title: Demand and supply of invasive and noninvasive ventilators at the peak of the COVID-19 outbreak in Okinawa

text: Abstract While Okinawa has been facing outbreak of the coronavirus disease 2019 (COVID-19) pandemic, healthcare collapse should be prevented by sufficient supply of ventilators for caring the rapidly growing number of critically ill patients with COVID-19 We estimated the number of invasive and noninvasive ventilators that would be required in Okinawa at the peak of the COVID-19 outbreak based on recent data of COVID-19 cases in Okinawa and data on the proportion of patients with COVID-19 in the ICU requiring ventilation Based on our results using the current supply of all ventilators, demand for ventilators could be prepared for patients with COVID-19 who would require it and demand for noninvasive ventilators could also be prepared for those with COVID-19 who would require it The higher supply over the demand would be achieved by flattening the epidemic curve by implementing public health interventions to delay and suppress the epidemic peak in Okinawa


title: Doubling time tells how effective Covid-19 prevention works

text: Covid-19 (coronavirus disease 2019) is a rapidly spreading pandemic in many countries. The total confirmed cases of Covid-19 are exponentially increasing and many countries are fighting Covid-19 with all strategies. However, there is still lacking consensus for effective strategies. Here, I demonstrate the time dependence of the doubling time in the Covid-19 exponential growths. Tracking the time-dependent doubling time tells how well Covid-19 prevention works, giving an index for successful fighting.


title: Necrocapitalist networks: COVID-19 and the ‘dark side’ of economic geography

text: The economic fallout from COVID-19 has precipitated a crisis in global supply chains. The lockdown of consumers worldwide has triggered a fall in demand that has so far led to the dismissal of up to one-third of Cambodia’s garment sector workforce. Though the pandemic is exceptional, this is a crisis rooted in the exemplary rather than extraordinary hyper-precarity of workers in global industry. Here, I argue that COVID-19 spotlights the elusive ‘dark sides’ of global production in economic geography, revealing the necrocapitalist logics of supply chains.


title: The male excess in case-fatality rates for COVID-19. A meta-analytic study of the age-related differences and consistency over six countries

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


title: Suramin inhibits SARS-CoV-2 infection in cell culture by interfering with early steps of the replication cycle

text: The SARS-CoV-2 pandemic that originated from Wuhan, China, in December 2019 has impacted public health, society and economy and the daily lives of billions of people in an unprecedented manner. There are currently no specific registered antiviral drugs to treat or prevent SARS-CoV-2 infections. Therefore, drug repurposing would be the fastest route to provide at least a temporary solution while better, more specific drugs are being developed. Here we demonstrate that the antiparasitic drug suramin inhibits SARS-CoV-2 replication, protecting Vero E6 cells with an EC50 of ∼20 µM, which is well below the maximum attainable level in human serum. Suramin also decreased the viral load by 2-3 logs when Vero E6 cells or cells of a human lung epithelial cell line (Calu-3) were treated. Time of addition and plaque reduction assays showed that suramin acts on early steps of the replication cycle, possibly preventing entry of the virus. In a primary human airway epithelial cell culture model, suramin also inhibited the progression of infection. The results of our preclinical study warrant further investigation and suggest it is worth evaluating whether suramin provides any benefit for COVID-19 patients, which obviously requires well-designed, properly controlled randomized clinical trials.


title: Understanding the Fundamentals of the Texture and Tribofilm Evolution

text: Abstract Several manufacturing processes experience the interaction between and among mating surfaces under the boundary lubrication (BL) regime. Textures evolve as a result of these multi-parametric interactions where physical and chemical parameters play a significant role. This research studies texture as a dynamic process with an emphasis on physical and chemical textures during process progression. The evolution of textures under the presence of lubricating tribofilm is presented. Tribological tests were conducted using a pin-on-disc setup while laser microscopy, SEM, Raman, and FIB/TEM techniques were used for characterization. Results show that the re-organization of surface asperities dictates the formation and stabilization of surface-protective tribofilm in three distinct texture evolution regions driven by physical and chemical events.


The impact of COVID-19 on Canadian urology residents


docid: vxrqtkde

title: An Overview of Novel Coronavirus SARS-Cov-2 Spanning around the Past, Present and Future Perspectives

text: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a new enveloped RNA virus known as Coronavirus (COVID-19) are most prevalent in humans and wild animals All four species that is alpha, beta, delta and theta have been identified till date and are responsible for human disease;causing influenza like illness (ILI) This virus has similar lineage of Middle East Respiratory Syndrome coronavirus (MERS-CoV) and related Coronavirus (SARS-CoV) This outbreak initially presented as pneumonia-like illness in a group of people in Wuhan, China The infection was said to be caused by seafood and unusual animals in the wholesale markets of this city SARS-CoV-2 is highly infectious and has resulted in a rapid pandemic As of now it has spread to 197 countries with total no of cases in the world being 3 76 million as of early march The mortality till now is 7 11% The cases have been increasing since its first discovery in China In India also the number has been increased Till now India has total of 39,980 cases and mortality is attributed to be 3 26% As per data from Ministry of health and family welfare (MoHFW) death is more commonly seen in males with age >60years Among these most of the deaths were related to other co-morbid conditions This article will help the readers with an overview of novel Coronavirus spanning around the clinical features, diagnostic modalities, treatment strategies and infection control measures It will also help in raising awareness among healthcare workers regarding COVID-19 and aid in early recognition of these patients Moreover, this review will also focus on the most recent information for the effective management, prevention, and treatment of patients worldwide


title: Global health diplomacy amid the COVID-19 pandemic: A strategic opportunity for improving health, peace, and well-being in the CARICOM region-A systematic review

text: Increased globalization has ushered in changes in diplomatic purposes and practices. As such, global health diplomacy (GHD) has become a growing field connecting the urgencies of global health and foreign affairs. More academics and policy-makers are thinking about how to structure and utilize diplomacy in pursuit of global health goals. This article aims to explore how the health, peace, and well-being of people in the region can be achieved through global health diplomacy. A systematic review of the literature was conducted on various terms such as "Global Health Diplomacy OR Foreign Policy"; "Disasters", "Infectious disease epidemics" OR "Non-Communicable diseases" AND "Caribbean" by searching PubMed, Scopus, Embase, Web of Science databases, and Google Scholar search engines. A total of 33 articles that met the inclusion criteria were analyzed, and the critical role of GHD was highlighted. There is an increasing need to understand the complex global health challenges, coupled with the need to design appropriate solutions. Many regional initiatives addressing infectious and chronic diseases have been successful in multiple ways by strengthening unity and also by showing directions for other nations at a global level, e.g., the Port of Spain Summit declaration. GHD has a great scope to enhance preparedness, mitigation, peace, and development in the region. Amid the COVID-19 pandemic, the region needs to strengthen its efforts on equity issues, health promotion, and sustainable development to promote peace and well-being.


The 2019-nCoV epidemic control strategies and future challenges of building healthy smart cities


title: Projections for first-wave COVID-19 deaths across the US using social-distancing measures derived from mobile phones

text: We propose a Bayesian model for projecting first-wave COVID-19 deaths in all 50 U.S. states. Our model's projections are based on data derived from mobile-phone GPS traces, which allows us to estimate how social-distancing behavior is "flattening the curve" in each state. In a two-week look-ahead test of out-of-sample forecasting accuracy, our model significantly outperforms the widely used model from the Institute for Health Metrics and Evaluation (IHME), achieving 42% lower prediction error: 13.2 deaths per day average error across all U.S. states, versus 22.8 deaths per day average error for the IHME model. Our model also provides an accurate, if slightly conservative, assessment of forecasting accuracy: in the same look-ahead test, 98% of data points fell within the model's 95% credible intervals. Our model's projections are updated daily at https://covid-19. tacc.utexas.edu/projections/


title: Carvedilol as a potential addition to the Covid-19 therapeutic arsenal

text: No single therapeutic agent has been recognized so far as the ultimate treatment for COVID-19 and many treatment strategies rely on associating different medications with proven or hypothetical anti-viral effects Carvedilol is a third-generation beta-blocker displaying potential inhibitory properties on several key enzymatic processes and pathways involved in SARS-CoV-2 or other coronaviruses replication, in addition to the modulatory effect on several inflammatory messengers of COVID-19 These data could provide a reasonable hypothetical background for further investigating specific anti-SARS-CoV-2 effects and could pave the way for further clinical verification


title: Making sense of publicly available data on COVID-19 in Ireland

text: This paper reports on the management of the COVID19 pandemic in Ireland over the period March to May 2020. During this period the Irish government implemented a series of policies designed to delay the spread of the pandemic culminating in a stay-at-home order that greatly restricted mobility for the majority of the population. In this paper we evaluate the policies enacted using evidence obtained from a number of novel sources, including census and real-time traffic data. The evidence suggests that the policies have impeded the spread of the virus, which has mostly been confined to Dublin and its commuter belt. At the same time, the virus has become concentrated in a number of clusters associated with nursing homes and workplaces that remained open during the delay phase. This evidence is used to hypothesise on the likely impact of the pandemic on high density and poor neighbourhoods in Dublin.


