docid: icpwfyss

title: Fast SARS-CoV-2 detection by RT-qPCR in preheated nasopharyngeal swab samples

text: The current reference for COVID-19 diagnosis is based on the detection of SARS-CoV-2 on RNA extracts using one-step retrotranscription and quantitative PCR (RT-qPCR). Based on the urgent need for high-throughput COVID-19 screening, we tested the performance of three alternative, simple and affordable protocols to rapidly detect SARS-CoV-2, overcoming the long and tedious RNA extraction step. Although with an average increase of 6.1 ( ±1.6) cycles compared to standard tests with RNA extracts, we show that RT-qPCR yielded consistent results in nasopharyngeal swab samples that were subject to a direct 70°C incubation for 10 min. Our findings provide viable options to overcome any supply chain issue and help to increase the throughput of diagnostic tests by using any qPCR device, thereby complementing standard COVID-19 testing.


title: Mental health in the UK during the COVID-19 pandemic: early observations

text: Background: Previous pandemics have resulted in significant consequences for mental health. Here we report the mental health sequela of the COVID-19 pandemic on the UK population and examine modifiable and non-modifiable explanatory factors associated with mental health outcomes. We focus on the short-term consequences for mental health, as reported during the first four-six weeks of social distancing measures being introduced. Methods: A community cohort study was conducted with adults aged [≥]18 years recruited through a mainstream and social media campaign between 3/4/20-30/4/20. Consenting participants completed an online survey measuring depression, anxiety and stress and explanatory variables hypothesised to be related to these mental health outcomes. Outcomes: N=3097 eligible individuals participated. The cohort was predominantly female (85%); mean age forty-four years; 10% from minority ethnic groups; 50% described themselves as key-workers and 20% identified as having clinical risk factors putting them at increased risk of COVID-19. Mean scores for depression, stress and anxiety significantly exceeded population norms. Analysis of non-modifiable factors indicated that being younger and female were associated with all outcomes, with the final multivariable models accounting for 7-13% of variance. When adding modifiable factors, significant independent effects emerged for positive mood, perceived loneliness and worry about getting COVID-19 for all outcomes, with the final multivariable models accounting for 54-57% of variance. Interpretation: Increased psychological morbidity was evident in this UK cohort, with younger people and women at particular risk. Interventions targeting perceptions of: loneliness, risk of COVID-19, worry about COVID-19, and positive mood may be effective.


docid: xvipnvnn

title: Relative wealth and inequality associate with health in a small-scale subsistence society

text: In high-income countries, relative wealth and inequality affect health by causing psychosocial stress. We test this hypothesis in a small-scale subsistence society, the Tsimane. We associated relative household wealth (n=1003) and community-level wealth inequality (n=35, Gini = 0.15 - 0.43) with a range of psychosocial and health outcomes (depressive symptoms [n=663], social conflicts [n=393], non-social problems [n=390], social support [n=392], cortisol [n=828], BMI [n=9378], blood pressure [n=1614]), self-rated health [n=809], morbidities [n=3140]) controlling for absolute wealth, age, sex, community size, distance to town and relevant random effects. Relative wealth and inequality were associated with self-rated health and morbidity, especially respiratory disease, the leading cause of mortality in the Tsimane. Inequality was also associated with higher blood pressure. However, psychosocial stress did not mediate these associations, suggesting other mechanisms. These findings are consistent with socio-economic hierarchies affecting some health outcomes in any society, while others might be exacerbated in high-income countries.


title: Born in Wuhan: Lessons from COVID-19 epidemic in China/ РОЖДЕННАЯ В УХАНЕ: УРОКИ ЭПИДЕМИИ COVID-19 В КИТАЕ

