title: Paucity and disparity of publicly available sex-disaggregated data for the COVID-19 epidemic hamper evidence-based decision-making

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


title: Separate Fever Clinics Prevent the Spread of COVID-19 and Offload Emergency Resources: Analysis from a large tertiary hospital in China

text: Objectives: COVID-19 began spreading widely in China in January 2020. Outpatient Fever Clinics (FCs), instituted during the SARS epidemic in 2003 were upgraded to provide COVID-19 screening and prevention attached to large tertiary hospitals. We sought to analyze the effect of upgraded FCs to detecting COVID-19 at our institution. Design: A population-based cross-sectional study. Participants: A total of 6,365 patients were screened in the FC. Methods: The FC of Peking Union Medical College Hospital (PUMCH) was upgraded on January 20, 2020. We performed a retrospective study of patients presenting to the FC between December 12, 2019 to February 29, 2020, covering a period of 40 days before and after upgrading the FC. All necessary data, including baseline patient information, diagnoses, follow-up conditions for critical patients, transfer information between the FC and emergency department (ED) were collected and analyzed. Results: 6,365 patients were screened in the FC, among whom 2,192 patients were screened before January 21, 2020, while 3,453 were screened afterwards. Screening results showed that upper respiratory infection was the major disease associated with fever. Compared to before the outbreak, patients transferred from the FC to ED decreased significantly [39.21% vs 15.75%, p<0.001] and tended to spend more time in the FC [55 vs 203mins, p<0.001]. For critically-ill patients waiting for a screening result, the total length of stay in the FC was 22mins before the outbreak, compared to 442mins after the outbreak (p< 0.001). The number of in-hospital deaths of critical-care patients seen first in the FC was 9 of 29 patients before the outbreak and 21 of 38 after (p<0.050). Nineteen COVID-19 cases were confirmed in the FC, but no other patients or medical care providers were cross-infected. Conclusion: The work-load of the FC increased after the COVID-19 outbreak and effectively prevented COVID-19 from spreading in the hospital as well as offload ED resources.


title: Routes for COVID-19 importation in Brazil

text: The global outbreak caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been declared a pandemic by the WHO. As the number of imported SARS-CoV-2 cases is on the rise in Brazil, we use incidence and historical air travel data to estimate the most important routes of importation into the country.


title: A follow-up study of children infected with SARS-CoV-2 from Western China

text: Background: To clarify the characteristic and the duration of positive nucleic acid in children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including asymptomatic children. Methods: A total of 32 children confirmed with SARS-CoV-2 infection between January 24 and February 12, 2020 from four provinces in Western China were enrolled in this study and followed up until discharge and quarantine 14 days later. Results: Eleven children (34%) were asymptomatic, among whom six children had normal computed tomographic (CT) scan images. Age and gender were not associated with clinical symptoms or the results of CT scan in children infected with SARS-CoV-2. The concentrations of white blood cells and neutrophils were higher in children with asymptomatic infection than in children with clinical symptoms or CT abnormalities. Patients who presented with CT abnormalities had lower D-dimer or lower total bilirubin than those who had normal CT scan but clinical symptoms. All children recovered and no one died or was admitted to the pediatric intensive care unit (PICU). The mean duration of positive SARS-CoV-2 nucleic acid was 15.4 (SD=7.2) days and similar for both asymptomatic children and children with symptoms or CT abnormalities. We found a significant negative correlation between the lymphocyte count and the duration of positive nucleic acid test. Conclusions: Children with asymptomatic infection should be quarantined for the same duration as symptomatic patients infected with SARS-CoV-2. The clinical significance and mechanism behind the negative correlation between the number of lymphocytes and the duration of positive SARS-CoV-2 needs further study.


title: FACTORS INFLUENCING MENTAL HEALTH DURING COVID-19 OUTBREAK: AN EXPLORATORY SURVEY AMONG INDIAN POPULATION

text: Purpose: Research on the impact of social distancing on mental health during epidemics is limited, especially in India. The purpose of this study is to scale the association between anxiety and socio-demographic factors during Covid19 lockdown among the general Indian population. Design/methodology/approach: A descriptive cross-sectional nationwide study was designed to enrol the general population. The inclusion criteria for this study were Indian citizens aged 15 years and above. The study was conducted from 29th March to 12th April 2020, using an online google questionnaire. The anxiety among respondents was detected and measured using a Generalised Anxiety Disorder Scale which consists of 7 questions (in English), i.e. GAD-7. Findings: Respondees were 398, and from these participants, the prevalence of anxiety was 25.4 per cent. Based on the bivariate logistic regression analysis, the predictors of anxiety were gender, religion, occupation as business/self- employed, marital status, family size, health status and sleep deprivation. Conclusion: This study reports the prevalence of anxiety among Indian population who were grounded at their homes during lockdown due to coronavirus pandemic in the country. Limitations: (1) The selection of participants through non-random sampling. (2) Because of the cross-sectional character of the study, causal conclusions cannot be drawn. Originality/Value: This paper fulfils an identified need to study the mental health status of the population under situations like lockdown, thereby helping fill a persistent gap in Indian research on this issue. Keywords: Anxiety, GAD-7, Lockdown, Coronavirus, Isolation, India


title: Inactivation analysis of SARS-CoV-2 by specimen transport media, nucleic acid extraction reagents, detergents and fixatives

text: The COVID-19 pandemic has necessitated a rapid multi-faceted response by the scientific community, bringing researchers, health officials and industry together to address the ongoing public health emergency. To meet this challenge, participants need an informed approach for working safely with the etiological agent, the novel human coronavirus SARS-CoV-2. Work with infectious SARS-CoV-2 is currently restricted to high-containment laboratories, but material can be handled at a lower containment level after inactivation. Given the wide array of inactivation reagents that are being used in laboratories during this pandemic, it is vital that their effectiveness is thoroughly investigated. Here, we evaluated a total of 23 commercial reagents designed for clinical sample transportation, nucleic acid extraction and virus inactivation for their ability to inactivate SARS-CoV-2, as well as seven other common chemicals including detergents and fixatives. As part of this study, we have also tested five filtration matrices for their effectiveness at removing the cytotoxic elements of each reagent, permitting accurate determination of levels of infectious virus remaining following treatment. In addition to providing critical data informing inactivation methods and risk assessments for diagnostic and research laboratories working with SARS-CoV-2, these data provide a framework for other laboratories to validate their inactivation processes and to guide similar studies for other pathogens.


title: Epidemiologic and Clinical Characteristics of 26 Cases of COVID-19 Arising from Patient-to-Patient Transmission in Liaocheng, China

text: INTRODUCTION: Over 40,000 cases of coronavirus (CoV) disease 2019 (COVID-19) have been confirmed in China. The causative agent, 2019 novel CoV (2019-nCoV), has spread rapidly to more than 25 countries worldwide. Human-to-human transmission has accounted for most of the infections outside Wuhan. Most studies to date on COVID-19 have focused on disease etiology and the genomics of 2019-nCoV, with few reports on the epidemiologic and clinical characteristics of infected patients. METHODS: We report early clinical features of 26 patients with confirmed COVID-19 who were admitted to Liaocheng Infectious Disease Hospital in Shandong Province. RESULTS: The median age of the 26 patients with COVID-19 in this study was 42 years. The most common occupation was retail staff (16 patients, 61.54%), with 11 patients or their family members working at the same supermarket. Only 2 patients had visited Wuhan since December 2019; the other cases of 2019-nCoV infection arose from patient-to-patient transmission. Twelve patients had more than one sign or symptom; however, seven patients had no sign or symptom. The average time from symptom onset to admission was 4.5 days. CT revealed signs of bronchitis in 2 patients and unilateral and bilateral pneumonia in 9 and 15 patients, respectively. The patients received the following treatments: antiviral therapy (100%), Chinese medicine (76.92%), antibiotics (50%), gastric mucosal protection (19.23%), immunotherapy (7.69%), and glucocorticoids (3.85%). Most patients (25/26) required ≥1 treatment. DISCUSSION: In contrast to previous reports, most patients (24/26) had not been in close contact with individuals from Wuhan. Additionally, 11 patients or their family members worked at the same supermarket, suggesting active viral transmission in a location frequented by a large number of people. Close monitoring is essential for preventing the large-scale spread of the virus in such places.


Forum introduction: Moving the UHC agenda forward without waiting for the next health crisis


title: Pericarditis and myocarditis long after SARS-CoV-2 infection: a cross-sectional descriptive study in health-care workers

text: Background: Cardiac sequelae of past SARS-CoV-2 infection are still poorly documented. We conducted a cross-sectional study in health-care workers to report evidence of pericarditis and myocarditis after SARS-CoV-2 infection. Methods We studied 139 health-care workers with confirmed past SARS-CoV-2 infection (103 diagnosed by RT-PCR and 36 by serology). Participants underwent clinical assessment, electrocardiography, laboratory tests including immune cell profiling and cardiac magnetic resonance (CMR) imaging. Pericarditis was diagnosed when classical criteria were present, and the diagnosis of myocarditis was based on the updated CMR Lake-Louise-Criteria. Results: Median age was 52 years (IQR 41-57), 100 (72%) were women, and 23 (16%) were previously hospitalized for Covid-19 pneumonia. At examination (10.4 [9.3-11.0] weeks after infection-like symptoms), all participants presented hemodynamic stability. Chest pain, dyspnoea or palpitations were observed in 58 (42%) participants; electrocardiographic abnormalities in 69 (50%); NT-pro-BNP was elevated in 11 (8%); troponin in 1 (1%); and CMR abnormalities in 104 (75%). Isolated pericarditis was diagnosed in 4 (3%) participants, myopericarditis in 15 (11%) and isolated myocarditis in 36 (26%). Participants diagnosed by RT-PCR were more likely to still present symptoms than participants diagnosed by serology (73 [71%] vs 18 [50%]; p=0.027); nonetheless, the prevalence of pericarditis or myocarditis was high in both groups (44 [43%] vs 11 [31%]; p=0.238). Most participants (101 [73%]) showed altered immune cell counts in blood, particularly decreased eosinophil (37 [27%]; p<0.001) and increased CD4-CD8-/loT alpha beta-cell numbers (24 [17%]; p<0.001). Pericarditis was associated with elevated CD4-CD8-/loT alpha beta-cell numbers (p=0.011), while participants diagnosed with myopericarditis or myocarditis had lower (p<0.05) plasmacytoid dendritic cell, NK-cell and plasma cell counts and lower anti-SARS-CoV-2-IgG antibody levels (p=0.027). Conclusions: Pericarditis and myocarditis with clinical stability are frequent long after SARS-CoV-2 infection, even in presently asymptomatic subjects. These observations will probably apply to the general population infected and may indicate that cardiac sequelae might occur late in association with an altered (delayed) innate and adaptative immune response.