title: Outcomes and Cardiovascular Comorbidities in a Predominantly African-American Population with COVID-19

text: Importance: Racial disparities in COVID-19 outcomes have been amplified during this pandemic and reports on outcomes in African-American (AA) populations, known to have higher rates of cardiovascular (CV) comorbidities, remain limited. Objective: To examine prevalence of comorbidities, rates of hospitalization and survival, and incidence of CV manifestations of COVID-19 in a predominantly AA population in south metropolitan Chicago. Design, Setting, Participants: This was an observational cohort study of COVID-19 patients encountered from March 16 to April 16, 2020 at the University of Chicago. Deidentified data were obtained from an institutional data warehouse. Group comparisons and logistic regression modeling based on baseline demographics, clinical characteristics, laboratory and diagnostic testing was performed. Exposures: COVID-19 was diagnosed by nasopharyngeal swab testing and clinical management was at the discretion of treating physicians. Main Outcomes and Measures: Primary outcomes were hospitalization and in-hospital mortality, and secondary outcomes included incident CV manifestations of COVID-19 in the context of overall cardiology service utilization. Results: During the 30 day study period, 1008 patients tested positive for COVID-19 and 689 had available encounter data. Of these, 596 (87%) were AA and 356 (52%) were hospitalized, of which 319 (90%) were AA. Age > 60 years, tobacco use, BMI >40 kg/m2, diabetes mellitus (DM), insulin use, hypertension, chronic kidney disease, coronary artery disease (CAD), and atrial fibrillation (AF) were more common in hospitalized patients. Age > 60 years, tobacco use, CAD, and AF were associated with greater risk of in-hospital mortality along with several elevated initial laboratory markers including troponin, NT-proBNP, blood urea nitrogen, and ferritin. Despite this, cardiac manifestations of COVID-19 were uncommon, coincident with a 69% decrease in cardiology service utilization. For hospitalized patients, median length of stay was 6.2 days (3.4-11.9 days) and mortality was 13%. AA patients were more commonly hospitalized, but without increased mortality. Conclusions and Relevance: In this AA-predominant experience from south metropolitan Chicago, CV comorbidities and chronic diseases were highly prevalent and associated with increased hospitalization and mortality. Insulin-requiring DM and CKD emerged as novel predictors for hospitalization. Despite the highest rate of comorbidities reported to date, CV manifestations of COVID-19 and mortality were relatively low. The unexpectedly low rate of mortality merits further study.


title: Excess mortality in mental health service users during the COVID-19 pandemic described by ethnic group: South London and Maudsley data

text: The COVID-19 pandemic in the UK was accompanied by excess all-cause mortality at a national level, only part of which was accounted for by known infections. Excess mortality has previously been described in people who had received care from the South London and Maudsley NHS Foundation Trust (SLaM), a large mental health service provider for 1.2m residents in south London. The SLaM Clinical Record Interactive Search (CRIS) data resource receives 24-hourly updates from its full electronic health record, including regularly sourced national mortality on all past and present SLaM service users. The SLaM urban catchment has high levels of deprivation and is ethnically diverse, so the objective of the descriptive analyses reported in this manuscript was to compare mortality in SLaM service users from 16th March to 15th May 2020 to that for the same period in 2019 within specific ethnic groups: i) White British, ii) Other White, iii) Black African/Caribbean, iv) South Asian, v) Other, and vi) missing/not stated. For Black African/Caribbean patients (the largest minority ethnic group) this ratio was 3.33, compared to 2.47 for White British patients. Considering premature mortality (restricting to deaths below age 70), these ratios were 2.74 and 1.96 respectively. Ratios were also high for those from Other ethnic groups (2.63 for all mortality, 3.07 for premature mortality).


title: Resource requirements for reintroducing elective surgery in England during the COVID-19 pandemic: a modelling study

text: Background: The response to COVID-19 has required cancellation of all but the most urgent surgeries, including many cancer operations. We estimated the number of cancelled surgical procedures in the National Health Service (NHS) in England due to COVID-19 and how this deficit would change over time once elective surgery was reintroduced. Methods: Modelling study using Hospital Episode Statistics (HES) data from 2014 to 2019. Using NHS England definitions, surgical procedures were grouped into four classes of urgency. We calculated time-weighted average numbers of surgical procedures from 1st March 2020 and extrapolated to 28th February 2021 informed by activity in previous years. We estimated the procedure deficit using multiple conservative assumptions and then modelled the reintroduction of elective surgery between 1st June 2020 and 28th February 2021, estimating the resources required to achieve this. Costs of surgery were calculated using NHS reference costs. Estimates are reported with 95% confidence intervals. Findings: 4,547,534 (3,318,195 - 6,250,771) patients with pooled mean age of 53.5 years were expected to undergo surgery in the NHS in England between 1st March 2020 and 28th February 2021. Due to COVID-19, 749,248 (513,565 - 1,077,448) surgical procedures were cancelled by 31st May 2020. As current guidelines require a gradual reintroduction of elective surgery, this deficit will increase further and 2,270,178 (1,453,057 - 3,363,472) patients will be awaiting surgery by 28th February 2021. The cost of these delayed procedures is {pound}4,688,318,443 ({pound}2,726,364,240 - {pound}7,070,166,056). However, the safe delivery of surgery during the pandemic will require substantial extra resources including personal protective equipment and universal preoperative screening, leading to additional costs of {pound}606,252,901 ({pound}521,159,931 - {pound}730,720,808). Interpretation: Reintroduction of elective surgery during the pandemic response in NHS England will be associated with substantial treatment delays for many patients, and a large increase in treatment costs.


CT suggests discharged Covid-19 patients who were retested RT-PCR positive again for SARS-CoV-2 more likely had false negative RT-PCR tests before discharging


title: Impact of Comorbidities on SARS-CoV-2 Viral Entry-Related Genes

text: Viral entry mechanisms for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are an important aspect of virulence. Proposed mechanisms involve host cell membrane-bound angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine proteases (TTSPs), such as transmembrane serine protease isoform 2 (TMPRSS2). The distribution of expression of these genes across cell types representing multiple organ systems in healthy individuals has been recently demonstrated. However, comorbidities such as diabetes and cardiovascular disease are highly prevalent in patients with Coronavirus Disease 2019 (COVID-19) and associated with worse outcomes. Whether these conditions contribute directly to SARS-CoV-2 virulence remain unclear. Here we show that the expression levels of ACE2, TMPRSS2 and other viral entry-related genes are modulated in target organs of select disease states. In tissues such as heart, which normally express ACE2 but minimal TMPRSS2, we found that TMPRSS2 as well as other TTSPs are elevated in individuals with comorbidities vs healthy individuals. Additionally, we found increased expression of viral entry-related genes in the settings of hypertension, cancer or smoking across target organ systems. Our results demonstrate that common comorbidities may contribute directly to SARS-CoV-2 virulence and suggest new therapeutic targets to improve outcomes in vulnerable patient populations.


title: Comparison of three TaqMan Real-Time Reverse Transcription-PCR assays in detecting SARS-CoV-2

text: Quick and accurate detection of SARS-CoV-2 is critical for COVID-19 control. Dozens of real-time reverse transcription PCR (qRT-PCR) assays have been developed to meet the urgent need of COVID-19 control. However, methodological comparisons among the developed qRT-PCR assays are limited. In the present study, we evaluated the sensitivity, specificity, amplification efficiency, and linear detection ranges of three qRT-PCR assays, including the assays developed by our group (IPBCAMS), and the assays recommended by WHO and China CDC (CCDC). The three qRT-PCR assays exhibited similar sensitivities, with the limit of detection (LOD) at about 10 copies per reaction (except the ORF 1b gene assay in CCDC assays with a LOD at about 100 copies per reaction). No cross reaction with other respiratory viruses were observed in all of the three qRT-PCR assays. Wide linear detection ranges from 106 to 101 copies per reaction and acceptable reproducibility were obtained. By using 25 clinical specimens, the N gene assay of IPBCAMS assays and CCDC assays performed better (with detection rates of 92% and 100%, respectively) than that of the WHO assays (with a detection rate of 60%), and the ORF 1b gene assay in IPBCAMS assays performed better (with a detection rate of 64%) than those of the WHO assays and the CCDC assays (with detection rates of 48% and 20%, respectively). In conclusion, the N gene assays of CCDC assays and IPBCAMS assays and the ORF 1b gene assay of IPBCAMS assays were recommended for qRT-PCR screening of SARS-CoV-2.


title: Covid-19 Incidence Rate Evolution Modeling using Dual Wave Gaussian-Lorentzian Composite Functions

text: Modeling the evolution of Covid-19 incidence rate is critical to deciding and assessing non-medical intervention strategies that can lead to successful containment of the pandemic. This research presents a mathematical model to empirically assess measures related to various pandemic containment strategies, their similarities and a probabilistic estimate on the evolution of Covid-19 incidence rates. The model is built on the principle that, the exponential rise and decay of the number of confirmed Covid-19 infections can be construed as a set of concurrent non-linear waves. These waves can be characterized by a linear combination of Gaussian and Cauchy Lorentz functions collectively termed as Gaussian-Lorentzian Composite (GLC) function. The GLC function is used for non-linear approximation of officially confirmed Covid-19 incidence rates in each country. Results of fitting GLC based models to incidence rate trends of 20 different countries proves that the models can empirically explain the growth and decay trajectory Covid-19 infections in a given population.


title: COVID-19 Public Sentiment Insights and MachineLearning for Tweets Classification

text: Along with the Coronavirus pandemic, another crisis has manifested itself in the form of mass fear and panic phenomena, fueled by incomplete and often inaccurate information. There is therefore a tremendous need to address and better understand COVID-19's informational crisis and gauge public sentiment, so that appropriate messaging and policy decisions can be implemented. In this research article, we identify public sentiment associated with the pandemic using Coronavirus specific Tweets and R statistical software, along with its sentiment analysis packages. We demonstrate insights into the progress of fear-sentiment over time as COVID-19 approached peak levels in the United States, using descriptive textual analytics supported by necessary textual data visualizations. Furthermore, we provide a methodological overview of two essential machine learning (ML) classification methods, in the context of textual analytics, and compare their effectiveness in classifying Coronavirus Tweets of varying lengths. We observe a strong classification accuracy of 91% for short Tweets, with the Na"ive Bayes method. We also observe that the logistic regression classification method provides a reasonable accuracy of 74% with shorter Tweets, and both methods showed relatively weaker performance for longer Tweets. This research provides insights into Coronavirus fear sentiment progression, and outlines associated methods, implications, limitations and opportunities.


