct values of the NP samples. Patient-collected nasal or MT sampling may improve efficiency for COVID-19 testing while reducing the risk of exposure of the health workforce.


title: Covid-19 treatment: The race against time

text: The new outbreak of the novel coronavirus infection emerged in Wuhan-China in late 2019, by the end of Mar 2020, it has spread in more than 178 countries and territories. There is no vaccine or antiviral treatment for COVID-19. Currently, there are several drugs and vaccines being tested for their potential activity against the disease. In this review, we briefly discuss some of the investigational drugs and vaccines being tested against COVID-19 as well as their potential drawbacks.


title: 5-axis milling of complex parts with barrel-shape cutter: cutting force model and experimental validation

text: Abstract The manufacturing of turbomachinery components for the aerospace sector is an important topic in machining research. Aeroengine manufacturing companies forecast increasing levels of design complexity and demand in the following years. Key elements are the Integral Bladed Rotor (IBR) parts, such as impellers and blade-disks. Despite advances in five-axis machining, manufacturing a reliable and efficient IBR component is still a challenge. In this work, the mechanics of the milling process with barrel-shape cutter is studied. These recently developed tools offer a potential advantage for a productive, chatter-free, high-performance machining of IBR parts. In this work, the cutting forces model is developed for this type of tools, then the model is verified in inclined milling operations.


title: Universal coronavirus vaccines: the time to start is now

text: The continued explosive spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) despite aggressive public health measures has triggered an unprecedented international vaccine effort. However, correlates of protection, which can help guide intelligent vaccine design, are not known for SARS-CoV-2. Research on influenza immunity and vaccine development may provide valuable lessons for coronavirus efforts, especially considering similarities in rapid evolutionary potential. The apparent inevitability of future novel coronavirus outbreaks must prompt work on a universal coronavirus vaccine.


title: The Relationship Between COVID-19 Infection and Risk Perception, Knowledge, Attitude As Well As Four Non-pharmaceutical Interventions (NPIs) During the Late Period Of The COVID-19 Epidemic In China An Online Cross-sectional Survey of 8158 Adults

text: Background: So far, there has been no published population study on the relationship between COVID19 infection and public risk perception, information source, knowledge, attitude and four nonpharmaceutical interventions(NPI: hand washing, proper coughing habits, social distancing and mask wearing) during the COVID-19 outbreak in China. Methods: An online survey of 8158 Chinese adults between 22 February to 5 March 2020 was conducted. Bivariate associations between categorical variables were examined using Fisher exact test. We also explored the determinants of four NPIs as well as their association with COVID19 infection using logistic regression. Results: Of 8158 adults included, 57 (0.73%) were infected with COVID19. The overwhelming majority of respondents showed a positive attitude (99.2%), positive risk perception (99.9%) and high knowledge levels that were among the strongest predictors of four highly adopted NPIs (hand washing:96.8%; proper coughing: 93.1%; social distancing:87.1%; mask wearing:97.9%). There was an increased risk of COVID19 infection for those who not washing hands (2.28% vs 0.65%; RR=3.53: 95%CI: 1.538.15; P<0.009); not practicing proper coughing (1.79% vs 0.73%; RR=2.44: 95%CI: 1.15-5.15;P=0.026); not practicing social distancing (1.52% vs 0.58%; RR=2.63:95%CI:1.48 4.67; P=0.002); and not wearing a mask (7.41% vs 0.6%; RR=12.38:95%CI:5.81-26.36; P<0.001). For those who did practice all other three NPIs, wearing mask was associated with significantly reduced risk of infection compared to those who did not wear a mask (0.6% vs 16.7%; p=0.035). Similarly, for those who did not practice all or part of the other three NPIs, wearing mask was also associated with significantly reduced risk of infection. In a penalised logistic regression model including all four NPIs, wearing a mask was the only significant predictor of COVID19 infection among four NPIs (OR=7.20; 95%CI:2.2423.11; p<0.001). Conclusions: We found high levels of risk perception, positive attitude, desirable knowledge as well as a high level of adopting four NPIs. The relevant knowledge, risk perception and attitude were strong predictors of adapting the four NPIs. Mask wearing, among four personal NPIs, is the most effective protective measure against COVID19 infection with added preventive effect among those who practised all or part of the other three NPIs.