title: SARS-CoV-2 Spike Glycoprotein Receptor Binding Domain is Subject to Negative Selection with Predicted Positive Selection Mutations

text: COVID-19 is a highly contagious disease caused by a novel coronavirus SARS-CoV-2. The interaction between SARS-CoV-2 spike protein and the host cell surface receptor ACE2 is responsible for mediating SARS-CoV-2 infection. By analyzing the spike-hACE2 interacting surface, we predicted many hot spot residues that make major contributions to the binding affinity. Mutations on most of these residues are likely to be deleterious, leading to less infectious virus strains that may suffer from negative selection. Meanwhile, several residues with mostly advantageous mutations have been predicted. It is more probable that mutations on these residues increase the transmission ability of the virus by enhancing spike-hACE2 interaction. So far, only a limited number of mutations has been reported in this region. However, the list of hot spot residues with predicted downstream effects from this study can still serve as a tracking list for SARS-CoV-2 evolution studies. Coincidentally, one advantageous mutation, p.476G>S, started to surge in the last couple of weeks based on the data submitted to the public domain, indicating that virus strains with increased transmission ability may have already spread.


Covid-19: Weathering the storm


title: A Note on COVID-19 Diagnosis Number Prediction Model in China

text: Importance: To predict the diagnosed COVID-19 patients and the trend of the epidemic in China. It may give the public some scientific information to ease the fear of the epidemic. Objective: In December 2019, pneumonia infected with the novel coronavirus burst in Wuhan, China. We aimed to use a mathematical model to predict number of diagnosed patients in future to ease anxiety on the emergent situation. Design: According to all diagnosis number from WHO website and combining with the transmission mode of infectious diseases, the mathematical model was fitted to predict future trend of outbreak. Setting: Our model was based on the epidemic situation in China, which could provide referential significance for disease prediction in other countries, and provide clues for prevention and intervention of relevant health authorities. Participants: In this retrospective, all diagnosis number from Jan 21 to Feb 10, 2020 reported from China was included and downloaded from WHO website. Main Outcome(s) and Measure(s): We develop a simple but accurate formula to predict the next day diagnosis number:N_i/N_(i-1) =[(N_(i-1)/N_(i-2) )]^α，where Ni is the total diagnosed patient till the ith day, and α was estimated as 0.904 at Feb 10. Results: Based on this model, it is predicted that the rate of disease infection will decrease exponentially. The total number of infected people is limited; thus, the disease will have limited impact. However, new diagnosis will last to March. Conclusions and Relevance: Through the establishment of our model, we can better predict the trend of the epidemic in China.


title: Racial and ethnic determinants of Covid-19 risk

text: Background Racial and ethnic minorities have disproportionately high hospitalization rates and mortality related to the novel coronavirus disease 2019 (Covid-19). There are comparatively scant data on race and ethnicity as determinants of infection risk. Methods We used a smartphone application (beginning March 24, 2020 in the United Kingdom [U.K.] and March 29, 2020 in the United States [U.S.]) to recruit 2,414,601 participants who reported their race/ethnicity through May 25, 2020 and employed logistic regression to determine the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for a positive Covid-19 test among racial and ethnic groups. Results We documented 8,858 self-reported cases of Covid-19 among 2,259,841 non-Hispanic white; 79 among 9,615 Hispanic; 186 among 18,176 Black; 598 among 63,316 Asian; and 347 among 63,653 other racial minority participants. Compared with non-Hispanic white participants, the risk for a positive Covid-19 test was increased across racial minorities (aORs ranging from 1.24 to 3.51). After adjustment for socioeconomic indices and Covid-19 exposure risk factors, the associations (aOR [95% CI]) were attenuated but remained significant for Hispanic (1.58 [1.24-2.02]) and Black participants (2.56 [1.93-3.39]) in the U.S. and South Asian (1.52 [1.38-1.67]) and Middle Eastern participants (1.56 [1.25-1.95]) in the U.K. A higher risk of Covid-19 and seeking or receiving treatment was also observed for several racial/ethnic minority subgroups. Conclusions Our results demonstrate an increase in Covid-19 risk among racial and ethnic minorities not completely explained by other risk factors for Covid-19, comorbidities, and sociodemographic characteristics. Further research investigating these disparities are needed to inform public health measures.


title: COVID-19 pandemic and precautionary measures in Pakistan

text: The current outbreak of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has attained the dimensions of a pandemic and World Health Organization (WHO) has declared it a global emergency and given it a name of COVID-19. It may remain asymptomatic, but usually presents as influenza-like symptoms initially. It spreads from zoonotic sources, which are still under investigation. Real Time Polymerase Chain Reaction (RT-PCR) is the only available diagnostic and confirmatory lab assay for SARS-CoV-2. There is no specific antiviral drug or vaccine against SARS-CoV-2, hence infected and suspected cases are dependent on supportive treatment along with few anti-HIV drugs. Evidence suggests that, in Pakistan, all cases have returned from Iran and Saudi Arabia after pilgrimage. The number of patients has been increasing gradually. Almost all of the neighboring countries of Pakistan are suffering from an outbreak. So, a big threat is there. Pakistani health authorities need to take critical action urgently. Moreover, it is necessary to take basic preventive measurements including hand washing, use of face masks, keeping the distance from suspected patients and avoiding unnecessary traveling to overcrowded areas. It is concluded that the developing countries might be at higher risk including Pakistan. Personnel and community-based strategy is required to avoid any serious consequences in Pakistan. We searched relevant studies and papers from Google, Google Scholar, National Institute of Health (Pakistan) and WHO by using various medical subject heading (MeSH) terms including COVID-19, SARS-CoV-2, MERS, Preventive Measurements of COVID etc. All downloaded articles were carefully read and conclusions drawn.


title: Sustaining containment of COVID-19: global sharing for pandemic response

text: The coronavirus disease 2019 (COVID-19) outbreak, caused by SARS-CoV-2, has rapidly escalated into a global pandemic One of our significant concerns is that we have no data as to whether people, who acquired immunity against this deadly virus and recovered from COVID-19, are protected from further infections with the same virus Moreover, we have no data as to whether this pandemic will persist in our societies and continue vexing us for long periods of time Implementing science-based response strategy is essential to sustain containment of COVID-19 globally Rapidly sharing scientific information means providing real-time research data and relevant findings As an international academic journal, Global Health & Medicine publishes this special issue entitled "GHM Special Topic: COVID-19" It includes a range of articles describing COVID-19 based on frontline data from Japan, China, the United States, Italy, the United Kingdom, and other countries and areas worldwide Our hope is that the rapid publication and sharing of information contribute, in whichever possible way, to this global fight against COVID-19


title: A Machine Learning Model Reveals Older Age and Delayed Hospitalization as Predictors of Mortality in Patients with COVID-19

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


Audiology education amid COVID-19


title: Associations between state-level healthcare access and COVID-19 case trajectories in the United States

text: Introduction: We conducted an ecological study to determine if state-level healthcare access is associated with trajectories of daily reported COVID-19 cases in the United States. Our focus is on trajectories of daily reported COVID-19 cases, rather than cumulative cases, as trajectories help us identify trends in how the pandemic naturally develops over time, and study the shapes of the curve in different states. Methods: We analyzed data on daily reported confirmed and probable COVID-19 cases from January 21 to June 16, 2020 in 50 states, adjusted for the population size of each state. Cluster analysis for time-series data was used to split the states into clusters that have distinct trajectories of daily cases. Differences in socio-demographic characteristics and healthcare access between clusters were tested. Adjusted models were used to determine if healthcare access is associated with reporting a high trajectory of COVID-19 cases. Results: Two clusters of states were identified. One cluster had a high trajectory of population-adjusted COVID-19 cases, and comprised of 19 states, including New York and New Jersey. The other cluster of states (n=31) had a low trajectory of population-adjusted COVID-19 cases. There were significantly more Black residents (p=0.027) and more nursing facility residents (p=0.001) in states reporting high trajectory of COVID-19 cases. States reporting a high trajectory of COVID-19 cases also had fewer uninsured persons (p=0.005), fewer persons who reported having to forgo medical care due to cost (p=0.016), more registered physicians (p=0.002) and more nurses (p=0.03), higher health spending per capita (p=0.01), fewer residents in Health Professional Shortage Areas per 100,000 population (p=0.027), and higher adoption of Medicaid Expansion (p=0.05). In adjusted models, a higher proportion of uninsured persons (OR: 0.51 [0.25-0.85]; p=0.032), higher proportion of patients who had to forgo medical care due to cost (OR: 0.55 [0.28-0.95]; p=0.048), and no adoption of Medicaid expansion (OR: 0.05 [0-0.59]; p=0.04), were associated with reporting a low trajectory of COVID-19 cases. Conclusion: Our findings from adjusted models suggest that healthcare access can partially explain variations in COVID-19 case trajectories by state.


