title: How Are We Facing It? Dispatches From Pathology Residents in a COVID-19 Lombardy Hospital

text: At the end of February, the Italian National Health Service reported a hot spot of Coronavirus disease in the Lombardy region. COVID-19 is a highly pathogenic viral infection which poses some challenges for healthcare workers. Indeed, Pathology Departments are involved in reorganizing samples' management, from their delivery until their processing, according to National and WHO guidelines. Since Lombardy has been declared COVID-19 hot spot, due to decreasing number of surgical procedures, our Department adopted a policy to reduce personnel, allowing pathologists to work remotely during the outbreak. Lacking clear information about viral load on tissue samples, all human specimens must be considered potentially infectious, as well as patients during post-mortem examinations, and clinical information on COVID-19 status is mandatory. It is also important that Pathology staff receive an adequate training, and adherence to rules should be always accompanied by common sense.


title: COVID-3D: An online resource to explore the structural distribution of genetic variation in SARS-CoV-2 and its implication on therapeutic development

text: The emergence of the COVID-19 pandemic has spurred a global rush to uncover basic biological mechanisms, to inform effective vaccine and drug development. Despite viral novelty, global sequencing efforts have already identified genomic variation across isolates. To enable easy exploration and spatial visualization of the potential implications of SARS-CoV-2 mutations on infection, host immunity and drug development we have developed COVID-3D (http://biosig.unimelb.edu.au/covid3d/).


title: Luminore CopperTouchâ¢ surface coating effectively inactivates SARS-CoV-2, Ebola and Marburg viruses in vitro

text: We investigated the ability of Luminore CopperTouch copper and copper-nickel surfaces to inactivate filoviruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For this purpose, we compared viral titers in Vero cells from viral droplets exposed to copper surfaces for 30 min. The copper and copper-nickel surfaces inactivated 99.9% of the viral titer of both Ebola and Marburg viruses. The copper surfaces also inactivated 99% of SARS-CoV-2 titers in 2 hours to close to the limit of detection. These data add Ebolavirus, Marburgvirus, and SARS-CoV-2 (COVID-19) to the list of pathogens that can be inactivated by exposure to copper ions, validating Luminore CopperTouch technology (currently the only Environmental Protection Agency [EPA]-registered cold spray antimicrobial surface technology) as an efficacious, cost-friendly tool to improve infection control in hospitals, long-term care facilities, schools, hotels, buses, trains, airports, and other highly trafficked areas.


title: Almitrine as a non ventilatory strategy to improve intrapulmonary shunt in COVID-19 patients

text: In severe COVID-19 pulmonary failure, hypoxia is mainly related to pulmonary vasodilation with altered hypoxic pulmonary vasoconstriction (HPV). Besides prone positioning, other non-ventilatory strategies may reduce the intrapulmonary shunt. This study has investigated almitrine, a pharmacological option to improve oxygenation. Patients and Method. A case control series of 17 confirmed COVID-19 mechanically ventilated patients in prone or supine positioning was collected: 10 patients received two doses of almitrine (4 and 12 mcg/kg/min) at 30-45 min interval each, and were compared to 7 control COVID-matched patients conventionally treated. The end-point was the reduction of intra-pulmonary shunt increasing the PaO2 and ScvO2. Results Patients were male (59%) with median (25th, 75th percentiles) age of 70 (54-78) years and a BMI of 29 (23-34). At stable mechanical ventilatory settings, PaO2 (mmHg) at FiO2 1 (135 (85, 195) to 214 (121, 275); p = 0.06) tended to increase with almitrine. This difference was significant when the best PaO2 between the 2 doses was used : 215 (123,294) vs baseline (p = 0.01). A concomitant increase in ScvO2 occurred ((73 (72, 76) to 82 (80, 87); p = 0.02). Eight over 10 almitrine-treated patients increased their PaO2, with no clear dose-effect. During the same time, the controls did not change PaO2. In conclusion, in early COVID-19 with severe hypoxemia, almitrine infusion is associated with improved oxygenation in prone or supine positioning. This pharmacological intervention may offer an alternative and/or an additional effect to proning and might delay or avoid more demanding modalities such as ECMO.


title: Opioid substitution therapy with buprenorphine-naloxone during COVID-19 outbreak in India: Sharing our experience and interim standard operating procedure

text: Coronavirus disease 2019 (COVID-19) has been declared as a pandemic by the World Health Organization on March 11, 2020. It has affected most countries of the world, including India. Both the disease and the unavoidable national response to it have posed unique challenges to our health-care system. A particular vulnerable group of patients is those with opioid dependence maintained on opioid substitution therapy (OST). These patients are pharmacologically dependent on the OST medication (buprenorphine, buprenorphine-naloxone combination [BNX], and methadone) for their healthy functioning and recovery. COVID-19 outbreak, lock-down, and difficult access to medical care, all are likely to induce stress and withdrawal, which is a potential risk for relapse among individuals with opioid dependence, who are anyway more vulnerable due to social, housing, living, and medical conditions. In this context, it is essential to re-strategize the existing OST services to adapt to the challenging circumstances. In this communication, we share our experience and formulate interim standard operating procedures (SOPs) for running a hospital-based OST service utilizing take-home BNX. The challenges, principles to meet the challenges, and interim SOPs are shared as being currently practiced in our center. Individual institutes, agencies, hospitals, and clinics running OST service with BNX can adapt these SOPs according to their characteristics, needs, demand, and resources; so long as, the basic principles are adhered to.


title: Between-centre differences for COVID-19 ICU mortality from early data in England

text: The high numbers of COVID-19 patients developing severe respiratory failure has placed exceptional demands on ICU capacity around the world. Understanding the determinants of ICU mortality is important for surge planning and shared decision making. We used early data from the COVID-19 Hospitalisation in England Surveillance System (from the start of data collection 8th February -14th April 2020) to look for factors associated with ICU outcome in the hope that information from such timely analysis may be actionable before the outbreak peak. Immunosuppression, chronic renal disease and age were key determinants of ICU mortality in a proportional hazards mixed effects model. However variation in site-stratified random effects were even more appreciable, suggesting substantial between-centre variability in mortality. Notwithstanding possible ascertainment and lead-time effects, these early results motivate comparative effectiveness research to understand the origin of such differences and optimise surge ICU provision.


title: Transmission of corona virus disease 2019 during the incubation period may lead to a quarantine loophole

text: Background: The ongoing outbreak of novel corona virus disease 2019 (COVID-19) in Wuhan, China, is arousing international concern. This study evaluated whether and when the infected but asymptomatic cases during the incubation period could infect others. Methods: We collected data on demographic characteristics, exposure history, and symptom onset day of the confirmed cases, which had been announced by the Chinese local authorities. We evaluated the potential of transmission during the incubation period in 50 infection clusters, including 124 cases. All the secondary cases had a history of contact with their first-generation cases prior to symptom onset. Results: The estimated mean incubation period for COVID-19 was 4.9 days (95% confidence interval [CI], 4.4 to 5.4) days, ranging from 0.8 to 11.1 days (2.5th to 97.5th percentile). The observed mean and standard deviation (SD) of serial interval was 4.1±3.3 days, with the 2.5th and 97.5th percentiles at -1 and 13 days. The infectious curve showed that in 73.0% of the secondary cases, their date of getting infected was before symptom onset of the first-generation cases, particularly in the last three days of the incubation period. Conclusions: The results indicated the transmission of COVID-9 occurs among close contacts during the incubation period, which may lead to a quarantine loophole. Strong and effective countermeasures should be implemented to prevent or mitigate asymptomatic transmission during the incubation period in populations at high risk.


title: A CRISPR-based SARS-CoV-2 diagnostic assay that is robust against viral evolution and RNA editing

text: Extensive testing is essential to break the transmission of the new coronavirus SARS-CoV-2, which causes the ongoing COVID-19 pandemic. Recently, CRISPR-based diagnostics have emerged as attractive alternatives to quantitative real-time PCR due to their faster turnaround time and their potential to be used in point-of-care testing scenarios. However, existing CRISPR-based assays for COVID-19 have not considered viral genome mutations and RNA editing in human cells. Here, we present the VaNGuard (Variant Nucleotide Guard) test that is not only specific and sensitive for SARS-CoV-2, but can also detect the virus when its genome or transcriptome has evolved or has been edited by deaminases in infected human cells. We show that an engineered AsCas12a enzyme is more tolerant of mismatches than wildtype LbCas12a and that multiplexed Cas12a targeting can overcome the presence of single nucleotide variations. Our assay can be completed in 30 minutes with a dipstick for a rapid point-of-care test.


title: Real-time tracking and forecasting of the of COVID-19 outbreak in Kuwait: a mathematical modeling study

text: Kuwait has been experiencing a COVID-19 outbreak since the first imported case on Feb 24, 2020. Analysis of data from the early stage of COVID-19 outbreak in Kuwait can provide important information about the potential epidemic and healthcare burdens as well as assist in evaluating the potential impact of various outbreak control measures. Such control measures are essentially implemented to achieve a sufficient reduction in the effective reproduction number during an outbreak. In this study, we use a mathematical modeling framework to simulate the outbreak dynamics of SARS-CoV-2 transmission in Kuwait and forecast the potential burden on the healthcare system. We calibrate the model against daily numbers of detected infection and death cases using a maximum likelihood framework and estimate both the basic and effective reproduction numbers. Our results indicate that the early control measures implemented in Kuwait had the effect of delaying the intensity of the outbreak but were unsuccessful in reducing Rt below 1. This highlights a need for a systematic investigation of the current public health interventions as well as a scientific surveillance tool that is sufficiently sensitive to outbreak temporal dynamics. Meanwhile, the developed model can serve as a public health tool to control the current outbreak and can be used to anticipate effective measures should a second wave re-emerge in Kuwait.


title: Angiotensin-converting enzyme (ACE1, ACE2) gene variants are associated with COVID19 severity depending on the hypertension status.