title: COVID-19 and Pulmonary Embolism: Not a Coincidence

text: In December 2019, a novel coronavirus called SARS-CoV-2 was reported to be responsible for a cluster of acute atypical respiratory pneumonia cases in Wuhan, in Hubei province, China. The disease caused by this virus is called COVID-19 (coronavirus disease 2019). The virus is transmitted between humans and the outbreak was declared a pandemic by the World Health Organization (WHO) on 11 March 2020. Coagulopathy is a common abnormality in patients with COVID-19 due to inflammation, hypoxia, immobilisation, endothelial damage and diffuse intravascular coagulation. However, the data on this topic are still limited. Here we report the case of a man presenting with pneumonia complicated by bilateral pulmonary embolism LEARNING POINTS: SARS-CoV-2 is a novel infectious agent that causes COVID-19, which can manifest in several ways, affecting endothelial cells and most organs. There is growing evidence that SARS-CoV-2-mediated endothelial damage is due to direct viral injury and the systemic inflammatory response, possibly together with a cytokine storm. As endothelial damage can manifest as thromboembolic disease, such as pulmonary thromboembolism, appropriate anti-thrombotic preventive strategies should be followed, and proper screening and treatment for thromboembolic complications should be implemented.


title: Epidemiological characteristics of COVID-19 cases in Italy and estimates of the reproductive numbers one month into the epidemic

text: Background In February 2020, a locally-acquired COVID-19 case was detected in Lombardia, Italy. This was the first signal of ongoing transmission of SARS-CoV-2 in the country. The outbreak rapidly escalated to a national level epidemic, amid the WHO declaration of a pandemic. Methods We analysed data from the national case-based integrated surveillance system of all RT-PCR confirmed COVID-19 infections as of March 24th 2020, collected from all Italian regions and autonomous provinces. Here we provide a descriptive epidemiological summary on the first 62,843 COVID-19 cases in Italy as well as estimates of the basic and net reproductive numbers by region. Findings Of the 62,843 cases of COVID-19 analysed, 71.6% were reported from three Regions (Lombardia, Veneto and Emilia-Romagna). All cases reported after February 20th were locally acquired. Estimates of R0 varied between 2.5 (95%CI: 2.18-2.83) in Toscana and 3 (95%CI: 2.68-3.33) in Lazio, with epidemic doubling time of 3.2 days (95%CI: 2.3-5.2) and 2.9 days (95%CI: 2.2-4.3), respectively. The net reproduction number showed a decreasing trend starting around February 20-25, 2020 in northern regions. Notably, 5,760 cases were reported among health care workers. Of the 5,541 reported COVID-19 associated deaths, 49% occurred in people aged 80 years or above with an overall crude CFR of 8.8%. Male sex and age were independent risk factors for COVID-19 death. Interpretation The COVID-19 infection in Italy emerged with a clustering onset similar to the one described in Wuhan, China and likewise showed worse outcomes in older males with comorbidities. Initial R0 at 2.96 in Lombardia, explains the high case-load and rapid geographical spread observed. Overall Rt in Italian regions is currently decreasing albeit with large diversities across the country, supporting the importance of combined non-pharmacological control measures.


title: Mathematical Modeling of Coronavirus Reproduction Rate with Policy and Behavioral Effects

text: In this paper a modified mathematical model based on the SIR model used which can predict the spreading of the corona virus disease (COVID-19) and its effects on people in the days ahead. This model takes into account all the death, infected and recovered characteristics of this disease. To determine the extent of the risk posed by this novel coronavirus; the transmission rate (R0) is utilized for a time period from the beginning of spreading virus. In particular, it includes a novel policy to capture the R0 response in the virus spreading over time. The model estimates the vulnerability of the pandemic with a prediction of new cases by estimating a time-varying R0 to capture changes in the behavior of SIR model implies to new policy taken at different times and different locations of the world. This modified SIR model with the different values of R0 can be applied to different country scenario using the real time data report provided by the authorities during this pandemic. The effective evaluation of R0 can forecast the necessity of lockdown as well as reopening the economy.


title: Optimal Pool Size for COVID-19 Group Testing

text: This paper presents an analytical formulation for determining optimal pool size in the initial pooling stage and the subsequent retests for COVID-19. A generalized constant compaction approach confirms the efficiency of halving targeted population between retest stages. An analytical gain formula is derived to aid future test designs. It is observed that optimal gain relies on the proper choice of the initial pool size. This optimal compaction scheme could outperform the conventional algorithms in most cases and may provide a mathematically-native road map for us to operate beyond the standard super-even-number-based (64, 32, 16, 8, 1) group testing algorithms.


title: Sex differences in clinical findings among patients with coronavirus disease 2019 (COVID-19) and severe condition

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


title: Diagnostic performance of CT and its key signs for COVID-19: A systematic review and meta-analysis

text: Abstract Purpose: To evaluate the diagnostic value of chest CT in 2019 novel coronavirus disease (COVID-19), using the reverse transcription polymerase chain reaction(RT-PCR)as a reference standard. At the same time, the imaging features of CT in confirmed COVID-19 patients would be summarized. Methods: A comprehensive literature search of 5 electronic databases was performed. The pooled sensitivity, specificity, positive predictive value, and negative predictive value were calculated using the random-effects model and the summary receiver operating characteristic (SROC) curve. We also conducted a meta-analysis to estimate the pooled incidence of the chest CT imaging findings and the 95% confidence interval (95%CI). Meta-regression analysis was used to explore the source of heterogeneity. Results: Overall, 25 articles comprising 4,857 patients were included. The pooled sensitivity of CT was 93% (95% CI, 89-96%) and specificity was 44% (95% CI, 27-62%). The area under the SROC curve was 0.94 (95% CI, 0.91-0.96). For the RT-PCR assay, the pooled sensitivity of the initial test and the missed diagnosis rate after the second-round test were 76% (95% CI: 59-89%; I2=96%) and 26% (95% CI: 14-39%; I2=45%), respectively. According to the subgroup analysis, the diagnostic sensitivity of CT in Hubei was higher than that in other regions. Besides, the most common patterns on CT imaging finding was ground glass opacities (GGO) 58% (95% CI: 49-70%), followed by air bronchogram 51% (95% CI: 31-70%). Lesions were inclined to distribute in peripheral 64% (95% CI: 49-78%), and the incidence of bilateral lung involvement was 69% (95% CI: 58-79%). Conclusions: There were still several cases of missed diagnosis after multiple RT-PCR examinations. In high-prevalence areas, CT could be recommended as an auxiliary screening method for RT-PCR.


title: Replication of SARS-CoV-2 in human respiratory epithelium

text: SARS-CoV-2 emerged by the end of 2019 to rapidly spread in 2020. At present, it is of utmost importance to understand the virus biology and to rapidly assess the potential of existing drugs and develop new active compounds. While some animal models for such studies are under development, most of the research is carried out in the Vero E6 cells. Here, we propose fully differentiated human airway epithelium cultures as a model for studies on the SARS-CoV-2. Further, we also provide basic characteristics of the system.


title: Prediction and Evolution of B Cell Epitopes of Surface Protein in SARS-CoV-2

text: The discovery of epitopes is helpful to the development of SARS-CoV-2 vaccine. The sequences of the surface protein of SARS-CoV-2 and its proximal sequences were obtained by BLAST, the sequences of the whole genome of SARS-CoV-2 were obtained from the GenBank. Based on the NCBI Reference Sequence: NC_045512.2, the conformational and linear B cell epitopes of the surface protein were predicted separately by various prediction methods. Furthermore, the conservation of the epitopes, the adaptability and other evolutionary characteristics were also analyzed. 7 epitopes were predicted, including 5 linear epitopes and 2 conformational epitopes, one of the linear and one of the conformational were coincide. The epitope D mutated easily, but the other epitopes were very conservative and the epitope C was the most conservative. It is worth mentioning that all of the 6 dominated epitopes were absolutely conservative in nearly 1000 SARS-CoV-2 genomes, and they deserved further study. The findings would facilitate the vaccine development, had the potential to be directly applied on the treatment in this disease, but also have the potential to prevent the possible threats caused by other types of coronavirus.


title: Greater risk of severe COVID-19 in non-White ethnicities is not explained by cardiometabolic, socioeconomic, or behavioural factors, or by 25(OH)-vitamin D status: study of 1,326 cases from the UK Biobank

text: Background We examined whether the greater severity of coronavirus disease 2019 (COVID-19) amongst men and non-White ethnicities is explained by cardiometabolic, socio-economic, or behavioural factors. Methods We studied 4,510 UK Biobank participants tested for COVID-19 (positive, n=1,326). Multivariate logistic regression models including age, sex, and ethnicity were used to test whether addition of: 1)cardiometabolic factors (diabetes, hypertension, high cholesterol, prior myocardial infarction, smoking, BMI); 2)25(OH)-vitamin D; 3)poor diet; 4)Townsend deprivation score; 5)housing (home type, overcrowding); or 6)behavioural factors (sociability, risk taking) attenuated sex/ethnicity associations with COVID-19 status. Results There was over-representation of men and non-White ethnicities in the COVID-19 positive group. Non-Whites had, on average, poorer cardiometabolic profile, lower 25(OH)-vitamin D, greater material deprivation, and were more likely to live in larger households and flats/apartments. Male sex, non-White ethnicity, higher BMI, Townsend deprivation score, and household overcrowding were independently associated with significantly greater odds of COVID-19. The pattern of association was consistent for men and women; cardiometabolic, socio-demographic and behavioural factors did not attenuate sex/ethnicity associations. Conclusions Sex and ethnicity differential pattern of COVID-19 is not adequately explained by variations in cardiometabolic factors, 25(OH)-vitamin D levels, or socio-economic factors. Investigation of alternative biological pathways and different genetic susceptibilities is warranted.