title: Daily viral kinetics and innate and adaptive immune responses assessment in COVID-19: a case series

text: Background Viral shedding patterns and its correlation with the immune responses of mildly symptomatic COVID-19 patients are still poorly characterized. Methods: We enrolled the first five COVID-19 patients quarantined in our institution; none received immunomodulatory treatment. We monitored shedding of viral RNA and infectious virus by RT-PCR and cell culture from the upper respiratory tract, and characterized the kinetics of systemic innate and adaptive immune responses. Results Despite mild clinical disease, high viral loads and shedding of infectious virus were observed from the respiratory tract, with isolation of infectious virus and prolonged positivity by PCR up to day 7 and 19 post onset of symptoms, respectively. Robust innate responses characterized by an increase in activated CD14+CD16+ monocytes and cytokine responses were observed as early as 2 days after symptoms onset. Cellular and humoral SARS-CoV-2 specific adaptive responses were detectable in all patients. Conclusion Infectious virus shedding was limited to the first week of symptom onset in mild cases. A strong innate response, characterized by the mobilization of activated monocytes during the first days of infection, as well as SARS-CoV-2 specific antibodies were detectable, even in patients with mild disease.


title: Social distancing across vulnerability, race, politics, and employment: How different Americans changed behaviors before and after major COVID-19 policy announcements

text: Background: As states reopen in May 2020, the United States is still trying to curb the spread of the COVID-19 pandemic. To appropriately design policies and anticipate behavioral change, it is important to understand how different Americans' social distancing behavior shifts in relation to policy announcements according to individual characteristics, and community vulnerability. Methods: This cross-sectional study used Unacast's social distancing data from February 24th - May 10th, 2020 to study how social distancing changed before and after: 1) The World Health Organization's declaration of a global pandemic, 2) White House announcement of "Opening Up America Again" (OUAA) guidelines, and 3) the week of April 27 when several states reopened. To measure intention to social distance, we assessed the difference between weekday and weekend behavior as more individuals have more control over weekend leisure time. To investigate social distancing's sensitivity to different population characteristics, we compared social distancing time-series data across county vulnerability as measured by the COVID-19 Community Vulnerability Index (CCVI) which defines vulnerability across socioeconomic, household composition, minority status, epidemiological, and healthcare-system related factors. We also compared social distancing across population groupings by race, 2016 presidential election voting choice, and employment sectors. Results: Movement reduced significantly throughout March reaching peak reduction on April 12th (-56.1%) prior the enactment of any reopening policies. Shifts in social distancing began after major announcements but prior to specific applied policies: Following the WHO declaration, national social distancing significantly increased on weekdays and weekends (-18.6% and -41.3% decline in mobility, respectively). Social distancing significantly declined on weekdays and weekends after OUAA guidelines (i.e. before state reopening) (+1.1% and +5.3% increase in mobility, respectively) with additional significant decline after state reopening (+10.0% and +20.9% increase in mobility, respectively). Social distancing was significantly greater on weekends than weekdays throughout March, however, the trend reversed by early May with significantly less social distancing on weekends, suggesting a shift in intent to social distance during leisure time. In general, vulnerable counties social distanced less than non-vulnerable counties, and had a greater difference between weekday and weekend behavior until state reopening. This may be driven by structural barriers that vulnerable communities face, such as higher rates of employment in particular sectors. At all time periods studied, the average black individual in the US social distanced significantly more than the average white individual, and the average 2016 Clinton voter social distanced significantly more than the average 2016 Trump voter. Social distancing behavior differed across industries with three clusters of employment sectors. Conclusion: Both signaling of a policy change and implementation of a policy are important factors that seem to influence social distancing. Behaviors shifted with national announcements prior to mandates, though social distancing further declined nationwide as the first states reopened. The variation in behavioral drivers including vulnerability, race, political affiliation, and employment industry demonstrates the need for targeted policy messaging and interventions tailored to address specific barriers for improved social distancing and mitigation.


title: Social Isolation as a predictor for mortality: Implications for COVID-19 prognosis

text: The health benefits of social support have been widely documented. However, the social distancing practices from the COVID-19 pandemic is causing social disruption on a grand scale, potentially causing poor health outcomes. Through Google Trends analysis, we found a COVID-19-related surge in interest surrounding loneliness. We assessed if social isolation and loneliness increase the risk for all-cause and cardiovascular disease (CVD) mortality (ICD-10: I00-I99) and used the data to create a conceptual framework. Using the 10-year overall and cardiovascular mortality follow-up data (n = 12,019) from the National Health and Nutrition Examination Survey (1999-2008), we conducted survival analyses and found that individuals who experience social isolation or loneliness have a significantly higher likelihood of overall and CVD mortality than those without support. These effects generally remained strong with further adjustment for NHANES-detected health and demographic differences showing the need to address COVID-19 related loneliness through increasing social nearing.


title: Cardiac Structural and Functional Characteristics in Patients with Coronavirus Disease 2019: A Serial Echocardiographic Study

text: BACKGROUND: Increasing attention has been paid to cardiac involvement in patients with coronavirus disease 2019 (COVID-19). Yet, scarce information is available regarding the morphological and functional features of cardiac impairments in these patients. METHODS: We conducted a prospective and serial echocardiographic study to investigate the structural and functional cardiac changes among COVID-19 patients admitted to the intensive care unit (ICU). From January 21 to April 8, 2020, a total of 51 ICU patients (31 critically ill and 20 severely ill) with confirmed COVID-19 were monitored by serial transthoracic echocardiography examinations. Outcomes were followed up until April 8, 2020. RESULTS: Of 51 ICU patients, 33 (64.7%) had cardiovascular comorbidities. Elevations of levels of cardiac biomarkers including high-sensitivity cardiac troponin-I (hs-cTnI) and brain natriuretic peptide were observed in 62.7% and 86.3% of patients, respectively. Forty-two (82.3%) had at least one left-heart and/or right-heart echocardiographic abnormality. The overall median left ventricular ejection fraction (LVEF) was 65.0% (IQR 58.0-69.0%), with most (44,86.3%) having preserved LVEF. Sixteen patients (31.4%) had increased pulmonary artery systolic pressure, and 14 (27.5%) had right-ventricle (RV) enlargement. During the study period, 12 (23.5%) patients died. LVEF was comparable between survivors and non-survivors, while non-survivors had more often pulmonary hypertension (58.3% vs. 23.1%; P=0.028) and RV enlargement (58.3% vs. 17.9%, P=0.011). Kaplan-Meier analysis demonstrated similar survival curves between patients with vs. without echocardiographic left-heart abnormalities (P=0.450 by log-rank test), while right-heart abnormalities had adverse impact on mortality (P=0.012 by log-rank test). CONCLUSIONS: Typical cardiac abnormality in ICU patients with COVID-19 was right-heart dysfunction with preserved LVEF. Echocardiographic right-heart dysfunction was associated with disease severity and increased mortality in patients affected by COVID-19.


title: Unprecedented nationwide blood studies seek to track U.S. coronavirus spread

text: We still don’t know how many people have been infected with the novel coronavirus, SARS-CoV-2 Not only have countries struggled to roll out wide-scale testing for the virus, those efforts inevitably will miss people who have recovered from an infection The best way to figure out how far and wide the virus has spread in a population is to look at blood Antibodies, blood proteins that the immune system produces to attack pathogens, are viral fingerprints that remain long after infections are cleared Sensitive tests can detect them even in people who never felt a single symptom of COVID-19 The World Health Organization has announced an ambitious global effort, called Solidarity II, of so-called serosurveys, studies that look for antibodies to SARS-CoV-2 in the population


title: Covid-19 Outbreak Progression in Italian Regions: Approaching the Peak by March 29th

text: Setting: Italy and especially Lombardy is experiencing a heavy burden of Covid-19 infection. The peak of the epidemics has not yet been reached and it is expected to be delayed in Central and Southern Italian regions compared to Northern ones. Objective: We have modeled the Covid-19 outbreak progression in Italian Regions vs. Lombardy to assess the epidemics. Primary and Secondary Measures: In our models, we have estimated the basic reproduction number (R0) which represents the average number of people that can be infected by a person who has already acquired the infection both by fitting the exponential growth rate of the infection across a 1month period and also by using day by day assessment, based on single observations. We used the susceptible exposed infected removed (SEIR) compartment model to predict the spreading of the pandemic in Italy. Results. The two methods provide agreements of values, although the first method based on exponential fit should provide a better estimation, being computed on the entire time series. Taking into account the growth rate of the infection across a 1-month period, in Lombardy each infected person has involved other 5 people (4.94 based on data of March 22nd) compared to a value of R0=2.68 reported in the Chinese city of Whuan. According to our model and Piedmont, Veneto, Emilia Romagna, Tuscany and Marche reach an R0 value up to 4. The R0 is 3.7 for Lazio and 3.6 for Campania region, where this latter shows the highest value among the Southern Italian regions, followed by Apulia (3.5), Sicily (3.4), Abruzzo (3.4), Calabria (3.1), Basilicata (2.5) and Molise (2.4). The value of R0 is decreasing in Lombardy and Northern Regions, while it is increasing in Central and Southern Regions. Conclusion. The peak is expected by March 29th at national level.