text: The COVID-19 epidemic curve in China can be divided into several stages. Despite transparency in informing the world public about clusters of undiagnosed viral pneumonia, the country's health care at the first stage of the epidemic was not ready to provide adequate and rapid response for a fast increase in the number of patients with COVID-19, infection control measures were not fully implemented, which also led to a large number of nosocomial cases of infection among medical workers and patients. Socially vulnerable groups of the population did not refer for medical assistance in a timely manner due to the lack of the disease danger understanding and also in connection with the high cost for them of medical aid. At the second stage, simultaneously with the restrictive measures introduced by the government, the entire health care system was rebooted: free medical care for patients with COVID-19 was provided and the strictest infection control measures were implemented, multi-level contact tracking system using IT technologies was organized, and the capacity of hospitals was increased many times. Through the joint efforts of ministries, mass media, social networks and volunteer movements, an unprecedented social mobilization of the population was achieved. Strict implementation of the entire set of measures aimed at fighting the epidemic allowed to take it under strict control at the third stage and practically eliminate the epidemic after 2,5 months. China's response to the COVID-19 epidemic can be useful to other countries, in fighting the current pandemic and in preparing for a response to biological threats in the future.


title: Parasites and their protection against COVID-19- Ecology or Immunology?

text: Background: Despite the high infectivity of SARS-CoV-2, the incidence of COVID-19 in Africa has been slower than predicted. We aimed to investigate a possible association between parasitic infections and COVID-19. Methods: An ecological study in which we analysed WHO data on COVID-19 cases in comparison to WHO data on helminths and malaria cases using correlation, regression, and Geographical Information Services analyses. Results: Of the global 3.34 million COVID-19 cases and 238,628 deaths as at May 4th 2020, Africa reported 0.029/3.3 million (0.88%) cases and 1,064/238,628 (0.45%) deaths. In 2018, Africa reported 213/229 million (93%) of all malaria cases, 204/229 million (89%) of schistosomiasis cases, and 271/1068 million (25%) of soil-transmitted helminth cases globally. In contrast, Europe reported 1.5/3.3 million (45%) of global COVID-19 cases and 142,667/238,628 (59%) deaths. Europe had 5.8/1068 million (0.55%) soil-transmitted helminths cases and no malaria/schistosomiasis cases in 2018. We found an inverse correlation between the incidence of COVID-19 and malaria (r -0.17, p =0.002) and COVID-19 and soil-transmitted helminths (r -0.25, p <0.001). Malaria-endemic countries were less likely to have COVID-19 (OR 0.51, 95% CI 0.29-0.90; p =0.02). Similarly, countries endemic for soil-transmitted helminths were less likely to have COVID-19 (OR 0.24, 95% CI 0.13-0.44; p <0.001), as were countries endemic for schistosomiasis (OR 0.22, 95% CI 0.11-0.45; p<0.001). Conclusions: One plausible hypothesis for the comparatively low COVID-19 cases/deaths in parasite-endemic areas is immunomodulation induced by parasites. Studies to elucidate the relationship between parasitic infections and susceptibility to COVID-19 at an individual level are warranted.


title: Continuous flexibility analysis of SARS-CoV-2 Spike prefusion structures

text: With the help of novel processing workflows and algorithms, we have obtained a better understanding of the flexibility and conformational dynamics of the SARS-CoV-2 spike in the prefusion state. We have re-analyzed previous cryo-EM data combining 3D clustering approaches with ways to explore a continuous flexibility space based on 3D Principal Component Analysis. These advanced analyses revealed a concerted motion involving the receptor-binding domain (RBD), N-terminal domain (NTD), and subdomain 1 and 2 (SD1 & SD2) around the previously characterized 1-RBD-up state, which have been modeled as elastic deformations. We show that in this dataset there are not well-defined, stable, spike conformations, but virtually a continuum of states moving in a concerted fashion. We obtained an improved resolution ensemble map with minimum bias, from which we model by flexible fitting the extremes of the change along the direction of maximal variance. Moreover, a high-resolution structure of a recently described biochemically stabilized form of the spike is shown to greatly reduce the dynamics observed for the wild-type spike. Our results provide new detailed avenues to potentially restrain the spike dynamics for structure-based drug and vaccine design and at the same time give a warning of the potential image processing classification instability of these complicated datasets, having a direct impact on the interpretability of the results.