title: Staying Ahead of the Curve: Modified Approach to Emergency Caesarean Section Under General Anaesthesia in COVID-19 Pandemic

text: The recent outbreak of SARS-CoV-2 has prompted healthcare professionals to re-design and modify the standards of care and operating procedures relevant to dealing with suspected or confirmed cases of COVID-19. The aim of this review is to highlight the key recommendations related to obstetric anaesthesia from scientific bodies in the United Kingdom and United States and to summarize recently developed and implemented clinical pathways for care of obstetric patients – specifically those requiring urgent general anaesthesia for caesarean section within a large maternity unit in London. The need to perform an emergency operative delivery in a timely manner while ensuring clinicians are suitably equipped and protected represents a uniquely challenging scenario, given the higher risk of viral transmission with aerosol generating procedures. In these settings, emphasis needs to be put on meticulous preparation, safety checklists and specific equipment and staffing adjustments. We present a structured framework comprised of four critical steps aimed to facilitate the development of local strategies and protocols.


Disconnect between community testing and hospitalization for SARS-CoV-2 (COVID-19) infection


title: Immunogenic profile of SARS-CoV-2 spike in individuals recovered from COVID-19

text: The rapid global spread of SARS-CoV-2 and resultant mortality and social disruption have highlighted the need to better understand coronavirus immunity to expedite vaccine development efforts. Multiple candidate vaccines, designed to elicit protective neutralising antibodies targeting the viral spike glycoprotein, are rapidly advancing to clinical trial. However, the immunogenic properties of the spike protein in humans are unresolved. To address this, we undertook an in-depth characterisation of humoral and cellular immunity against SARS-CoV-2 spike in humans following mild to moderate SARS-CoV-2 infection. We find serological antibody responses against spike are routinely elicited by infection and correlate with plasma neutralising activity and capacity to block ACE2/RBD interaction. Expanded populations of spike-specific memory B cells and circulating T follicular helper cells (cTFH) were detected within convalescent donors, while responses to the receptor binding domain (RBD) constitute a minor fraction. Using regression analysis, we find high plasma neutralisation activity was associated with increased spike-specific antibody, but notably also with the relative distribution of spike-specific cTFH subsets. Thus both qualitative and quantitative features of B and T cell immunity to spike constitute informative biomarkers of the protective potential of novel SARS-CoV-2 vaccines.


COVID-2019 outbreak: Negative swab but positive bronchoalveolar lavage?


title: Ostwald growth rate in controlled Covid-19 epidemic spreading as in arrested growth in quantum complex matter

text: Here, we focus on the data analysis of the growth of epidemic spread of Covid-19 in countries where different policies of containment were activated. It is known that the growth of pandemic spread at its threshold is exponential, but it is not known how to quantify the success of different containment policies. We identify that a successful approach gives an arrested phase regime following the Ostwald growth, where, over the course of time, one phase transforms into another metastable phase with a similar free energy as observed in oxygen interstitial diffusion in quantum complex matter and in crystallization of proteins. We introduce the s factor which provides a quantitative measure of the efficiency and speed of the adopted containment policy, which is very helpful not only to monitor the Covid-19 pandemic spread but also for other countries to choose the best containment policy. The results show that a policy based on joint confinement, targeted tests, and tracking positive cases is the most rapid pandemic containment policy; in fact, we found values of 9, 5, and 31 for the success s factor for China, South Korea, and Italy, respectively, where the lowest s factor indicates the best containment policy


title: COVIDier: A Deep-learning Tool For Coronaviruses Genome And Virulence Proteins Classification