News: Toxic Gas Leak Holds Lessons for COVID-19


docid: finxjwty

title: Oxygen needs in austere environment: French military health service experience

text: INTRODUCTION: Management of Oxygen supplies is a recurring problem for the intensivists and anesthesiologists working in an austere environment. The French military health service has chosen oxygen concentrators (OC) as the primary source of oxygen. OBJECTIVES: The main objective was to evaluate the feasibility of using OC as the main source of 02 for intensive care patients. We assess the need to use pressurized 02 during the ICU hospitalization. The secondary objectives were to identify the causes of the use of pressurized 02. MATERIAL AND METHOD: We realize an interventional cohort study at the French role 3 hospitals located in the Republic of Djibouti. The criteria of inclusion were all patients aged over 18 years, requiring oxygen and admitted to intensive care. RESULTS: We include 35 patients over 6-month period for 251 days of oxygenation, including 142 days of invasive mechanical ventilation. The population include 21 (60%) men, aged of 35 (30 - 49) years. Twenty-eight (80%) patients benefits of invasive ventilation. Median 02 administration duration was 6 (3-10) days, and the median duration of mechanical ventilation was 3 (1-5) days. Nineteen pressurized O2 treatments were required over 251 days of oxygen therapy, or 7.5% of the total oxygen therapy time. The causes of recourse were in 10 cases (52.6%) severe ARDS, in 6 cases (31.6%) an emergency orotracheal intubation and in 3 cases (15.8%) a transfer. Only one OC dysfunction occurred during the study. CONCLUSION: OC can be used as a primary source for intensive care patients in an austere environment. The use of pressurized 02 remains imperative in the event of an electrical failure and the need to use high Fi02 over 60%.


title: Transmission of SARS-CoV-2 in Georgia, USA, 2020

text: Objective: SARS-CoV-2 has significantly impacted Georgia, USA including two major hotspots, Metro Atlanta and Dougherty County in southwestern Georgia. With government deliberations about relaxing social distancing measures, it is important to understand the trajectory of the epidemic in the state of Georgia. Methods: We collected daily cumulative incidence of confirmed COVID-19 cases in Georgia. We estimated the reproductive number (Re) of the COVID-19 epidemic on April 18 and May 2 by characterizing the initial growth phase of the epidemic using the generalized-growth model. Results: The data presents a sub-exponential growth pattern in the cumulative incidence curves. On April 18, 2020, Re was estimated as 1.20 (95% CI: 1.10, 1.20) for the state of Georgia, 1.10 (95% CI: 1.00, 1.20) for Dougherty County, and 1.20 (95% CI: 1.10, 1.20) for Metro Atlanta. Extending our analysis to May 2, 2020, Re estimates decreased to 1.10 (95% CI: 1.10, 1.10) for the state of Georgia, 1.00 (95% CI: 1.00, 1.10) for Dougherty County, and 1.10 (95% CI: 1.10, 1.10) for Metro Atlanta. Conclusions: Transmission appeared to be decreasing after the implementation of social distancing measures. However, these results should be interpreted with caution when considering relaxing control measures due to low testing rates.


title: Spike protein fusion loop controls SARS-CoV-2 fusogenicity and infectivity

text: The Spike is a hallmark coronavirus protein that determines virus fusion, entry and spread in the host, and thus holds clues for the rapid spread of the SARS-CoV-2 pandemic. We have investigated the Spike from six β-coronaviruses, including the SARS-CoV-2, and find that their surface-exposed fusion peptides constituting the fusion loop are spatially organized contiguous to each other to work synergistically for triggering the virus-host membrane fusion process. The SARS-CoV-2 fusion peptides have unique physicochemical properties, accrued in part from the presence of consecutive prolines that impart backbone rigidity which aids the virus fusogenicity. The specific contribution of these prolines has been inferred from comparative studies of their deletion mutant in a fellow murine β-coronavirus MHV-A59 that show significantly diminished fusogenicity in vitro and associated pathogenesis in vivo. The Spike cleavage-linked priming and fusogenic conformational transition steered by the fusion loop may be critical for the SARS-CoV-2 spread. Summary The Spike protein on the SARS-CoV-2 surface is the prime mediator of COVID-191 because of its central role in virus-host attachment, virus-entry, and virus-spread2. The contagious nature of SARS-CoV-2 infection has been attributed to dense glycosylation of the Spike glycoprotein3, its high affinity of binding to human ACE2 receptor4, and cleavage5. While these may be imperative, it does not explain the uncontrolled infectivity. Here we show that properties of the fusion peptides constituting the fusion loop of SARS-CoV-2 Spike that triggers the virus fusion, distinguishes it from the other five β-coronaviruses. The SARS-CoV-2 Spike trimer surface is relatively more hydrophobic, including the surface contributed by the fusion peptides. The fusion peptides are structurally rigid owing to its consecutive prolines, aromatic/hydrophobic clusters, a stretch of consecutive β-branched amino acids, and the hydrogen bonds. The role of rigidity accrued from the presence of consecutive prolines contributing to virus fusogenicity can be deciphered from our previous murine β-coronavirus, MHV-A59 studies6. The synergy brought about by the global location of the surface exposed fusion peptides, their physicochemical features, and the fusogenic conformational transition appears to drive the fusion process, which may explain the severity of the infection and widespread nature of the COVID-19 pandemic.


title: Ionophore antibiotic X-206 is a potent and selective inhibitor of SARS-CoV-2 infection in vitro

text: Pandemic spread of emerging human pathogenic viruses such as the current SARS-CoV-2, poses both an immediate and future challenge to human health and society. Currently, effective treatment of infection with SARS-CoV-2 is limited and broad spectrum antiviral therapies to meet other emerging pandemics are absent leaving the World population largely unprotected. Here, we have identified distinct members of the family of polyether ionophore antibiotics with potent ability to inhibit SARS-CoV-2 replication and cytopathogenicity in cells. Several compounds from this class displayed more than 100-fold selectivity between viral-induced cytopathogenicity and inhibition of cell viability, however the compound X-206 displayed >500-fold selectivity and was furthermore able to inhibit viral replication even at sub-nM levels. The antiviral mechanism of the polyether ionophores is currently not understood in detail. We demonstrate, through unbiased bioactivity profiling, that their effects on the host cells differ from those of cationic amphiphiles such as hydroxychloroquine. Collectively, our data suggest that polyether ionophore antibiotics should be subject to further investigations as potential broad-spectrum antiviral agents.


Commentary: When Hospitality turns into Hostility in Prolonged Forced Migration


title: Distinct systems serology features in children, elderly and COVID patients

text: SARS-CoV-2, the pandemic coronavirus that causes COVID-19, has infected millions worldwide, causing unparalleled social and economic disruptions. COVID-19 results in higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive coronavirus immunological responses, induced by circulating human coronaviruses, is critical to understand such divergent clinical outcomes. The cross-reactivity of coronavirus antibody responses of healthy children (n=89), adults (n=98), elderly (n=57), and COVID-19 patients (n=19) were analysed by systems serology. While moderate levels of cross-reactive SARS-CoV-2 IgG, IgM, and IgA were detected in healthy individuals, we identified serological signatures associated with SARS-CoV-2 antigen-specific Fc{gamma} receptor binding, which accurately distinguished COVID-19 patients from healthy individuals and suggested that SARS-CoV-2 induces qualitative changes to antibody Fc upon infection, enhancing Fc{gamma} receptor engagement. Vastly different serological signatures were observed between healthy children and elderly, with markedly higher cross-reactive SARS-CoV-2 IgA and IgG observed in elderly, whereas children displayed elevated SARS-CoV-2 IgM, including receptor binding domain-specific IgM with higher avidity. These results suggest that less-experienced humoral immunity associated with higher IgM, as observed in children, may have the potential to induce more potent antibodies upon SARS-CoV-2 infection. These key insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics.


docid: nitqrrfb

title: Early experiences with antibody testing in a Flemish nursing home during an acute COVID-19 outbreak: a retrospective cohort study.

text: objectives: to assess the prevalence of COVID-19 (PCR-test) in residents and staff of a nursing home. To examine the presence of IgM and IgG antibodies in the sample and the relation between PCR and antibody test results. design: cross-sectional and (retrospective) cohort study setting: a nursing home for the elderly Bessemerberg in Lanaken (Belgium) with up to 130 beds. Lanaken is situated in the Belgian province with the highest COVID-19 prevalence. participants: residents (N=108) and staff members (N=93) of the nursing home outcomes: PCR, IgM and IgG results: the prevalence of COVID-19, based on PCR test was 34% (N=40) for residents and 13% (N=11) for staff members, respectively. Of the residents, 13% showed positive IgM results and 15% positive IgG results. In 17% of the residents, at least one of the antibodies was positive. In total 13% of the staff members had positive IgM and 16% had a positive IgG. In 20% of the staff members at least one of these antibody tests was positive. In PCR positive residents, the percentage of IgM positive, IgG positive, and at least one of both was 28%, 34%, and 41%. In PCR positive staff, we found 30%, 60%, and 60%. Additional antibody tests were performed in nine residents between day 11 and 14 after the positive PCR test. Of those, 7 (78%) tested positive on at least one antibody. When retesting three weeks later, all remaining residents also tested positive. conclusions: Recently it was reported that in Belgium antibodies are present in 3-4% of the general population. Although, the prevalence in our residents is higher, the number is largely insufficient for herd immunity. In staff members of the regional hospital the prevalence of antibodies was 6%. The higher prevalence in nursing home staff (21%) may be related to the complete absence of good quality protection in the first weeks of the outbreak.


Pulmonary rehabilitation at a time of social distancing: Prime time for tele-rehabilitation?


title: Nasopharyngeal wash in preventing and treating upper respiratory tract infections: Could it prevent COVID-19?

text: Rapid transmission of the severe acute respiratory syndrome coronavirus 2 has led to the novel coronavirus disease 2019 (COVID-19) pandemic. The current emphasis is on preventive strategies such as social distancing, face mask, and hand washing. The technique of nasopharyngeal wash to prevent the virus from inhabiting and replicating in the nasal and pharyngeal mucosa has been suggested to be useful in reducing symptoms, transmission, and viral shedding in cases of viral acute respiratory tract infections. In rapid systematic review, we found studies showing some improvement in prevention and treatment of upper respiratory tract infections. We postulate that hypertonic saline gargles and nasal wash may be useful in prevention and for care of patients with COVID-19. The present evidence emphasizes the need of randomized controlled trials to evaluate the role and mechanism of nasopharyngeal wash in COVID-19.