title: Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: a computational biology approach

text: The newly identified SARS-CoV-2 has now been reported from around 183 countries with more than a million confirmed human cases including more than 68000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins have gotten substantial attention recently. Spike glycoprotein is widely considered as a possible target to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment tools. In this study, 483 unique variations have been identified among the genomes including 25 non-synonymous mutations and one deletion in the spike protein of SARS-CoV-2. Among the 26 variations detected, 12 variations were located at the N-terminal domain and 6 variations at the receptor-binding domain (RBD) which might alter the interaction with receptor molecules. In addition, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on our findings, potential inhibitors can be designed and tested targeting these proposed sites of variation.


title: Nationwide system to centralize decisions around ECMO use for severe COVID-19 pneumonia in Japan (Special Correspondence)

text: The novel coronavirus disease 2019 (COVID-19) is spreading in Japan. We have collected a total of 26 patients with COVID-19 who required extracorporeal membranous oxygenation (ECMO). The available data from the first 14 cases demonstrated that the median age of patients was 71 and the median PaO(2)/FIO(2) ratio, positive end-expiratory pressure, mean airway pressure, and lung compliance were 70, 15 cmH(2)O, 21 cmH(2)O, and 28 mL/cmH(2)O, respectively. Median serum KL-6 level was 333 U/mL. Consequently, 16 (62%) out of the 26 have been weaned off and 6 (26%) have been extubated and on rehabilitation, while the other 10 (38%) remain on ECMO. There seemed to be two phenotypes of COVID-19: one with impaired lung compliance and one with preserved lung compliance. The latter phenotype was likely to be favored from the use of ECMO. Further investigation is necessary to clasrify the optimal use of ECMO in patients with COVID-19.


title: Pre-outbreak determinants of perceived risks of corona infection and preventive measures taken. A prospective population-based study

text: Objectives. Assess how people perceive the risks of coronavirus infection, whether people take preventive measures, and which (pre-outbreak) factors contribute to the perceived risks and measures taken, such as (pre-outbreak) respiratory problems, heart problems, diabetes, anxiety and depression symptoms, loneliness, age, gender, marital status and education level. Methods. Data were collected in the longitudinal LISS panel, based on a random sample of the Dutch population. The coronavirus survey started on March 2, and the data collection ended on March 17 2020. Data were linked with surveys on health and social integration conducted at the end of 2019 (Nstudy sample=3,540). Results. About 15% perceived the risk of infection as high, and 11% the risk becoming ill when infected. Multivariate logistic regression analyses showed the following. Older age-groups perceived the risk for coronavirus infection as lower (all adjusted Odd Ratios [aOR] smaller than .058). In total, 43.8% had taken preventive measures, especially females (aOR=1.47, 95% CI=1.27-1.69). Those with lower education levels less often used preventive measures (aOR=0.56, 95% CI=0.46-0.69). Those with pre-outbreak respiratory problems (aOR=2.89, 95% CI=2.24-3.73), heart problems (aOR=2.17, 95% CI=1.49-3.16) and diabetes (aOR=3.10, 95% CI=2.02-4.74) perceived the risk becoming ill when infected as higher than others. However, respondents with pre-outbreak respiratory problems and diabetes did not more often take preventive measures. Conclusions. Vulnerable patients more often recognize that they are at risk becoming ill when infected by the coronavirus, but many do not take preventive measures. Interventions to stimulate the use of preventive measures should pay additional attention to physically vulnerable patients, men and those with lower education levels.


title: SARS-CoV-2 RNA extraction using magnetic beads for rapid large-scale testing by RT-qPCR and RT-LAMP

text: Rapid large-scale testing is essential for controlling the ongoing pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The standard diagnostic pipeline for testing SARS-CoV-2 presence in patients with an ongoing infection is predominantly based on pharyngeal swabs, from which the viral RNA is extracted using commercial kits followed by reverse transcription and quantitative PCR detection. As a result of the large demand for testing, commercial RNA extraction kits may be limited and alternative, non-commercial protocols are needed. Here, we provide a magnetic bead RNA extraction protocol that is predominantly based on in-house made reagents and is performed in 96-well plates supporting large-scale testing. Magnetic bead RNA extraction was benchmarked against the commercial QIAcube extraction platform. Comparable viral RNA detection sensitivity and specificity were obtained by fluorescent and colorimetric RT-LAMP using N primers, as well as RT-qPCR using E gene primers showing that the here presented RNA extraction protocol can be combined with a variety of detection methods at high throughput. Importantly, the presented diagnostic workflow can be quickly set up in a laboratory without access to an automated pipetting robot.