text: COVID-19, caused by SARS-CoV-2 infection, has already reached pandemic proportions in a matter of a few weeks. At the time of writing this manuscript, the unprecedented public health crisis caused more than 2.5 million cases with a mortality range of 5-7%. The SARS-CoV-2, also called novel Coronavirus, is related to both SARS-CoV and bat SARS. Great efforts have been spent to control the pandemic that has become a significant burden on the health systems in a short time. Since the emergence of the crisis, a great number of researchers started to use the AI tools to identify drugs, diagnosing using CT scan images, scanning body temperature, and classifying the severity of the disease. The emergence of variants of the SARS-CoV-2 genome is a challenging problem with expected serious consequences on the management of the disease. Here, we introduce COVIDier, a deep learning-based software that is enabled to classify the different genomes of Alpha coronavirus, Beta coronavirus, MERS, SARS-CoV-1, SARS-CoV-2, and bronchitis-CoV. COVIDier was trained on 1925 genomes, belonging to the three families of SARS retrieved from NCBI Database to propose a new method to train deep learning model trained on genome data using Multi-layer Perceptron Classifier (MLPClassifier), a deep learning algorithm, that could blindly predict the virus family name from the genome of by predicting the statistically similar genome from training data to the given genome. COVIDier able to predict how close the emerging novel genomes of SARS to the known genomes with accuracy 99%. COVIDier can replace tools like BLAST that consume higher CPU and time.


title: The role of spatial structure in the infection spread models: population density map of England example

text: In the current situation of a pandemic caused by COVID-19 developing models accurately predicting the dynamics of the outbreaks in time and space became extremely important. Individual-based models (IBM) simulating the spread of infection in a population have a few advantages compared to classical equation-based approach. First, they use individuals as units, which represent the population, and reflect the local variations happening in real life. Second, the simplicity of modelling the interactions between the individuals, which may not be the case when using differential equations. We propose to use freely available population density maps to simulate the infection spread in the human population on the scale of an individual country or a city. We explore the effect of social distancing and show that it can reduce the outbreak when applied before or during peak time, but it can also inflict the second wave when relaxed after the peak. This can be explained by a large proportion of susceptible individuals, even in the large cities, after the first wave. The model can be adapted to any spatial scale from a single hospital to multiple countries.


title: In search for the hotspots of Disease X: A biogeographic approach to mapping the predictive risk of WHO s Blueprint Priority Diseases

text: Anthropization of natural habitats including climate change along with overpopulation and global travel have been contributing to emerging infectious diseases outbreaks. The recent COVID-19 outbreak in Wuhan, highlights such threats to human health, social stability and global trade and economy. We used species distribution modelling and environmental data from satellite imagery to model Blueprint Priority Diseases occurrences. We constructed classical regression and Support Vector Machine models based on environmental predictor variables such as landscape, tree cover loss, climatic covariates. Models were evaluated and a weighed mean was used to map the predictive risk of disease emergence. We mapped the predictive risk for filovirus, Nipah, Rift Valley Fever and coronavirus diseases. Elevation, tree cover loss and climatic covariates were found to significant factors influencing disease emergence. We also showed the relevance of disease biogeography and in the identification potential hotspots for Disease X in regions in Uganda and China.


title: Antibody dynamics to SARS-CoV-2 in Asymptomatic and Mild COVID-19 patients

text: Humoral immunity in asymptomatic infections with SARS-CoV-2 has not been well established. 63 healthy contacts, 63 asymptomatic individuals, and 51 mild patients were enrolled in this study and screened using nucleic acid testing (NAT) and commercial kits of serum IgM and IgG antibodies against recombinant nucleoprotein (N) and spike (S) proteins of SARS-CoV-2. Asymptomatic and mild patients were classified into at least four types based on NAT and serological tests, especially 81% and 25.4% negative NAT but positive IgM/IgG responses, respectively. Antibody dynamics were further demonstrated by IgM and IgG profile responses to SARS-CoV-2 proteome. IgM antibody responses against S1 were elicited in asymptomatic individuals as early to the seventh day after exposure and peaked on days from 17d to 25d, which might be used as early diagnostic biomarkers. Moreover, asymptomatic individuals evoked weaker S1 specific IgM and neutralizing antibody responses than mild patients. Most importantly, S1 specific IgM/IgG responses and the titers of neutralizing antibody in asymptomatic individuals gradually vanished in two months. Our findings might have important implications for serological survey, public health and immunization strategy.