text: Background: The Angiotensin system is implicated in the pathogenesis of COVID19. First, ACE2 is the cellular receptor for SARS-COv-2, and expression of the ACE2 gene could regulate the individuals susceptibility to infection. In addition, the balance between ACE1 and ACE activity has been implicated in the pathogenesis of respiratory diseases and could play a role in the severity of COVID19. Functional ACE1 and ACE2 gene polymorphisms have been associated with the risk of cardiovascular and pulmonary diseases, and could thus also contribute to the outcome of COVID19. Methods: We studied 204 COVID19 patients (137 non-severe and 67 severe-ICU cases) and 536 age-matched controls. The ACE1 indel and ACE2 rs2285666 polymorphism were determined. Variables frequencies were compared between the groups by logistic regression. We also sequenced the ACE2 coding nucleotides in a group of patients. Results: Severe COVID19 was associated with hypertension male gender (p<0.001), hypertension (p=0.006), hypercholesterolaemia (p=0.046), and the ACE1-DD genotype (p=0.049). In the multiple logistic regression hypertension (p=0.02, OR=2.26, 95CI=1.12-4.63) and male gender (p=0.002; OR=3.15, 95CI=1.56-6.66) remained as independent significant predictors of severity. The ACE2 polymorphism was not associated with the disease outcome. The ACE2 sequencing showed no coding sequence variants that could explain an increased risk of developing COVID19. Conclusions: Adverse outcome of COVID19 was associated with male gender, hypertension, hypercholesterolemia and the ACE1 genotype. The ACE1-indel was a significant risk factor for severe COVID19, but the effect was dependent on the hypertensive status.


title: Undue burdens in the time of coronavirus

text: Beginning early in March of this year, postsecondary schools across the country responded to the COVID-19 pandemic by quickly reconfiguring classroom instruction to exclusively online education


title: Combating sars-cov-2 through lipoxins, proteasome, caveolin and nuclear factor-kappa b pathways in non-pregnant and pregnant populations

text: It can be misleading to think that the new severe acute respiratory-syndrome coronavirus (SARS-COV2) which has a very strong mutation and adaptation capabilities, uses only the angiotensin-converting enzyme II (ACE2) pathway to reach target cells Despite all the precautions taken, the pandemic attack continues and the rapid increase in the number of deaths suggest that this virus has entered the cell through different pathways and caused damage through different mechanisms The main reason why the ACE2 pathway comes to the fore in all scientific studies is that this receptor is located at the entry point of basic mechanisms that provide alveolo-capillary homeostasis SARS-CoV-2 has to use nuclear factor-kappa B (NF-kappa B), caveloae, clathrin, lipoxin, senile protease and pro-teasome pathways in addition to ACE2 to enter the target cell and initiate damage For this reason, while new drug development studies are continuing, in order to be beneficial to patients in their acute period, it is imperative that we are able to come up with drugs that activate or inhibit these pathways and are currently in clinical use It is also critical that we adopt these new pathways to the treatment of pregnant women affected by SARS-CoV-2, based on the scientific data we use to treat the general population


title: Multi-city modeling of epidemics using spatial networks: Application to 2019-nCov (COVID-19) coronavirus in India

text: The ongoing pandemic of 2019-nCov (COVID-19) coronavirus has made reliable epidemiological modeling an urgent necessity. Unfortunately, most of the existing models are either too fine-grained to be efficient or too coarse-grained to be reliable. Here we propose a computationally efficient hybrid approach that uses SIR model for individual cities which are in turn coupled via empirical transportation networks that facilitate migration among them. The treatment presented here differs from existing models in two crucial ways: first, self-consistent determination of coupling parameters so as to maintain the populations of individual cities, and second, the incorporation of distance dependent temporal delays in migration. We apply our model to Indian aviation as well as railway networks taking into account populations of more than 300 cities. Our results project that through the domestic transportation, the significant population is poised to be exposed within 90 days of the onset of epidemic. Thus, serious supervision of domestic transport networks is warranted even after restricting international migration.


title: Early analysis of the Australian COVID-19 epidemic

text: As of 18 April 2020, there had been 6,533 confirmed cases of COVID-19 in Australia. Of these, 67 had died from the disease. The daily count of new confirmed cases was declining. This suggests that the collective actions of the Australian public and government authorities in response to COVID-19 were sufficiently early and assiduous to avert a public health crisis - for now. Analysing factors, such as the intensity and timing public health interventions, that contribute to individual country experiences of COVID-19 will assist in the next stage of response planning globally. Using data from the Australian national COVID-19 database, we describe how the epidemic and public health response unfolded in Australia up to 13 April 2020. We estimate that the effective reproduction number was likely below 1 (the threshold value for control) in each Australian state since mid-March and forecast that hospital ward and intensive care unit occupancy will remain below capacity thresholds over the next two weeks.


title: Prior infection by seasonal coronaviruses does not prevent SARS-CoV-2 infection and associated Multisystem Inflammatory Syndrome in children

text: Background: Children have a lower rate of COVID-19, potentially related to cross-protective immunity conferred by seasonal coronaviruses (HCoVs). We tested if prior infections with seasonal coronaviruses impacted SARS-CoV-2 infections and related Multisystem Inflammatory Syndrome (MIS). Methods: This cross-sectional observational study in Paris hospitals enrolled 739 pauci or asymptomatic children (HOS group) plus 36 children with suspected MIS (MIS group). Prevalence, antigen specificity and neutralizing capability of SARS-CoV-2 antibodies were tested. Antibody frequency and titres against Nucleocapsid (N) and Spike (S) of the four seasonal coronaviruses (NL63, HKU1, 229E, OC43) were measured in a subset of seropositive patients (54 SARS-CoV-2 (HOS-P subgroup) and 15 MIS (MIS-P subgroup)), and in 118 matched SARS-CoV-2 seronegative patients (CTL subgroup). Findings: SARS-CoV-2 mean prevalence rate in HOSP children was 11.7% from April 1 to June 1. Neutralizing antibodies were found in 55.6% of seropositive children, and their relative frequency increased with time (up to 100 % by mid-May). A majority of MIS children (25/36) were SARS-CoV-2 seropositive, of which all tested (n=15) had neutralizing antibodies. On average, seropositive MIS children had higher N and S1 SARS-CoV-2 titres as compared to HOS children. Patients from HOS-P, MIS-P, and CTL subgroups had a similar prevalence of antibodies against the four seasonal HCoVs (66.9 -100%). The level of anti-SARS-CoV-2 antibodies was not significantly different in children who had prior seasonal coronavirus infection. Interpretation: Prior infection with HCoVs does not prevent SARS-CoV-2 infection and related MIS in children. Children develop neutralizing antibodies after SARS-CoV-2 infection.


title: A Hitchhiker's Guide to caring for an older person before and during coronavirus-19

text: Coronavirus-19 (COVID-19) has reconfigured working lives with astonishing velocity. Older people have suffered the worst effects of the pandemic, with governments marginalizing or overlooking their needs. Women perform the majority of care for older people, often compromising their working lives and health. Yet in academic articles their voices are often filtered or aggregated in quantitative studies. Based on a weave of personal experiences and secondary research, the article traces a path through UK forms of care and shows how the inadequate response to COVID-19 stemmed from existing policies embedded in health and social care. COVID-19 has severed important informal care work, rendering the vulnerable yet more exposed and carers anxious and bereft. Longitudinal research capturing the trajectory of care from the perspective of older people and their carers would lead to improved support hence gender equality.


title: Operationalizing genomic epidemiology during the Nord-Kivu Ebola outbreak, Democratic Republic of the Congo.

text: The Democratic Republic of the Congo declared its tenth Ebola virus disease outbreak in July 2018, which has circulated primarily in the Nord Kivu province. In addition to standard epidemiologic surveillance and response efforts, the Institut National de Recherche Biom&eacutedicale implemented an end-to-end genomic surveillance system, including sequencing, bioinformatic analysis, and dissemination of genomic epidemiologic results to frontline public health workers. Here we report 538 new genomes from this outbreak; together with previously available sequence data (n = 48 genomes), this represents an unprecedented 17% of all laboratory-confirmed infections. To support outbreak response efforts, we reconstructed spatiotemporal transmission dynamics at broad and at fine scales as new data were available and disseminated the results via an interactive narrative-based platform. Our innovative system enables actionable information sharing between scientists and epidemiologists coordinating the day-to-day response on the time scales necessary to guide response efforts. The development of this genomic surveillance pipeline, within a resource-limited setting, represents significant technological and scientific progress in genomic epidemiology. Here we present a phylodynamic analysis of the outbreak as of February 2020, and describe the types of epidemiologic dynamics that we monitor the genomic data for, including resolution of co-circulating transmission chains, detection of superspreading events, inference of regions that act as transmission sources and sinks, and differentiation of closely linked cases versus propagated transmission. These findings have ameliorated the current outbreak response and are directly applicable to future outbreaks.