title: Serology in Children with Multisystem Inflammatory Syndrome (MIS-C) associated with COVID-19

text: Objectives: We aimed to measure SARS-CoV-2 serologic responses in children hospitalized with multisystem inflammatory syndrome (MIS-C) compared to COVID-19, Kawasaki Disease (KD) and other hospitalized pediatric controls. Methods: From March 17, 2020 - May 26, 2020, we prospectively identified hospitalized children at Children's Healthcare of Atlanta with MIS-C (n=10), symptomatic PCR-confirmed COVID-19 (n=10), KD (n=5), and hospitalized controls (n=4). With IRB approval, we obtained prospective and residual blood samples from these children and measured SARS-CoV-2 spike (S) receptor binding domain (RBD) IgM and IgG binding antibodies by quantitative ELISA and SARS-CoV-2 neutralizing antibodies by live-virus focus reduction neutralization assay. We statistically compared the log-transformed antibody titers among groups and performed correlation analyses using linear regression. Results: All children with MIS-C had high titers of SARS-CoV-2 RBD IgG antibodies, which correlated strongly with neutralizing antibodies (R2=0.667, P<0.001). Children with MIS-C had significantly higher SARS-CoV-2 RBD IgG antibody titers (geometric mean titer [GMT] 6800, 95%CI 3495-13231) than children with COVID-19 (GMT 626, 95%CI 251-1563, P<0.001), children with KD (GMT 124, 95%CI 91-170, P<0.001) and other hospitalized pediatric controls (GMT 85 [all below assay limit of detection], P<0.001). All children with MIS-C also had detectable RBD IgM antibodies, indicating recent SARS-CoV-2 infection. RBD IgG titers correlated with erythrocyte sedimentation rate (ESR) (R2=0.512, P<0.046) and with hospital and ICU lengths of stay (R2=0.590, P=0.010). Conclusion: Quantitative SARS-CoV-2 RBD antibody titers may have a role in establishing the diagnosis of MIS-C, distinguishing it from other similar clinical entities, and stratifying risk for adverse outcomes.


title: The Zinc Finger Antiviral Protein restricts SARS-CoV-2

text: Recent evidence shows that the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is highly sensitive to interferons (IFNs). However, the underlying antiviral effectors remain to be defined. Here, we show that Zinc finger antiviral protein (ZAP) that specifically targets CpG dinucleotides in viral RNA sequences restricts SARS-CoV-2. We demonstrate that ZAP and its cofactors KHNYN and TRIM25 are expressed in human lung cells. Type I, II and III IFNs all strongly inhibited SARS-CoV-2 and further induced ZAP expression. Strikingly, SARS-CoV-2 and its closest relatives from bats show the strongest CpG suppression among all known human and bat coronaviruses, respectively. Nevertheless, knock-down of ZAP significantly increased SARS-CoV-2 production in lung cells, particularly upon treatment with IFN-α or IFN-γ. Thus, our results identify ZAP as an effector of the IFN response against SARS-CoV-2, although this pandemic pathogen may be preadapted to the low CpG environment in humans. Highlights SARS-CoV-2 and its closest bat relatives show strong CpG suppression IFN-β, -γ and -λ inhibit SARS-CoV-2 with high efficiency ZAP restricts SARS-CoV-2 and contributes to the antiviral effect of IFNs


title: Sensitivity of commercial Anti-SARS-CoV-2 serological assays in a high-prevalence setting

text: We analysed SARS-CoV-2 specific antibody responses in 42 social and working contacts of a super-spreader from the Heinsberg area in Germany. Consistent with a high-prevalence setting 26 individuals had SARS-CoV-2 antibodies determined by in-house neutralisation testing. These results were compared with four commercial assays, suggesting limited sensitivity of the assays in such a high-prevalence setting. Although SARS-CoV-2 nucleocapsid restricted tests showed a better sensitivity, spike based assays had a stronger correlation with neutralisation capacity.