title: Highly efficient intercellular spreading of protein misfolding mediated by viral ligand - receptor interactions

text: Pathological protein aggregates associated with neurodegenerative diseases have the ability to transmit to unaffected cells, thereby templating their own aberrant conformation onto soluble proteins of the same kind. Proteopathic seeds can be released into the extracellular space, secreted in association with extracellular vesicles (EV) or exchanged by direct cell-to-cell contact. The extent to which each of these pathways contributes to the prion-like spreading of protein misfolding is unclear. Exchange of cellular cargo by both direct cell-to-cell contact as well as via EV depends on receptor-ligand interactions and subsequent release of cargo into the cytosol. We hypothesized that enabling these interactions through viral ligands enhances the aggregate-inducing capacity of EV-associated proteopathic seeds. Using different cellular models propagating model prion-like protein aggregates, mouse-adapted prions or pathogenic Tau aggregates, we demonstrate that vesicular stomatitis virus glycoprotein and SARS-CoV-2 spike S increase protein aggregate induction by direct cell-to-cell contact or via viral glycoprotein-decorated EV. Thus, receptor-ligand interactions are major determinants of intercellular aggregate dissemination. Further, our data raise the intriguing possibility that acute or latent viral infections contribute to proteopathic seed spreading by facilitating intercellular cargo transfer. HIGHLIGHTS Different types of proteopathic seeds are secreted in association with extracellular vesicles Receptor-ligand interactions are important drivers of direct cell-to-cell and extracellular vesicle-mediated spreading of protein misfolding Viral glycoproteins mediating attachment and membrane fusion strongly enhance aggregate inducing capacity in recipient cells GRAPHICAL ABSTRACT


title: Review of published systematic reviews and meta-analyses on COVID-19

text: Purpose: The rapid spread of the COVID-19 pandemic has prompted researchers from all over the world to share their experience. The results were numerous reports with variable quality. The latter has provided an impetus to examine all published meta-analyses and systematic reviews on COVID-19 to date to examine available evidence. Methods: Using predefined selection criteria, a literature search identified 43 eligible meta-analyses and/or systematic reviews. Results: Most (N=17) studies addressed clinical manifestations and associated comorbidity, 6 studies addressed clinical manifestations in pregnant women and younger individuals, 8 studies addressed diagnostic data, 9 studies addressed various interventions, and 9 studies addressed prevention and control. The number of studies included in the various systemic reviews and meta-analyses ranged from 2 to 89. While there were some similarities and consistency for some findings, e.g. the relation between comorbidities and disease severity, we also noted occasionally conflicting data. Conclusion: As more data are collected from patients infected with COVID-19 all over the world, more studies will undoubtedly be published and attention to scientific accuracy in the performance of trials must be exercised to inform clinical decision-making and treatment guidelines.


title: Does the coronavirus pandemic level the gender inequality curve? (It doesn't)

text: Does the coronavirus pandemic level the gender inequality curve? Or does the economic downturn following the coronavirus pandemic enhance gender inequality? To answer these questions, we collected data on Israeli men and women who were employed in the first week of March prior to the lockdown of the economy, and again in the last week of April (after the economy was shut down, but before it was reopened). We find that the consequences of the economic downturn following the coronavirus for gender equality are harsh, with women's employment and income more severely affected than men's.


title: Ultrasound diagnosis in pregnancy in the evolving coronavirus (COVID-19) pandemic

text: The paper reviews current international and Russian recommendations for organizing and conducting ultrasound examinations in obstetric practice during the pandemic of the novel coronavirus infection COVID-19. It discusses questions on disease control measures and choices of type of personal protective equipment for healthcare workers. The algorithms for scheduling screening and fetal monitoring examinations, invasive procedures in cases of fetal malformations and pregnancy complications in patients with suspected or confirmed COVID-19 and in cases with limited human resources in diagnostic departments have been provided. Using the given information in daily practice will ensure the epidemiological safety and clinical effectiveness of the diagnostic departments in our country during COIVID-19 pandemic.


title: Comparison of SARS-CoV-2 Indirect and Direct Detection Methods

text: The COVID-19 pandemic caused by the SARS-CoV-2 virus has placed extensive strain on RNA isolation and RT-qPCR reagents. Rapid development of new test kits has helped to alleviate these shortages. However, comparisons of these new detection systems are largely lacking. Here, we compare indirect methods that require RNA extraction, and direct RT-qPCR on patient samples. For RNA isolation we compared four different companies (Qiagen, Invitrogen, BGI and Norgen Biotek). For detection we compared two recently developed Taqman-based modules (BGI and Norgen Biotek), a SYBR green-based approach (NEB Luna Universal One-Step Kit) with published and newly-developed primers, and clinical results (Seegene STARMag RNA extraction system and Allplex 2019-nCoV RT-qPCR assay). Most RNA isolation procedures performed similarly, and while all RT-qPCR modules effectively detected purified viral RNA, the BGI system proved most sensitive, generating comparable results to clinical diagnostic data, and identifying samples ranging from 65 copies – 2.1×105 copies of viral Orf1ab/μl. However, the BGI detection system is ∼4x more expensive than other options tested here. With direct RT-qPCR we found that simply adding RNase inhibitor greatly improved sensitivity, without need for any other treatments (e.g. lysis buffers or boiling). The best direct methods were ∼10 fold less sensitive than indirect methods, but reduce sample handling, as well as assay time and cost. These studies will help guide the selection of COVID-19 detection systems and provide a framework for the comparison of additional systems.


title: Dengue antibodies can cross-react with SARS-CoV-2 and vice versa-Antibody detection kits can give false-positive results for both viruses in regions where both COVID-19 and Dengue co-exist

text: Five of thirteen Dengue antibody- positive serum samples, dated 2017 (pre-dating the COVID-19 outbreak) produced false-positive results in SARS-CoV-2 IgG/IgM rapid strip tests. Our results emphasize the importance of NAT and/or virus antigen tests to complement sero-surveillance for definitive diagnosis of COVID-19/Dengue in regions where both viruses are co-endemic.


title: Super-Spreader Businesses and Risk of COVID-19 Transmission

text: Purpose: The United States has the highest number of confirmed COVID-19 cases in the world to date, with over 94,000 COVID-19-related deaths. The true risk of a COVID-19 resurgence as states prepare to reopen businesses is unknown. This paper aims to classify businesses by their risk of transmission and quantify the relationship between the density of super-spreader businesses and COVID-19 cases. Methods: We constructed a COVID-19 Business Transmission Risk Index based upon the frequency and duration of visits and square footage of businesses pre-pandemic in 2019 in 8 states (Massachusetts, Rhode Island, Connecticut, New Hampshire, Vermont, Maine, New York, and California). We used this index to classify businesses as super-spreaders. Then, we analyzed the association between the density of super-spreader businesses in a county and the rate of COVID-19 cases. We performed significance testing using a negative binomial regression. The main outcome of interest is the cumulative number of COVID-19 cases each week. Results: We found a positive association between the density of super-spreader businesses and COVID-19 cases. A 1 percentage point increase in the density of super-spreader businesses is associated with 5% higher COVID-19 cases, all else equal. Conclusion: Higher densities of super-spreader businesses are associated with higher rates of COVID-19 cases. This may have important implications for how states reopen super-spreader businesses.


title: Handyfuge-LAMP: low-cost and electricity-free centrifugation forisothermal SARS-CoV-2 detection in saliva.

text: Point of care diagnostics for COVID-19 detection are vital to assess infection quickly and at the source so appropriate measures can be taken. The loop-mediated isothermal amplification (LAMP) assay has proven to be a reliable and simple protocol that can detect small amounts of viral RNA in patient samples (<10 genomes per L) (Nagamine, Hase, and Notomi 2002) Recently, Rabe and Cepko at Harvard published a sensitive and simple protocol for COVID-19 RNA detection in saliva using an optimized LAMP assay (Rabe and Cepko, 2020). This LAMP protocol has the benefits of being simple, requiring no specialized equipment; rapid, requiring less than an hour from sample collection to readout; and cheap, costing around $1 per reaction using commercial reagents. The pH based colorimetric readout also leaves little ambiguity and is intuitive. However, a shortfall in many nucleic acid-based methods for detection in saliva samples has been the variability in output due to the presence of inhibitory substances in saliva. Centrifugation to separate the reaction inhibitors from inactivated sample was shown to be an effective way to ensure reliable LAMP amplification. However, a centrifuge capable of safely achieving the necessary speeds of 2000 RPM for several minutes often costs hundreds of dollars and requires a power supply. We present here an open hardware solution- Handyfuge - that can be assembled with readily available components for the cost of <5 dollars a unit and could be used together with the LAMP assay for point of care detection of COVID-19 RNA from saliva. The device is then validated using the LAMP protocol from Rabe and Cepko. With the use of insulated coolers for reagent supply chain and delivery, the assay presented can be completed without the need for electricity or any laboratory scale infrastructure.


title: Assessment of clinical characteristics and mortality-associated factors in COVID-19 Critical cases in Kuwait

text: Purpose To assess the clinical characteristics and identify mortality predicting factors in intensive care unit (ICU)-admitted COVID-19 confirmed patients. Methods We recruited and analyzed COVID-19 infected adult patients (age[≥] 18 years) who were admitted to the ICU at Jaber AlAhmad Al Sabah Hospital,Kuwait, between 1st March, 2020and 30th April 2020. The patients were followed up to 20th May, 2020. The risk factors associated with in-hospital mortality were assessed using multiple regression analysis. Results We recruited a total of 103 ICU patients in this retrospective cohort. The median age of the patients was 53 years (Interquartile Range (IQR): 44-63 years). The fatality rate was 43.7%. Among the patients, majority were males (85.5%) and 38% patients had more than two comorbidities. Pre-existing hypertension (OR:3.2,95%CI: 1.2-8.9), moderate/severe ARDS (OR: 3.4, 95%CI: 1.1-10.8),lymphocyte counts <0.5 (OR: 6.1, 95%CI: 1.2-29.8) albumin < 22 (OR: 7.5, 95%CI: 2.1-26.2), procalcitonin >0.2 (OR: 3.8, 95%CI: 1.3-7.8), D-Dimer >1200 (OR: 5.1, 95%CI: 1.2-21.6), and the need for continuous renal replacement therapy (OR: 9.3, 95%CI: 2.4-36.2) were significantly associated with mortality. Conclusion This study describes the clinical characteristics and predictors of mortality among ICU patients. Early identification of risk factors to mortality might help in their better outcome.


