title: Covid-19 and Inequity: A comparative spatial analysis of New York City and Chicago hot spots

text: There have been numerous reports that the impact of the ongoing COVID-19 epidemic has disproportionately impacted traditionally vulnerable communities, including well-researched social determinants of health, such as racial and ethnic minorities, migrants, and the economically challenged. The goal of this ecological cross-sectional study is to examine the demographic and economic nature of spatial hot and cold spots of SARS-CoV-2 rates in New York City and Chicago as of April 13, 2020. In both cities, cold spots (clusters of low SARS-CoV-2 rate ZIP code tabulation areas) demonstrated typical protective factors associated with the social determinants of health and the ability to social distance. These neighborhoods tended to be wealthier, have higher educational attainment, higher proportions of non-Hispanic white residents, and more workers in managerial occupations. Hot spots (clusters of high SARS-CoV-2 rate ZIP code tabulation areas) also had similarities, such as lower rates of college graduates and higher proportions of people of color. It also appears to be larger households (more people per household), rather than overall population density, that may to be a more strongly associated with hot spots. Findings suggest important differences between the cities' hot spots as well. They can be generalized by describing the NYC hot spots as working-class and middle-income communities, perhaps indicative of service workers and other occupations (including those classified as "essential services" during the pandemic) that may not require a college degree but pay wages above poverty levels. Chicago's hot spot neighborhoods, on the other hand, are among the city's most vulnerable, low-income neighborhoods with extremely high rates of poverty, unemployment, and non-Hispanic Black residents.


title: Early temporal dynamics of cellular responses to SARS-CoV-2

text: Two highly pathogenic human coronaviruses that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) have evolved proteins that can inhibit host antiviral responses, likely contributing to disease progression and high case-fatality rates. SARS-CoV-2 emerged in December 2019 resulting in a global pandemic. Recent studies have shown that SARS-CoV-2 is unable to induce a robust type I interferon (IFN) response in human cells, leading to speculation about the ability of SARS-CoV-2 to inhibit innate antiviral responses. However, innate antiviral responses are dynamic in nature and gene expression levels rapidly change within minutes to hours. In this study, we have performed a time series RNA-seq and selective immunoblot analysis of SARS-CoV-2 infected lung (Calu-3) cells to characterize early virus-host processes. SARS-CoV-2 infection upregulated transcripts for type I IFNs and interferon stimulated genes (ISGs) after 12 hours. Furthermore, we analyzed the ability of SARS-CoV-2 to inhibit type I IFN production and downstream antiviral signaling in human cells. Using exogenous stimuli, we discovered that SARS-CoV-2 is unable to modulate IFNβ production and downstream expression of ISGs, such as IRF7 and IFIT1. Thus, data from our study indicate that SARS-CoV-2 may have evolved additional mechanisms, such as masking of viral nucleic acid sensing by host cells to mount a dampened innate antiviral response. Further studies are required to fully identify the range of immune-modulatory strategies of SARS-CoV-2. Significance Highly pathogenic coronaviruses that cause SARS and MERS have evolved proteins to shutdown antiviral responses. The emergence and rapid spread of SARS-CoV-2, along with its relatively low case-fatality rate have led to speculation about its ability to modulate antiviral responses. We show that SARS-CoV-2 is unable to block antiviral responses that are mounted by exogenous stimuli. Data from our study provide promising support for the use of recombinant type I IFN as combination therapy to treat COVID-19 patients. Furthermore, our data also suggest that the inability of SARS-CoV-2 to efficiently modulate antiviral responses may be associated with its low case-fatality rate compared to other pathogenic CoVs that cause SARS and MERS.


title: How do environmental, economic and health factors influence regional vulnerability to COVID-19?

text: We have studied the correlations between twelve environmental, economic and health variables, by carrying out a statistical analysis of the fatality rate of COVID-19 in 14 countries. Our statistical analysis indicates that, among the 12 variables, the diabetes percentage of the total population and the extent of the population ages 65 and older in each country are correlated most strongly with the total number of deaths in them. Although the strength of the correlations between the variables and the total ND may change as the ongoing pandemic evolves, the study highlights the importance of integrating regional-specific variables in the modelling efforts aimed at projecting how the spread of the virus may influence different parts of the world.


title: The Efficacy of Contact Tracing for the Containment of the 2019 Novel Coronavirus (COVID-19).

text: Contact tracing is a central public health response to infectious disease outbreaks, especially in the early stages of an outbreak when specific treatments are limited. Importation of novel Coronavirus (COVID-19) from China and elsewhere into the United Kingdom highlights the need to understand the impact of contact tracing as a control measure. Using detailed survey information on social encounters coupled to predictive models, we investigate the likely efficacy of the current UK definition of a close contact (within 2 meters for 15 minutes or more) and the distribution of secondary cases that may go untraced. Taking recent estimates for COVID-19 transmission, we show that less than 1 in 5 cases will generate any subsequent untraced cases, although this comes at a high logistical burden with an average of 36.1 individuals (95th percentiles 0-182) traced per case. Changes to the definition of a close contact can reduce this burden, but with increased risk of untraced cases; we estimate that any definition where close contact requires more than 4 hours of contact is likely to lead to uncontrolled spread.


title: The focus and timing of COVID-19 pandemic control measures under healthcare resource constraints

text: Generalizing COVID-19 control strategies in one community to others is confounded by community′s unique demographic and socioeconomic attributes. Here we propose a tailored dynamic model accounting for community-specific transmission controls and medical resource availability. We trained the model using data from Wuhan and applied it to other countries. We show that isolating suspected cases is most effective in reducing transmission rate if the intervention starts early. Having more hospital beds provides leverage that diminishes with delayed intervention onset. The importance of transmission control in turn increases by 65% with a 7-day delay. Furthermore, prolonging outbreak duration by applying an intermediate, rather than strict, transmission control would not prevent hospital overload regardless of bed capacity, and would likely result in a high ratio (21% ~ 84%) of the population being infected but not treated. The model could help different countries design control policies and gauge the severity of suppression failure.


title: Concentration-dependent mortality of chloroquine in overdose

text: Background: Hydroxychloroquine and chloroquine have been used extensively in malaria and rheumatological conditions. Although generally safe and well tolerated they are potentially lethal in overdose. These two drugs are now candidates for the prevention and treatment of COVID19. In vitro data suggest that high concentrations and thus high doses will be needed if they are to be of benefit, but as yet there is no convincing evidence they are clinically effective. Nevertheless they are already being used very widely and fatal accidental overdoses have been reported. Methods: Individual data from prospectively studied French patients who had taken intentional chloroquine overdoses and were managed in the national toxicology intensive care unit in Paris were pooled. Bayesian logistic regression was used to estimate a concentration-fatality curve. The probabilities of fatal iatrogenic toxicity with the chloroquine regimens currently being trialled for the treatment of COVID19 were estimated from a combined pharmacokinetic-pharmacodynamic model. Findings: In total, 258 patients were studied of whom 26 died (10%). There was a steep sigmoid relationship between admission whole blood chloroquine concentrations and death. Concentrations above 13umol/L (95% credible interval (C.I.), 10 to 16) were associated with greater than 1% mortality. Based on peak concentrations, absolute fatality ratios in the high dose arm (chloroquine base equivalent adult dose of 600mg given twice daily for ten days) of a recently terminated trial were estimated between 0.06% (90kg adult, 95%C.I. 0 to 0.3%) and 4.8% (40kg adult, 95% C.I. 1.9 to 9.7%). This regimen results in peak concentrations above 10umol/L in more than 60% of adults weighing 70kg. The other high dose regimens trialled currently for COVID19 result in peak concentrations above 10umol/L in only 0.2% of adults weighting 70kg. Interpretation:} High-dose chloroquine treatment regimens which result in whole blood chloroquine concentrations below 10umol/L for the majority of patients should not result in life-threatening cardiovascular toxicity.


title: Weather Conditions and COVID-19 Transmission: Estimates and Projections

text: Background: Understanding and projecting the spread of COVID-19 requires reliable estimates of how weather components are associated with the transmission of the virus. Prior research on this topic has been inconclusive. Identifying key challenges to reliable estimation of weather impact on transmission we study this question using one of the largest assembled databases of COVID-19 infections and weather. Methods: We assemble a dataset that includes virus transmission and weather data across 3,739 locations from December 12, 2019 to April 22, 2020. Using simulation, we identify key challenges to reliable estimation of weather impacts on transmission, design a statistical method to overcome these challenges, and validate it in a blinded simulation study. Using this method and controlling for location-specific response trends we estimate how different weather variables are associated with the reproduction number for COVID-19. We then use the estimates to project the relative weather-related risk of COVID-19 transmission across the world and in large cities. Results: We show that the delay between exposure and detection of infection complicates the estimation of weather impact on COVID-19 transmission, potentially explaining significant variability in results to-date. Correcting for that distributed delay and offering conservative estimates, we find a negative relationship between temperatures above 25 degrees Celsius and estimated reproduction number ([R]), with each degree Celsius associated with a 3.1% (95% CI, 1.5% to 4.8%) reduction in [R]. Higher levels of relative humidity strengthen the negative effect of temperature above 25 degrees. Moreover, one millibar of additional pressure increases [R] by approximately 0.8 percent (95% CI, 0.6% to 1%) at the median pressure (1016 millibars) in our sample. We also find significant positive effects for wind speed, precipitation, and diurnal temperature on [R]. Sensitivity analysis and simulations show that results are robust to multiple assumptions. Despite conservative estimates, weather effects are associated with a 43% change in [R] between the 5th and 95th percentile of weather conditions in our sample. Conclusions: These results provide evidence for the relationship between several weather variables and the spread of COVID-19. However, the (conservatively) estimated relationships are not strong enough to seasonally control the epidemic in most locations.