title: Mathematical Modeling and Analysis of COVID-19 pandemic in Nigeria

text: A novel Coronavirus (COVID-19), caused by SARS-CoV-2, emerged from the Wuhan city of China at the end of 2019, causing devastating public health and socio-economic burden around the world. In the absence of a safe and effective vaccine or antiviral for use in humans, control and mitigation efforts against COVID-19 are focussed on using non-pharmaceutical interventions (aimed at reducing community transmission of COVID-19), such as social (physical)-distancing, community lockdown, use of face masks in public, isolation and contact tracing of confirmed cases and quarantine of people suspected of being exposed to COVID-19. We developed a mathematical model for understanding the transmission dynamics and control of COVID-19 in Nigeria, one of the main epicenters of COVID-19 in Africa. Rigorous analysis of the Kermack-McKendrick-type compartmental epidemic model we developed, which takes the form of a deterministic system of nonlinear differential equations, reveal that the model has a continuum of disease-free equilibria which is locally-asymptotically stable whenever a certain epidemiological threshold, called the it control reproduction (denoted by Rc), is less than unity. The epidemiological implication of this result is that the pandemic can be effectively controlled (or even eliminated) in Nigeria if the control strategies implemented can bring (and maintain) the epidemiological threshold (Rc) to a value less than unity. The model, which was parametrized using COVID-19 data published by Nigeria Centre for Disease Control (NCDC), was used to assess the community-wide impact of various control and mitigation strategies in the entire Nigerian nation, as well as in two states (Kano and Lagos) within the Nigerian federation and the Federal Capital Territory (FCT Abuja). It was shown that, for the worst-case scenario where social-distancing, lockdown and other community transmission reduction measures are not implemented, Nigeria would have recorded a devastatingly high COVID-19 mortality by April 2021 (in hundreds of thousands). It was, however, shown that COVID-19 can be effectively controlled using social-distancing measures provided its effectiveness level is at least moderate. Although the use of face masks in the public can significantly reduce COVID-19 in Nigeria, its use as a sole intervention strategy may fail to lead to the realistic elimination of the disease (since such elimination requires unrealistic high compliance in face mask usage in the public, in the range of 80% to 95%). COVID-19 elimination is feasible in both the entire Nigerian nation, and the States of Kano and Lagos, as well as the FCT, if the public face masks use strategy (using mask with moderate efficacy, and moderate compliance in its usage) is complemented with a social-distancing strategy. The lockdown measures implemented in Nigeria on March 30, 2020 need to be maintained for at least three to four months to lead to the effective containment of COVID-19 outbreaks in the country. Relaxing, or fully lifting, the lockdown measures sooner, in an effort to re-open the economy or the country, may trigger a deadly second wave of the pandemic.


title: Disparities in COVID-19 Reported Incidence, Knowledge, and Behavior

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


title: Hospital readmissions of discharged patients with COVID-19

text: Background. COVID-19 infection has led to an overwhelming effort by health institutions to meet the high demand for hospital admissions. Aim. To analyse the clinical variables associated with readmission of patients who had previously been discharged after admission for COVID-19. Design and methods. We studied a retrospective cohort of patients with laboratory-confirmed SARS-CoV-2 infection who were admitted and subsequently discharged alive. We then conducted a nested case-control study paired (1:1 ratio) by age, sex and period of admission. Results. Out of 1368 patients who were discharged during the study period, 61 patients (4.4%) were readmitted. Immunocompromised patients were at increased risk for readmission. There was also a trend towards a higher probability of readmission in hypertensive patients (p=0.07). Cases had had a shorter hospital stay and a higher prevalence of fever during the 48 hours prior to discharge. There were no significant differences in oxygen levels measured at admission and discharge by pulse oximetry intra-subject or between the groups. Neutrophil/lymphocyte ratio at hospital admission tended to be higher in cases than in controls (p=0.06). The motive for readmission in 10 patients (16.4%), was a thrombotic event in venous or arterial territory (p<0.001). Neither glucocorticoids nor anticoagulants prescribed at hospital discharge were associated with a lower readmission rate. Conclusions. The rate of readmission after discharge from hospital for COVID-19 was low. Immunocompromised patients and those presenting with fever during the 48 hours prior to discharge are at greater risk of readmission to hospital.


title: The Influence of Contextual Factors on the Initial Phases of the COVID-19 Outbreak across U.S. Counties

text: Objectives: The COVID-19 pandemic in early 2020 poses an unprecedented threat to the health and economic prosperity of the world's population. Given incomplete reporting of contextual disaggregation in cumulative case data reported by health departments in the U.S., this research links county- and state-level characteristics to the COVID-19 outbreak. Methods: A statistical exponential growth model is estimated to describe the outbreak rate using publicly available county-level outbreak data. County- and state-level effects are simultaneously tested with a multilevel linear model using full maximum likelihood. Results: Mirroring findings from international cultural research, collectivism as a value is positively associated with the outbreak rate. The racial and ethnic composition of counties contributes to differences in the outbreak, with Black/African and Asian Americans being more affected. As expected, counties with a higher median age have a stronger outbreak, and so do counties with more people below the age of 18. Higher income, education, and personal health are generally associated with a lower outbreak. Contrariwise, obesity is negatively and significantly related to the outbreak, in agreement with the value expectancy concepts of the health belief model. Smoking is negatively related, but only directionally informative. Air pollution is another significant contributor to the outbreak, but population density does not give statistical significance. Conclusions: The results show that contextual factors influence the initial outbreak of COVID-19. Because of a high intrastate and intercounty variation in these factors, policy makers need to look at pandemics from the smallest subdivision possible, so that countermeasures can be implemented effectively.


title: A Retrospective Analysis of the Clinical and Epidemiological Characteristics of COVID-19 Patients in Henan Provincial People's Hospital, Zhengzhou, China

text: Objective: This study evaluated the clinical and epidemiological characteristics of patients with confirmed coronavirus disease 2019 (COVID-19). Methods: This retrospective study evaluated 29 patients with confirmed COVID-19 infection admitted to Henan Provincial People's Hospital between January 27 and February 27, 2020, with follow-up until April 01, 2020. Results: The median age of the patients was 56 years. Nineteen (19/29; 65.5%) had underlying conditions including cardiovascular disease, digestive disease, or type 2 diabetes mellitus. Twenty-two (22/29; 76%) had close contact with acquaintances or family members who were confirmed or probable COVID-19 cases. Many patients had white blood cell counts with abnormal neutrophil and lymphocyte numbers, abnormal hemoglobin concentration, coagulation profiles, and blood biochemistry, and increased infection markers. Mottling and multiple ground-glass opacities were seen in X-ray images of 19 patients (19/29; 65.5%). Most patients (23/29; 79.8%) received supplemental oxygen therapy and antibiotics (23/29; 79.8%) in addition to traditional Chinese medicines (26/29; 89.7%). The most frequent presenting symptoms were fever, cough, and sputum production. One patient, an 86-years-old woman with more than one underlying disease, died during follow-up. Patients with severe disease were significantly older and more likely to have been transferred from other healthcare facilities than those with mild disease. Anemia, decreased activated partial thromboplastin time, calcium, and albumin, and increased D-dimer and interleukin-6 were more frequent in severe disease. Need of oxygen therapy, mechanical ventilation, intravascular immunoglobulin, and duration of antibiotic therapy were increased in those with severe disease. Conclusions: Significant differences in demographical and clinical characteristics were observed in patients with moderate and severe COVID-19.


COVID-19: Advice from CDC Neurovirologist and Epidemiologist James J. Sejvar, MD


title: A single-dose live-attenuated YF17D-vectored SARS-CoV2 vaccine candidate

text: The explosively expanding COVID-19 pandemic urges the development of safe, efficacious and fast-acting vaccines to quench the unrestrained spread of SARS-CoV-2. Several promising vaccine platforms, developed in recent years, are leveraged for a rapid emergency response to COVID-191. We employed the live-attenuated yellow fever 17D (YF17D) vaccine as a vector to express the prefusion form of the SARS-CoV-2 Spike antigen. In mice, the vaccine candidate, tentatively named YF-S0, induces high levels of SARS-CoV-2 neutralizing antibodies and a favorable Th1 cell-mediated immune response. In a stringent hamster SARS-CoV-2 challenge model2, vaccine candidate YF-S0 prevents infection with SARS-CoV-2. Moreover, a single dose confers protection from lung disease in most vaccinated animals even within 10 days. These results warrant further development of YF-S0 as a potent SARS-CoV-2 vaccine candidate.


title: Leukopenia of Asymptomatic COVID-19 Infections under 18 Years Old in Recovery Stage

text: Background In December, 2019, a type of novel coronavirus which was designated novel coronavirus 2019 (2019-nCoV) by World Health Organization (WHO) occurred in Wuhan, Hubei, China. The epidemiological and clinical characteristics of those patients under 18 years old in the recovery stage are limited. To compare the difference of epidemiological and clinical characteristics of COVID-19 involving 25 patients under 18 years old in recovery stage between confirmed and asymptomatic infections. Methods Retrospective, single-center cohort study of COVID-19 involving 25 patients under 18 years old in the recovery stage at Guizhou Provincial Staff Hospital in Guiyang, China, from January 29, to March 31, 2020; final date of follow-up was April 22. Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Epidemiological and clinical characteristics of confirmed COVID-19 infections and asymptomatic infections were compared. Results Among the 25 COVID infections under 18 years old, 16 (64%) were mild or moderate confirmed cases, and 9 (36%) were asymptomatic. The shortest treatment period was 6 days, the longest 26 days, and the average treatment period 14 days. Four cases (44.4%) had visited Wuhan or had a living story in the city. There were 9 (100%) asymptomatic cases were familial cluster outbreak, with an average infection number was 6 cases among all families. The number of asymptomatic COVID-19 infections with leukopenia were significantly more than confirmed cases (p=0.04). Conclusions Leukopenia mostly occurred in asymptomatic COVID-19 infections under 18 years old compared with the confirmed patients.


title: COVID-19 lockdown during field work—Challenges and strategies in continuing the ReGES study

text: This paper describes the consequences that the non-pharmacological interventions (NPI) in the context of the COVID-19 pandemic had on the data collection of the panel study ReGES and the solution adopted to continue the field work. The NPI were introduced during the 7th wave of the ReGES study and led to a disruption of the field work. In order to continue the field and to keep the data collected after the NPI comparable to the one collected before the NPI, we decided to switch the face-to-face mode to a telephone interview. The switch made content-related as well as technical and methodological adjustments to the instruments necessary. We also discuss methodological issues that must be taken into account when preparing and analysing the data.