Community, work, and family in times of COVID-19


title: Physiologic RNA Targets and Refined Sequence Specificity of Coronavirus EndoU

text: Coronavirus EndoU inhibits dsRNA-activated antiviral responses; however, the physiologic RNA substrates of EndoU are unknown. In this study, we used mouse hepatitis virus (MHV)-infected bone-marrow-derived macrophage (BMM) and cyclic phosphate cDNA sequencing to identify the RNA targets of EndoU. EndoU targeted viral RNA, cleaving the 3′ side of pyrimidines with a strong preference for U⬇A and C⬇A sequences (endoY⬇A). EndoU-dependent cleavage was detected in every region of MHV RNA, from the 5′ NTR to the 3′ NTR, including transcriptional regulatory sequences (TRS). Cleavage at two CA dinucleotides immediately adjacent to the MHV poly(A) tail suggest a mechanism to suppress negative-strand RNA synthesis and the accumulation of viral dsRNA. MHV with EndoU (EndoUmut) or 2′-5′ phosphodiesterase (PDEmut) mutations provoked the activation of RNase L in BMM, with corresponding cleavage of RNAs by RNase L. The physiologic targets of EndoU are viral RNA templates required for negative-strand RNA synthesis and dsRNA accumulation. Impact Coronavirus EndoU cleaves U⬇A and C⬇A sequences (endoY⬇A) within viral (+) strand RNA to evade dsRNA-activated host responses.


title: Quantitative Estimation of Covid-19 Related Unemployment On Suicide and Excess Mortality in the United States

text: Introduction: To date, reducing virus transmission to mitigate demand on health care systems has been a singular objective of Covid-19 policy action. This aim has driven widespread and rapid application of untested policies to control contagion, including the deployment of non-pharmaceutical interventions (NPIs), including travel restrictions, bans on gathering, and community-wide lockdowns. Risk models, public health experts and political leadership alike have given almost no attention to related, anticipated, and predictable societal and health impacts likely to result from behavioral responses to Covid-19 combined with the application of NPIs. Methods: This analysis demonstrates a standard risk assessment approach to quantify the impacts of Covid-19 unemployment in the United States on suicide and all cause mortality. Results: Applying observational epidemiological data to the population recently unemployed predicts 7444 deaths from suicide in the coming year and 556,000 avoidable deaths from all causes over the next ten years. Discussion: Indirect health impacts of societal responses to Covid-19 are likely and quantifiable. Decision-makers can now include indirect health impacts into their policy making calculus for Covid-19 to strike a balance between the benefits and costs of mitigation. A full trade-offs analysis of alternative planning scenarios will likely reveal multiple unconsidered ethical challenges that need transparent public discussion and solution.


title: Direct Quantification of in vivo Mutagenesis Using Duplex Sequencing

text: The ability to accurately measure mutations is critical for basic research and identification of potential drug and chemical carcinogens. Current methods for in vivo quantification of mutagenesis are limited because they rely on transgenic rodent systems that are low-throughput, expensive, prolonged, and don’t fully represent other species such as humans. Next generation sequencing (NGS) is a conceptually attractive alternative for mutation detection in the DNA of any organism, however, the limit of resolution for standard NGS is poor. Technical error rates (~1×10−3) of NGS obscure the true abundance of somatic mutations, which can exist at frequencies ≤1×10−7. Using Duplex Sequencing, an extremely accurate error-corrected NGS (ecNGS) technology, we were able to detect mutations induced by 3 carcinogens in 5 tissues of 2 strains of mice within 31 days following exposure. We observed a strong correlation between mutation induction measured by Duplex Sequencing and the gold-standard transgenic rodent mutation assay. We identified exposure-specific mutation spectra of each compound through trinucleotide patterns of base substitution. We observed variation in mutation susceptibility by genomic region, as well as by DNA strand. We also identified clear early signs of carcinogenesis in a cancer-predisposed strain of mice, as evidenced by apparent clonal expansions of cells carrying an activated oncogene, less than a month after carcinogen exposure. These findings demonstrate that ecNGS is a powerful method for sensitively detecting and characterizing mutagenesis and early clonal evolutionary hallmarks of carcinogenesis. Duplex Sequencing can be broadly applied to chemical safety testing, basic mutational research, and related clinical uses. SIGNIFICANCE STATEMENT Error-corrected next generation sequencing (ecNGS) can be used to rapidly detect and quantify the in vivo mutagenic impact of environmental exposures or endogenous processes in any tissue, from any species, at any genomic location. The greater speed, higher scalability, richer data outputs, as well as cross-species and cross-locus applicability of ecNGS compared to existing methods make it a powerful new tool for mutational research, regulatory safety testing, and emerging clinical applications.