From the Editor: The COVID-19 Pandemic


title: NIH’s axing of bat coronavirus grant a ‘horrible precedent’ and might break rules, critics say

text: The research community is reacting with alarm and anger to the National Institutes of Health’s (NIH’s) abrupt and unusual termination of a grant supporting research in China on how coronaviruses—such as the one causing the current pandemic—move from bats to humans The agency axed the grant last week, after conservative U S politicians and media repeatedly suggested—without evidence—that the pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) escaped from a laboratory in Wuhan, China, that employs a Chinese virologist who had been receiving funding from the grant The termination, which some analysts believe might violate regulations governing NIH, also came 7 days after President Donald Trump, asked about the project at a press conference, said: “We will end that grant very quickly ”


title: Prediction of the Peak, Effect of Intervention and Total Infected by the Coronavirus Disease in India

text: We study the effect of the coronavirus disease 2019 (COVID-19) in India using the SEIR compartmental model. After it's outbreak in Wuhan, China, it has been imported to India which is a densely populated country. India is fighting against this disease by ensuring nationwide social distancing. We estimate the infection rate to be 0.258 using a least square method with Poisson noise and estimate the reproduction number to be 2.58. We approximate the peak of the epidemic to be August 11, 2020. We estimate that a 25% drop in infection rate will delay the peak by 38 days for a 1 month intervention period. We estimate that the total individuals infected in India will be approximately 9% of the total population.


title: Modeling the COVID-19 pandemic - parameter identification and reliability of predictions

text: In this paper, we try to identify the parameters for two elementary epidemic models, the so-called SI- and SIS-models, via non-linear regression using data of the COVID-19 pandemic. This is done based on the data for the number of daily infections. Studying the history of predictions made, we attempt to estimate their reliability concerning the future course of the epidemic. We validate this procedure using data for the case numbers in China and South Korea. Then we apply it in order to find predictions for Germany, Italy and the United States. The results are encouraging, but no final judgment on the validity of the procedure can yet be made.


Special Issue: Crisis in the Eastern Mediterranean and COVID-19


title: Performance Characteristics of the Abbott Architect SARS-CoV-2 IgG Assay and Seroprevalence Testing in Idaho

text: Coronavirus disease-19 (COVID19), the novel respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with severe morbidity and mortality. The rollout of diagnostic testing in the United States was slow, leading to numerous cases that were not tested for SARS-CoV-2 in February and March 2020, necessitating the use of serological testing to determine past infections. Here, we evaluated the Abbott SARS-CoV-2 IgG test for detection of anti-SARS-CoV-2 IgG antibodies by testing 3 distinct patient populations. We tested 1,020 serum specimens collected prior to SARS-CoV-2 circulation in the United States and found one false positive, indicating a specificity of 99.90%. We tested 125 patients who tested RT-PCR positive for SARS-CoV-2 for which 689 excess serum specimens were available and found sensitivity reached 100% at day 17 after symptom onset and day 13 after PCR positivity. Alternative index value thresholds for positivity resulted in 100% sensitivity and 100% specificity. We then tested 4,856 individuals from Boise, Idaho collected over one week in April 2020 as part of the Crush the Curve initiative and detected 87 positives for a positivity rate of 1.79%. These data demonstrate excellent analytical performance of the Abbott SARS-CoV-2 IgG test as well as the limited circulation of the virus on the West Coast. We expect the availability of high-quality serological testing will be a key tool in the fight against SARS-CoV-2.


title: What does and does not correlate with COVID-19 death rates

text: We correlate county-level COVID-19 death rates with key variables using both linear regression and negative binomial mixed models, although we focus on linear regression models. We include four sets of variables: socio-economic variables, county-level health variables, modes of commuting, and climate and pollution patterns. Our analysis studies daily death rates from April 4, 2020 to May 27, 2020. We estimate correlation patterns both across states, as well as within states. For both models, we find higher shares of African American residents in the county are correlated with higher death rates. However, when we restrict ourselves to correlation patterns within a given state, the statistical significance of the correlation of death rates with the share of African Americans, while remaining positive, wanes. We find similar results for the share of elderly in the county. We find that higher amounts of commuting via public transportation, relative to telecommuting, is correlated with higher death rates. The correlation between driving into work, relative to telecommuting, and death rates is also positive across both models, but statistically significant only when we look across states and counties. We also find that a higher share of people not working, and thus not commuting either because they are elderly, children or unemployed, is correlated with higher death rates. Counties with higher home values, higher summer temperatures, and lower winter temperatures have higher death rates. Contrary to past work, we do not find a correlation between pollution and death rates. Also importantly, we do not find that death rates are correlated with obesity rates, ICU beds per capita, or poverty rates. Finally, our model that looks within states yields estimates of how a given state's death rate compares to other states after controlling for the variables included in our model; this may be interpreted as a measure of how states are doing relative to others. We find that death rates in the Northeast are substantially higher compared to other states, even when we control for the four sets of variables above. Death rates are also statistically significantly higher in Michigan, Louisiana, Iowa, Indiana, and Colorado. California's death rate is the lowest across all states.


title: Rapid detection of SARS-CoV-2 infection by multicapillary column coupled ion mobility spectrometry (MCC-IMS) of breath. A proof of concept study

text: There is an urgent need for screening patients of having a communicable viral disease to cut infection chains. We could recently demonstrate that MCC-IMS of breath is able to identify Influenza-A infected patients. With decreasing Influenza epidemic and upcoming SARS-CoV-2 infections we extended our study to the analysis of patients with suspected SARS-CoV-2 infections. 51 patients, 23m, 28f, aged 64 +/- 16 years, were included in this study. Besides RT-PCR analysis of nasopharyngeal swabs all patients underwent MCC-IMS analysis of breath. 16 patients, 7m, 9f, were positive for SARS-CoV-2 by RT-PCR. There was no difference in gender or age according to the groups. Stepwise canonical discriminant analysis could correctly classify the infected and non- infected subjects in 98% by cross-validation. Afterwards we combined the Influenza-A sub study and the SARS-CoV-2- sub study for a total of 75 patients, 34m, 41f, aged 64.8 +/- 1.8 years, 14 positive for Influenza-A, 16 positive for SARS-CoV-2, the remaining 44 patients were used as controls. In one patient RT-PCR was highly suspicious of SARS-CoV-2 but inconclusive. There was no imbalance between the groups for age or gender. 97.3% of the patients could be correctly classified to the respective group by discriminant analysis. Even the inconclusive patient could be mapped to the SARS-CoV-2 group applying the discrimination function. Conclusion: MCC-IMS is able to detect SARS-CoV-2 infection and Influenza-A infection in breath. As this method provides exact, fast non-invasive diagnosis it should be further developed for screening of communicable viral diseases. Study registration: NCT04282135


title: Treatment of 6 COVID-19 Patients with Convalescent Plasma

text: Objectives To describe the efficacy of convalescent plasma transfusion for COVID-19 patients. Methods Through the review of the electronic medical records of Guizhou Jiangjunshan Hospital, clinical data of 6 patients were obtained. Three of the patients used convalescent plasma therapy for the first treatment, while the other three patients were used during in the recurrence. The efficacy of convalescent plasma depends on the relief of symptoms, changes in laboratory indicators and chest imaging abnormalities. Results The PaO2 / FiO2 and lymphocyte count of patients 1, 2 and 3 treated with convalescent plasma treatment for the first treatment period were changed from abnormal to normal. The levels of inflammation markers CRP and IL-6 of the patients decreased significantly. Chest imaging examination showed that the lung lesions gradually subsided. The relapsed patients (No. 4 and No. 6), after using convalescent plasma therapy, turned negative on two consecutive throat swab tests on Day 24 and Day 3, respectively. The basic condition of patient 4 with in the recurrence was too poor, and only one round of convalescent plasma transfusion was performed, so the laryngeal swab test paper has been consistently positive so far. Conclusions Six patients with COVID-19 were treated with antivirals and systemic corticosteroids combined with appropriate rounds of convalescent plasma therapy, and their clinical conditions were effectively improved.


title: A link between inflammatory biomarkers and lung ultrasound observations in patients with SARS-CoV-2 infection

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


title: Epidemiological and clinical features of COVID-19 patients with and without pneumonia in Beijing, China