title: A Novel Approach to Data Driven Pandemic Recovery: The Pandemic Recovery Acceleration Model

text: A data driven approach to guide the global, regional and local pandemic recovery planning is key to the safety, efficacy and sustainability of all pandemic recovery efforts. The Pandemic Recovery Acceleration Model (PRAM) analytic tool was developed and implemented state wide in Nebraska to allow health officials, public officials, industry leaders and community leaders to capture a real time snapshot of how the COVID-19 pandemic is affecting their local community, a region or the state and use this novel lens to aid in making key mitigation and recovery decisions. This is done by using six commonly available metrics that are monitored daily across the state describing the pandemic impact: number of new cases, percent positive tests, deaths, occupied hospital beds, occupied intensive care beds and utilized ventilators, all directly related to confirmed COVID-19 patients. Nebraska is separated into six Health Care Coalitions based on geography, public health and medical care systems. The PRAM aggregates the data for each of these geographic regions based on disease prevalence acceleration and health care resource utilization acceleration, producing real time analysis of the acceleration of change for each metric individually and also combined into a single weighted index, the PRAM Recovery Index. These indices are then shared daily with the state leadership, coalition leaders and public health directors and also tracked over time, aiding in real time regional and statewide decisions of resource allocation and the extent of use of comprehensive non-pharmacologic interventions.


title: COVID-19: The unreasonable effectiveness of simple models

text: When the novel coronavirus disease SARS-CoV2 (COVID-19) was officially declared a pandemic by the WHO in March 2020, the scientific community had already braced up in the effort of making sense of the fast-growing wealth of data gathered by national authorities all over the world. However, despite the diversity of novel theoretical approaches and the comprehensiveness of many widely established models, the official figures that recount the course of the outbreak still sketch a largely elusive and intimidating picture. Here we show unambiguously that the dynamics of the COVID-19 outbreak belongs to the simple universality class of the SIR model and extensions thereof. Our analysis naturally leads us to establish that there exists a fundamental limitation to any theoretical approach, namely the unpredictable non-stationarity of the testing frames behind the reported figures. However, we show how such bias can be quantified self-consistently and employed to mine useful and accurate information from the data. In particular, we describe how the time evolution of the reporting rates controls the occurrence of the apparent epidemic peak, which typically follows the true one in countries that were not vigorous enough in their testing at the onset of the outbreak. The importance of testing early and resolutely appears as a natural corollary of our analysis, as countries that tested massively at the start clearly had their true peak earlier and less deaths overall.


title: Caution: The clinical characteristics of COVID-19 patients at admission are changing

text: Background With the emergence of 4rd generation transmission, the prevention and treatment of the novel coronavirus disease 2019 (COVID-19) has entered a new period. We aimed to report several changes in the clinical characteristics at admission of patients with COVID-19. Methods Clinical records and laboratory results of patients suffering from COVID-19 were retrospectively reviewed and matched with the admission dates to analyze the changes in characteristics at the onset of illness. Results Of the 89 affected patients, 31 [34.8%] patients were admitted from January 16 to 22, and 58 [65.2%] were admitted from January 23 to 29. Patients were admitted with more systemic symptoms, such as fever (21 [67.7%] of 31), fatigue (13 [41.9%] of 31), and myalgia (7 [22.6%] of 31), before January 23. More patients (10 [32.3%] of 31) admitted before January 23 had a small amount of sputum production compared with a smaller proportion (4 [6.9%] of 58) of the patients admitted after January 23. Other symptoms, such as cough, nausea, diarrhea, and chest tightness, were not significantly different between the two groups. In addition, the group admitted before January 23 had a larger proportion of patients with reduced lymphocyte (13 [54.2%] of 24), CD3 (11 [54.4%] of 21), and CD8 (9 [42.9%] of 21) counts and elevated serum amyloid A (SAA, 18 [75%] of 24). Conclusions The initial symptoms of recently infected patients seem more insidious, indicating that the new coronavirus may gradually evolve into a virus similar to influenza and latent in asymptomatic carriers for a long time.