title: Serial measurements in COVID-19-induced acute respiratory disease to unravel heterogeneity of the disease course: design of the Maastricht Intensive Care COVID cohort; MaastrICCht

text: Background: The course of the disease in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in mechanically ventilated patients is unknown. To unravel the clinical heterogeneity of the SARS-CoV-2 infection in these patients, we designed the prospective observational Maastricht Intensive Care COVID cohort; MaastrICCht. We incorporated serial measurements that harbour aetiological, diagnostic and predictive information. The study aims to investigate the heterogeneity of the natural course of critically ill patients with SARS-CoV-2 infection. Study population: Mechanically ventilated patients admitted to the Intensive Care with SARS-CoV-2 infection. Main message: We will collect clinical variables, vital parameters, laboratory variables, mechanical ventilator settings, chest electrical impedance tomography, electrocardiograms, echocardiography as well as other imaging modalities to assess heterogeneity of the natural course of SARS-CoV-2 infection in critically ill patients. The MaastrICCht cohort is, also designed to foster various other studies and registries and intends to create an open-source database for investigators. Therefore, a major part of the data collection is aligned with an existing national Intensive Care data registry and two international COVID-19 data collection initiatives. Additionally, we create a flexible design, so that additional measures can be added during the ongoing study based on new knowledge obtained from the rapidly growing body of evidence. Conclusion: The spread of the COVID-19 pandemic requires the swift implementation of observational research to unravel heterogeneity of the natural course of the disease of SARS-CoV-2 infection in mechanically ventilated patients. Our design is expected to enhance aetiological, diagnostic and prognostic understanding of the disease. This paper describes the design of the MaastrICCht cohort.


title: Transplantation of ACE2(-) Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia

text: A coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak in Wuhan, China. Preventing and reversing the cytokine storm may be the key to save the patients with severe COVID-19 pneumonia. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate whether MSC transplantation improves the outcome of 7 enrolled patients with COVID-19 pneumonia in Beijing YouAn Hospital, China, from Jan 23, 2020 to Feb 16, 2020. The clinical outcomes, as well as changes of inflammatory and immune function levels and adverse effects of 7 enrolled patients were assessed for 14 days after MSC injection. MSCs could cure or significantly improve the functional outcomes of seven patients without observed adverse effects. The pulmonary function and symptoms of these seven patients were significantly improved in 2 days after MSC transplantation. Among them, two common and one severe patient were recovered and discharged in 10 days after treatment. After treatment, the peripheral lymphocytes were increased, the C-reactive protein decreased, and the overactivated cytokine-secreting immune cells CXCR3+CD4+ T cells, CXCR3+CD8+ T cells, and CXCR3+ NK cells disappeared in 3-6 days. In addition, a group of CD14+CD11c+CD11b(mid) regulatory DC cell population dramatically increased. Meanwhile, the level of TNF-α was significantly decreased, while IL-10 increased in MSC treatment group compared to the placebo control group. Furthermore, the gene expression profile showed MSCs were ACE2(-) and TMPRSS2(-) which indicated MSCs are free from COVID-19 infection. Thus, the intravenous transplantation of MSCs was safe and effective for treatment in patients with COVID-19 pneumonia, especially for the patients in critically severe condition.


Life in the Time of COVID-19


title: Early Phylogenetic Estimate Of The Effective Reproduction Number Of 2019-nCoV

text: To reconstruct the evolutionary dynamics of the 2019 novel coronavirus, 52 2019−nCOV genomes available on 04 February 2020 at GISAID were analysed. The two models used to estimate the reproduction number (coalescent−based exponential growth and a birth−death skyline method) indicated an estimated mean evolutionary rate of 7.8 x 10−4 subs/site/year (range 1.1x10−4−15x10−4). The estimated R value was 2.6 (range 2.1−5.1), and increased from 0.8 to 2.4 in December 2019. The estimated mean doubling time of the epidemic was between 3.6 and 4.1 days. This study proves the usefulness of phylogeny in supporting the surveillance of emerging new infections even as the epidemic is growing.


title: Projected early spread of COVID-19 in Africa

text: For African countries currently reporting COVID-19 cases, we estimate when they will report more than 1 000 and 10 000 cases. Assuming current trends, more than 80% are likely to exceed 1 000 cases by the end of April 2020, with most exceeding 10 000 a few weeks later.


title: Pakistan’s response to COVID-19 pandemic and efficacy of quarantine and partial lockdown: A review

text: Pakistan, being as a neighbor country of China and Iran was vulnerable most to COVID-19 pandemic. During receiving Pakistani pilgrims from Iran, Pakistani government reacted toward the spread of COVID-19 after report of first COVID-19 case on 25thof February, 2020. Quarantine facilities were arranged with delay and were the main cause of epidemic in Pakistan. Out of the total COVID-19 cases 78 percent cases were linked with the visitors coning from Iran. Simultaneously, Pakistan announced closure of all education institutions with a partial lockdown across the country. This badly affected the labor community. Due to lack of record/ database, Pakistani government faced problem in supporting the labor community. The partial lockdown was effective to some extent and the epidemic was brought under control. To cope with such pandemic/epidemic situations in future, the various lessons learned have been given as recombinations for the future.


title: How simulation modelling can help reduce the impact of COVID-19

text: Modelling has been used extensively by all national governments and the World Health Organisation in deciding on the best strategies to pursue in mitigating the effects of COVID-19. Principally these have been epidemiological models aimed at understanding the spread of the disease and the impacts of different interventions. But a global pandemic generates a large number of problems and questions, not just those related to disease transmission, and each requires a different model to find the best solution. In this article we identify challenges resulting from the COVID-19 pandemic and discuss how simulation modelling could help to support decision-makers in making the most informed decisions. Modellers should see the article as a call to arms and decision-makers as a guide to what support is available from the simulation community.


Letter to the Editor regarding “Could pulmonary arterial hypertension patients be at lower risk from severe COVID-19?”


title: The dashboard pandemic

text: The dashboard is the most striking cultural artefact of the current coronavirus (SARS-CoV-2) pandemic. It reveals the fraught pandemic politics which are centred around territorial approaches on the scale of the state rather than international cooperation, democratic liberation, and local care. The dashboard is a biopolitical technology of anxiety, prompting national states of emergency. This narrow approach to framing the COVID-19 crisis is rooted in military-style pandemic preparedness planning that became fashionable in the 21st century. However, there is mounting evidence that this approach does not adequately address the uneven and unjust geographies of the present.


Vitamin D insufficiency and deficiency and mortality from respiratory diseases in a cohort of older adults: potential for limiting the death toll during and beyond the COVID-19 pandemic


title: Causal Impact of Masks, Policies, Behavior on Early Covid-19 Pandemic in the U.S.

text: This paper evaluates the dynamic impact of various policies, such as school, business, and restaurant closures, adopted by the US states on the growth rates of confirmed Covid-19 cases and social distancing behavior measured by Google Mobility Reports, where we take into consideration of people's voluntarily behavioral response to new information of transmission risks. Using the US state-level data, our analysis finds that both policies and information on transmission risks are important determinants of people's social distancing behavior, and shows that a change in policies explains a large fraction of observed changes in social distancing behavior. Our counterfactual experiments indicate that removing all policies on April 1st of 2020 would have lead to 30 to 200 times more additional cases by late May. Removing only the non-essential businesses closures (while maintaining restrictions on movie theaters and restaurants) would have increased the weekly growth rate of cases between -0.02 and 0.06 and would have lead to -10% to 40% more cases by late May. Finally, nationally mandating face masks for employees on April 1st would have reduced the case growth rate by 0.1-0.25. This leads to 30% to 57% fewer reported cases by late May, which translates into, roughly, 30-57 thousand saved lives.


title: Minimising lockdown periods for regional elimination of covid-19

text: Some nations have the option of pursuing a policy of complete elimination of covid-19 instead of a policy of "flattening the curve" so that the load the dis- ease places on medical facilities is bearable. A policy of elimination requires a rather onerous "lockdown". As the goal of elimination is approached, it is therefore important that there be an informed trade-off between the risk of disease re-emergence and the duration of the "lockdown". Here it is shown that an important factor in assessing this trade-off, is the distribution of secondary cases, not just the expected value of this distribution, R0 . It is shown that a distribution in which "super-spreaders" are more prominent in the epidemiology, allows for an earlier release from "lockdown" with reasonable safety despite some probability of asymptomatic cases. There is some evidence to support such a distribution for covid-19. Analytical calculations and simulations show that once there is only one recognised case in some subregion, release from "lockdown" will be reasonably safe after just one or two further incubation periods.


title: Convalescent Plasma to Treat COVID-19: Chinese Strategy and Experiences

text: The COVID-19 is currently spreading around the world, which has posed significant threats to global health and economy. Convalescent plasma is confirmed effective against the novel corona virus in preliminary studies. In this paper, we first described the therapeutic schedule, antibody detection method, indications, contraindications of the convalescent plasmas, and reported the operability of the treatment by case study.