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


title: Pervasive RNA secondary structure in the genomes of SARS-CoV-2 and other coronaviruses – an endeavour to understand its biological purpose

text: The ultimate outcome of the COVID-19 pandemic is unknown and is dependent on a complex interplay of its pathogenicity, transmissibility and population immunity. In the current study, SARS coronavirus 2 (SARS-CoV-2) was investigated for the presence of large scale internal RNA base pairing in its genome. This property, termed genome scale ordered RNA structure (GORS) has been previously associated with host persistence in other positive-strand RNA viruses, potentially through its shielding effect on viral RNA recognition in the cell. Genomes of SARS-CoV-2 were remarkably structured, with minimum folding energy differences (MFEDs) of 15%, substantially greater than previously examined viruses such as HCV (MFED 7-9%). High MFED values were shared with all coronavirus genomes analysed created by several hundred consecutive energetically favoured stem-loops throughout the genome. In contrast to replication-association RNA structure, GORS was poorly conserved in the positions and identities of base pairing with other sarbecoviruses – even similarly positioned stem-loops in SARS-CoV-2 and SARS-CoV rarely shared homologous pairings, indicative of more rapid evolutionary change in RNA structure than in the underlying coding sequences. Sites predicted to be base-paired in SARS-CoV-2 showed substantially less sequence diversity than unpaired sites, suggesting that disruption of RNA structure by mutation imposes a fitness cost on the virus which is potentially restrictive to its longer evolution. Although functionally uncharacterised, GORS in SARS-CoV-2 and other coronaviruses represent important elements in their cellular interactions that may contribute to their persistence and transmissibility.


title: SARS-CoV-2 (COVID-19): Zoonotic Origin and Susceptibility of Domestic and Wild Animals

text: Coronaviruses (CoVs) are responsible for causing economically significant diseases both in animals and humans The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), causing Coronavirus Diseases (COVID-19), outbreak has become the first pandemic of the 21st century and is the deadliest pandemic after the 1918 Spanish Flu Except, the two previous epidemics, SARS-CoV (2002 epidemic, China) and MERS-CoV (2012 epidemic, Middle Eastern region), CoVs are known the world over as the mild pathogens of humans and animals Despite several measures to control the COVID-19 pandemic, it has affected more than 210 countries and regional territories distressing more than 5 3 million people and claiming nearly 0 34 million lives globally Several findings point towards the appearance of the SARS-CoV-2 virus in the humans through animals, especially the wild animals of the Chinese live seafood wet market The ongoing COVID-19 pandemic is another example of diseases originating from the human-animal interface and spreading through international borders causing global health emergencies Most of the countries around the globe are stumbling due to the COVID-19 pandemic with severe threats and panic among the mass population World Health Organization ( WHO), international and national health authorities are working with excessive efforts for effective and impactful interventions to contain the virus It is significant to comprehend the inclination of these viruses to jump between different species, and the establishment of infection in the entirely new host, identification of significant reservoirs of coronaviruses Several animal species such as cats, dogs, tiger, and minks have been confirmed to get SARS-CoV-2 infections from COVID-19 infected person Laboratory investigations point out those cats are the most susceptible species for SARS-CoV-2, and it can evidence with clinical disease The studies carried out on animal's susceptibility to SARS-CoV-2 further support the human-to-animal spread of the virus In this review, we focus on addressing COVID-19 infections in domestic and wild animals


title: Sample Pooling as an efficient strategy for SARS-COV-2 RT-PCR screening: a multicenter study in Spain

text: Importance: The actual demand on SARS-CoV-2 diagnosis is a current challenge for clinical laboratories. Sample pooling may help to ameliorate workload in clinical laboratories. Objective: to evaluate the efficacy of sample pooling compared to the individual analysis for the diagnosis of CoVID-19, by using different commercial platforms for nucleic acid extraction and amplification. Design and settings: observational, prospective, multicentre study across 9 Spanish clinical microbiology laboratories including SARS-CoV-2 RNA testing performed in April 2020, during the first three days after acceptance to participate. Participants and Methods: 3519 naso-oro-pharyngeal samples received at the participating laboratories were processed individually and in pools (351 pools) according to the existing methodology in each of the centres. Results: We found that 253 pools (2519 samples) were negative, and 99 pools (990 samples) were positive; with 241 positive samples (6.85%), our pooling strategy would have saved 2167 PCR tests. For 29 pools (made out of 290 samples) we found discordant results when compared to their correspondent individual samples: in 24/29 pools (30 samples), minor discordances were found; for five pools (5 samples), we found major discordances. Sensitivity, specificity, positive and negative predictive values for pooling were 97.93%, 100%, 100% and 99.85% respectively; accuracy was 99.86% and kappa concordant coefficient was 0.988. As a result of the sample dilution effect of pooling, a loss of 2-3 Cts was observed for E, N or RdRP genes. Conclusion: we show a high efficiency of pooling strategies for SARS-CoV-2 RNA testing, across different RNA extraction and amplification platforms, with excellent performance in terms of sensitivity, specificity, and positive and negative predictive values. We believe that our results may help clinical laboratories to respond to the actual demand and clinical need on SARS-CoV-2 testing, especially for the screening of low prevalence populations.


title: From first COVID-19 case to current outbreak: A vietnamese report

text: The 2019 novel coronavirus outbreak (now recognized as SARS-CoV-2, triggering the COVID-19 disease) has spread from Wuhan throughout China and has been distributed to an increasing range of countries. Early activity has concentrated on explaining the course of the disease, reporting critical incidents, and handling the ill. Currently, Vietnam, an Association of Southeast Asian Nations (ASEAN) country that shares a long border with China, has successfully controlled COVID-19. In this article, we aimed to provide updated information regarding COVID-19 in Vietnam, from the first case to the current outbreak. We hope the information in this article will help the world understand more about the surveillance and prevention policies of Vietnam’s COVID-19. The numerous lessons learned will serve as a guide for handling possible pandemics, but a permanently new global framework is expected in the immediate future.


title: Clinical characteristics and durations of hospitalized patients with COVID-19 in Beijing: a retrospective cohort study

text: Background: COVID-19 is still becoming an increasing global threat to public health. More detailed and specific characteristics of COVID-19 are needed to better understand this disease. Additionally, durations of COVID-19, e.g., the average time from exposure to recovery, which is of great value in understanding this disease, has not been reported so far. Aims: To give the information on clinical characteristics and different durations of COVID-19 and to identify the potential risk factors for longer hospitalization duration. Methods: In this retrospective study, we enrolled 77 patients (mean age: 52 years; 44.2% males) with laboratory-confirmed COVID-19 admitted to Beijing YouAn Hospital during 21st Jan and 8th February 2020. Epidemiological, clinical and radiological data on admission were collected; complications and outcomes were followed up until 29th February 2020. The study endpoint was the discharge within two weeks. Cox proportional-hazards regression was performed to identify risk factors for longer hospitalization duration. Results: Of 77 patients, there are 34 (44.2%) males, 24 (31.2%) with comorbidities, 22 (28.6%) lymphopenia, 20 (26.0%) categorized as severe patients, and 28 (36.4%) occurred complications. By the end of follow-up, 64 (83.1%) patients were discharged home after being tested negative for SARS-CoV-2 infections, 8 remained in hospital and 5 died. 36 (46.8%) patients were discharged within 14 days and thus reached the study endpoint, including 34 (59.6%) of 57 non-severe patients and 2 (10%) of 20 severe patients. The overall cumulative probability of the endpoint was 48.3%. Hospital length of stay and duration of exposure to discharge for 64 discharged patients were 13 (10-16.5) and 23 (18-24.5) days, respectively. Multivariable stepwise Cox regression model showed bilateral pneumonia on CT scan, shorter time from the illness onset to admission, the severity of disease and lymphopenia were independently associated with longer hospitalized duration. Conclusions: COVID-19 has significantly shorter duration of disease and hospital length of stay than SARS. Bilateral pneumonia on CT scan, shorter period of illness onset to admission, lymphopenia, the severity of disease are the risk factors for longer hospitalization duration of COVID-19.


title: Cohort profile: Preliminary experience of 500 COVID-19 postive cases at a South West London District General Hospital.

text: This retrospective cohort analysis, reports the demographic data and early outcome of the first 500 patients who were admitted to a District General Hospital in South West London, UK and tested positive to COVID-19. The patients were admitted between 10 January and 10 April 2020; with the first COVID-19 positive diagnosis on 6 March. A surge in admissions started around the 15 March and peaked at the beginning of April. 56.8% of the admissions were male and 43.2% were female. The average age of the 500 admissions was 69.32 years (SD 19.23 years, range 1 week to 99.21 years). By the morning of 14 April 2020, 199 patients had been discharged (Female 89, Male 111), 163 patients had died (female 61, male 102) and 131 remained as in-patients (female 66, male 71). Fewer than one in twenty deaths occurred in patients below the age of 50 years, in either gender. Mortality rose dramatically, for both genders, after the age of sixty with males being almost twice as vulnerable to dying, as females, during the 7th decade. Males older than their mid-fifties were more likely to die than leave hospital. The same applied to females beyond their mid seventies. We did not see any evidence of a poorer outcome associated with a lower decile for Index of Multiple Deprivation or convincing evidence that any Ethnic minority groups were more likely to die than the White subgroups. When compared to the equivalent medical conditions, normally treated in the early spring, COVID-19 has an increased mortality, adversely affecting more men and an older population. The mean duration from admission to discharge was 11.29 days (SD 11.50 days). For admission to death, the mean interval was 11.72 days (SD 11.05 days). 62 of the 500 admissions required ventilator support. Of this subgroup, 71% were male and 29% were female. By the morning of the 14 April, no female over the age of 60 had left the intensive care unit alive and no male over the age of 50 had left the intensive care unit alive. At this time-point, 1.2% of the 500 admitted patients had returned alive from the intensive care units, following a period of ventilator support. This figure will rise if prolonged ventilator and renal support proves effective. While only providing a snapshot of a relatively small number of patients, reviewed over a short time period, from a small geographic area, the data supports the view that the younger members of society are less vulnerable to the adverse sequelae of COVID-19 infection and that any return to normal work and social activities should be considered initially for the individuals who are less than 40-50 years of age. There is an ongoing need for analyses on larger patient cohorts using both demographic and detailed clinical data.