title: Do COVID-19 patients admitted to the ICU require anti-Pneumocystis jirovecii prophylaxis?

text: We are currently facing a frightening increase in COVID-19 patients admitted to the ICU. Aiming at screening for secondary pneumonia, we collected the data of our first twelve ICU patients who underwent bronchoalveolar lavage (BAL). Surprisingly, four were detected with Pneumocystis jirovecii (Pj) DNA and RNA, resulting in Pj prevalence of 17%. Pj is a ubiquitous ascomycetes fungus that thrives at the surface of type-I pneumocytes, specifically in human alveoli, leading to pneumocystosis in immunocompromised patients. Interestingly, none of our patients was immunocompromised per se before admission, while all presented the recognized risk factors for life-threatening COVID-19 infection. Observing such high prevalence in COVID-infected patients was unexpected. Almost all patients developed ARDS and received high-dose steroids to prevent worsening, as suggested by reports from China. In Pj-positive patients requiring steroids, prophylaxis was given to avoid the risk of pneumocystosis and increased lung inflammation that may compromise the outcome. We are strongly convinced that testing deep lung specimens for Pj in severe COVID-19 patients should be recommended and Pj-positive patients treated with steroids, and given anti-Pj prophylaxis. This message is important, given the high mortality rate of COVID-19 patients in the ICU.


title: Survival and liveability in #COVIDtimes: Queer women’s transnational witnessing of COVID-19

text: Exploring liveabilities as more than survival, this commentary underscores how survival remains important in these #COVIDtimes. Discussing our privileges and resistances as queer women with various intersectionalities, we offer transnational notes on negotiating, surviving, and living in these non-normative times.


title: The Current and Future State of Vaccines, Antivirals and Gene Therapies Against Emerging Coronaviruses

text: Emerging coronaviruses (CoV) are constant global public health threats to society. Multiple ongoing clinical trials for vaccines and antivirals against CoVs showcase the availability of medical interventions to both prevent and treat the future emergence of highly pathogenic CoVs in human. However, given the diverse nature of CoVs and our close interactions with wild, domestic and companion animals, the next epidemic zoonotic CoV could resist the existing vaccines and antivirals developed, which are primarily focused on Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS CoV). In late 2019, the novel CoV (SARS-CoV-2) emerged in Wuhan, China, causing global public health concern. In this review, we will summarize the key advancements of current vaccines and antivirals against SARS-CoV and MERS-CoV as well as discuss the challenge and opportunity in the current SARS-CoV-2 crisis. At the end, we advocate the development of a “plug-and-play” platform technologies that could allow quick manufacturing and administration of broad-spectrum countermeasures in an outbreak setting. We will discuss the potential of AAV-based gene therapy technology for in vivo therapeutic antibody delivery to combat SARS-CoV-2 outbreak and the future emergence of severe CoVs.


title: Triaging patients in the outbreak of the 2019 novel coronavirus

text: In the end of 2019, the epidemic of a new coronavirus (SARS-CoV-2) occurred in Wuhan and spread rapidly. Changsha, a city located south to the epicenter, was soon impacted. To control the transmission of the coronavirus and avoid nosocomial infection, triage procedures based on epidemiology were implemented in a local hospital of the city. This retrospective study analyzed the data collected during the triage period and found that COVID-19 patients were enriched seven folds into the Section A designated for rapid detection and quarantine. On the other side, roughly triple amounts of visits were received at the Section B for patients without obvious epidemiological history. Eight COVID-19 cases were spotted out of 247 suspected patients. More than 50% of the suspected patients were submitted to multiple rounds of nucleic acid analysis for SARS-CoV-2 infection. Of the 239 patients who were diagnosed as negative of the virus infection,188 were successfully revisited and none was reported as a COVID-19 case. Of the eight COVID-19 patients, three were confirmed only after multiple rounds of nucleic acid analysis. Besides comorbidities, delayed sharing of epidemiological history added another layer of complexity to the diagnosis in practice. While SARS-CoV-2 epidemic is being alerted in many countries, our report will be helpful to other colleagues in rapid identification of COVID-19 cases and controlling the transmission of the disease.