Chaos with Coronavirus


docid: vxmsgmzu

title: Effectiveness of N95 facepiece respirators in filtering aerosol following storage and sterilization

text: The use of electret N95 filtering facepiece respirators (N95FFRs) after prolonged storage or treatment can reduce the expense of buying non-expired N95 and thus enable developing and developed countries to optimize their use of limited resources to against airborne particles and diseases, such as coronavirus disease 2019 (COVID-19). The filtration performance of five N95FFR models following long-term storage, removal of charge using isopropanol alcohol (IPA), autoclaving, or treatment with gamma-radiation was assessed using a TSI 8130 automated filter tester. Statistically significant differences were found in the penetration (P), pressure drop (Δp) and quality factor (qf) between non-expired and expired N95 models 3M-8210 and 3M-8511. A statistically significant linear correlation was also obtained between the N95 penetration ratio (PR) and the difference between year of manufacture and time of test (DYM). The PR of N95 was more strongly influenced by eliminating the charge (for extremely out-of-date respirators) on the electret filter than by the DYM. Sterilization by gamma irradiation increased the P into non-expired and expired N95FFR models (p < 0.05), reducing their qf. The qfof all N95FFR models, except UVEX-3200, was strongly affected by gamma irradiation, the removal of charge using IPA, autoclaving, and storage in that order. All expired models maintained acceptable filtration performance and still could be used to collect aerosol effectively, even though models 3M-8511 and 3M-1860 had been manufactured up to 13 years previously. As the COVID-19 outbreaks in 2019 and is getting worse in 2020, these data are useful in developing a global stockpiling strategy to maximize the longevity of N95FFRs for public health and healthcare workers. However, the aging of the straps and seal materials (rubbers, plastics) of the N95FFRs may affect their fit factor and effectiveness.


What CEC Member Teachers Are Learning From the COVID-19 Crisis


title: National age and co-residence patterns shape covid-19 vulnerability

text: Based on harmonized census data from 81 countries, we estimate how age and co-residence patterns shape the vulnerability of countries' populations to outbreaks of covid-19. We estimate variation in deaths arising due to a simulated random infection of 10% of the population living in private households and subsequent within-household transmission of the virus. The age-structures of European and North American countries increase their vulnerability to covid-related deaths in general. The co-residence patterns of elderly persons in Africa and parts of Asia increase these countries' vulnerability to deaths induced by within-household transmission of covid-19. Southern European countries, which have aged populations and relatively high levels of intergenerational co-residence are, all else equal, the most vulnerable to outbreaks of covid-19. In a second step, we estimate to what extent avoiding primary infections for specific age-groups would prevent subsequent deaths due to within-household transmission of the virus. Preventing primary infections among the elderly is the most effective in countries with small households and little intergenerational co-residence such as France, whereas confining younger age groups can have a greater impact in countries with large and inter-generational households such as Bangladesh.


title: SARS-CoV-2 detection from nasopharyngeal swab samples without RNA extraction

text: The ongoing COVID-19 pandemic has reached more than 200 countries and territories worldwide. Given the large requirement of SARS-CoV-2 diagnosis and considering that RNA extraction kits are in short supply, we investigated whether two commercial RT-qPCR kits were compatible with direct SARS-CoV-2 detection from nasopharyngeal swab samples. We show that one of the tested kits is fully compatible with direct SARS-CoV-2 detection suggesting that omission of an RNA extraction step should be considered in SARS-CoV-2 diagnosis.


title: No SARS-CoV-2 carriage observed in children attending daycare centers during the first weeks of the epidemic in Belgium.

text: To gain knowledge about the role of young children attending daycare in transmission risk of SARS-CoV-2, a random sample of children (n=84) aged between 6 and 30 months attending daycare in Belgium was studied shortly after the start of the epidemic (February 29th) and before the lockdown (March 18th). No asymptomatic carriage of SARS-CoV-2 was detected, whereas common cold symptoms were common (51.2%).


title: Impact of anxiety associated with COVID 19 on tinnitus

text: Background We investigated how the anxiety associated with COVID 19 impacts the severity of tinnitus and the outcomes of tinnitus therapy. Methods and Findings A retrospective research design was used to compare the clinical characteristics of tinnitus between patients from March to April 2020 under pandemic pressure and those from the matching period in 2019. Tinnitus severity was evaluated using the Tinnitus Handicap Inventory (THI) questionnaire and the minimum masking level (MML) measure while anxiety was quantified using the Zung Self-rating Anxiety Scale (SAS). The assessments were repeated after a 2-month interval, in which sound therapy was applied to a subgroup of patients. In all, 94 and 70 cases were reported in the 2020 and 2019 groups, respectively. The effects of the pandemic on emotional status were evident from a higher incidence of anxiety and much higher SAS scores in the 2020 group. There was also an increase in the THI scores in the 2020 group, but the between-year difference was smaller than that of the SAS score. Moreover, there was no between-year difference in MML or the treatment effect, as measured via both THI and MML. Furthermore, the reduction in SAS score in the second assessment was significantly smaller in the 2020 group. However, a positive correlation between the initial SAS score and the improvement was seen within the 2020 group. Conclusions Anxiety increased greatly in tinnitus subjects due to the COVID 19 pandemic. However, this was not associated with an increase in tinnitus severity in 2020. Instead, there was no between-year difference in the THI score or MML or in the improvement of either measure after treatment. The smaller improvement in SAS score and the positive correlation with the initial SAS score in the 2020 group suggests that the SAS score change in this group might largely be due to the natural relief of pressure as the pandemic decelerated in China. Therefore, the anxiety change induced by the COVID 19 pandemic is not likely to have a strong impact on tinnitus.


More theory, please: Call for papers “Building Transport History Ontologies”


title: 2019 年新型冠状病毒的应急处理: 对皮肤科的启示

text: Summary ? 2019 ? 12 ?????????,COVID-19(??????)?????????????????? COVID-19 ?????(???????)?????????????????? ??????????????,?????????????,?????????????????????????????????????????? ?????????????????????????????????????,???????,???????? COVID-19 ???,??????????????? COVID-19 ??,????????????,????????? ????????????? N95 ???????????????????????? CT ???? COVID-19 ????,??????????????????????????????,???????????????????,????????? COVID-19 ?????,?????????????????????????? ???????????????COVID-19 ????????????????????????????????????????,?????(?????????????????)????????????????????????????,????????????,????????????? ????????,?? 2020 ? 2 ? 20 ?,??????????????? ???????: ????? 2019 ????????????????: ???????


title: The aging transcriptome and cellular landscape of the human lung in relation to SARS-CoV-2

text: Since the emergence of SARS-CoV-2 in December 2019, Coronavirus Disease-2019 (COVID-19) has rapidly spread across the globe. Epidemiologic studies have demonstrated that age is one of the strongest risk factors influencing the morbidity and mortality of COVID-19. Here, we interrogate the transcriptional features and cellular landscapes of the aging human lung through integrative analysis of bulk and single-cell transcriptomics. By intersecting these age-associated changes with experimental data on host interactions between SARS-CoV-2 or its relative SARS-CoV, we identify several age-associated factors that may contribute to the heightened severity of COVID-19 in older populations. We observed that age-associated gene expression and cell populations are significantly linked to the heightened severity of COVID-19 in older populations. The aging lung is characterized by increased vascular smooth muscle contraction, reduced mitochondrial activity, and decreased lipid metabolism. Lung epithelial cells, macrophages, and Th1 cells decrease in abundance with age, whereas fibroblasts, pericytes and CD4+ Tcm cells increase in abundance with age. Several age-associated genes have functional effects on SARS-CoV replication, and directly interact with the SARS-CoV-2 proteome. Interestingly, age-associated genes are heavily enriched among those induced or suppressed by SARS-CoV-2 infection. These analyses illuminate potential avenues for further studies on the relationship between the aging lung and COVID-19 pathogenesis, which may inform strategies to more effectively treat this disease.


title: Impact of non-pharmaceutical interventions on documented cases of COVID-19

text: Background: The novel coronavirus (SARS-CoV-2) has rapidly evolved into a global epidemic. To control its spread, countries have implemented non pharmaceutical interventions (NPIs), such as school or border closures, while others have even enforced complete lockdowns. Here we study the impact of NPIs in reducing documented cases of COVID-19. Documented case numbers are selected because they are essential for decision-makers in the area of health-policy when monitoring and evaluating current control mechanisms. Methods: We empirically estimate the relative reduction in the number of new cases attributed to each NPI. A cross-country analysis is performed using documented cases through April 15, 2020 from n=20 countries (i.e., the United States, Canada, Australia, the EU-15 countries, Norway, and Switzerland). Results: As of April 15, venue closures were associated with a reduction in the number of new cases by 36 % (95% credible interval [CrI] 20-48 %), closely followed by gathering bans (34 %; 95% CrI 21-45 %), border closures (31 %; 95% CrI 19-42 %), and work bans on non-essential business activities (31 %; 95% CrI 16-44 %). Event bans lead to a slightly less pronounced reduction (23 %; 95% CrI 8-35 %). School closures (8 %; 95% CrI 0-23 %) and lockdowns (5 %; 95% CrI 0-14 %) appeared to be the least effective among the NPIs considered in this analysis. Conclusions: With this cross-country analysis, we provide early estimates regarding the impact of different NPIs for controlling the COVID-19 epidemic. These findings are relevant for evaluating current health-policies. Keywords: COVID-19, coronavirus, non-pharmaceutical interventions, policy measures, health-policy, public health, health services research


title: Tissue-resident CD8+ T cells drive age-associated chronic lung sequelae following viral pneumonia

text: Lower respiratory viral infections, such as influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infections, often cause severe viral pneumonia in aged individuals. Here, we report that influenza viral pneumonia leads to chronic non-resolving lung pathology and exaggerated accumulation of CD8+ tissue-resident memory T cells (TRM) in the respiratory tract of aged hosts. TRM accumulation relies on elevated TGF-β present in aged tissues. Further, we show that TRM isolated from aged lungs lack a subpopulation characterized by expression of molecules involved in TCR signaling and effector function. Consequently, TRM cells from aged lungs were insufficient to provide heterologous protective immunity. Strikingly, the depletion of CD8+ TRM cells dampens persistent chronic lung inflammation and ameliorates tissue fibrosis in aged, but not young, animals. Collectively, our data demonstrate that age-associated TRM cell malfunction supports chronic lung inflammatory and fibrotic sequelae following viral pneumonia in aged hosts.