title: Impact of COVID-19 Lockdown Policy on Homicide, Suicide, and Motor Vehicle Deaths in Peru

text: Introduction: Although lockdown measures to stop COVID-19 have direct effects on disease transmission, their impact on violent and accidental deaths remains unknown. Our study aims to assess the early impact of COVID-19 lockdown on violent and accidental deaths in Peru. Methods: Based on data from the Peruvian National Death Information System, an interrupted time series analysis was performed to assess the immediate impact and change in the trend of COVID-19 lockdown on external causes of death including homicide, suicide, and traffic accidents. The analysis was stratified by sex and the time unit was every 15 days. Results: All forms of deaths examined presented a sudden drop after the lockdown. The biggest drop was in deaths related to traffic accidents, with a reduction of 12.66 deaths per million men per month (95% CI: -15.56, -9.76) and 3.64 deaths per million women per month (95% CI:-5.25, -2.03). Homicide and suicide presented similar level drop in women, while the homicide reduction was twice the size of the suicide reduction in men. The slope in suicide in men during the lock-down period increased by 3.62 deaths per million men per year (95% CI:0.06, 7.18). No other change in slope was detected. Conclusions: Violent and accidental deaths presented a sudden drop after the lockdown was implemented and an increase in suicide in men was observed. Falls in mobility have a natural impact on traffic accidents, however, the patterns for suicide and homicide are less intuitive and reveal important characteristics of these events, although we expect all of these changes to be transient.


title: Serum Mycoplasma Pneumoniae IgG in COVID-19: A Protective Factor

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


title: Validation and comparison of PICTURE analytic and Epic Deterioration Index for COVID-19

text: Introduction The 2019 coronavirus (COVID-19) has led to unprecedented strain on healthcare facilities across the United States. Accurately identifying patients at an increased risk of deterioration may help hospitals manage their resources while improving the quality of patient care. Here we present the results of an analytical model, PICTURE (Predicting Intensive Care Transfers and other UnfoReseen Events), to identify patients at a high risk for imminent intensive care unit (ICU) transfer, respiratory failure, or death with the intention to improve prediction of deterioration due to COVID-19. We compare PICTURE to the Epic Deterioration Index (EDI), a widespread system which has recently been assessed for use to triage COVID-19 patients. Methods The PICTURE model was trained and validated on a cohort of hospitalized non-COVID-19 patients using electronic health record data from 2014-2018. It was then applied to two hold-out test sets: non-COVID-19 patients from 2019 and patients testing positive for COVID-19 in 2020. PICTURE results were aligned to the EDI for head-to-head comparison via Area Under the Receiver Operator Curve (AUROC) and Area Under the Precision Recall Curve (AUPRC). We compared the models' ability to predict an adverse event (defined as ICU transfer, mechanical ventilation use, or death) at two levels of granularity: (1) maximum score across an encounter with a minimum lead time before the first adverse event and (2) predictions at every observation with instances in the last 24 hours before the adverse event labeled as positive. PICTURE and the EDI were also compared on the encounter level using different lead times extending out to 24 hours. Shapley values were used to provide explanations for PICTURE predictions. Results PICTURE successfully delineated between high- and low-risk patients and consistently outperformed the EDI in both of our cohorts. In non-COVID-19 patients, PICTURE achieved an AUROC (95% CI) of 0.819 (0.805 - 0.834) and AUPRC of 0.109 (0.089 - 0.125) on the observation level, compared to the EDI AUROC of 0.762 (0.746 - 0.780) and AUPRC of 0.077 (0.062 - 0.090). On COVID-19 positive patients, PICTURE achieved an AUROC of 0.828 (0.794 - 0.869) and AUPRC of 0.160 (0.089 - 0.199), while the EDI scored an AUROC of 0.792 (0.754 - 0.835) and AUPRC of 0.131 (0.092 - 0.159). The most important variables influencing PICTURE predictions in the COVID-19 cohort were a rapid respiratory rate, a high level of oxygen support, low oxygen saturation, and impaired mental status (Glasgow coma score). Conclusion The PICTURE model is more accurate in predicting adverse patient outcomes for both general ward patients and COVID-19 positive patients in our cohorts compared to the EDI. The ability to consistently anticipate these events may be especially valuable when considering a potential incipient second wave of COVID-19 infections. PICTURE also has the ability to explain individual predictions to clinicians by ranking the most important features for a prediction. The generalizability of the model will require testing in other health care systems for validation.


title: Application value of chest multi-detector spiral CT in diagnosis and follow-up of corona virus disease 2019/ 胸部多排螺旋CT在新型冠状病毒肺炎诊断及随访中的应用价值

text: Objective: To explore the application value of chest multi-detector spiral CT (MDSCT) in diagnosis and follow-up of corona virus disease 2019 (COVID-19). Methods: The first time chest MDSCT images of 40 common type COVID-19 patients and 20 times re-examinations of MDSCT during follow-up of 15 patients were analyzed retrospectively. Results: The first time MDSCT showed that the distribution of lesions were mainly bilateral (36/40, 90.00%) and subpleural extramedullary (38/40, 95.00%), involved 5 lobes in 28 cases (28/40, 70.00%), which were patchy, flaky and irregular shaped in 36 cases (36/40, 90.00%). Among 40 patients, 16 cases were in the early stage, 24 cases of the progressive stage, no case in the dissipation stage. Early stage MDSCT showed multiple ground glass opacity (GGO) in both lungs, 18.75% (3/16) cases with thin consolidation, 31.25% (5/16) cases with obvious consolidation. All progressive stage cases were found with varying degrees of consolidation. Fifteen patients underwent MDSCT follow-up, the absorption of lesions changed from the progressive stage to the dissipated stage in 4 cases, while lesions progressed in 11 cases. Conclusion: MDSCT can be used to evaluate the changes of lung condition, which is valuable for early diagnosis and follow-up of COVID-19.


title: Extracellular electron transfer-dependent anaerobic oxidation of ammonium by anammox bacteria

text: Anaerobic ammonium oxidation (anammox) by anammox bacteria contributes significantly to the global nitrogen cycle, and plays a major role in sustainable wastewater treatment. Anammox bacteria convert ammonium (NH4+) to dinitrogen gas (N2) using nitrite (NO2−) or nitric oxide (NO) as the electron acceptor. In the absence of NO2− or NO, anammox bacteria can couple formate oxidation to the reduction of metal oxides such as Fe(III) or Mn(IV). Their genomes contain homologs of Geobacter and Shewanella cytochromes involved in extracellular electron transfer (EET). However, it is still unknown whether anammox bacteria have EET capability and can couple the oxidation of NH4+ with transfer of electrons to carbon-based insoluble extracellular electron acceptors. Here we show using complementary approaches that in the absence of NO2−, freshwater and marine anammox bacteria couple the oxidation of NH4+ with transfer of electrons to carbon-based insoluble extracellular electron acceptors such as graphene oxide (GO) or electrodes poised at a certain potential in microbial electrolysis cells (MECs). Metagenomics, fluorescence in-situ hybridization and electrochemical analyses coupled with MEC performance confirmed that anammox electrode biofilms were responsible for current generation through EET-dependent oxidation of NH4+. 15N-labelling experiments revealed the molecular mechanism of the EET-dependent anammox process. NH4+ was oxidized to N2 via hydroxylamine (NH2OH) as intermediate when electrode was the terminal electron acceptor. Comparative transcriptomics analysis supported isotope labelling experiments and revealed an alternative pathway for NH4+ oxidation coupled to EET when electrode is used as electron acceptor compared to NO2−as electron acceptor. To our knowledge, our results provide the first experimental evidence that marine and freshwater anammox bacteria can couple NH4+ oxidation with EET, which is a significant finding, and challenges our perception of a key player of anaerobic oxidation of NH4+ in natural environments and engineered systems.


title: Rapid identification of SARS-CoV-2-infected patients at the emergency department using routine testing

text: Background: The novel coronavirus disease 19 (COVID-19), caused by SARS-CoV-2, spreads rapidly across the world. The exponential increase in the number of cases has resulted in overcrowding of emergency departments (ED). Detection of SARS-CoV-2 is based on an RT-PCR of nasopharyngeal swab material. However, RT-PCR testing is time-consuming and many hospitals deal with a shortage of testing materials. Therefore, we aimed to develop an algorithm to rapidly evaluate an individual′s risk of SARS-CoV-2 infection at the ED. Methods: In this multicenter retrospective study, routine laboratory parameters (C-reactive protein, lactate dehydrogenase, ferritin, absolute neutrophil and lymphocyte counts), demographic data and the chest X-ray/CT result from 967 patients entering the ED with respiratory symptoms were gathered. Using these parameters, an easy-to-use point-based algorithm, called the corona-score, was developed to discriminate between patients that tested positive for SARS-CoV-2 by RT-PCR and those testing negative. Computational sampling was used to optimize the corona-score. Validation of the model was performed using data from 592 patients. Results: The corona-score model yielded an area under the receiver operating characteristic curve of 0.91 in the validation population. Patients testing negative for SARS-CoV-2 showed a median corona-score of 3 versus 11 (scale 0-14) in patients testing positive for SARS-CoV-2 (p<0.001). Using cut-off values of 4 and 11 the model has a sensitivity and specificity of 96% and 95%, respectively. Conclusion: The corona-score effectively predicts SARS-CoV-2 RT-PCR outcome based on routine parameters. This algorithm provides the means for medical professionals to rapidly evaluate SARS-CoV-2 infection status of patients presenting at the ED with respiratory symptoms.