title: Clinical, Behavioral and Social Factors Associated with Racial Disparities in Hospitalized and Ambulatory COVID-19 Patients from an Integrated Health Care System in Georgia

text: Introduction: Racial and ethnic minorities have shouldered a disproportioned burden of coronavirus disease 2019 (COVID-19) infection to date in the US, but data on the various drivers of these disparities is limited. Objectives: To describe the characteristics and outcomes of COVID-19 patients and explore factors associated with hospitalization risk by race. Methods: Case series of 448 consecutive patients with confirmed COVID-19 seen at Kaiser Permanente Georgia (KPGA), an integrated health care system serving the Atlanta metropolitan area, from March 3 to May 12, 2020. KPGA members with laboratory-confirmed COVID-19. Multivariable analyses for hospitalization risk also included an additional 3489 persons under investigation (PUI) with suspected infection. COVID-19 treatment and outcomes, underlying comorbidities and quality of care management metrics, socio-demographic and other individual and community-level social determinants of health (SDOH) indicators. Results: Of 448 COVID-19 positive members, 68,3% was non-Hispanic Black (n=306), 18% non-Hispanic White (n=81) and 13,7% Other race (n=61). Median age was 54 [IQR 43-63) years. Overall, 224 patients were hospitalized, median age 60 (50-69) years. Black race was a significant factor in the Confirmed + PUI, female and male models (ORs from 1.98 to 2.19). Obesity was associated with higher hospitalization odds in the confirmed, confirmed + PUI, Black and male models (ORs from 1.78 to 2.77). Chronic disease control metrics (diabetes, hypertension, hyperlipidemia) were associated with lower odds of hospitalization ranging from 48% to 35% in the confirmed + PUI and Black models. Self-reported physical inactivity was associated with 50% higher hospitalization odds in the Black and Female models. Residence in the Northeast region of Atlanta was associated with lower hospitalization odds in the Confirmed + PUI, White and female models (ORs from 0.22 to 0.64) Conclusions: We found that non-Hispanic Black KPGA members had a disproportionately higher risk of infection and, after adjusting for covariates, twice the risk of hospitalization compared to other race groups. We found no significant differences in clinical outcomes or mortality across race/ethnicity groups. In addition to age, sex and comorbidity burden, pre-pandemic self-reported exercise, metrics on quality of care and control of underlying cardio-metabolic diseases, and location of residence in Atlanta were significantly associated with hospitalization risk by race groups. Beyond well-known physiologic and clinical factors, individual and community-level social indicators and health behaviors must be considered as interventions designed to reduce COVID-19 disparities and the systemic effects of racism are implemented.


title: Epidemic Models for Personalised COVID-19 Isolation and Exit Policies Using Clinical Risk Predictions

text: Background: In mid April 2020, with more than 2.5 billion people in the world following social distancing measures due to COVID-19, governments are considering relaxing lock-down. We combined individual clinical risk predictions with epidemic modelling to examine simulations of isolation and exit policies. Methods: We developed a method to include personalised risk predictions in epidemic models based on data science principles. We extended a standard susceptible-exposed-infected-removed (SEIR) model to account for predictions of severity, defined by the risk of an individual needing intensive care in case of infection. We studied example isolation policies using simulations with the risk-extended epidemic model, using COVID-19 data and estimates in France as of mid April 2020 (4 000 patients in ICU, around 7 250 total ICU beds occupied at the peak of the outbreak, 0.5% percent of patients requiring ICU upon infection). We considered scenarios varying in the discrimination performance of a risk prediction model, in the degree of social distancing, and in the severity rate upon infection. Confidence intervals were obtained using an Approximate Bayesian Computation approach. The framework may be used with other epidemic models, with other risk predictions, and for other epidemic outbreaks. Findings: Based on the data for France as of mid April 2020, simulations indicated that an exit policy considering clinical risk predictions starting on May 11, as planned by the government, could enable to immediately relax restrictions for an extra 10% (6 700 000 people) or more of the lowest-risk population, and consequently relax the restrictions on the remaining population up to two times (or several months) faster, with only a small proportion of the population remaining in isolation for an extended period of time -- while abiding to the current ICU capacity. In contrast, implementing the same exit policy without risk predictions would exceed the ICU capacity by a multiple. Sensitivity analyses showed that when the assumed percentage of severe patients among the population decreased, or the prediction model discrimination improved, or ICU capacity increased, policies based on risk models had a greater impact on the results of epidemic simulations. At the same time, sensitivity analyses also showed that differential isolation policies require that higher risk individuals comply with recommended restrictions. In general, our simulations showed that risk prediction models could always improve policy effectiveness, keeping everything else constant, in line with value of information arguments, even for models with moderate discrimination power. Interpretation: Clinical risk prediction models should be considered to manage outbreaks using a framework as the one developed. They can inform personalised isolation policies, for example by gradually restricting (relaxing) isolation from the highest (lowest) to the lowest (highest) predicted risk individuals, when such policies are considered. This may lead to both safer and faster outcomes than what can be achieved without such prediction models. They enable personalisation of policies, which are known to improve effectiveness in other non-healthcare contexts.


title: An enzyme-based immunodetection assay to quantify SARS-CoV-2 infection

text: SARS-CoV-2 is a novel pandemic coronavirus that caused a global health and economic crisis. The development of efficient drugs and vaccines against COVID-19 requires detailed knowledge about SARS-CoV-2 biology. Several techniques to detect SARS-CoV-2 infection have been established, mainly based on counting infected cells by staining plaques or foci, or by quantifying the viral genome by PCR. These methods are laborious, time-consuming and expensive and therefore not suitable for a high sample throughput or rapid diagnostics. We here report a novel enzyme-based immunodetection assay that directly quantifies the amount of de novo synthesized viral spike protein within fixed and permeabilized cells. This in-cell ELISA enables a rapid and quantitative detection of SARS-CoV-2 infection in microtiter format, regardless of the virus isolate or target cell culture. It follows the established method of performing ELISA assays and does not require expensive instrumentation. Utilization of the in-cell ELISA allows to e.g. determine TCID50 of virus stocks, antiviral efficiencies (IC50 values) of drugs or neutralizing activity of sera. Thus, the in-cell spike ELISA represents a promising alternative to study SARS-CoV-2 infection and inhibition and may facilitate future research. Highlights Determination of SARS-CoV-2 infection by enzymatically quantifying the expression of viral spike protein in bulk cell cultures Targeting a highly conserved region in the S2 subunit of the S protein allows broad detection of several SARS-CoV-2 isolates in different cell lines Screening of antivirals in microtiter format and determining the antiviral activity as inhibitory concentrations 50 (IC50)


title: Placental SARS-CoV-2 in a patient with mild COVID-19 disease

text: Background: The full impact of COVID-19 on pregnancy remains uncharacterized. Current literature suggests minimal maternal, fetal, and neonatal morbidity and mortality,1 and COVID-19 manifestations appear similar between pregnant and non-pregnant women.2 We present a case of placental SARS-CoV-2 virus in a woman with an uncomplicated pregnancy and mild COVID-19 disease. Methods: A pregnant woman was evaluated at University of Missouri Women and Childrens Hospital. Institutional review board approval was obtained; information was obtained from medical records. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to detect SARS-CoV-2. A gynecological pathologist examined the placenta and performed histolopathology. Sections were formalin-fixed and paraffin-embedded; slides were cut and subjected to hematoxylin-and-eosin or immunohistochemistry (IHC) staining. IHC was performed with specific monoclonal antibodies to detect SARS-CoV-2 antigen or to identify trophoblasts. Findings: A 29 year-old multigravida presented at 40-4/7 weeks for labor induction. With myalgias two days prior, she tested positive for SARS-CoV-2. Her parents were in self-isolation for COVID-19 positivity; husband was asymptomatic and tested negative for COVID-19, but exposed to a workplace (meatpacking facility) outbreak. Prenatal course was uncomplicated, with no gestational hypertension. She was afebrile and asymptomatic with normal vital signs throughout hospitalization. Her myalgias improved prior to admission. A liveborn male infant was delivered vaginally. Newborn course was uneventful; he was appropriate for gestational age, physical was unremarkable, and he was discharged home at 36 hours. COVID-19 RT-PCR test was negative at 24 hours. At one-week follow-up, newborn was breastfeeding well, with no fevers or respiratory distress. Overall placental histology is consistent with acute uterine hypoxia (subchorionic laminar necrosis) superimposed on chronic uterine hypoxia (extra-villous trophoblasts and focal chronic villitis). IHC using SARS-CoV-2 nucleocapsid-specific monoclonal antibody demonstrated SARS-CoV-2 antigens throughout the placenta in chorionic villi endothelial cells, and rarely in CK7-expressing trophoblasts. Negative control placenta (November 2019 delivery) and ferret nasal turbinate tissues (not shown) were negative for SARS-CoV-2. Interpretation: In this report, SARS-CoV-2 was found in the placenta, but newborn was COVID-19 negative. Our case shows maternal vascular malperfusion, with no features of fetal vascular malperfusion. To our knowledge, this is the first report of placental COVID-19 despite mild COVID-19 disease in pregnancy (with no symptoms of COVID-19 aside from myalgias); specifically, this patient had no fever, cough, or shortness of breath, but only myalgias and sick contacts. Despite her having mild COVID-19 disease in pregnancy, we demonstrate placental vasculopathy and presence of SARS-CoV-2 virus across the placenta. Evidence of placental COVID-19 raises concern for possible placental vasculopathy (potentially leading to fetal growth restriction, pre-eclampsia, and other pregnancy complications) as well as for potential vertical transmission -- especially for pregnant women who may be exposed to COVID-19 in early pregnancy. Further studies are urgently needed, to determine whether women with mild, pre-symptomatic, or asymptomatic COVID-19 may have SARS-CoV-2 virus that can cross the placenta, cause fetal vascular malperfusion, and possibly affect the fetus. This raises important public health and public policy questions of whether future pregnancy guidance should include stricter pandemic precautions, such as screening for a wider array of COVID-19 symptoms, increased antenatal surveillance, and possibly routine COVID-19 testing on a regular basis throughout pregnancy.