title: The RNA-binding site of poliovirus 3C protein doubles as a phosphoinositide-binding domain

text: Some viruses use phosphatidylinositol phosphate (PIP) to mark membranes used for genome replication or virion assembly. PIP-binding motifs of cellular proteins do not exist in viral proteins. Molecular-docking simulations revealed a putative site of PIP binding to poliovirus (PV) 3C protein that was validated using NMR spectroscopy. The PIP-binding site was located on a highly dynamic α-helix that also functions in RNA binding. Broad PIP-binding activity was observed in solution using a fluorescence polarization assay or in the context of a lipid bilayer using an on-chip, fluorescence assay. All-atom molecular dynamics simulations of the 3C protein-membrane interface revealed PIP clustering and perhaps PIP-dependent conformations. PIP clustering was mediated by interaction with residues that interact with the RNA phosphodiester backbone. We conclude that 3C binding to membranes will be determined by PIP abundance. We suggest that the duality of function observed for 3C may extend to RNA-binding proteins of other viruses. Highlights A viral PIP-binding site identified, validated and characterized PIP-binding site overlaps the known RNA-binding site PIP-binding site clusters PIPs and perhaps regulates conformation and function Duality of PIP- and RNA-binding sites may extend to other viruses In Brief The absence of conventional PIP-binding domains in viral proteins suggests unique structural solutions to this problem. Shengjuler et al. show that a viral RNA-binding site can be repurposed for PIP binding. PIP clustering can be achieved. The nature of the PIP may regulate protein conformation.


title: Knowledge, Attitudes, and Fear of COVID-19 during the Rapid Rise Period in Bangladesh

text: Objectives: To determine the level of Knowledge, Attitude, and Practice (KAP) related to COVID-19 preventive health habits and perception of Fear towards COVID-19 in subjects living in Bangladesh. Design: Prospective, cross-sectional survey of (n= 2157) male and female subjects, 13-90 years of age, living in Bangladesh. Methods: Ethical Approval and Trial registration were obtained prior to the commencement of the study. Subjects who volunteered to participate and signed the informed consent were enrolled in the study and completed the Fear of COVID-19 Scale (FCS). Results: Twenty-eight percent (28.69%) of subjects reported one or more COVID-19 symptoms and 21.4% of subjects reported one or more comorbidities. Knowledge scores were slightly higher in males (8.75, SD 1.58) than females (8.66, SD 1.70). Knowledge was significantly correlated with age (p<.005), an education level (p<.001), Attitude (p<.001), and urban location (p<.001). Knowledge scores showed an inverse correlation with Fear scores (p<.001). Eighty-three percent (83.7%) of subjects with COVID-19 symptoms reported wearing a mask in public and 75.4% of subjects reported staying away from crowded places. Subjects with one or more symptoms reported higher Fear compared to subjects without (18.73, SD 4.6; 18.45, SD 5.1). Conclusions: Overall, Bangladeshis reported a high prevalence of self-isolation, positive preventive health behaviors related to COVID-19, and moderate to high fear levels. Higher Knowledge and Practice were found in males, higher education levels, older age, and urban location. Fear of COVID-19 was more prevalent in female and elderly subjects. Positive Attitude was reported for the majority of subjects, reflecting the belief that COVID-19 was controllable and containable.


title: Clinical Data on Hospital Environmental Hygiene Monitoring and Medical Staff Protection during the Coronavirus Disease 2019 Outbreak

text: Background: The outbreak of coronavirus disease 2019 (COVID-19) has placed unprecedented challenges on hospital environmental hygiene and medical staff protection. It is crucial to assess hospital environmental hygiene to understand the most important environmental issues for controlling the spread of COVID-19 in hospitals. Objective: To detect the presence of COVID-19 in the samples from the area at risk of contamination in the First Hospital of Jilin University. Methods: Viruses in the air were collected by natural sedimentation and air particle sampler methods. Predetermined environmental surfaces were sampled using swabs at seven o'clock in the morning before disinfection. The real-time reverse-transcription PCR method was used to detect the existence of COVID-19 pathogens. Results: Viruses could be detected on the surfaces of the nurse station in the isolation area with suspected patients and in the air of the isolation ward with an intensive care patient. Conclusion: Comprehensive monitoring of hospital environmental hygiene during pandemic outbreaks is conducive to the refinement of hospital infection control. It is of great significance to ensure the safety of medical treatment and the quality of hospital infection control through the monitoring of environmental hygiene.


title: Links between air pollution and COVID-19 in England

text: In December 2019 a novel disease [coronavirus disease 19 (COVID-19) emerged in the Wuhan province of the People's Republic of China. COVID-19 is caused by a novel coronavirus (SARS-CoV-2) thought to have jumped species, from another mammal to humans. A pandemic caused by this virus is running rampant throughout the world. Thousands of cases of COVID-19 are reported in England and over 10,000 patients have died. Whilst there has been progress in managing this disease, it is not clear which factors, besides age, affect the severity and mortality of COVID-19. A recent analysis of COVID-19 in Italy identified links between air pollution and death rates. Here, we explored the correlation between three major air pollutants linked to fossil fuels and SARS-CoV-2 lethality in England. We compare up-to-date, real-time SARS-CoV-2 cases and death measurements from public databases to air pollution data monitored across over 120 sites in different regions. We found that the levels of some markers of poor air quality, nitrogen oxides and ozone, are associated with COVID-19 lethality in different English regions. We conclude that the levels of some air pollutants are linked to COVID-19 cases and morbidity. We suggest that our study provides a useful framework to guide health policy in countries affected by this pandemic.


COVID-19 Pandemic and Cardiovascular Challenges


The role of entrepreneurship and innovation during and after the Coronavirus (COVID-19) crisis


title: COVID-19 immunopathology and the central nervous system: Implication for multiple sclerosis and other autoimmune diseases with associated demyelination

text: In the frame of the coronavirus disease 2019 (COVID-19) pandemic, recent reports on SARS-CoV-2 potential neuroinvasion placed neurologists on increased alertness in order to assess early neurological manifestations and their potentially prognostic value for the COVID-19 disease. Moreover, the management of chronic neurological diseases, such as Multiple Sclerosis (MS), underwent guided modifications, such as an Extended Interval Dose (EID) of Disease-Modifying Treatment (DMT) administration, in order to minimize patients’ exposure to the health system, thus reducing the risk of SARS-CoV-2 infection. In this review, we summarize existing evidence of key immune pathways that the SARS-CoV-2 modifies during COVID-19 and the relevant implication for MS and other autoimmune diseases with associated demyelination (such as Systemic lupus erythematosus and Antiphospholipid syndrome), including the context of potential neuroinvasion by SARS-Cov-2 and the alterations that DMT induces to the immune system. Moreover we hereby aim to provide an overview of the possible consequences that COVID-19 may carry for the Central Nervous System (CNS) in People with MS (PwMS) and other demyelinating diseases, which are likely to pose challenges for treating Neurologists with respect to the long-term disease management of these diseases.


title: Repurposed prophylaxis strategies for COVID-19: a systematic review

text: Introduction Efficient therapeutic strategies are needed to counter the COVID-19 pandemic, caused by the SARS- CoV-2 virus. In a context where specific vaccines are not yet available, the containment of the pandemic would be facilitated with efficient prophylaxis. Methods We screened several clinical trials repositories and platforms in search of the prophylactic strategies that are investigated against COVID-19 in late April 2020. Results Up to April 27, 2020, we found 68 clinical trials targeting medical workers (n=43, 63%), patients relatives (n=16, 24%) or individuals at risk of severe COVID-19 (n=5, 7%). (Hydroxy)chloroquine was the most frequently evaluated treatment (n=46, 68%), before BCG vaccine (n=5, 7%). Sixty-one (90%) clinical trials were randomized with a median of planned inclusions of 600 (IQR 255-1515). Conclusion The investigated prophylaxis strategies cover both pre- and post-exposure prophylaxis and study numerous immune enhancers and antivirals, although most research efforts are focused on (hydroxy)chloroquine.


title: Social innovation and food provisioning during Covid-19: The case of urban-rural initiatives in the Province Of Naples

text: This paper draws on the theoretical framework based on social innovation determinants to analyze how and to what extent the recent and self-organized initiatives for food provisioning are contributing to increase food accessibility at the time of personal and mobility restrictions due to Covid-19. Based on this, the paper firstly maps the initiatives activated during the first months of the Covid-19 emergency (March and April 2020) in the urban-rural territories in the province of Naples (Italy). Secondly, it characterizes these initiatives in relation to their capacity to enhance outcome and social well-being, as well as to involve local society in answer to social challenges through a desk research. Thirdly, the paper describes the case of Masseria Ferraioli, which emerges as social innovative best practice among the previous mapped initiatives. Even in these days, the Masseria distributes to people who cannot afford the purchase due to the emergency vegetables grown on land confiscated from the Camorra, the local mafia. Its configuration as social innovative experience is also confirmed directly by the Masserias project manager, who was required to answer to a semi-structured interview. Based on the evidence of the desk research and this interview, the paper demonstrates the importance of the combined commitment of local communities and volunteering association as a reaction to food provisioning problems in the time of Covid-19, as well as an increasing interest in reconnecting with local food practices, above all when food access has become a priority.


title: Risk Factors Prediction, Clinical Outcomes, and Mortality of COVID-19 Patients