title: Mechanistic rationale of drugs, Primary endpoints, Geographical distribution of clinical trials against Severe acute respiratory syndrome-related coronavirus-2: A Systematic Review

text: Objective To do a systematic review and critical appraisal of the ongoing clinical trials that are assessing various therapeutic interventions against SARS-CoV-2 with an aim to provide insight into the various interventions tested, clinical rationale, geographical distribution of the trials as well as the endpoints assessed in the studies. Design Rapid systematic review and critical appraisal of the ongoing clinical trials against SARS-CoV-2. Data sources ClinicalTrials.gov, World health organization (WHO) International Clinical Trials Registry Platform (ICTRP) and Cochrane COVID registry were assessed till May 11th 2020. Study selection Studies on any intervention based randomized controlled trials (RCTs), prospective clinical studies on SARS-CoV-2 in patients [≥]18 years of age. Studies on autopsy series, preclinical studies, diagnostic methods, mathematical modelling, epidemiology and health services research, pediatric populations were excluded. Data extraction The data was extracted by two authors independently into pre-defined forms based on the SPIRIT 2013 checklist. The data was extracted on various domains such as trial number, study title, abstract of the study, interventions assessed, sample size, phase of the study, study sponsor, primary endpoint assessed and country of study. Results The search resulted in 3242 ongoing studies of which 829 studies were included. There are 134 different drug-based interventions being assessed in 463 clinical trials as treatment options. Seventy-two studies assessed preventive options of which 53 are drug-based prophylaxis and 19 assessed vaccines. Herbal medicines are being assessed in 79 studies; convalescent plasma therapy in 56 studies; stem cell based interventions in 42 studies; anesthesia-based interventions in 31 studies, machine-based interventions in 24 studies, mental health- based interventions in18 studies, rehabilitation based interventions in 12 studies and miscellaneous interventions in 32 studies. China accounts for 35% of all ongoing clinical studies followed by USA 23%, France 7%, Spain 3.3%,Canada 2%, multi-country studies account only for 1.5% (13) and other countries together account for 28%.Amongst the 463 studies assessing drug-based treatment options, studies that are funded by federal and academic institutions are 79.6%, pharmaceutical company funded studies are 15.11% and no funding information is available in 5.10%. The definitive outcomes like mortality are being assessed as primary outcome in 22.8% of the studies only and need for ventilator in 6.2% of the studies. Rest of the studies has primary outcomes such as clinical recovery (15.9%), viral clearance(17.4%), time to recovery (10.1%), oxygen improvement (5.6%), ICU admission (1.9%), lab and imaging(6.4%), adverse effects (5.3%) and symptom reduction(1.5%),no outcome reported(6.2%) which account for 71% of the studies. Amongst the pharmaceutical company funded drug-based studies, only 20% of the studies had mortality as the primary outcome. Only 5.5% of the ongoing clinical trials are specifically designed to assess the most vulnerable population like elderly, patients with comorbidities and cancer. The most common intervention being tested against COVID-19 are antimalarial medications with 105 clinical studies. Hydroxychloroquine is the most common drug being tested with 83 ongoing studies. Conclusion Multiple intervention based clinical studies against SARS-CoV-2 are being performed throughout the world with a high concentration of clinical trials in the developed world. There is a high concern that most of the studies maybe repetitive; elderly and patients with comorbidities are being underrepresented; definite endpoints like mortality are being assessed in only one-fifth of the studies.