title: The National Early Warning Score (NEWS2) systematically underestimates the risk of in-hospital mortality in unplanned COVID-19 admissions to hospital.

text: Background: Although the National Early Warning Score (NEWS) and its latest version NEWS2 are recommended for monitoring for deterioration in patients admitted to hospital, little is known about their performance in COVID-19 patients. We analysed the performance of National Early Warning Score (NEWS2) during the first phase of the COVID-19 pandemic. Methods: Adult non-elective admissions discharged between 11-March-2020 to 13-June-2020 with an index NEWS2 electronically recorded within 24 hours of admission are used to predict mortality at four time points (in-hospital, 24hours, 48hours, and 72hours) in COVID-19 versus non-COVID-19 admissions. Results: Out of 6480 non-elective admissions, 620 (9.6%) had a diagnosis of COVID-19. They were older (73.3 vs 67.7yrs), more often male (54.7% vs 50.1%), had higher index NEWS (4 vs 2.5) and NEWS2 (4.6 vs 2.8) scores and higher in-hospital mortality (32.1% vs 5.8%). The c-statistics for predicting in-hospital mortality in COVID-19 admissions was significantly lower using NEWS (0.64 vs 0.74) or NEWS2 (0.64 vs 0.74), however these differences reduced at 72hours (NEWS: 0.75 vs 0.81; NEWS2: 0.71 vs 0.81), 48 hours (NEWS: 0.78 vs 0.81; NEWS2: 0.76 vs 0.82) and 24hours (NEWS: 0.84 vs 0.84; NEWS2: 0.86 vs 0.84). Increasing NEWS2 values reflected increased mortality, but for any given value the absolute risk was on average 24% higher (e.g.NEWS2=5: 36% vs 9%). Interpretation: NEWS2 is a valid predictor of the mortality risk but substantially underestimates the absolute mortality risk in COVID-19 patients. Clinical staff


title: Establishment of a Replicon System for Bourbon Virus and Identification of Small Molecules that Efficiently Inhibit Virus Replication

text: Bourbon virus (BRBV) was first isolated from a patient hospitalized at the University of Kansas Hospital in 2014. Since then, several deaths have been reported to be caused by BRBV infection in the Midwest and Southern United States. BRBV is a tick-borne virus that is widely carried by lone star ticks. It belongs to genus Thogotovirus of the Orthomyxoviridae family. Currently, there are no treatments or vaccines available for BRBV or thogotovirus infection caused diseases. In this study, we reconstituted a replicon reporter system, composed of plasmids expressing the RNA-dependent RNA polymerase (RdRP) complex (PA, PB1 and PB2), nucleocapsid (NP) protein, and a reporter gene flanked by the 3’ and 5’ UTR of the envelope glycoprotein (GP) genome segment. By using the luciferase reporter, we screened a few small molecule compounds of anti-endonuclease that inhibited the nicking activity by parvovirus B19 (B19V) NS1, as well as FDA-approved drugs targeting the RdRP of influenza virus. Our results demonstrated that myricetin, and an anti-B19V NS1 nicking inhibitor, efficiently inhibited the RdRP activity of BRBV and virus replication. The IC50 and EC50 of myricetin are 2.22 μM and 4.6 μM, respectively, in cells. Myricetin had minimal cytotoxicity in cells, and therefore the therapeutic index of the compound is high. In conclusion, the BRBV replicon system is a useful tool to study viral RNA replication and to develop antivirals, and myricetin may hold promise in treatment of BRBV infected patients.


title: Comprehensive characterization of N- and O- glycosylation of SARS-CoV-2 human receptor angiotensin converting enzyme 2

text: Emergence of COVID-19 pandemic caused by SARS-CoV-2 demanded development of new therapeutic strategies and thus the understanding the mode of viral attachment, entry and replication has become key aspect for such interventions. The coronavirus surface features a trimeric spike (S) protein that is essential in viral attachment, entry and membrane fusion. The S protein of SARS-CoV-2 binds to the human angiotensin converting enzyme 2 (hACE2) for the entry and the serine protease TMPRSS2 for S protein priming. The heavily glycosylated S protein is comprised of two protein subunits (S1 and S2), and the receptor binding domain within S1 subunit binds with to the hACE2 receptor. Even though hACE2 has been known for two decades and has been recognized as the entry point of several human coronaviruses, no comprehensive glycosylation characterization of hACE2 has been reported. Herein, we describe the quantitative glycosylation mapping on hACE2 expressed in human cells by both glycoproteomics and glycomics. We observed heavy glycan occupancy at all the seven possible N-glycosylation sites and surprisingly, detected three novel O-glycosylation sites. In order to deduce the detailed structure of glycan epitopes on hACE2 involved with viral binding, we have characterized the terminal sialic acid linkages, presence of bisecting GlcNAc and also the pattern of N-glycan fucosylation. We have conducted extensive manual interpretation of each glycopeptide and glycan spectra in addition to the use of bioinformatics tools to validate the hACE2 glycosylation. Elucidation of the site-specific glycosylation and its terminal orientations on the hACE2 receptor can aid in understanding the intriguing virus-receptor interactions and help in the development of novel therapeutics to circumvent the viral entry.


Statements about COVID-19/ Statements zu COVID-19


title: A non-parametric mathematical model to investigate the dynamic of a pandemic

text: Populations are diverse in size, capacity response, and measures to contain a pandemic such covid19. Then, it rises serious and critical questions to whether general measures can be taken worldwide. Also, it is unclear if conventional parametric methods are suitable to study pandemics since their dynamic is modulated by biological, economical, environmental, social, and cultural factors. In this manuscript, we apply a recently developed non-parametric mathematical method that comes from regional economy, to investigate the dynamic of a pandemic. We apply this novel methodology to study the ongoing covid19 pandemic in all USA states and in the country itself. The generality of our methodology makes it suitable to investigate also the worldwide dynamics of diseases such HIV or tuberculosis.


title: Analysis and Prediction of the COVID-19 outbreak in Pakistan

text: In this study, we estimate the severity of the COVID-19 outbreak in Pakistan prior to and after lockdown restrictions were eased. We also project the epidemic curve considering realistic quarantine, social distancing, and possible medication scenarios. We use a deterministic epidemic model that includes asymptomatic, quarantined, isolated, and medicated population compartments for our analysis. We calculate the basic reproduction number R0 for the pre and post lockdown periods, noting that during this time, no medication was available. The pre-lock down the value of R0 is estimated to be 1.07, and the post lockdown value is estimated to be 1.86. We use this analysis to project the epidemic curve for a variety of lockdown, social distancing, and medication scenarios. We note that if no substantial efforts are made to contain the epidemic, it will peak in mid of September, with the maximum projected active cases being close to 700,000. In a realistic, best-case scenario, we project that the epidemic peaks in early to mid-July with the maximum active cases being around 120000.We note that social distancing measures and medication, if available, will help flatten the curve, however without the reintroduction of further lockdown, it would be very difficult to bring R0 below 1. Our study strongly supports the recent WHO recommendation of reintroducing lockdowns to control the epidemic.


title: Brief Review on COVID-19: The 2020 Pandemic Caused by SARS-CoV-2

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


Public management reform in global context


title: Poolkeh Finds the Optimal Pooling Strategy for a Population-wide COVID-19 Testing (Israel, UK, and US as Test Cases)

text: The SARS-CoV-2 pandemic has changed the lifestyle of citizens of the world. In order for decision makers to manage the viral spread of COVID-19 both in the intra-national and the international frontiers, it is essential to operate based on data-driven assessments. It's crucial to do so rapidly and frequently, since the nature of the viral spread grows exponentially and can burst worldwide again. A fast and accurate health status of individuals globally during a pandemic can save many lives and bring life back to a new normal. Herein, we present a data-driven tool to allow decision-makers to assess the spread of the virus among the world population. Our framework allows health agencies to maximize the throughput of COVID-19 tests among the world population by finding the best test pooling that fits the current SIR-D status of the nation.


title: Estimation of the final size of the second phase of the coronavirus epidemic by the logistic model

text: In the note, the logistic growth regression model is used for the estimation of the final size and its peak time of the coronavirus epidemic in China, South Korea, and the rest of the World.