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


title: Chansu Injection Improves the Respiratory Function of Severe COVID-19 Patients

text: Chansu and its major active constituent of bufalin have been reported to have broad-spectrum antiviral effects. This study aims to assess the efficacy of Chansu injection in treating patients with severe COVID-19. The patients diagnosed as severe or critical COVID-19 in The First People's Hospital of Jiangxia District, Wuhan, China from February 5 to March 5, 2020 were randomly allocated in a 1:1 ratio to receive general treatment plus Chansu injection or only general treatment as the control group. The treatment course was 7 days. The changes of PaO2/FiO2 and ROX index indicating respiratory function, the white blood cell (WBC) count, peripheral blood mononuclear lymphocyte (PBML) count, respiratory support step-down time (RSST), and safety indicators for the 7th day were retrospectively analyzed. After 7 days treatment, the oxygenation index was improved in 20 of 21 patients (95.2%) in the treatment group, as compared with 13 of 19 patients (68.4%) in the control group. The PaO2/FiO2 and ROX indices in the treatment group (mean, 226.27 and 14.01 respectively) were significantly higher than the control group (mean, 143.23 and 9.64 respectively). The RSST was 1 day shorter in the treatment group than the control group. Multivariate regression analysis suggested that Chansu injection contributed the most to the outcome of PaO2/FiO2. No obvious adverse effects were observed. Preliminary data showed that Chansu injection had apparent efficacy in treating patients with severe COVID-19.


title: Suppressing Epidemics with a Limited Amount of Immunization Units

text: The way diseases spread through schools, epidemics through countries, and viruses through the Internet is crucial in determining their risk. Although each of these threats has its own characteristics, its underlying network determines the spreading. To restrain the spreading, a widely used approach is the fragmentation of these networks through immunization, so that epidemics cannot spread. Here we develop an immunization approach based on optimizing the susceptible size, which outperforms the best known strategy based on immunizing the highest-betweenness links or nodes. We find that the network's vulnerability can be significantly reduced, demonstrating this on three different real networks: the global flight network, a school friendship network, and the internet. In all cases, we find that not only is the average infection probability significantly suppressed, but also for the most relevant case of a small and limited number of immunization units the infection probability can be reduced by up to 55%.


title: Exploring active compounds of Jinhua Qinggan Granules for prevention of COVID-19 based on network pharmacology and molecular docking/ 基于网络药理学与分子对接技术的金花清感颗粒防治新型冠状病毒肺炎的潜在药效物质研究

text: Objective: To explore the effective chemical constituents of Jinhua Qinggan Granules for treatment of coronavirus disease 2019 (COVID-19). Methods: The compounds and action targets of eleven herbal medicines in Jinhua Qinggan Granules were collected via TCMSP. The genes corresponding to the targets were queried by the UniProt database, then the “herbal medicine-compound-target” network was established by Cytoscape software. The gene ontology (GO) function enrichment analysis and KEGG pathway enrichment analysis were performed by DAVID to predict their mechanism. Molecular docking was used to analyze the binding force of the core effective compounds in the “herbal medicine-compound-target” network with SARS-CoV-2 3CL hydrolase and angiotensin converting enzyme II (ACE2). Results: The “herbal medicine-compound-target” network contained 154 compounds and 276 targets, and the key targets involved PTGS2, HSP90AB1, HSP90AA1, PTGS1, NCOA2, etc. GO function enrichment analysis revealed 278 items, including ATP binding, transcription factor activation and regulation of apoptosis process, etc. KEGG pathway enrichment screened 127 signaling pathways, including TNF, PI3K/Akt and HIF-1 signaling pathways related to lung injury protection. The results of molecular docking showed that formononetin, stigmasterol, beta-sitosterol, anhydroicaritin and other key compounds have a certain degree of affinity with SARS-CoV-2 3CL hydrolase and ACE2. Conclusion: The effective compounds in Jinhua Qinggan Granules regulate multiple signaling pathways via binding ACE2 and acting on targets such as PTGS2, HSP90AB1, HSP90AA1, PTGS1, NCOA2 for the prevention of COVID-19.


title: The impact of purifying and background selection on the inference of population history: problems and prospects

text: Current procedures for inferring population history are generally performed under the assumption of complete neutrality - that is, by neglecting both direct selection and the effects of selection on linked sites. We here examine how the presence of direct purifying and background selection may bias demographic inference by evaluating two commonly-used methods (MSMC and fastsimcoal2), specifically studying how the underlying shape of the distribution of fitness effects (DFE) and the fraction of directly selected sites interact with demographic parameter estimation. The results show that, even after masking functional genomic regions, background selection effects may result in the mis-inference of population growth under models of both constant population size as well as decline. This effect is amplified as the strength of purifying selection and the density of directly selected sites increases, as indicated by the distortion of the site frequency spectrum and levels of nucleotide diversity at linked neutral sites. We also show how simulated changes in background selection effects caused by population size changes can be predicted analytically. We propose a potential method for correcting for the mis-inference of population growth caused by selection. By treating the DFE as a nuisance parameter and averaging across all potential realizations, we demonstrate that even directly selected sites may be used to infer demographic histories with reasonable accuracy.


docid: ptxrchih

title: Characteristics and outcome of SARS-CoV-2 infection in cancer patients.

text: Abstract Background: Concerns have emerged about the higher risk of fatal COVID-19 in cancer patients. In this paper, we review the experience of a comprehensive cancer center. Methods: A prospective registry was set up at Institut Curie at the beginning of the COVID-19 pandemic. All cancer patients with suspected or proven COVID-19 were entered and actively followed for 28 days. Results: Among 9,842 patients treated at Institut Curie between mid-March and early May 2020, 141 (1.4%) were diagnosed with COVID-19, based on RT-PCR testing and/or CT-scan. In line with our case-mix, breast cancer (40%) was the most common tumor type, followed by hematological and lung malignancies (both 13%). Patients with active cancer therapy or/and advanced cancer accounted for 88% and 69% of patients, respectively. At diagnosis, 79% of patients had COVID-19 related symptoms, with an extent of lung parenchyma involvement [≤]50% in 90% of patients. Blood count variations and C-reactive protein elevation were the most common laboratory abnormalities. Antibiotics and antiviral agents were administered in 48% and 7% of patients, respectively. At the time of analysis, 26 patients (18%) have died from COVID-19, and 81 (57%) were cured. Independent prognostic factors at the time of COVID-19 diagnosis associated with death or intensive care unit admission were extent of COVID-19 pneumonia and decreased O2 saturation. Conclusions: COVID-19 incidence and presentation in cancer patients appear to be very similar to those in the general population. The outcome of COVID-19 is primarily driven by the initial severity of infection rather than patient or cancer characteristics.


title: Facemask shortage and the coronavirus disease (COVID-19) outbreak: Reflection on public health measures

text: To the best of our knowledge, this is the first study to investigate the facemask shortage during the novel coronavirus pneumonia (COVID-19) outbreak in China. We have summarized in detail the management strategies implemented by the Chinese governments during the outbreaks. By considering three scenarios for the outbreak development, we simulated the facemasks availability from late-December 2019 to late-April 2020 and estimated the duration of sufficient facemask supplies. Our findings showed that if the COVID-19 outbreak occurred only in Wuhan city or Hubei province, facemask shortage would not appear with the existing public health measures. However, if the outbreak occurred in the whole of China, a shortage of facemask could be substantial assuming no alternative public health measures. Supplies of facemasks in the whole of China would have been sufficient for both healthcare workers and the general population if the COVID-19 outbreak only occurred in Wuhan city or Hubei province. However, if the outbreak occurred in the whole of China, facemask supplies in China could last for 5 days if under the existing public health measures and a shortage of 853 million facemasks is expected by 30 Apr 2020. Assuming a gradually decreased import volume, we estimated that dramatic increase in productivity (42.7 times of the usual level) is needed to mitigate the facemask crisis by the end of April. In light of the COVID-19 outbreak in China, a shortage of facemasks and other medical resources can considerably compromise the efficacy of public health measures. Effective public health measures should also consider the adequacy and affordability of medical resources. Global collaboration should be strengthened to prevent the development of a global pandemic from a regional epidemic via easing the medical resources crisis in the affected countries.


title: COVID-19 in Iran: A Deeper Look Into The Future

text: The novel corona-virus (COVID-19) has led to a pandemic, affecting almost all countries and regions in a few weeks, and therefore a global plan is needed to overcome this battle. Iran has been among the first few countries that has been affected severely, after China, which forced the government to put some restriction and enforce social distancing in majority of the country. In less than 2 months, Iran has more than 80,000 confirmed cases, and more than 5,000 death. Based on the official statistics from Iran's government, the number of daily cases has started to go down recently, but many people believe if the lockdown is lifted without proper social distancing enforcement, there is a possibility for a second wave of COVID-19 cases. In this work, we analyze at the data for the number cases in Iran in the past few weeks, and train a predictive model to estimate the possible future trends for the number of cases in Iran, depending on the government policy in the coming weeks and months. Our analysis may help political leaders and health officials to take proper action toward handling COVID-19 in the coming months.


title: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection During Pregnancy In China: A Retrospective Cohort Study

text: Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as the cause of the ongoing worldwide epidemic of Coronavirus Disease 2019 (COVID-19) in China and worldwide. However, there were few studies about the effects of SARS-CoV-2 infection on pregnant women. Methods In this retrospective cohort study, we enrolled 31 pregnant women and 35 non-pregnant women from Jan 28 to Feb 28, 2020 to evaluate the effects of SARS-CoV-2 infection during pregnancy. Inflammatory indices were used to assess the severity of COVID-19. Evidence of vertical transmission was determined by laboratory confirmation of SARS-CoV-2 in amniotic fluid, placenta, neonatal throat and anal swab and breastmilk samples. Findings Compared with non-pregnant women, pregnant women had a significantly lower proportion of fever (54.8% vs. 87.5%, p= 0.006), a shorter average interval from onset to hospitalization, and a higher proportion of severe or critical COVID-19 (32.3% vs. 11.4%, p=0.039). Neutrophil-to-lymphocyte ratio (NLR) and systematic immune-inflammation-based prognostic index (SII) were significantly higher on admission in severe/critical pneumonia group than moderate pneumonia group. We could not detect the presence of SARS-CoV-2 by RT-PCR in amniotic fluid, placenta, neonatal throat and anal swab and breastmilk samples. Conclusions The clinical symptoms of COVID-19 in pregnant women were insidious and atypical, compared with those in non-pregnant patients. SII and NLR could be a useful marker to evaluate the severity of COVID-19. There was no evidence of vertical transmission during pregnancy with SARS-CoV-2 infection.