title: Genomic modeling as an approach to identify surrogates for use in experimental validation of SARS-CoV-2 and HuNoVs inactivation by UV-C treatment

text: Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) is responsible for the COVID-19 pandemic that continues to pose significant public health concerns. While research to deliver vaccines and antivirals are being pursued, various effective technologies to control its environmental spread are also being targeted. Ultraviolet light (UV-C) technologies are effective against a broad spectrum of microorganisms when used even on large surface areas. In this study, we developed a pyrimidine dinucleotide frequency based genomic model to predict the sensitivity of select enveloped and non-enveloped viruses to UV-C treatments in order to identify potential SARS-CoV-2 and human noroviruses surrogates. The results revealed that this model was best fitted using linear regression with r2=0.90. The predicted UV-C sensitivity (D90 - dose for 90% inactivation) for SARS-CoV-2 and MERS-CoV was found to be 21 and 28 J/m2, respectively (with an estimated 18 J/m2 as published for SARS-CoV-1), suggesting that coronaviruses are highly sensitive to UV-C light compared to other ssRNA viruses used in this modeling study. Murine hepatitis virus (MHV) A59 strain with a D90 of 21 J/m2 close to that of SARS-CoV-2 was identified as a suitable surrogate to validate SARS-CoV-2 inactivation by UV-C treatment. Furthermore, the non-enveloped human noroviruses (HuNoVs), had predicted D90 values of 69.1, 89 and 77.6 J/m2 for genogroups GI, GII and GIV, respectively. Murine norovirus (MNV-1) of GV with a D90 = 100 J/m2 was identified as a potential conservative surrogate for UV-C inactivation of these HuNoVs. This study provides useful insights for the identification of potential nonpathogenic surrogates to understand inactivation kinetics and their use in experimental validation of UV-C disinfection systems. This approach can be used to narrow the number of surrogates used in testing UV-C inactivation of other human and animal ssRNA viral pathogens for experimental validation that can save cost, labor and time.


title: Nursing care for patients with COVID-19 on extracorporeal membrane oxygenation (ECMO) support

text: In Japan, four medical facilities including our own - the National Center for Global health and Medicine (NCGM) - have been designated for the treatment of specified infectious diseases by the Minister of Health, Labour, and Welfare Here, we report our nursing care for patients with severe COVID-19 on extracorporeal membrane oxygenation (ECMO) support In addition to infection control measures in the form of an N95 mask, a water-repellent isolation gown, a cap, a shielded mask on top of the N95, and double-layered gloves, nurses were required to wear one-piece suits (DuPont™ Tyvek®) and use powered air-purifying respirators (PAPRs) While closed system catheters are normally changed once a day to limit aerosol exposure, they are now changed once every 4 days Nursing care included equipment checks, monitoring of hemodynamics and respiratory status, management of anticoagulants, observation of the patient’s general condition, management of sedatives and analgesics, prevention of medical device-related pressure ulcers and bedsores, and maintenance of hygiene Fundamentally sound nursing remains the best practice for patient treatment and management During nursing care for patients with COVID-19 on ECMO, infection control measures should be faithfully and properly followed


title: Blood glucose levels in elderly subjects with type 2 diabetes during COVID-19 outbreak: a retrospective study in a single center

text: Aims: Ideal glycemic control is of great importance for diabetic patients during public health emergencies of infectious diseases as long-term hyperglycemic are not only associated with chronic complications but also vital drivers of common and life-threatening infections. The present study was designed to investigate the changes of blood glucose levels in elderly subjects with type 2 diabetes(T2D) during COVID-19 outbreak. Methods: This retrospective study focused on the T2D outpatients at Fujian Provincial Hospital aged 65 years old and above who received baseline test for fasting plasma glucose and/or glycated hemoglobin (HbA1c) between January 1, 2019 and March 8, 2019 and were followed up on fasting plasma glucose and/or HbA1c in the same period in 2020. The baseline and follow-up data were analyzed with the paired-samples T-test. Results: A total of 135 elderly subjects with T2D with baseline and follow-up fasting plasma glucose and 50 elderly subjects with T2D with baseline and follow-up HbA1c were analyzed, respectively. The baseline and follow-up mean fasting plasma glucose were 7.08 and 7.48 mmol/L, respectively (P=0.008). The mean baseline and follow-up HbA1c were 7.2 and 7.4, respectively (P=0.158). Conclusions: Elderly subjects with T2D had higher fasting plasma glucose levels during COVID-19 outbreak. We should pay more attension to the management of diabetics during public health emergencies.


La psicología clínica ante la pandemia COVID-19 en España


title: Cytotoxicity evaluation of chloroquine and hydroxychloroquine in multiple cell lines and tissues by dynamic imaging system and PBPK model

text: Chloroquine (CQ) and hydroxychloroquine (HCQ) have been used in treating COVID-19 patients recently. However, both drugs have some contradictions and rare but severe side effects, such as hypoglycemia, retina and cardiac toxicity. To further uncover the toxicity profile of CQ and HCQ in different tissues, we evaluated the cytotoxicity of them in 8 cell lines, and further adopted the physiologically-based pharmacokinetic models (PBPK) to predict the tissue risk respectively. Retina, myocardium, lung, liver, kidney, vascular endothelium and intestinal epithelium originated cells were included in the toxicity evaluation of CQ and HCQ respectively. The proliferation pattern was monitored in 0-72 hours by IncuCyte S3, which could perform long-term continuous image and video of cells upon CQ or HCQ treatment. CC50 and the ratio of tissue trough concentrations to CC50 (RTTCC) were brought into predicted toxicity profiles. The CC50 at 24 h, 48 h, 72 h of CQ and HCQ decreased in the time-dependent manner, which indicates the accumulative cytotoxic effect. HCQ was found to be less toxic in 7 cell types except cardiomyocytes H9C2 cells (CC50-48 h=29.55 μM; CC50-72 h=15.26 μM). In addition, RTTCC is significant higher in CQ treatment group compared to HCQ group, which indicates that relative safety of HCQ. Both CQ and HCQ have certain cytotoxicity in time dependent manner which indicates the necessity of short period administration clinically. HCQ has the less impact in 7 cell lines proliferation and less toxicity compared to CQ in heart, liver, kidney and lung.


title: A seven-day cycle in COVID-19 infection and mortality rates: Are inter-generational social interactions on the weekends killing susceptible people?

text: We observed a significant seven-day cycle in (i) reported COVID-19 new casesa (in 7/12 countries), and in (ii) reported COVID-19 deathsb (in 7/12 countries), based on data from the 12 developed North-American and European countries that reported more than 1,000 deaths by April 28th (Spaina, Italya and Switzerlanda, Belgiumb, Canadab and the USAb, Germanya,b, the Netherlandsa,b, Swedena,b and the UKa,b). Daily reported numbers (March 29th to April 28th) are based on Our World in Data database (derived from the European Center for Disease Control and Prevention, ECDC). In all seven countries, numbers of new cases peaked on Thursday-Friday, five days after the weekend, corresponding with a reported ~5-day lag between contact with an infected person and the manifestation of clinical symptoms. Death tolls peaked on Wednesday-Thursday in all seven countries, ~12-14 days following a weekend, corresponding with the reported median of 14-day hospitalization before death. One may suspect that the weekend restricts the availability of testing or reporting of new cases, that are eventually reported during the following week. However, to completely account for both observations, this artifact should occur uniformly in all the above-mentioned countries and consistently along the entire month studied. Moreover, deaths are defined events and seems less likely to be recorded or reported inaccurately, at least for the vast majority of cases. Thus, we hypothesize that an increase in inter-generational social interactions occurs during the weekend, which facilitates transfer of COVID-19 from younger people to older vulnerable individuals. These and additional infected older people account for most recognized COVID-19 cases and deaths, which may occur at regular time intervals, specifically in this vulnerable population. Additional explanations may include weekly rhythms in immune functions, hospital care quality, or other various health-related behaviors. Our hypotheses should be re-tested and refined based on databases that accurately report events times when these will become available.


COVID-19 and International Business: A Viewpoint


title: Temporal evolution and adaptation of SARS-COV 2 codon usage

text: The outbreak of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has caused an unprecedented pandemic. Since the first sequenced whole-genome of SARS-CoV-2 on January 2020, the identification of its genetic variants has become crucial in tracking and evaluating their spread across the globe. In this study, we compared 15,259 SARS-CoV-2 genomes isolated from 60 countries since the outbreak of this novel coronavirus with the first sequenced genome in Wuhan to quantify the evolutionary divergence of SARS-CoV-2. Thus, we compared the codon usage patterns, every two weeks, of 13 of SARS-CoV-2 genes encoding for the membrane protein (M), envelope (E), spike surface glycoprotein (S), nucleoprotein (N), non-structural 3C-like proteinase (3CLpro), ssRNA-binding protein (RBP), 2’-O-ribose methyltransferase (OMT), endoRNase (RNase), helicase, RNA-dependent RNA polymerase (RdRp), Nsp7, Nsp8, and exonuclease ExoN. As a general rule, we find that SARS-CoV-2 genome tends to diverge over time by accumulating mutations on its genome and, specifically, on the coding sequences for proteins N and S. Interestingly, different patterns of codon usage were observed among these genes. Genes S, Nsp7, NSp8, tend to use a norrower set of synonymous codons that are better optimized to the human host. Conversely, genes E and M consistently use a broader set of synonymous codons, which does not vary with respect to the reference genome. We identified key SARS-CoV-2 genes (S, N, ExoN, RNase, RdRp, Nsp7 and Nsp8) suggested to be causally implicated in the virus adaptation to the human host.


title: Monitoring and predicting SARS-CoV-2 epidemic in France after deconfinement using a multiscale age-stratified rate model

text: The entire world and France were strongly impacted by the SARS-COV-2 epidemic. Finding appropriate measures that effectively contain the spread of the epidemic without putting a too severe pressure on social and economic life is major challenge for modern predictive approaches. To assess the impact of confinement (March 17th till May 11th) and deconfinement, we develop a novel rate model to monitor and predict the spread of the epidemic and its impact on the health care system. The model accounts for age-dependent interactions between population groups and predicts consequences for various infection categories such as number of infected, hospitalized, load of intensive care units (ICU), number of death, recovered and more. We use online health care data for the five most infected regions of France to calibrate the model. At day of deconfinement (May 11th), we find that 13% (around 4.8M) of the population is infected in the five most affected regions of France (extrapolating to 5.8M for France). The model predicts that if the reproduction rate R0 is reduced by at least a factor of 2.5-3 for all age groups, which could be achieved by wearing masks and social distancing, a significant second peak could be prevented. However, if the reduction in R0 for the age group 0-25 would be less and below 2 (school openings), a second peak is unavoidable in which case the ICU will be saturated. In that context testing should be focused on children, but it will nevertheless have a limited impact on reducing the spread.