title: Accounting for nature

text: Gretchen Daily's efforts to encourage people to value nature have taken her around the world, from Latin America and the Caribbean to China, and from government offices and boardrooms to tropical rainforests. Adam Vaughan caught up with her


title: Cell-based therapies for COVID-19: A living systematic review

text: OBJECTIVE: This living systematic review aims to provide a timely, rigorous and continuously updated summary of the available evidence on the role of cell-based therapies in the treatment of patients with COVID-19. DATA SOURCES: We conducted searches in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), grey literature and in a centralised repository in L-OVE (Living OVerview of Evidence). L-OVE is a platform that maps PICO questions to evidence from Epistemonikos database. In response to the COVID-19 emergency, L-OVE was adapted to expand the range of evidence it covers and customised to group all COVID-19 evidence in one place. All the searches covered the period until April 23, 2020 (one day before submission). ELIGIBILITY CRITERIA FOR SELECTING STUDIES AND METHODS: We adapted an already published common protocol for multiple parallel systematic reviews to the specificities of this question. We searched for randomised trials evaluating the effect of cell-based therapies versus placebo or no treatment in patients with COVID-19. Anticipating the lack of randomised trials directly addressing this question, we also searched for trials evaluating other coronavirus infections, such as MERS-CoV and SARS-CoV, and non-randomised studies in COVID-19. Two reviewers independently screened each study for eligibility. A living, web-based version of this review will be openly available during the COVID-19 pandemic. We will resubmit it every time the conclusions change or whenever there are substantial updates. RESULTS: We screened 1,043 records but no study was considered eligible. We identified 61 ongoing studies, including 39 randomised trials evaluating different types of cell-based therapies in COVID-19. CONCLUSIONS: We did not find any studies that met our inclusion criteria and hence there is no evidence to support or refute the use of cell-based therapies in the treatment of patients with COVID-19. A substantial number of ongoing studies should provide valuable evidence to inform researchers and decision makers in the near future. PROSPERO REGISTRATION NUMBER: CRD42020179711


title: Event-specific interventions to minimize COVID-19 transmission

text: Coronavirus disease 2019 (COVID-19) is a global pandemic with over 11 million cases worldwide. Currently there is no treatment and no vaccine. Interventions such as hand washing, masks, social distancing, and "social bubbles" are used to limit community transmission, but it is challenging to choose the best interventions for a given activity. Here, we provide a quantitative framework to determine which interventions are likely to have the most impact in which settings. We introduce the concept of "event R", the expected number of new infections due to the presence of a single infected individual at an event. We obtain a fundamental relationship between event R and four parameters: transmission intensity, duration of exposure, the proximity of individuals, and the degree of mixing. We use reports of small outbreaks to establish event R and transmission intensity in a range of settings. We identify principles that guide whether physical distancing, masks and other barriers to transmission, or social bubbles will be most effective. We outline how this information can be obtained and used to re-open economies with principled measures to reduce COVID-19 transmission.


title: Using EpiRank for Analyzing Emerging Coronavirus Epidemic Patterns

text: Huang et al. (2019) used their EpiRank algorithm, which emphasizes forward-and-backward commuter flow between homes and workplaces, to analyze the distribution patterns of two infectious diseases in Taiwan: the 2009-H1N1 influenza virus and the widespread emergence of the 2000-2008 type 71 enterovirus (EV). As this article was being prepared, the spreading mechanism of the novel coronavirus disease now designated as COVID-19 had yet to be identified, but according to the American Centers for Disease Control, its spreading mechanism and patterns are likely more similar to influenza than to other coronaviruses such as Severe Acute Respiratory Syndrome (SARS-CoV-1) or Middle East Respiratory Syndrome (MERS-CoV). To consider potential COVID-19 spatial patterns, we applied EpiRank to the 2003 SARS outbreak in north Taiwan for comparison with H1N1 and EV. SARS was found to be less contagious than H1N1 or EV, but with a significantly higher fatality rate. The characteristics of these diseases determined their specific spatial spreading patterns, as reflected in the different effects of forward and backward commuting movement. Our motivation is to highlight these differences and to illustrate EpiRank spatial patterns for the 2003 SARS outbreak for comparison with EpiRank-determined distributions for the H1N1 and EV outbreaks. Our results indicate that the daytime parameter (i.e., forward movement effect) range was slightly higher (0.5-0.55) for the SARS outbreak than for either the influenza (0.4-0.5) or EV (0.3-0.5) outbreaks, suggesting that the forward-and-backward movements of individuals between residential and core urban areas with concentrated populations were equally important regarding the spread of SARS. While COVID-19 might resemble either SARS or H1N1 in terms of spatial spreading, its daytime parameter is likely somewhere in-between, with backward movement being dominant (similar to H1N1) or with forward and backward movement being equally important (similar to SARS). Building on Huang et al. (2019) paper, we present an estimated risk distribution pattern for the Taipei Metropolitan Area for a daytime parameter of 0.55.


title: Development and Evaluation of an AI System for COVID-19

text: Early detection of COVID-19 based on chest CT will enable timely treatment of patients and help control the spread of the disease. With rapid spreading of COVID-19 in many countries, however, CT volumes of suspicious patients are increasing at a speed much faster than the availability of human experts. Here, we propose an artificial intelligence (AI) system for fast COVID-19 diagnosis with an accuracy comparable to experienced radiologists. A large dataset was constructed by collecting 970 CT volumes of 496 patients with confirmed COVID-19 and 260 negative cases from three hospitals in Wuhan, China, and 1,125 negative cases from two publicly available chest CT datasets. Trained using only 312 cases, our diagnosis system, which is based on deep convolutional neural network, is able to achieve an accuracy of 94.98%, an area under the receiver operating characteristic curve (AUC) of 97.91%, a sensitivity of 94.06%, and a specificity of 95.47% on an independent external verification dataset of 1,255 cases. In a reader study involving five radiologists, only one radiologist is slightly more accurate than the AI system. The AI system is two orders of magnitude faster than radiologists and the code is available at https://github.com/ChenWWWeixiang/diagnosis_covid19.


title: CoV-Seq: SARS-CoV-2 Genome Analysis and Visualization

text: Summary COVID-19 has become a global pandemic not long after its inception in late 2019. SARS-CoV-2 genomes are being sequenced and shared on public repositories at a fast pace. To keep up with these updates, scientists need to frequently refresh and reclean datasets, which is ad hoc and labor-intensive. Further, scientists with limited bioinformatics or programming knowledge may find it difficult to analyze SARS-CoV-2 genomes. In order to address these challenges, we developed CoV-Seq, a webserver to enable simple and rapid analysis of SARS-CoV-2 genomes. Given a new sequence, CoV-Seq automatically predicts gene boundaries and identifies genetic variants, which are presented in an interactive genome visualizer and are downloadable for further analysis. A command-line interface is also available for high-throughput processing. Availability and Implementation CoV-Seq is implemented in Python and Javascript. The webserver is available at http://covseq.baidu.com/ and the source code is available from https://github.com/boxiangliu/covseq. Contact jollier.liu@gmail.com Supplementary information Supplementary information are available at bioRxiv online.


title: The role of intolerance of uncertainty in the acquisition and extinction of reward

text: Individuals, who score high in self-reported intolerance of uncertainty (IU), tend to find uncertainty anxiety-provoking. IU has been reliably associated with disrupted threat extinction. However, it remains unclear whether IU would be related to disrupted extinction to other arousing stimuli that are not threatening (i.e., rewarding). We addressed this question by conducting a reward associative learning task with acquisition and extinction training phases (n = 58). Throughout the associative learning task, we recorded valence ratings (i.e. liking), skin conductance response (SCR) (i.e. sweating), and corrugator supercilii activity (i.e. brow muscle indicative or negative and positive affect) to learned reward and neutral cues. During acquisition training with partial reward reinforcement, higher IU was associated with greater corrugator supercilii activity to neutral compared to reward cues. IU was not related to valence ratings or SCR’s during the acquisition or extinction training phases. These preliminary results suggest that IU-related deficits during extinction may be limited to situations with threat. The findings further our conceptual understanding of IU’s role in the associative learning and extinction of reward, and in relation to the processing of threat and reward more generally.


COVID-19: A new digital dawn?


title: Biotech start-ups hit by coronavirus work stoppages

text: s the outbreak of the new coronavirus, now officially named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to mushroom, the related work stoppages in China have put a spotlight on Western biotech companies’ dependence on Chinese contract research organizations (CROs) The situation has prompted some start-ups to rethink their contingency plans—particularly when it comes to chemistry services Biotech firms had anticipated delays related to the Lunar New Year holidays, and so far outbreak-related travel restrictions have extended that work gap by only a week But as the virus spreads—according to Chinese authorities, as of Feb 13, more than 60,100 people had been infected and nearly 1,400 had died, most of them in China—some biotech firms that rely on China are becoming nervous about how long their projects could be on hold Much attention is on WuXi AppTec, the largest Chinese CRO


Role of Canadian pharmacists in managing drug shortage concerns amid the COVID-19 pandemic


title: Computational fluid dynamic (CFD), air flow-droplet dispersion, and indoor CO2 analysis for healthy public space configuration to complywith COVID 19 protocol

text: The droplet has a limited travel distance. Nonetheless, especially in the indoor public space the air flow can propagate the droplet to travel long distance. Based on this situation, this paper aims to study the relationships of seat configuration-social distance-air flow-droplet dispersions. The analysis was based on the computational fluid dynamic (CFD) using lattice Boltzmann model (LBM). The result confirms that by modifying public space configuration in this case by providing more space and increasing seating distance can reduce the vulnerability towards droplet dispersions. Whereas, providing shield including adding protection is far more effective in avoiding dispersions. The public space reconfiguration including increasing seat distance and reducing seating capacity also has an effect in reducing the indoor CO2. Capacity reduction from full capacity to 30% can decrease the CO2 from 5722 to 2144 ppm.