title: Foundational research and NIH funding enabling Emergency Use Authorization of remdesivir for COVID-19

text: Emergency Use Authorization for remdesivir months after discovery of COVID19 is unprecedented. Typically, decades of research and public sector funding are required to establish the mature body of foundational research requisite for efficient, targeted drug discovery and development. This work quantifies the body of research related to the biological target of remdesivir, RNA-dependent RNA polymerase (RdRp), or parent chemical structure, nucleoside analogs (NcAn), through 2019, as well as NIH funding for this research from 2000 to 2019. There were 6,567 RdRp related publications in PubMed, including 1,263 with NIH support, and 11,073 NcAn-related publications, including 2,319 with NIH support. NIH support for RdRp research comprised 2,203 Project Years with Costs of $1,875 million. NIH support for NcAn research comprised 4,607 Project Years with Costs of $4,612 million. Research Project grants accounted for 63% and 48% of Project Years for RdRp and NcAn respectively, but only 19% and 12% of Project Costs. Analytical modeling of research maturation estimates that RdRp and NcAn research passed an established maturity threshold in 2008 and 1994 respectively. Of 97 investigational compounds targeting RdRp since 1989, the three authorized for use entered clinical trials after both thresholds. This work demonstrates the scale of foundational research on the biological target and parent chemical structure of remdesivir that supported its discovery and development for COVID19. This work identifies $6.5 billion in NIH funding for research leading to remdesivir, underscoring the role of public sector investments in basic research and research infrastructure that underlie new drugs and the response to emergent disease.


title: The effect of RAS blockers on the clinical characteristics of COVID-19 patients with hypertension

text: Background: Coronavirus disease 2019 (COVID-19), caused by a novel coronavirus (designated as SARS-CoV-2) has become a pandemic worldwide. Based on the current reports, hypertension may be associated with increased risk of sever condition in hospitalized COVID-19 patients. Angiotensin-converting enzyme 2 (ACE2) was recently identified to functional receptor of SARS-CoV-2. Previous experimental data revealed ACE2 level was increased following treatment with ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). Currently doctors concern whether these commonly used renin-angiotensin system (RAS) blockers-ACEIs/ARBs may increase the severity of COVID-19. Methods: We extracted data regarding 50 hospitalized hypertension patients with laboratory confirmed COVID-19 in the Renmin Hospital of Wuhan University from Feb 7 to Mar 03, 2020. These patients were grouped into RAS blockers group (Group A, n=20) and non-RAS blockers group (Group B, n=30) according to the basic blood pressure medications. All patients continued to use pre-admission antihypertensive drugs. Clinical severity (symptoms, laboratory and chest CT findings, etc.), clinical course, and short time outcome were analyzed after hospital admission. Results: Ten (50%) and seventeen (56.7%) of the Group A and Group B participants were males (P=0.643), and the average age was 52.65±13.12 and 67.77±12.84 years (P=0.000), respectively. The blood pressure of both groups was under effective control. There was no significant difference in clinical severity, clinical course and in-hospital mortality between Group A and Group B. Serum cardiac troponin I (cTnI) (P=0.03), and N-terminal (NT)-pro hormone BNP (NT-proBNP) (P=0.04) showed significant lower level in Group A than in Group B. But the patients with more than 0.04ng/mL or elevated NT-proBNP level had no statistical significance between the two groups. In patients over 65 years or under 65 years, cTnI or NT-proBNP level showed no difference between the two groups. Conclusions: We observed there was no obvious difference in clinical characteristics between RAS blockers and non-RAS blockers groups. These data suggest ACEIs/ARBs may have few effects on increasing the clinical severe conditions of COVID-19.


title: Serum anti-NMDA-receptor antibodies and cognitive function after ischemic stroke (PROSCIS-B)

text: Objective: We aimed to investigate whether serum anti-N-Methyl-D-Aspartate-receptor GluN1 antibodies (NMDAR1-abs) are associated with worse cognitive function over three years after first ischemic stroke. Methods: Data were used from the PROSpective Cohort with Incident Stroke-Berlin (PROSCIS-B;NCT01363856). NMDAR1-abs (IgM/IgA/IgG) were measured with cell-based assays from serum obtained within seven days after first-ever stroke. Seropositivity was defined as titers >1:10, low titers as <1:100 and high titers as >1:100. We assessed cognitive status annually up to three years after stroke with the Telephone Interview for Cognitive Status - modified (TICS-m) and used crude and adjusted linear mixed models to estimate the impact of NMDAR1-abs exposure on TICS-m over time. Results: Data on NMDAR1-abs (median day of sampling=4[IQR=2-5]) were available in 583 of 621 PROSCIS-B patients (39% female; median NIHSS=2[IQR=1-4]; median MMSE=28[IQR:26-30]; median mRS=2[IQR=1-3]) of whom 76(13%) were seropositive (IgM:n=48/IgA:n=43/IgG:n=2). TICS-m over time was not different in NMDAR1-abs seropositive compared to seronegative patients (Crude beta=0.38[95%CI=-1.00 to 1.76]; adjusted beta Model3=0.30[95%CI=-1.14 to 1.73]). In subgroups, TICS-m over time was not different in patients with low titers (Crude beta=1.53[95%CI=-0.06 to 3.11]; adjusted beta Model3=1.42[95%CI= 0.23 to 3.08]), however, in patients with high titers TICS-m was lower in the crude model (Crude beta= 2.54[95%CI=-4.99 to -0.08]), with a similar effect size after confounder adjustment (adjusted beta Model3=-2.30[95%CI=-4.82 to 0.21]). All groups were compared to seronegative patients, respectively. Conclusion: Overall NMDAR1-abs seropositivity was not associated with cognitive function over time after first-ever mild-to-moderate ischemic stroke. Our data suggest that high titers associate with impaired cognitive function after stroke, warranting larger studies.


title: Low levels of the prognostic biomarker suPAR are predictive of mild outcome in patients with symptoms of COVID-19 - a prospective cohort study

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


title: A preliminary study on serological assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 238 admitted hospital patients

text: Background The outbreak of the recently emerged novel corona virus disease 2019 (COVID-19) poses a challenge for public health laboratories. We aimed to evaluate the diagnostic value of serological assay for SARS-CoV-2. Methods A newly-developed ELISA assay for IgM and IgG antibodies against N protein of SARS-CoV-2 were used to screen the serums of 238 admitted hospital patients with confirmed or suspected SARS-CoV-2 infection from February 6 to February 14, 2020. SARS-CoV-2 RNA was detected by real time RT-PCR on pharyngeal swab specimens. Findings Of the 238 patients, 194 (81.5%) were detected to be antibody (IgM and/or IgG) positive, which was significantly higher than the positive rate of viral RNA (64.3%). There was no difference in the positive rate of antibody between the confirmed patients (83.0%, 127/153) and the suspected patients (78.8%, 67/85) whose nucleic acid tests were negative. After the patients were defined to the different stages of disease based on the day when the test samples were collected, the analysis results showed that the antibody positive rates were very low in the first five days after initial onset of symptoms, and then rapidly increased as the disease progressed. After 10 days, the antibody positive rates jumped to above 80% from less than 50%. On the contrary, the positive rates of viral RNA kept above 60% in the first 11 days after initial onset of symptoms, and then rapidly decreased. In addition, half of the suspected patients with symptoms for 6-10 days were detected to be antibody positive. Interpretation The suspected patients were most likely infected by SARS-CoV-2. Before the 11th day after initial onset of symptoms, nucleic acid test is important for confirmation of viral infection. The combination of serological assay can greatly improve the diagnostic efficacy. After that, the diagnosis for viral infection should be majorly dependent on serological assay. Keywords. SARS-CoV-2; diagnosis; serological assay; nucleic acid test


title: Controlling the SARS-CoV-2 outbreak, insights from large scale whole genome sequences generated across the world

text: Background SARS-CoV-2 most likely evolved from a bat beta-coronavirus and started infecting humans in December 2019. Since then it has rapidly infected people around the world, with more than 4.5 million confirmed cases by the middle of May 2020. Early genome sequencing of the virus has enabled the development of molecular diagnostics and the commencement of therapy and vaccine development. The analysis of the early sequences showed relatively few evolutionary selection pressures. However, with the rapid worldwide expansion into diverse human populations, significant genetic variations are becoming increasingly likely. The current limitations on social movement between countries also offers the opportunity for these viral variants to become distinct strains with potential implications for diagnostics, therapies and vaccines. Methods We used the current sequencing archives (NCBI and GISAID) to investigate 15,487 whole genomes, looking for evidence of strain diversification and selective pressure. Results We used 6,294 SNPs to build a phylogenetic tree of SARS-CoV-2 diversity and noted strong evidence for the existence of two major clades and six sub-clades, unevenly distributed across the world. We also noted that convergent evolution has potentially occurred across several locations in the genome, showing selection pressures, including on the spike glycoprotein where we noted a potentially critical mutation that could affect its binding to the ACE2 receptor. We also report on mutations that could prevent current molecular diagnostics from detecting some of the sub-clades. Conclusion The worldwide whole genome sequencing effort is revealing the challenge of developing SARS-CoV-2 containment tools suitable for everyone and the need for data to be continually evaluated to ensure accuracy in outbreak estimations.


title: Covid-19 is an unnatural disaster: Hope in revelatory moments of crisis

text: The unfolding COVID-19 pandemic has closed borders, grounded planes, quarantined more than half of the world’s population, triggered anxiety en masse, and shaken global capitalism to its core. Scholars of the political ecology of disasters have sought to denaturalize so-called “natural” disasters by demonstrating their uneven consequences. Work in the political ecology of health similarly accounts for how risk of illness and disease are socio-economically mediated. While this scholarship has demonstrated the need to contextualize the unequal fallout from ecological and health disasters in ways that reveal the festering wounds of structural inequality, we know much less about how hope is cultivated in moments of crisis. The current revelatory moment of the COVID-19 pandemic offers an opportunity to find hope in the rubble through the deconstruction of framings of crisis as “error” and by homing in on the current and potential role of tourism to contribute to a more socially and environmentally just society. This reframing the pandemic as an "unnatural" disaster opens new debates at the intersection of tourism geographies and political ecologies of hope in revelatory moments of crisis.