title: Quantitative form and fit of N95 filtering facepiece respirators are retained and coronavirus surrogate is inactivated after heat treatments

text: Re-use of filtering facepiece respirators (FFRs, commonly referred to as N95s) normally meant for single use only is becoming common in healthcare facilities due to shortages caused by the COVID19 pandemic. Here we report that mouse hepatitis virus (MHV) initially seeded on FFR filter material is inactivated (6 log reduction as measured by 50% tissue culture infective dose (TCID50)) after dry heating at 75 °C for 30 minutes. We also find that the quantitative fit of FFRs after heat treatment at this temperature, under dry conditions or at 90% relative humidity, is not affected by single or ten heating cycles. Previous studies have reported that the filtration efficiency of FFR filters is not negatively impacted by these heating conditions. These results suggest that thermal inactivation of coronaviruses is a potentially rapid and widely deployable method to re-use N95 FFRs in emergency situations where re-using FFRs is a necessity and broad-spectrum sterilization is unavailable. However, we also found that a heat source that emits radiation (e.g., an exposed heating element) results in rapid qualitative degradation of the FFR. Finally, we discuss differences in the results reported here and other recent studies investing heat as a means to recycle FFRs and suggest that overall wear time and donning/doffing cycles are important factors that need to be considered.


title: The National Health Service (NHS) response to the COVID-19 pandemic: a colorectal surgeon’s experience in the UK

text: The UK government was arguably slow to take action against the COVID-19 pandemic However, since switching their policy from "mitigation" to "suppression", swift changes have been implemented to all aspects of life In this unprecedented crisis healthcare has been on the battlefront across the globe Every effort has been made in the UK to stop the National Health Service (NHS) from being overwhelmed, leading to the national slogan: "Stay at home Protect the NHS Save lives" In this article, a consultant general and colorectal surgeon in Southampton reports on the NHS response to the COVID-19 pandemic


title: Drug-Drug interactions between COVID-19 treatments and antipsychotics drugs: integrated evidence from 4 databases and a systematic review

text: Relevance: Management of symptoms like anxiety, delirium and agitation cannot be neglected in COVID-19 patients. Antipsychotics are usually used for the pharmacological management of delirium, and confusion and behavioral disturbances. The selection of concomitant COVID-19 medications and antipsychotics should be evidence-based and closely monitored Objective: To systematically review evidence-based available on drug-drug interactions between COVID-19 treatments and antipsychotics. Evidence Review: Three databases were consulted: (a) Lexicomp Drug Interactions, (b) Micromedex Solutions Drugs Interactions, (c) Liverpool Drug Interaction Group for COVID-19 therapies. To acquire more information on QT prolongation and TdP, the CredibleMeds QTDrugs List was searched. Based on the information collected, the authors made a recommendation agreed to by consensus. In addition, a systematic review was conducted to find the clinical outcomes of drug-drug interactions between COVID-19 treatments and antipsychotics Results: The main interaction between COVID-19 drugs and antipsychotics are the risk of QT prolongation and TdP, and CYP interactions. Remdesivir, favipiravir, baricinitib, and anakinra can be used concomitantly with antipsychotics with no risk of drug-drug interaction (except for hematological risk with clozapine and baricinitib). Tocilizumab is rather safe to use in combination with antipsychotics, although it can restore the activity of CYP3A4 and therefore its substrate metabolism may increase. The most demanding COVID-19 treatments for co-administration with antipsychotics are chloroquine, hydroxychloroquine, azithromycin (all prolong QT interval) and lopinavir / ritonavir (CYP interaction and risk of QT prolongation). Conclusions: We urge to development of evidence-based guidelines that can help clinicians decide the safest treatment combination and monitoring necessary for each particular patient. The selection of concomitant COVID-19 medications and antipsychotics should be evidence-based and closely monitored.