title: Effects of environmental factors on severity and mortality of COVID-19

text: Background Most respiratory viruses show pronounced seasonality, but for SARS-CoV-2 this still needs to be documented. Methods We examined the disease progression of COVID-19 in 6,911 patients admitted to hospitals in Europe and China. In addition, we evaluated progress of disease symptoms in 37,187 individuals reporting symptoms into the COVID Symptom Study application. Findings Meta-analysis of the mortality risk in eight European hospitals estimated odds ratios per one day increase in the admission date to be 0.981 (0.973-0.988, p<0.001) and per increase in ambient temperature of one degree Celsius to be 0.854 (0.773-0.944, p=0.007). Statistically significant decreases of comparable magnitude in median hospital stay, probability of transfer to Intensive Care Unit and need for mechanical ventilation were also observed in most, but not all hospitals. The analysis of individually reported symptoms of 37,187 individuals in the UK also showed the decrease in symptom duration and disease severity with time. Interpretation Severity of COVID-19 in Europe decreased significantly between March and May and the seasonality of COVID-19 is the most likely explanation. Mucosal barrier and mucociliary clearance can significantly decrease viral load and disease progression, and their inactivation by low relative humidity of indoor air might significantly contribute to severity of the disease.


title: A pragmatic model to forecast the COVID-19 epidemic in different countries and allowing for daily updates

text: Due to high infections rates and a high death toll of the COVID-19 pandemic, it is important to have daily updated forecasted estimates for the next weeks in order to allocate the scare resources as good as possible. We propose a pragmatic model to forecast the COVID-19 epidemic by applying a mixture normal distribution to open accessible WHO data. We specified a simple joint model on data from 20 countries with number of confirmed COVID-19 infections and number of COVID-19 deaths. We found that the duration of an epidemic wave (99% of total size) was usually between 45-48 days. Using data up to April 6, 2020, we found in six of 20 counties two waves, spaced between 21 and 47 days. In China and Korea the first wave was bigger, and in Denmark, Iran, Japan, and Sweden the second wave was stronger. Lag time between time trends in confirmed infections and time trends in deaths varied between 3.1 and 9.5 days. We obtained a good fit between observed and modelled data in almost all countries. In about halve of the countries the highest peak of the COVID-19 epidemic had been reached until April 6, 2020. Among the 20 countries, it is predicted that the USA will reach the highest numbers of confirmed infections (653 683-802 205) and number of deaths (36 591-53 286). Taken together, for many countries reasonable and up-to-date forecasting seems to be feasible. This method therefore bears a high potential for assisting decision makers to adjust the measures aiming at reducing the spread of the virus appropriately.


title: Biophysical characterization of the SARS-CoV-2 spike protein binding with the ACE2 receptor and implications for infectivity

text: SARS-CoV-2 is a novel highly virulent pathogen which gains entry to human cells by binding with the cell surface receptor – angiotensin converting enzyme (ACE2). We computationally contrasted the binding interactions between human ACE2 and coronavirus spike protein receptor binding domain (RBD) of the 2002 epidemic-causing SARS-CoV-1, SARS-CoV-2, and bat coronavirus RaTG13 using the Rosetta energy function. We find that the RBD of the spike protein of SARS-CoV-2 is highly optimized to achieve very strong binding with human ACE2 (hACE2) which is consistent with its enhanced infectivity. SARS-CoV-2 forms the most stable complex with hACE2 compared to SARS-CoV-1 (23% less stable) or RaTG13 (11% less stable) while occupying the greatest number of residues in the ATR1 binding site. Notably, the SARS-CoV-2 RBD out-competes the angiotensin 2 receptor type I (ATR1) which is the native binding partner of ACE2 by 35% in terms of the calculated binding affinity. Strong binding is mediated through strong electrostatic attachments with every fourth residue on the N-terminus alpha-helix (starting from Ser19 to Asn53) as the turn of the helix makes these residues solvent accessible. By contrasting the spike protein SARS-CoV-2 Rosetta binding energy with ACE2 of different livestock and pet species we find strongest binding with bat ACE2 followed by human, feline, equine, canine and finally chicken. This is consistent with the hypothesis that bats are the viral origin and reservoir species. These results offer a computational explanation for the increased infectivity of SARS-CoV-2 and allude to therapeutic modalities by identifying and rank-ordering the ACE2 residues involved in binding with the virus.


title: Strategic partnership between Japan and New Zealand: foundation, development and prospect

text: There is an increasing proliferation of bilateral strategic partnerships in and beyond the Indo-Pacific region. Yet such a partnership between Japan and New Zealand is underexplored. The central aim of this article is to fill the gap. This article first clarifies the definition of, and then provides an analytical framework for, a ‘strategic partnership’. The article then analyses how these countries laid the foundation of their strategic partnership and how they have since built upon that foundation. In the implementation process of the strategic partnership, this article examines three elements: 1) the consolidation of their strategic partnership in official documents; 2) the institutionalisation of regular meetings; and 3) participation in defence and security exercises. Although the Japan-New Zealand strategic partnership is still in the early stages, this article argues that it has the potential to grow further given bipartisan support and positive perceptions in civil society in both countries. This article also analyses three factors that exert an impact on the development of their strategic partnership: China’s continued assertive maritime presence, the rejuvenation of the US-New Zealand bilateral relationship, and Japan and New Zealand’s ongoing commitment to the South Pacific region.


title: Coronavirus found in Paris sewage points to early warning system

text: By sampling sewage across greater Paris for more than 1 month, researchers have detected a rise and fall in novel coronavirus concentrations that correspond to the shape of the COVID-19 outbreak in the region, where a lockdown is now suppressing spread of the disease Although several research groups have reported detecting coronavirus in wastewater, the researchers say the new study is the first to show that the technique can pick up a sharp rise in viral concentrations in sewage before cases explode in the clinic That points to its potential as a cheap, noninvasive tool to warn against outbreaks, they say


title: COVID-19 Outbreak Response for an Emergency Department Using In Situ Simulation

text: In January 2020, the WHO declared COVID-19 an epidemic in China and the possibility of evolving into a pandemic. During early phases, most emergency departments did not have contingency plans for an outbreak of this scale and therefore necessitating adequate preparation. This study aims to describe the utility of in situ simulation in identifying system errors and latent safety hazards in response to preparation for the expected COVID-19 surge. We also aim to describe the corrective measures taken to improve our outbreak response locally. We hope that others may be able to use this information as foresight in preparing their own departments for this outbreak. The emergency department and anesthesiology department of Galway University Hospital conducted a series of multidisciplinary, in situ simulations to rapidly identify operational errors and latent safety hazards in response to this outbreak. Each simulation involved an interdisciplinary response to a suspected/COVID-19 patient. The cases were used as a training opportunity for staff and ultimately a platform to expeditiously implement system changes in response to deficits identified during the simulations. Conclusively, with the complexities and intricate structure of every emergency department, we understood that preparation for an outbreak requires evaluation of the current system before implementing any changes. It is not a "one size fits all" concept. Therefore, conducting in situ simulations and the use of foresight, is pivotal as it could prevent loss of resources and time in preparing for an outbreak.


title: A reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay for the rapid detection of SARS-CoV-2 within nasopharyngeal and oropharyngeal swabs at Hampshire Hospitals NHS Foundation Trust

text: The COVID-19 pandemic has illustrated the importance of rapid, accurate diagnostic testing for the effective triaging and cohorting of patients and timely tracking and tracing of cases. However, a surge in diagnostic testing quickly resulted in worldwide competition for the same sample preparation and real-time RT-PCR diagnostic reagents (rRT-PCR). Consequently, Hampshire Hospitals NHS Foundation Trust, UK sought to diversify their diagnostic portfolio by exploring alternative amplification chemistries including those that permit direct testing without RNA extraction. This study describes the validation of a SARS-CoV-2 RT-LAMP assay, which is an isothermal, autocycling, strand displacement nucleic acid amplification technique which can be performed on extracted RNA, (RNA RT-LAMP) or directly from swab (Direct RT-LAMP). Analytical specificity (ASp) of this new RT-LAMP assay was 100% and analytical sensitivity (ASe) was between 1x101 and 1x102 copies when using a synthetic DNA target. The overall diagnostic sensitivity (DSe) and specificity (DSp) of RNA RT LAMP was 97% and 99% respectively, relative to the standard of care (SoC) rRT-PCR. When a CT cut-off of 33 was employed, above which increasingly, evidence suggests there is a very low risk of patients shedding infectious virus, the diagnostic sensitivity was 100%. The DSe and DSp of Direct-RT LAMP was 67% and 97%, respectively. When setting CT cut-offs of <33 and <25, the DSe increased to 75% and 100%, respectively. Time from swab-to-result for a strong positive sample (CT < 25) was < 15 minutes. We propose that RNA RT-LAMP could replace rRT-PCR where there is a need for increase in throughput, whereas Direct RT-LAMP could be used as a screening tool for triaging patients into appropriate hospitals wards, at GP surgeries and in care homes, or for population screening to identify highly contagious individuals (super shedders). Direct RT-LAMP could also be used during times of high prevalence to save critical extraction and rRT-PCR reagents by screening out those strong positives from diagnostic pipelines.


title: Prediction of the Epidemic of COVID-19 Based on Quarantined Surveillance in China

text: Background and Objective: To predict the epidemic of COVID-19 based on quarantined surveillance from real world in China by modified SEIR model different from the previous simply mathematical model. Design and Methods: We forecasted the epidemic of COVID-19 based on current clinical and epidemiological data and built a modified SEIR model to consider both the infectivity during incubation period and the influence on the epidemic from strict quarantined measures. Results: The peak time of the curve for the infected newly diagnosed as COVID-19 should substantially present on Feb.5,2020(in non-Hubei areas) and Feb.19,2020(in Hubei. It is estimated that the peak of the curve of the cumulative confirmed cases will appear in non-Hubei areas on Mar.3,2020 and in Hubei province on Mar.10,2020,and the total number of the patients diagnosed as COVID-19 is 18,000 in non-Hubei areas and 78,000-96,000 in Hubei.The Chinese COVID-19 epidemic can be completely controlled in May,2020. Conclusions: COVID-19 is only a local outbreak in Hubei Province,China.It can be probably avoided the pandemic of global SARS-CoV-2 cases rise with the great efforts by Chinese government and its people.