title: Hospital-acquired infective endocarditis during Covid-19 pandemic

text: Background. The COVID pandemic has had a major impact on healthcare in hospitals, including the diagnosis and treatment of infections. Hospital-acquired infective endocarditis (HAIE) is a severe complication of medical procedures that has shown a progressive increase in recent years. Objectives. to determine whether the incidence of HAIE during the first two months of the epidemic (March-April 2020) was higher than previously observed and to describe the clinical characteristics of these cases. The probability of studied event (HAIE) during the studied period was calculate by Poisson distribution. Results. Four cases of HAIE were diagnosed in our institution during the study period. The incidence of HAIE during the study period was 2/patient-month and 0.25/patient-month during the previous 5 years (p=0.024). Two cases appeared during admission for COVID-19 with pulmonary involvement treated with metilprednisolone and tocilizumab. The other two cases were admitted to the hospital during the epidemic. All cases underwent central venous and urinary catheterization during admission. The etiology of HAIE was Enterococcus faecalis (2 cases), Staphylococcus aureus and Candida albicans (one case each). A source of infection was identified in three cases (central venous catheter, peripheral venous catheter, sternal wound infection, respectively). One patient was operated on. There were no fatalities during the first 30 days of follow-up. Conclusion. The incidence of HAIE during COVID-19 pandemic in our institution was higher than usual. In order to reduce the risk of this serious infection, optimal catheter care, appropriate use of corticosteroids and interleukin antagonists and early treatment of every local infection should be prioritized during coronavirus outbreaks.


title: A two-wave epidemiological model of COVID-19 outbreaks using MS-Excel(R)

text: The emergence of the coronavirus SARS-CoV-2 has raised a global issue and a pandemic disease outbreak, COVID-19, was declared by the World Health Organization on March 12th, 2020. The new virus is rapidly spreading in humans and cases of severe acute respiratory syndromes are being reported worldwide. Health authority advisors and governments from small towns to large countries need to quickly manage and deal with growing epidemiological data on a daily basis. In this work, current available data from reported cases and deaths over time were analyzed and treated. Lethality has been calculated by finding linearization of death cases against reported ones, using a time-delayed data transposition. A two-wave statistical model, 2WM, based on the superposition of normal distributions was used to fit current data and to estimate the evolution of infections and deaths, using Microsoft Excel(R). The model showed good agreement even for apparent single wave behavior in some countries and can easily be extended to any number of waves. A gamma distribution was used as a risk function to estimate death probability from patient admission to reported death. Evolution of fatality cases over time can then be estimated from the model with reasonable accuracy. Data from South Korea, China, Australia, Germany, Italy and Spain were used to validate the model. Data from The United States, United Kingdom and Brazil were used to study the epidemiology as the pandemic progresses. Additionally, the 2WM was applied to world data and to the Brazilian state of Santa Catarina. The model was implemented in MS-Excel, a popular and easy to use analytical tool. A template spreadsheet is provided as supplementary material. Constant lethality can be determined from the initial stage of the pandemic wave. Values ranged from 1.7% to 15.3%, depending on the degree of possible sub notification cases. Even for places with low testing, a linear relationship can be found. The two-wave model can be fine-tuned to properly adjust the data. The second wave pattern was estimated according to the first wave parameter. The accuracy for estimating COVID-19 evolution was compared to the classic SIR model with good agreement. According to the model, based on current trends, health protocols and policies, approximately 10,000,000 cases and 860,000 deaths will be recorded worldwide. Approximately 99% of that number would be reached by the end of July 2020 given constant conditions.


title: Chloroquine and hydroxychloroquine for the treatment of COVID-19: A living systematic review protocol

text: OBJECTIVE: To determine the relative impact of the use of chloroquine and hydroxychloroquine on outcomes important to patients with COVID 19. DESIGN: This is the protocol of a living systematic review. DATA SOURCES: We will conduct searches in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), trial registries, grey literature and in a centralised repository in L-OVE (Living OVerview of Evidence). L-OVE is a platform that maps PICO questions to evidence from Epistemonikos database. In response to the COVID-19 emergency, L-OVE was adapted to expand the range of evidence it covers and customised to group all COVID-19 evidence in one place. The search will cover the period until the day before submission to a journal. ELIGIBILITY CRITERIA FOR SELECTING STUDIES AND METHODS: We will follow a common protocol for multiple parallel systematic reviews, already published and submitted to PROSPERO (awaiting ID allocation). We will include randomised controlled trials evaluating the effect of chloroquine and hydroxychloroquine - as monotherapy or in combination with other drugs - versus placebo or no treatment in patients with COVID-19. Randomised trials evaluating chloroquine and hydroxychloroquine in infections caused by other coronaviruses, such as MERS-CoV and SARS-CoV, and non-randomised studies in COVID-19 will be searched in case no direct evidence from randomised trials is found, or if the direct evidence provides low- or very low-certainty for critical outcomes. Two reviewers will independently screen each study for eligibility, extract data, and assess the risk of bias. We will perform random-effects meta-analyses and use GRADE to assess the certainty of the evidence for each outcome. A living, web-based version of this review will be openly available during the COVID-19 pandemic. We will resubmit it if the conclusions change or there are substantial updates. ETHICS AND DISSEMINATION: No ethics approval is considered necessary. The results of this review will be widely disseminated via peer-reviewed publications, social networks and traditional media.


title: Triaging of Respiratory Protective Equipment on the assumed risk of SARS-CoV-2 aerosol exposure in patient-facing healthcare workers delivering secondary care: a rapid review

text: ABSTRACT BACKGROUND Objectives: "In patient-facing healthcare workers delivering secondary care, what is the evidence behind UK Government PPE Guidance on surgical masks versus respirators for SARS-CoV-2 protection?" METHODS Two independent reviewers searched MEDLINE, Google Scholar and grey literature 11th-30th April 2020. Studies published on any date containing primary data comparing surgical facemasks and respirators specific to SARS-CoV-2, and studies underpinning government PPE guidance, were included. Appraisal was performed using CASP checklists. Results were synthesised by comparison of findings and appraisals. RESULTS In all three laboratory studies of 14 different respirators and 12 surgical facemasks, respirators were significantly more effective than facemasks in protection factors, reduction factors, filter penetrations, and total inspiratory leakages at differing particle sizes, mean inspiratory flows, and breathing rates. Tests included live viruses and inert particles on dummies and humans. In six clinical studies, 6,502 participants, there was no consistent definition of "exposure" to determine the efficacy of RPE. It is difficult to define "safe". The only statistically significant result found continuous use of respirators more effective in clinical respiratory illness compared to targeted use or surgical facemask. CONCLUSIONS There is a paucity of evidence on the comparison of FRSMs and respirators specific to SARS-CoV-2, and poor-quality evidence in other contexts. Indirectness results in extrapolation of non-SARS-CoV-2 specific data to guide UK Government PPE guidance. The appropriateness of this is unknown given the uncertainty over the transmission of SARS-CoV-2. 1. The evidence base for UK Government PPE guidelines is not based on SARS-CoV-2 and requires generalisation from low-quality evidence of other pathogens/particles. 2. There is a paucity of high-quality evidence regarding the efficacy of RPE specific to SARS-CoV-2. 3. HMG's PPE guidelines are underpinned by the assumption of droplet transmission of SARS-CoV-2. Triaging the use of FFP3 respirators might increase the risk of COVID-19 faced by some. FUNDING This review was unfunded and unsponsored.


title: Mechanobiology predicts raft formations triggered by ligand-receptor activity across the cell membrane

text: Clustering of ligand-binding receptors of different types on thickened isles of the cell membrane, namely lipid rafts, is an experimentally observed phenomenon. Although its influence on cell’s response is deeply investigated, the role of the coupling between mechanical processes and multiphysics involving the active receptors and the surrounding lipid membrane during ligand-binding has not yet been understood. Specifically, the focus of this work is on G-protein-coupled receptors (GPCRs), the widest group of transmembrane proteins in animals, which regulate specific cell processes through chemical signalling pathways involving a synergistic balance between the cyclic Adenosine Monophosphate (cAMP) produced by active GPCRs in the intracellular environment and its efflux, mediated by the Multidrug Resistance Proteins (MRPs) transporters. This paper develops a multiphysics approach based on the interplay among energetics, multiscale geometrical changes and mass balance of species, i.e. active GPCRs and MRPs, including diffusion and kinetics of binding and unbinding. Because the obtained energy depends upon both the kinematics and the changes of species densities, balance of mass and of linear momentum are coupled and govern the space-time evolution of the cell membrane. The mechanobiology involving remodelling and change of lipid ordering of the cell membrane allows to predict dynamics of transporters and active receptors –in full agreement with experimentally observed cAMP levels– and how the latter trigger rafts formation and cluster on such sites. Within the current scientific debate on Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) and on the basis of the ascertained fact that lipid rafts often serve as an entry port for viruses, it is felt that approaches accounting for strong coupling among mechanobiological aspects could even turn helpful in better understanding membrane-mediated phenomena such as COVID-19 virus-cell interaction.