title: Development of a severity of disease score and classification model by machine learning for hospitalized COVID-19 patients

text: BACKGROUND: Efficient and early triage of hospitalized Covid-19 patients to detect those with higher risk of severe disease is essential for appropriate case management. METHODS: We trained, validated, and externally tested a machine-learning model to early identify patients who will die or require mechanical ventilation during hospitalization from clinical and laboratory features obtained at admission. A development cohort with 918 Covid-19 patients was used for training and internal validation, and 352 patients from another hospital were used for external testing. Performance of the model was evaluated by calculating the area under the receiver-operating-characteristic curve (AUC), sensitivity and specificity. RESULTS: A total of 363 of 918 (39.5%) and 128 of 352 (36.4%) Covid-19 patients from the development and external testing cohort, respectively, required mechanical ventilation or died during hospitalization. In the development cohort, the model obtained an AUC of 0.85 (95% confidence interval [CI], 0.82 to 0.87) for predicting severity of disease progression. Variables ranked according to their contribution to the model were the peripheral blood oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2) ratio, age, estimated glomerular filtration rate, procalcitonin, C-reactive protein, updated Charlson comorbidity index and lymphocytes. In the external testing cohort, the model performed an AUC of 0.83 (95% CI, 0.81 to 0.85). This model is deployed in an open source calculator, in which Covid-19 patients at admission are individually stratified as being at high or non-high risk for severe disease progression. CONCLUSIONS: This machine-learning model, applied at hospital admission, predicts risk of severe disease progression in Covid-19 patients.


title: Distribution of ACE2, CD147, cyclophilins, CD26 and other SARS-CoV-2 associated molecules in human tissues and immune cells in health and disease

text: Background Morbidity and mortality from COVID-19 caused by novel coronavirus SARS-CoV-2 is accelerating worldwide and novel clinical presentations of COVID-19 are often reported. The range of human cells and tissues targeted by SARS-CoV-2, its potential receptors and associated regulating factors are still largely unknown. The aim of our study was to analyze the expression of known and potential SARS-CoV-2 receptors and related molecules in the extensive collection of primary human cells and tissues from healthy subjects of different age and from patients with risk factors and known comorbidities of COVID-19. Methods We performed RNA sequencing and explored available RNA-Seq databases to study gene expression and co-expression of ACE2, CD147 (BSG), CD26 (DPP4) and their direct and indirect molecular partners in primary human bronchial epithelial cells, bronchial and skin biopsies, bronchoalveolar lavage fluid, whole blood, peripheral blood mononuclear cells (PBMCs), monocytes, neutrophils, DCs, NK cells, ILC1, ILC2, ILC3, CD4+ and CD8+ T cells, B cells and plasmablasts. We analyzed the material from healthy children and adults, and from adults in relation to their disease or COVID-19 risk factor status. Results ACE2 and TMPRSS2 were coexpressed at the epithelial sites of the lung and skin, whereas CD147 (BSG), cyclophilins (PPIA and PPIB), CD26 (DPP4) and related molecules were expressed in both, epithelium and in immune cells. We also observed a distinct age-related expression profile of these genes in the PBMCs and T cells from healthy children and adults. Asthma, COPD, hypertension, smoking, obesity, and male gender status generally led to the higher expression of ACE2- and CD147-related genes in the bronchial biopsy, BAL or blood. Additionally, CD147-related genes correlated positively with age and BMI. Interestingly, we also observed higher expression of ACE2- and CD147-related genes in the lesional skin of patients with atopic dermatitis. Conclusions Our data suggest different receptor repertoire potentially involved in the SARS-CoV-2 infection at the epithelial barriers and in the immune cells. Altered expression of these receptors related with age, gender, obesity and smoking, as well as with the disease status might contribute to COVID-19 morbidity and severity patterns.


title: Performance evaluation of the point-of-care SAMBA II SARS-CoV-2 Test for detection of SARS-CoV-2

text: Background: Nucleic acid amplification for the detection of SARS-CoV-2 RNA in respiratory samples is the standard method for diagnosis. These tests are centralised and therefore turnaround times can be 2-5 days. Point-of-care testing with rapid turnaround times would allow more effective triage in settings where patient management and infection control decisions need to be made rapidly. Methods: Analytical and clinical sensitivity and specificity of the SAMBA II SARS-CoV-2 Test was evaluated on panels and residual clinical samples. The clinical performance was compared to the Public Health England reference tests. Results: The limit of detection of the SAMBA II SARS-CoV-2 Test is 250 cp/mL and is specific for detection of 2 regions of the SARS-CoV-2 genome. The clinical sensitivity was evaluated in 172 clinical samples provided by Public Health England, Cambridge, which showed a sensitivity of 98.9% (95% CI 94.03-99.97%), specificity of 100% (95% CI 95.55-100%), PPV of 100% and NPV of 98.78% (92.02-99.82%) compared to testing by Public Health England (PHE). SAMBA detected 3 positive samples that were initially negative by PHE. Discussion: The data shows that the SAMBA II SARS-CoV-2 Test performs equivalently to the centralised testing methods with a much quicker turnaround time. Point of care testing, such as SAMBA, should enable rapid patient management and effective implementation of infection control measures.


title: Career Confidential: Teacher wonders how to help students during coronavirus shutdown

text: Phyllis Fagell provides workplace advice to educators in this Kappan column. This month, a teacher wants to know how she can provide emotional support to students when the school is closed for the COVID-19 pandemic. A teachers’ colleagues provide a lot of free after-school help to students, making her feel obligated to do the same, even when it interferes with her family time or when students have not been doing the work during class.


title: Orthotopic Transplantation and Engraftment of Human Induced Pluripotent Stem Cell-Derived Alveolar Progenitor Cells into Murine Lungs

text: Humanized mice possessing human cells, tissues, or organ systems provide an unparalleled platform for preclinical studies in oncology, immunology, and infectious diseases. While the lungs are a vital organ subject to a wide variety of pathologies, exemplified by the ongoing COVID-19 pandemic, discrete differences in murine and human lungs can obfuscate interpretation of murine models of lung disease. Here we provide proof-of-concept methodology for the potential humanization of murine lungs via orthotopic transplantation of human NKX2.1+ progenitor cells and alveolar type 2 cells derived from induced pluripotent stem cells. We show that these cells engraft readily into highly immunocompromised mice after pharmacological injury with bleomycin, which presumably generates “space” for human cells to access denuded basement membrane and engraft. Transplanted cells stably retain their pulmonary lineage restriction and persist as superficially differentiated alveolar type 2 and type 1 cells. Future work should focus on strategies to promote xenorepopulation of most / all of the murine lung with human cells while retaining appropriate regio-specific epithelial differentiation and normal physiological function.


title: In-depth virological assessment of kidney transplant recipients with COVID-19

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread widely, causing coronavirus disease 2019 (COVID-19) and significant mortality. However, data on viral loads and antibody kinetics in immunocompromised populations are lacking. We aimed to determine nasopharyngeal and plasma viral loads via RT-PCR and SARS-CoV-2 serology via ELISA and study their association with severe forms of COVID-19 and death in kidney transplant recipients. In this study we examined hospitalized kidney transplant recipients with non-severe (n = 21) and severe (n =19) COVID-19. SARS-CoV-2 nasopharyngeal and plasma viral load and serological response were evaluated based on outcomes and disease severity. Ten recipients (25%) displayed persistent viral shedding 30 days after symptom onset. The SARS-CoV-2 viral load of the upper respiratory tract was not associated with severe COVID-19, whereas the plasma viral load was associated with COVID-19 severity (p=0.0087) and mortality (p=0.024). All patients harbored antibodies the second week after symptom onset that persisted for two months. We conclude that plasma viral load is associated with COVID-19 morbidity and mortality, whereas nasopharyngeal viral load is not. SARS-CoV-2 shedding is prolonged in kidney transplant recipients and the humoral response to SARS-CoV-2 does not show significant impairment in this series of transplant recipients.


title: Recombinant SARS-CoV-2 spike S1-Fc fusion protein induced high levels of neutralizing responses in nonhuman primates

text: The COVID-19 outbreak has become a global pandemic responsible for over 2,000,000 confirmed cases and over 126,000 deaths worldwide. In this study, we examined the immunogenicity of CHO-expressed recombinant SARS-CoV-2 S1-Fc fusion protein in mice, rabbits, and monkeys as a potential candidate for a COVID-19 vaccine. We demonstrate that the S1-Fc fusion protein is extremely immunogenic, as evidenced by strong antibody titers observed by day 7. Strong virus neutralizing activity was observed on day 14 in rabbits immunized with the S1-Fc fusion protein using a pseudovirus neutralization assay. Most importantly, in less than 20 days and three injections of the S1-Fc fusion protein, two monkeys developed higher virus neutralizing titers than a recovered COVID-19 patient in a live SARS-CoV-2 infection assay. Our data strongly suggests that the CHO-expressed SARS-CoV-2 S1-Fc recombinant protein could be a strong candidate for vaccine development against COVID-19. Highlights CHO-expressed S1-Fc protein is very immunogenic in various animals and can rapidly induce strong antibody production S1-Fc protein solicits strong neutralizing activities against live virus Stable CHO cell line expressing 50 mg/L of S1-Fc and a 3,000 L Bioreactor can produce 3 million doses of human COVID-19 vaccine every 10 days, making it an accessible and affordable option for worldwide vaccination


title: Evaluation of nCoV-QS (MiCo BioMed) for RT-qPCR detection of SARS-CoV-2 from nasopharyngeal samples using CDC FDA EUA qPCR kit as a gold standard: an example of the need of validation studies.