docid: thazunob

title: Biosurfactants: A Covid-19 Perspective

text: The recent outbreak in severe acute respiratory syndrome – coronavirus-2 (SARS-CoV-2) has demonstrated the complete inability of nations across the world to cope with the pressures of a global pandemic, especially one in which the only current feasible treatments are those which deal with the symptoms alone and not the viral cause. As the death toll rises, scientists begin to fall toward new avenues of research, with novelty showing itself to be an incredible and so far, underrated resource. In this case, the use of biosurfactants in dealing with this pandemic justifies extensive study with their potential applications being in the prevention of viral spread; dealing with the symptoms that develop after the incubation period; directly targeting viral infected cells and preventing the spread of the virus throughout the host, all in addition to also acting as potential drug delivery systems and cleaning agents. This extensive avenue of biosurfactants owes to the simplicity in their amphiphilic structure which permits them to interact directly with the lipid membrane of the coronavirus, in a way which wouldn't be of significant threat to the host. Although it could possibly interact and affect the virus, it could also affect human internal organs/cells by interacting with lipid membrane, if (biosurfactant is) ingested, and it still needs further studies in human models. The structure of the coronavirus, in this case SARS-CoV-2, is detrimentally dependent on the integrity of its lipid membrane which encloses its vital proteins and RNA. Biosurfactants possess the innate ability to threaten this membrane, a result of their own hydrophobic domains across their amphiphilic structure. With biosurfactants additionally being both natural and sustainable, while also possessing a remarkably low cytotoxicity, it is of no doubt that they are going to be of increasing significance in dealing with the current pandemic.


title: Phenotyping genetic differences in aldehyde dehydrogenase 2 after an alcohol challenge in humans

text: Inefficient aldehyde metabolism by an aldehyde dehydrogenase 2 (ALDH2) genetic variant, ALDH2*2 (rs671), increases the risk of esophageal cancer with alcohol consumption. Here we tested the hypothesis that additional genetic differences in ALDH2 besides ALDH2*2 exist resulting in inefficient acetaldehyde metabolism after alcohol consumption. Human volunteers were recruited who self-reported flushing after alcohol. The first stage recruited East Asians and the second stage non-East Asians. After phone screening and ALDH2 sequencing, volunteers were subjected to an alcohol challenge (0.25g/kg). Physiological parameters and breath acetaldehyde levels were assessed. Twenty-six participants were given an alcohol challenge. In the first stage, when comparing the ALDH2*1/*2 genotype to ALDH2*1/*1 genotype, tachycardia (104{+/-}3* versus 73{+/-}4 beats per minute), increases in facial skin temperature (99.6{+/-}0.4* versus 95.9{+/-}0.50F), and increases in breath acetaldehyde (peak: 2.1{+/-}0.4* versus 0.2{+/-}0.3ppm, n=8/group, *p<0.01) occurred after alcohol consumption. In the second stage, heterozygotes for an ALDH2 intron variant (rs4646777, G>A) caused increases in facial skin temperature (98{+/-}1* versus 94{+/-}1 OF, n=4, *p<0.01) without tachycardia or acetaldehyde accumulation after alcohol consumption. Subjects self-identifying as non-East Asian genotyped with an ALDH2*1/*2 variant also displayed a characteristic ALDH2*1/*2 phenotype after alcohol consumption. Further, ALDH2 point mutations rs747096195 (R101G) and rs190764869 (R114W) showed reduced acetaldehyde metabolism and increases in facial skin temperature after an alcohol challenge relative to wild type ALDH2 subjects. Taken together, we developed a method to non-invasively phenotype genetic differences for ALDH2 in humans including quantifying aldehyde metabolism in single subjects. We also discovered genetic differences besides ALDH2*2 that cause inefficient aldehyde metabolism.


title: Combined point of care nucleic acid and antibody testing for SARS-CoV-2: a prospective cohort study in suspected moderate to severe COVID-19 disease.

text: Abstract Background Rapid COVID-19 diagnosis in hospital is essential for patient management and identification of infectious patients to limit the potential for nosocomial transmission. The diagnosis is complicated by 30-50% of COVID-19 hospital admissions with negative nose/throat swabs negative for SARS-CoV-2 nucleic acid, frequently after the first week of illness when SARS-CoV-2 antibody responses become detectable. We assessed the diagnostic accuracy of combined rapid antibody point of care (POC) and nucleic acid assays for suspected COVID-19 disease in the emergency department. Methods We developed (i) an in vitro neutralization assay using a lentivirus expressing a genome encoding luciferase and pseudotyped with spike protein and (ii) an ELISA test to detect IgG antibodies to nucleocapsid (N) and spike (S) proteins from SARS-CoV-2. We tested two promising candidate lateral flow rapid fingerprick test with bands for IgG and IgM. We then prospectively recruited participants with suspected moderate to severe COVID-19 and tested for SARS-CoV-2 nucleic acid in a combined nasal/throat swab using the standard laboratory RT-PCR and a validated rapid nucleic acid test. Additionally, serum collected at admission was retrospectively tested by in vitro neutralization, ELISA and the candidate POC antibody tests. We determined the sensitivity and specificity of the individual and combined rapid POC diagnostic tests against a composite gold standard of neutralisation and the standard laboratory RT-PCR. Results 45 participants had specimens tested for nucleic acid in nose/throat swabs as well as stored sera for antibodies. Serum neutralisation assay, SARS-CoV-2 Spike IgG ELISA and the POC antibody test results were concordant. Using the composite gold standard, prevalence of COVID-19 disease was 53.3% (24/45). Median age was 73.5 (IQR 54.0-86.5) years in those with COVID-19 disease by our gold standard and 63.0 (IQR 41.0-72.0) years in those without disease. Median duration of symptoms was 7 days (IQR 1-8) in those with infection. The overall sensitivity of rapid NAAT diagnosis was 79.2% (95CI 57.8-92.9%) and 50.0% (11.8-88.2) at days 8-28. Sensitivity and specificity of the combined rapid POC diagnostic tests reached 100% (95CI 85.8-100) and 94.7% (95CI 74.0-99.0) overall. Conclusions Dual point of care SARS-CoV-2 testing can significantly improve diagnostic sensitivity, whilst maintaining high specificity. Rapid combined tests have the potential to transform our management of COVID-19, including inflammatory manifestations where nucleic acid test results are negative. A rapid combined approach will also aid recruitment into clinical trials and in prescribing therapeutics, particularly where potentially harmful immune modulators (including steroids) are used.


title: Clinical observations of low molecular weight heparin in relieving inflammation in COVID-19 patients: A retrospective cohort study

text: Abstract: Background On March 11, 2020, the World Health Organization declared its assessment of COVID-19 as a global pandemic. Effective therapeutic drugs are urgently needed to improve the overall prognosis of patients, but currently no such drugs are available. Methods Patients in the study were divided into a heparin and a control group based on whether low molecular weight heparin (LMWH) was used. D-dimer, C-reactive protein (CRP), peripheral blood lymphocyte percentage, interleukin-6, and other indices in 42 patients with novel coronavirus pneumonia were retrospectively analyzed to compare and evaluate the progress of patients before and after LMWH treatment. Results Compared to the control group, D-dimer levels in the heparin group significantly increased before treatment, and there was no significant difference after treatment. There was no significant difference in the change of CRP levels between the two groups of patients before and after LMWH treatment, and levels for both groups were significantly lower after, compared to before, treatment. Compared to the control group, patients in the heparin group had a higher percentage of lymphocytes after treatment and lower levels of interleukin-6; these differences were statistically significant. Conclusions Under conventional antiviral treatment regimens, LMWH can improve hypercoagulability, inhibit IL-6 release, and counteract IL-6 biological activity in patients. LMWH has potential antiviral effects and can help delay or block inflammatory cytokine storms. It can also increase the lymphocytes (LYM%)of patients and has the potential for treatment of COVID-19.


title: Targeting adenosinergic pathway and adenosine A(2A) receptor signaling for the treatment of COVID-19: A hypothesis

text: The most serious health issue today is the rapid outbreak of Coronavirus Disease 2019 (COVID-19). More than 6,973,427 confirmed cases were diagnosed in nearly 213 countries and territories around the world and two international conveyances, causing globally over 400,000 deaths. Epidemiology, risk factors, and clinical characteristics of COVID-19 patients have been identified, but the factors influencing the immune system against COVID-19 have not been well established. Upon infection or cell damage, high amounts of adenosine triphosphate (ATP) are released from damaged cells, which serve as mediators of inflammation through purinergic cell surface receptor signaling. As a protective mechanism to prevent excessive damage to host tissue, adenosine counteracts ATP's effects by adenosine receptor stimulation to suppress the pro-inflammatory response. Adenosine is seen as a major obstacle to the efficacy of immune therapies, and the adenosinergic axis components are critical therapeutic targets for cancer and microbial infections. Pharmacologic inhibitors or antibodies specific to adenosinergic pathway components or adenosine receptors in microbial and tumor therapy have shown efficacy in pre-clinical studies and are entering the clinical arena. In this review, we provide a novel hypothesis explaining the potential for improving the efficiency of innate and adaptive immune systems by targeting adenosinergic pathway components and adenosine A(2A) receptor signaling for the treatment of COVID-19.


title: Social isolation, loneliness, and all-cause mortality in patients with cardiovascular disease: a 10-year follow-up study

text: Objective: Social isolation and loneliness have been associated with increased incidence of cardiovascular disease CVD, but few studies have evaluated the impact of social isolation and loneliness on mortality in people with existing CVD, and these are limited to Western populations We examined whether social isolation and loneliness are associated with increased risk of mortality in individuals with established CVD in Taiwan