title: Acute kidney injury in patients hospitalized with COVID-19 in Wuhan, China: A single-center retrospective observational study

text: Background: The kidney may be affected in coronavirus-2019 disease (COVID-19). This study assessed the predictors and outcomes of acute kidney injury (AKI) among individuals with COVID-19. Methods: This observational study, included data on all patients with clinically confirmed COVID-19 admitted to Hankou Hospital, Wuhan, China from January 5 to March 8, 2020. Data were extracted from clinical and laboratory records. Follow-up was censored on March 8, 2020. This is a single-center, retrospective, observational study. Patients clinically confirmed COVID-19 and admitted to Hankou Hospital, Wuhan, China from January 5 to March 8, 2020 were enrolled. We evaluated the association between changes in the incidence of AKI and COVID-19 disease and clinical outcomes by using logistic regression models. Results: A total of 287 patients, 55 with AKI and 232 without AKI, were included in the analysis. Compared to patients without AKI, AKI patients were older, predominantly male, and were more likely to present with hypoxia and have pre-existing hypertension and cerebrovascular disease. Moreover, AKI patients had higher levels of white blood cells, D-dimer, aspartate aminotransferase, total bilirubin, creatine kinase, lactate dehydrogenase, procalcitonin, C-reactive protein, a higher prevalence of hyperkalemia, lower lymphocyte counts, and higher chest computed tomographic scores. The incidence of stage 1 AKI was 14.3%, and the incidence of stage 2 or 3 AKI was 4.9%. Patients with AKI had substantially higher mortality. Conclusions: AKI is an important complication of COVID-19. Older age, male, multiple pre-existing comorbidities, lymphopenia, increased infection indicators, elevated D-dimer, and impaired heart and liver functions were the risk factors of AKI. AKI patients who progressed to stages 2 or 3 AKI had a higher mortality rate. Prevention of AKI and monitoring of kidney function is very important for COVID 19 patients.


Health inequalities–Covid-19 will widen the gap


title: Mapping the changing Internet attention to the spread of coronavirus disease 2019 in China

text: The incessant spread of the coronavirus disease 2019 (COVID-19) has been a great threat to human health. By 17 March 2020, the number of laboratory-confirmed cases had exceeded 179,000, with more than 7000 deaths across at least 150 countries. Due to the extremely contagious nature of COVID-19, the Chinese government has made broad and aggressive responses to restrict movement, transportation, and business for six to eleven weeks. Wuhan, a city in Hubei province from which COVID-19 emanated, has been quarantined since 12 January 2020, and many other cities have been placed under travel restrictions. Citizens have been strongly encouraged to stay home and limit face-to-face contact; as a result, people’s daily lives are dominated by the Internet as never before. Here, we visualize the spread of COVID-19 and people’s Internet attention in China in the form of cartograms using the diffusion-based method.


Corona and no end/ Corona ohne Ende


title: Ethical issues related to the hydroxychloroquine treatment prescription for Covid-19

text: Abstract The 2019-20 coronavirus pandemic (COVID-19), has led to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, no drugs have demonstrated safety and efficacy in randomized controlled trials for patients with COVID-19. Although the association between Hydroxychloroquine and Azithromycin efficacy lack of solid evidence-base, several governments have adopted it for all virology confirmed Covid-19 cases even for those who are asymptomatic. In the following, we aim to discuss some of the ethical issues associated with the use of this treatment association. We mainly tried to discuss the following controversial questions: Is it ethical not to treat a patient while a treatment exists and is used for other indications than Covid-19 for which it’s not proven yet? If yes, is a randomized controlled trial to prove the hydroxychloroquine for the Covid-19 treatment, necessary, in the context of covid-19 pandemic? If No, is it the government’s right to decide the hydroxychloroquine treatment for all covid-19 patients? and what should be the physicians’ attitudes? Finally, what are the government, physicians, and patient’s rights and responsibilities? The paper conclude that, since health authorities in some countries recommended this off-label use treatment, physicians are challenged by the requirement of veracity while providing care to their patients and the implications of such a requirement; they are facing the challenge of balancing this guideline and their own conviction. Furthermore, the fundamental principles of beneficence and non-maleficence, and respect for persons should underlie any reflection process to address this dilemma. In addition, in a pandemic context, the limits between the government’s, practitioner’s and patient’s rights and obligations are not clear which could significantly endanger the universal ethical principles in clinical practice. It could also undermine any attempt to develop serious clinical trials to prove the considered off-label drug.


title: Chloroquine and COVID-19: A light at the end of the tunnel, or is it another train?

text: Over the last a few decades, the world has faced several viral disease outbreaks including Hendra, Nipah, severe acute respiratory syndrome (SARS), Influenza (H1N1), Middle East respiratory syndrome (MERS), Zika and most recently coronavirus disease 2019 (COVID-19). The economical and health impacts of the outbreaks were limited to certain affected areas only, but the recent outbreak of COVID-19 seems to have a global impact on human health, health resources and global economy.


title: Secondary bacterial infections in critical ill patients of COVID-19

text: Secondary bacterial infections occurred in 13.9% (5/36) of critical ill patients of COVID-19. All the five patients had been admitted to ICU and received mechanical ventilation before episode of bacterial infection. Active surveillance of culture should be performed for critical ill patients. Prevention of nosocomial infection needs to be taken seriously.


title: Non-Adherence Tree Analysis (NATA) - an adherence improvement framework: a COVID-19 case study

text: Poor adherence to medication is a global phenomenon that has received a significant amount of research attention yet remains largely unsolved. Medication non-adherence can blur drug efficacy results in clinical trials, lead to substantial financial losses, increase the risk of relapse and hospitalisation, or lead to death. The most common methods measuring adherence are post-treatment measures; that is, adherence is usually measured after the treatment has begun. What the authors are proposing in this multidisciplinary study is a technique for analysing the factors that can cause non-adherence before or during medication treatment. Fault Tree Analysis (FTA), allows system analysts to determine how combinations of simple faults of a system can propagate to cause a total system failure. Monte Carlo simulation is a mathematical algorithm that depends heavily on repeated random sampling to predict the behaviour of a system. In this study, the authors propose the use of Non-Adherence Tree Analysis (NATA), based on the FTA and Monte Carlo simulation techniques, to improve adherence. Firstly, the non-adherence factors of a medication treatment lifecycle are translated into what is referred to as a Non-Adherence Tree (NAT). Secondly, the NAT is coded into a format that is translated into the GoldSim software for performing dynamic system modelling and analysis using Monte Carlo. Finally, the GoldSim model is simulated and analysed to predict the behaviour of the NAT. This study produces a framework for improving adherence by analysing social and non-social adherence barriers. The results reveal that the biggest factor that could contribute to non-adherence to a COVID-19 treatment is a therapy-related factor (the side effects of the medication). This is closely followed by a condition-related factor (asymptomatic nature of the disease) then patient-related factors (forgetfulness and other causes). With this information, clinicians can implement relevant measures and allocate resources appropriately to minimise non-adherence.


title: Assessments of anxiety levels and working conditions of health employees working in COVİD-19 pandemic hospitals

text: The study aims to identify health care workers’ risk of COVID-19 and to determine employees’ views on working conditions and the fight against COVID-19 in general, and to present their concerns. The study utilized a survey form developed by researchers as a data collection tool. The research was conducted on 736 health workers in the Turkish population using the online survey method. Descriptive statistical methods, chi-square analysis, and correlation analysis were used in the analysis of the data. The data was carried out in a 95% confidence range. According to the study’s findings, 31.7% of the health care workers involved in the study had contact with 19 cases of COVID-19; 27.3% provided services to patients diagnosed with COVID-19. There is a relationship between the professional groups of health care workers who have been contacted by COVID-19 cases and the professional groups of those who provide services. Among the participants, only 35 people had a diagnostic test, 15 of which were positive for COVID-19 results. Although health care workers find working conditions and authorities to be moderate in tackling COVID-19, their anxiety levels are high. Although health care workers provide services to COVID-19 diagnosed patients, they are not protected against the risk of infection by adequate testing. The risk of transmission threatens more groups of nurses. Considering that COVID-19 is a global threat, measures should be taken to protect health care workers and their families and professional support should be given to address their concerns.


title: Variational-LSTM Autoencoder to forecast the spread of coronavirus across the globe

text: Modelling the spread of coronavirus globally while learning trends at global and country levels remains crucial for tackling the pandemic. We introduce a novel variational LSTM-Autoencoder model to predict the spread of coronavirus for each country across the globe. This deep spatio-temporal model does not only rely on historical data of the virus spread but also includes factors related to urban characteristics represented in locational and demographic data (such as population density, urban population, and fertility rate), an index that represent the governmental measures and response amid toward mitigating the outbreak (includes 13 measures such as: 1) school closing, 2) workplace closing, 3) cancelling public events, 4) close public transport, 5) public information campaigns, 6) restrictions on internal movements, 7) international travel controls, 8) fiscal measures, 9) monetary measures, 10) emergency investment in health care, 11) investment in vaccines, 12) virus testing framework, and 13) contact tracing). In addition, the introduced method learns to generate graph to adjust the spatial dependences among different countries while forecasting the spread. We trained two models for short and long-term forecasts. The first one is trained to output one step in future with three previous timestamps of all features across the globe, whereas the second model is trained to output 10 steps in future. Overall, the trained models show high validation for forecasting the spread for each country for short and long-term forecasts, which makes the introduce method a useful tool to assist decision and policymaking for the different corners of the globe.