text: Several qPCR kits are available for SARS-CoV-2 diagnosis, mostly lacking of evaluation due to covid19 emergency. We evaluated nCoV-QS (MiCo BioMed) kit using CDC kit as gold standard. We found limitations for nCoV-QS: 1) lower sensibility 2) lack of RNA quality control probe 3) no capacity to quantify viral load.


title: Obesity, walking pace and risk of severe COVID-19: Analysis of UK Biobank

text: Obesity is an emerging risk factor for coronavirus disease-2019 (COVID-19). Simple measures of physical fitness, such as self-reported walking pace, could also be important risk factors, but have not been well documented. This analysis includes 414,201 UK Biobank participants with complete covariate and linked COVID-19 data. We analysed the risk of severe (in-hospital) COVID-19 across categories of obesity status and walking pace. As of June 20th 2020 there were 972 cases of severe COVID-19 that had occurred within the cohort. Compared to normal weight individuals, the adjusted odds ratio (OR) for severe COVID-9 in those with obesity was 1.49 (1.24, 1.78). Compared to those with a brisk walking pace, the OR in slow walkers was 1.84 (1.49, 2.27). Slow walkers had the highest risk of severe COVID-19 regardless of obesity status. For example, compared to normal weight brisk walkers, the odds of severe COVID-19 in obese brisk walkers was 1.39 (0.99, 1.98), whereas the odds in normal weight slow walkers was 2.48 (1.56, 3.93). Self-reported walking pace, a simple measure of functional fitness, appears to be a risk factor for severe COVID-19 that is independent of obesity. This may help inform simple pragmatic public health risk stratification and preventative strategies.


title: Transmission interval estimates suggest pre-symptomatic spread of COVID-19

text: Background: As the COVID-19 epidemic is spreading, incoming data allows us to quantify values of key variables that determine the transmission and the effort required to control the epidemic. We determine the incubation period and serial interval distribution for transmission clusters in Singapore and in Tianjin. We infer the basic reproduction number and identify the extent of pre-symptomatic transmission. Methods: We collected outbreak information from Singapore and Tianjin, China, reported from Jan.19-Feb.26 and Jan.21-Feb.27, respectively. We estimated incubation periods and serial intervals in both populations. Results: The mean incubation period was 7.1 (6.13, 8.25) days for Singapore and 9 (7.92, 10.2)days for Tianjin. Both datasets had shorter incubation periods for earlier-occurring cases. The mean serial interval was 4.56 (2.69, 6.42) days for Singapore and 4.22 (3.43, 5.01) for Tianjin. We inferred that early in the outbreaks, infection was transmitted on average 2.55 and 2.89days before symptom onset (Singapore, Tianjin). The estimated basic reproduction number for Singapore was 1.97 (1.45, 2.48) secondary cases per infective; for Tianjin it was 1.87 (1.65,2.09) secondary cases per infective. Conclusions: Estimated serial intervals are shorter than incubation periods in both Singapore and Tianjin, suggesting that pre-symptomatic transmission is occurring. Shorter serial intervals lead to lower estimates of R0, which suggest that half of all secondary infections should be prevented to control spread.


title: Seroconversion of a city: Longitudinal monitoring of SARS-CoV-2 seroprevalence in New York City

text: By conducting a retrospective, cross-sectional analysis of SARS-CoV-2 seroprevalence in a sentinel group (enriched for SARS-CoV-2 infections) and a screening group (representative of the general population) using >5,000 plasma samples from patients at Mount Sinai Hospital in New York City (NYC), we identified seropositive samples as early as in the week ending February 23, 2020. A stark increase in seropositivity in the sentinel group started the week ending March 22 and in the screening group in the week ending March 29. By the week ending April 19, the seroprevalence in the screening group reached 19.3%, which is well below the estimated 67% needed to achieve community immunity to SARS-CoV-2. These data potentially suggest an earlier than previously documented introduction of SARS-CoV-2 into the NYC metropolitan area.


title: A Sparse Gaussian Network Model for Prediction the Growth Trend of COVID-19 Overseas Import Case: When can Hong Kong Lift the International Traffic Blockad?

text: The COVID-19 virus was first discovered from China. It has been widely spread internationally. Currently, compare with the rising trend of the overall international epidemic situation, China's domestic epidemic situation has been contained and shows a steady and upward trend. In this situation, overseas imports have become the main channel for china to increase the number of infected people. Therefore, how to track the spread channel of international epidemics and predict the growth of overseas case imports is become an open research question. This study proposes a Gaussian sparse network model based on lasso and uses Hong Kong as an example. To explore the COVID-19 virus from a network perspective and analyzes 75 consecutive days of COV-19 data in 188 countries and regions around the world. This article establishes an epidemic spread relationship network between Hong Kong and various countries and regions around the world and build a regression model based on network information to fit Hong Kong's COV-19 epidemic growth data. The results show that the regression model based on the relationship network can better fit the existing cumulative number growth curve. After combining the SEIJR model, we predict the future development trend of cumulative cases in Hong Kong (without blocking international traffic). Based on the prediction results, we suggest that Hong Kong can lift the international traffic blockade from early to mid-June


title: Consensus study of risk factors and symptoms of SARS-CoV-2 (COVID-19) using biomedical literature and social media data

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


title: On the heterogeneity of infections, containment measures and the preliminary forecast of COVID-19 epidemic

text: As of May 1, 2020, there had been over three million of officially confirmed cases of novel coronavirus (COVID-19) infections reported worldwide. The pandemic originated from a severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), a virus similar to severe acute respiratory syndrome (SARS). The dynamics of the pathogen incurred the incidence of the unidentified cases that were potentially substantial in magnitude. Unparalleled extensive measures, either in terms of medical quarantine or non-medical containment, were taken to deplete the growth of infected population and thereafter settle down the outbreak. We aimed to estimate the gap in sizes and peak dates between the confirmed and unconfirmed, and how containment measures impacted the dynamic trajectory of the COVID-19 in Japan. We performed simulations and desired to provide meaningful insight for the upcoming responses to the outbreak, for which much still remained to be unknown.


title: Flexibility and mobility of SARS-CoV-2-related protein structures

text: The worldwide CoVid-19 pandemic has led to an unprecedented push across the whole of the scientific community to develop a potent antiviral drug and vaccine as soon as possible. Existing academic, governmental and industrial institutions and companies have engaged in large-scale screening of existing drugs, in vitro, in vivo and in silico. Here, we are using in silico modelling of SARS-CoV-2 drug targets, i.e. SARS-CoV-2 protein structures as deposited on the Protein Databank (PDB). We study their flexibility, rigidity and mobility, an important first step in trying to ascertain their dynamics for further drug-related docking studies. We are using a recent protein flexibility modelling approach, combining protein structural rigidity with possible motion consistent with chemical bonds and sterics. For example, for the SARS-CoV-2 spike protein in the open configuration, our method identifies a possible further opening and closing of the S1 subunit through movement of SB domain. With full structural information of this process available, docking studies with possible drug structures are then possible in silico. In our study, we present full results for the more than 200 thus far published SARS-CoV-2-related protein structures in the PDB.


title: Epidemiology of CoViD-19 Pandemic: Recovery and mortality ratio around the globe

text: Coronavirus Disease 2019 (CoViD-19) is the third type of coronavirus disease after severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) that appears in human population from the past two decades. It is highly contagious and rapidly spread in the human population and compelled global public health institutions on high alert. Due to genetic similarity of this novel coronavirus 2019 with bat virus its emergence from bat to humans is possible. The virus survive in the droplets of coughing and sneezing and spread around the large areas through infected person resulting in its rapid spread among people. Clinical symptoms of CoViD-19 include fever, dry cough, dyspnea, loose stool, nausea and vomiting. The present review discuss the origin of CoViD-19, its rapid spread, mortality rate and recoveries ratio around the world. Since its origin from Wuhan, the CoViD-19 spread very rapidly all across the countries, on April 17, 2020 this disease has affected 210 countries of the globe. The data obtained showed over 2.4 million confirmed cases of CoViD-19. Higher mortality rate was found in Algeria and Belgium as 15% and 13.95%, respectively. Lower mortality rate was found in Qatar 0.17% and Singapore 0.2%. Recovery versus deceased ratio showed that recovery was 68, 59 and 35 times higher than the death in Singapore, Qatar and Thailand respectively. It is concluded that 2019-novel corona virus is a zoonotic pathogen similar to MERS and SARS. Therefore, a barrier should be maintained between and across the human, household and wild animals to avoid such pandemics.


Australian Social Work: Responding to the COVID-19 pandemic


title: Cell entry of SARS-CoV-2 conferred by angiotensin-converting enzyme 2 (ACE2) of different species

text: The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a huge threat to many countries around the world. However, where is it origin and which animals are sensitive to cross-species transmission is unclear. The interaction of virus and cell receptor is a key determinant of host range for the novel coronavirus. Angiotensin-converting enzyme 2 (ACE2) is demonstrated as the primary entry receptor for SARS-CoV-2. In this study, we evaluated the SARS-CoV-2 entry mediated by ACE2 of 11 different species of animals, and discovered that ACE2 of Rhinolophus sinicus (Chinese horseshoe bat), Felis catus (domestic cat), Canis lupus familiaris (dog), Sus scrofa (pig), Capra hircus (goat) and especially Manis javanica (Malayan pangolin) were able to render SARS-CoV-2 entry in non-susceptible cells. This is the first report that ACE2 of Pangolin could mediate SARS-CoV-2 entry which increases the presume that SARS-CoV-2 may have a pangolin origin. However, none of the ACE2 proteins from Rhinolophus ferrumequinum (greater horseshoe bat), Gallus gallus (chicken), Notechis scutatus (mainland tiger snake), Mus musculus (house mouse) rendered SARS-CoV-2 entry. Specifically, a natural isoform of Macaca mulatta (Rhesus monkey) ACE2 with a mutation of Y217N was resistance to infection, which rises the possible impact of this type of ACE2 during monkey studies of SARS-CoV-2. Overall, these results clarify that SARS-CoV-2 could engage receptors of multiple species of animals and it is a perplexed work to track SARS-CoV-2 origin and its intermediate hosts. IMPORTANCE In this study, we illustrated that SARS-CoV-2 is able to engage receptors of multiple species of animals. This indicated that it may be a perplexed work to track SARS-CoV-2 origin and discover its intermediate hosts. This feature of virus is considered to potentiate its diverse cross-species transmissibility. Of note, here is the first report that ACE2 of Pangolin could mediate SARS-CoV-2 entry which increases the possibility that SARS-CoV-2 may have a pangolin origin. And we also demonstrated that not all species of bat were sensitive to SARS-CoV-2 infection. At last, it is also important to detect the expression ratio of the Y217N ACE2 to the prototype in Rhesus monkeys to be recruited for studies on SARS-CoV-2 infection.


title: Willingness to Accept Tradeoffs among Covid-19 Cases, Social-Distancing Restrictions, and Economic Impact: A Nationwide US Study

text: We designed a discrete-choice experiment to quantify the extent to which US adults would accept greater risk of infection with SARS-CoV-2 in return for lifting social-distancing restrictions and diminishing the economic impact of the COVID-19 pandemic. 5953 adults representing all 50 states had 4 distinctly different preference patterns. About 37% were risk minimizers reluctant to accept any increases in risk of contracting the virus. Another group (26%) was primarily concerned about time required for economic recovery, accepting increases in COVID-19 risk levels up to 16% to shorten recovery from 3 to 2 years. The remaining two groups diverged on the relative importance of reopening nonessential businesses. The larger group (26%) strongly preferred delaying reopening while the smaller group (13%) would accept COVID-19 risks well beyond 20% to avoid a delay in reopening. Political affiliation, race, household income and employment status were predictive of group membership.


title: Early data on the performance of a combined SARS-CoV-2 spike-nucleocapsid antibody lateral flow device compared to a nucleocapsid-only device

text: Background There is a critical need for reliable antibody detection methods in order to study and evaluate the public health and clinical response to the ongoing COVID-19 pandemic. Lateral flow immunoassay (LFIA) devices offer the prospect of rapid point-of-care testing (POCT), but the performance of these devices must be evaluated for robustness before they can be adopted for routine clinical and public health use. Methods Plasma and serum specimens from SARS-CoV-2 RNA-positive (n = 131) and RNA-negative (n = 16) patients were taken from various time points with respect to the onset of symptoms. All 147 anonymised specimens were tested for IgM and IgG using the Hangzhou AllTest 2019-nCoV IgG/IgM Rapid Test Cassette and the Abbexa COVID-19 IgG/IgM Rapid Test Kit. Results IgM sensitivity ranged from 13% to 68%, depending on the date of symptom onset and the device. Regarding IgG, the Abbexa device outperformed the Hangzhou device at all cumulative timeline brackets, with sensitivity of 97·87% (Abbexa) versus 68·09% (Hangzhou) for samples beyond 21 days from symptom onset. Day 21 was therefore chosen as the cut-off for ascertaining test performance characteristics, beyond which the specificity was 100% for both devices and negative predictive value was 0·94 (Abbexa) versus 0·50 (Hangzhou). Discussion Based on this limited dataset, the performance characteristics of the Abbexa LFIA device were substantially better than those of the Hangzhou device. Applying a 21-day cut-off for the Abbexa device meets the minimum (98%) sensitivity and specificity thresholds set by the UK Medicine & Healthcare products Regulatory Agency. The Abbexa device captures antibodies against both SARS-CoV-2 spike and nucleocapsid proteins, as opposed to Hangzhou that targets only the nucleocapsid protein. We therefore propose that spike glycoprotein antibodies be considered as part of the standard diagnostic approach towards SARS-CoV-2 antibody profiling to improve clinical sensitivity and potentially specificity, pending follow-up studies to confirm this approach.


title: IoT and Neural Network-Based Water Pumping Control System For Smart Irrigation

text: This article aims at saving the wasted water in the process of irrigation using the Internet of Things (IoT) based on a set of sensors and Multi-Layer Perceptron (MLP) neural network. The developed system handles the sensor data using the Arduino board to control the water pump automatically. The sensors measure the environmental factors; namely temperature, humidity, and soil moisture to estimate the required time for the operation of water irrigation. The water pump control system consists of software and hardware tools such as Arduino Remote XY interface and electronic sensors in the framework of IoT technology. The machine learning algorithm such as the MLP neural network plays an important role to support the decision of automatic control of IoT-based irrigation system, managing the water consumption effectively.


title: A cluster identification framework illustrated by a filtering model for earthquake occurrences

text: A general dynamical cluster identification framework including both modeling and computation is developed. The earthquake declustering problem is studied to demonstrate how this framework applies. A stochastic model is proposed for earthquake occurrences that considers the sequence of occurrences as composed of two parts: earthquake clusters and single earthquakes. We suggest that earthquake clusters contain a ``mother quake'' and her ``offspring.'' Applying the filtering techniques, we use the solution of filtering equations as criteria for declustering. A procedure for calculating maximum likelihood estimations (MLE's) and the most likely cluster sequence is also presented.


title: Discovery of pharmaceutically-targetable pathways and prediction of survivorship for pneumonia and sepsis patients from the view point of ensemble gene noise

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


Neurology Residency Programs Adjust to an Uncertain World with COVID-19


Prioritization and management recommendations of pediatric urology conditions during the COVID-19 pandemic


title: How much of SARS-CoV-2 Infections is India detecting? A model-based estimation

text: Background and Rationale: Amid SARS-CoV-2 outbreak, the low number of infections for a population size of 1.38 billion is widely discussed, but with no definite answers. Methods: We used the model proposed by Bommer and Vollmer to assess the quality of official case records. The infection fatality rates were taken from Verity et al (2020). Age distribution of the population for India and states are taken from the Census of India (2011). Reported number of deaths and SARS-CoV-2 confirmed cases from https://www.covid19india.org. The reported numbers of samples tests were collected from the reports of the Indian Council for Medical Research (ICMR). Results: The findings suggest that India is detecting just 3.6% of the total number of infections with a huge variation across its states. Among 13 states which have more than 100 COVID-19 cases, the detection rate varies from 81.9% (of 410 estimated infections) in Kerala to 0.8% (of 35487 estimated infections) in Madhya Pradesh and 2.4% (of 7431 estimated infections) in Gujarat. Conclusion: As the study reports a lower number of deaths and higher recovery rates in the states with a high detection rate, thus suggest that India must enhance its testing capacity and go for widespread testing. Late detection puts patients in greater need of mechanical ventilation and ICU care, which imposes greater costs on the health system. The country should also adopt population-level random testing to assess the prevalence of the infection.


title: Comparison of the spatiotemporal characteristics of the COVID-19 and SARS outbreaks in mainland China

text: Background: Both coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS) are caused by coronaviruses and have infected people in China and worldwide. We aimed to investigate whether COVID-19 and SARS exhibited similar spatial and temporal features at the provincial level in mainland China. Methods: The number of people infected by COVID-19 and SARS were extracted from daily briefings on newly confirmed cases during the epidemics, as of Mar. 4, 2020 and Aug. 3, 2003, respectively. We depicted the spatiotemporal patterns of the COVID-19 and SARS epidemics using spatial statistics such as Moran's I and the local indicators of spatial association (LISA). Results: Compared to SARS, COVID-19 had a higher incidence. We identified 3 clusters (predominantly located in south-central China, highest RR=135.08) for COVID-19 and 4 clusters (mainly in Northern China, highest RR=423.51) for SARS. Fewer secondary clusters were identified after the “Wuhan lockdown”. The LISA cluster map detected a significantly high-low (Hubei) and low-high spatial clustering (Anhui, Hunan, and Jiangxi, in Central China) for COVID-19. Two significant high-high (Beijing and Tianjin) and low-high (Hebei) clusters were detected for SARS, although the global Moran's I value was not significant. Conclusions: The different spatiotemporal clustering patterns between COVID-19 and SARS could point to changes in social and demographic factors, local government containment strategies or differences in transmission mechanisms between these coronaviruses.


title: Estimation of the epidemic properties of the 2019 novel coronavirus: A mathematical modeling study

text: Background The 2019 novel Coronavirus (COVID-19) emerged in Wuhan, China in December 2019 and has been spreading rapidly in China. Decisions about its pandemic threat and the appropriate level of public health response depend heavily on estimates of its basic reproduction number and assessments of interventions conducted in the early stages of the epidemic. Methods We conducted a mathematical modeling study using five independent methods to assess the basic reproduction number (R0) of COVID-19, using data on confirmed cases obtained from the China National Health Commission for the period 10th January to 8th February. We analyzed the data for the period before the closure of Wuhan city (10th January to 23rd January) and the post-closure period (23rd January to 8th February) and for the whole period, to assess both the epidemic risk of the virus and the effectiveness of the closure of Wuhan city on spread of COVID-19. Findings Before the closure of Wuhan city the basic reproduction number of COVID-19 was 4.38 (95% CI: 3.63-5.13), dropping to 3.41 (95% CI: 3.16-3.65) after the closure of Wuhan city. Over the entire epidemic period COVID-19 had a basic reproduction number of 3.39 (95% CI: 3.09-3.70), indicating it has a very high transmissibility. Interpretation COVID-19 is a highly transmissible virus with a very high risk of epidemic outbreak once it emerges in metropolitan areas. The closure of Wuhan city was effective in reducing the severity of the epidemic, but even after closure of the city and the subsequent expansion of that closure to other parts of Hubei the virus remained extremely infectious. Emergency planners in other cities should consider this high infectiousness when considering responses to this virus.


title: Comparative efficacy and safety of pharmacological interventions for the treatment of COVID-19: A systematic review and network meta-analysis of confounder-adjusted 20212 hospitalized patients

text: Objective: To evaluate the comparative efficacy and safety of pharmacological interventions used in treating COVID-19 and form a basis for an evidence-based guideline of COVID-19 management by evaluating the level of evidence behind each treatment regimen in different clinical settings. Design: Systematic review and network meta-analysis Data Sources: PubMed, Google Scholar, MEDLINE, the Cochrane Library, medRxiv, SSRN, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov up to June 9th, 2020. Study Selection: Published and unpublished randomized controlled trials (RCTs) and baseline-adjusted observational studies which met our predefined eligibility criteria. Main Outcome Measures: The outcomes of interest were mortality, progression to severe disease (severe pneumonia or admission to intensive care unit (ICU)), time to viral clearance, QT prolongation, fatal cardiac complications, and non-cardiac serious adverse events. The level of evidence behind each outcome was also measured using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Results: 49 studies with a total of 20212 confounder-adjusted patients were included for analysis. The risk of progression to severe pneumonia or ICU admission was significantly reduced with tocilizumab (GRADE low), anakinra (GRADE very low), and remdesivir (GRADE high) compared to standard care. Tocilizumab was shown to reduce mortality rate for both moderate-severe patients in the non-ICU setting at admission (Odds ratio (OR) 0.31, 95% confidence interval (CI) 0.18 to 0.54, GRADE low) and critically ill patients in the ICU setting (OR 0.67, 95% CI 0.50 to 0.91, GRADE low). High dose IVIG reduced death rate (GRADE low) while corticosteroids increased mortality for critically ill patients (GRADE moderate). Convalescent plasma and hydroxychloroquine were shown to promote viral clearance (OR 11.39, 95% CI 3.91 to 33.18, GRADE low and OR 6.08, 95% CI 2.74 to 13.48, GRADE moderate, respectively) while not altering mortality or progression to the severe courses. The combination of hydroxychloroquine and azithromycin was shown to be associated with increased QT prolongation incidence (OR 1,85, 95% CI 1.05 to 3.26, GRADE low) and fatal cardiac complications in cardiac-impaired populations (OR 2.26, 95% CI 1.26 to 4.05, GRADE low). High-dose (>600mg/day) hydroxychloroquine monotherapy was significantly associated with increased non-cardiac serious adverse events (GRADE moderate). Conclusion: Anti-inflammatory agents (tocilizumab, anakinra, and IVIG) and remdesivir may safely and effectively improve outcomes of hospitalized COVID-19 patients. Widely used hydroxychloroquine provides marginal clinical benefit in improving viral clearance rates whilst posing both cardiac and non-cardiac safety risks, especially in the vulnerable population. Only 20% of current evidence on pharmacological management of COVID-19 is on moderate and high evidence certainty; remaining 80% are of low or very low certainty and warrant further studies to establish firm conclusions. Systematic Review Registration: PROSPERO 2020: CRD42020186527.


title: A semi-supervised approach for rapidly creating clinical biomarker phenotypes in the UK Biobank using different primary care EHR and clinical terminology systems.

text: Objectives The UK Biobank (UKB) is making primary care Electronic Health Records (EHR) for 500,000 participants available for COVID-19-related research. Data are extracted from four sources, recorded using five clinical terminologies and stored in different schemas. The aims of our research were to: a) develop a semi-supervised approach for bootstrapping EHR phenotyping algorithms in UKB EHR, and b) to evaluate our approach by implementing and evaluating phenotypes for 31 common biomarkers. Materials and Methods We describe an algorithmic approach to phenotyping biomarkers in primary care EHR involving a) bootstrapping definitions using existing phenotypes, b) excluding generic, rare or semantically distant terms, c) forward-mapping terminology terms, d) expert review, and e) data extraction. We evaluated the phenotypes by assessing the ability to reproduce known epidemiological associations with all-cause mortality using Cox proportional hazards models. Results We created and evaluated phenotyping algorithms for 31 biomarkers many of which are directly related to COVID-19 complications e.g. diabetes, cardiovascular disease, respiratory disease. Our algorithm identified 1651 Read v2 and Clinical Terms Version 3 terms and automatically excluded 1228 terms. Clinical review excluded 103 terms and included 44 terms, resulting in 364 terms for data extraction (sensitivity 0.89, specificity 0.92). We extracted 38,190,682 events and identified 220,978 participants with at least one biomarker measured. Discussion and conclusion Bootstrapping phenotyping algorithms from similar EHR can potentially address pre-existing methodological concerns that undermine the outputs of biomarker discovery pipelines and provide research-quality phenotyping algorithms.


title: Epidemiological features and medical care-seeking process of patients with COVID-19 in Wuhan, China

text: BACKGROUND: We aimed to investigate the epidemiological and clinical features, and medical care-seeking process of patients with the 2019 coronavirus disease (COVID-19) in Wuhan, China, to provide useful information to contain COVID-19 in other places with similar outbreaks of the virus. METHODS: We collected epidemiological and clinical information of patients with COVID-19 admitted to a makeshift Fangcang hospital between 7 and 26 February, 2020. The waiting time of each step during the medical care-seeking process was also analysed. RESULTS: Of the 205 patients with COVID-19 infection, 31% had presumed transmission from a family member. 10% of patients had hospital-related transmission. It took as long as a median of 6 days from the first medical visit to receive the COVID-19 nucleic acid test and 10 days from the first medical visit to hospital admission, indicating early recognition of COVID-19 was not achieved at the early stage of the outbreak, although these delays were shortened later. After clinical recovery from COVID-19, which took a mean of 21 days from illness onset, there was still a substantial proportion of patients who had persistent SARS-CoV-2 infection. CONCLUSIONS: The diagnostic evaluation process of suspected patients needs to be accelerated at the epicentre of the outbreak and early isolation of infected patients in a healthcare setting rather than at home is urgently required to stop the spread of the virus. Clinical recovery is not an appropriate criterion to release isolated patients and as long as 4 weeks' isolation for patients with COVID-19 is not enough to prevent the spread of the virus.


title: Chinese Public Attention to COVID-19 Epidemic: Based on Social Media

text: Background: Since the new coronavirus epidemic in China in December 2019, information and discussions about COVID-19 have spread rapidly on the Internet and have quickly become the focus of worldwide attention, especially on social media. Objective: This study aims to investigate and analyze the public's attention to COVID-19-related events in China at the beginning of the COVID-19 epidemic in China (December 31, 2019, to February 20, 2020) through the Sina Microblog hot search list. Methods: We collected topics related to the COVID-19 epidemic on the Sina Microblog hot search list from December 31, 2019, to February 20, 2020 and described the trend of public attention on COVID-19 epidemic-related topics. ROST CM6.0 (ROST Content Mining System Version 6.0) was used to analyze the collected text for word segmentation, word frequency, and sentiment analysis. We further described the hot topic keywords and sentiment trends of public attention. We used VOSviewer to implement a visual cluster analysis of hot keywords and build a social network of public opinion content. Results: The study has four main findings. First, we analyzed the changing trend of the public's attention to the COVID-19 epidemic, which can be divided into three stages. Second, the hot topic keywords of public attention at each stage are slightly different. In addition, the emotional tendency of the public toward the COVID-19 epidemic-related hot topics has changed from negative to neutral, with negative emotions weakening and positive emotions increasing as a whole. Finally, we divided the COVID-19 topics with the most public concern into five categories: (1) new COVID-19 epidemics and their impact; (2) frontline reporting of the epidemic and prevention and control measures; (3) expert interpretation and discussion on the source of infection; (4) medical services on the frontline of the epidemic; and (5) focus on the global epidemic and the search for suspected cases. Conclusions: This is the first study of public attention on the COVID-19 epidemic using a Chinese social media platform (i.e., Sina Microblog). Our study found that social media (e.g., Sina Microblog) can be used to measure public attention to public health emergencies. During the epidemic of the novel coronavirus, a large amount of information about the COVID-19 epidemic was disseminated on Sina Microblog and received widespread public attention. We have learned about the hotspots of public concern regarding the COVID-19 epidemic. These findings can help the government and health departments better communicate with the public on health and translate public health needs into practice to create targeted measures to prevent and control the spread of COVID-19. Keywords: COVID-19; Sina Microblog; Public attention; Social media; China; Public health emergency


ACCC Supports Oncology Community With COVID-19 Resources Oncologist Urges COVID-19 “Castrated” Live Vaccine Initiative


title: High-order Large Eddy Simulations of Confined Rotor-Stator Flows

text: In many engineering and industrial applications, the investigation of rotating turbulent flow is of great interest. In rotor-stator cavities, the centrifugal and Coriolis forces have a strong influence on the turbulence by producing a secondary flow in the meridian plane composed of two thin boundary layers along the disks separated by a non-viscous geostrophic core. Most numerical simulations have been performed using RANS and URANS modelling, and very few investigations have been performed using LES. This paper reports on quantitative comparisons of two high-order LES methods to predict a turbulent rotor-stator flow at the rotational Reynolds number Re=400000. The classical dynamic Smagorinsky model for the subgrid-scale stress (Germano et al., Phys Fluids A 3(7):1760-1765, 1991) is compared to a spectral vanishing viscosity technique (S\'everac&Serre, J Comp Phys 226(2):1234-1255, 2007). Numerical results include both instantaneous data and postprocessed statistics. The results show that both LES methods are able to accurately describe the unsteady flow structures and to satisfactorily predict mean velocities as well as Reynolds stress tensor components. A slight advantage is given to the spectral SVV approach in terms of accuracy and CPU cost. The strong improvements obtained in the present results with respect to RANS results confirm that LES is the appropriate level of modelling for flows in which fully turbulent and transition regimes are involved.


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