title: Bounding the Predictive Values of COVID-19 Antibody Tests

text: COVID-19 antibody tests have imperfect accuracy. There has been lack of clarity on the meaning of reported rates of false positives and false negatives. For risk assessment and clinical decision making, the rates of interest are the positive and negative predictive values of a test. Positive predictive value (PPV) is the chance that a person who tests positive has been infected. Negative predictive value (NPV) is the chance that someone who tests negative has not been infected. The medical literature regularly reports different statistics, sensitivity and specificity. Sensitivity is the chance that an infected person receives a positive test result. Specificity is the chance that a non-infected person receives a negative result. Knowledge of sensitivity and specificity permits one to predict the test result given a person's true infection status. These predictions are not directly relevant to risk assessment or clinical decisions, where one knows a test result and wants to predict whether a person has been infected. Given estimates of sensitivity and specificity, PPV and NPV can be derived if one knows the prevalence of the disease, the rate of illness in the population. There is considerable uncertainty about the prevalence of COVID-19. This paper addresses the problem of inference on the PPV and NPV of COVID-19 antibody tests given estimates of sensitivity and specificity and credible bounds on prevalence. I explain the methodological problem, show how to estimate bounds on PPV and NPV, and apply the findings to some tests authorized by the FDA.


title: AI-based multi-modal integration of clinical characteristics, lab tests and chest CTs improves COVID-19 outcome prediction of hospitalized patients

text: With 15% of severe cases among hospitalized patients1, the SARS-COV-2 pandemic has put tremendous pressure on Intensive Care Units, and made the identification of early predictors of severity a public health priority. We collected clinical and biological data, as well as CT scan images and radiology reports from 1,003 coronavirus-infected patients from two French hospitals. Radiologists' manual CT annotations were also available. We first identified 11 clinical variables and 3 types of radiologist-reported features significantly associated with prognosis. Next, focusing on the CT images, we trained deep learning models to automatically segment the scans and reproduce radiologists' annotations. We also built CT image-based deep learning models that predicted severity better than models based on the radiologists' scan reports. Finally, we showed that including CT scan features alongside the clinical and biological data yielded more accurate predictions than using clinical and biological data only. These findings show that CT scans provide insightful early predictors of severity.


ER Goddess: COVID-19 is What EPs Were Trained For


Chapter 6 Integumentary System


The potential use of Persian herbal medicines against COVID-19 through angiotensin-converting enzyme 2


title: Epidemiological And Clinical Characteristics of The First 18 Patients with COVID-19 in Taiwan

text: To understand the epidemiological and clinical characteristics of patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in Taiwan, we analyzed data from the National Notifiable Disease Surveillance System and epidemiological case investigation reports We included all real-time reverse-transcription polymerase chain reaction (real-time RT-PCR) confirmed cases of coronavirus disease-2019 (COVID-19) from Jan 21 to Feb 14, 2020, and followed up until Feb 27, 2020 Eighteen cases were confirmed and all survived Median follow-up period was 24 5 days (range: 14-35) Of them, 16 (88 9%) were imported cases, and 2 (11 1%) were infected by imported cases within household Their median age was 52 years (range: 21-74);8 (44 4%) were men, and 9 (50%) had comorbidities Symptoms included cough (72 2%), fever (66 7%), rhinorrhea (22 2%) and diarrhea (11 1%);one patient (5 5%) was asymptomatic According to the WHO definition of clinical syndromes associated with SARS-CoV-2, there were 8 (44 4%), 9 (50 0%), and 1 (5 6%) categorized as mild, moderate, and severe illness, respectively At the end of follow-up, 9 cases met the criteria of discontinuation of isolation and 8 of them were discharged The median time from admission to discontinuation of isolation was 21 days (range: 13-31) and the median duration of persistent RT-PCR positivity was 14 days (range: 4- 22) and 15 days (range: 4-24) for upper and lower respiratory samples, respectively The first 18 cases of COVID-19 in Taiwan were all imported or importation related, which were related to the early phase of COVID-19 epidemic Because viral clearance may take more than 2 weeks, management plans for patients with mild illness is necessary to ensure the best use of medical care capacities during the ongoing COVID-19 pandemic


title: 2019-NCoV: What Every Neurologist Should Know?

text: The 2019 novel Corona Virus pandemic beginning from Wuhan, China primarily affects the respiratory tract but its has impacted clinical practice across a range of specialities including neurology. We review the bearing of the 2019 NCoV infection on neurological practice. Neurological manifestations are less common than respiratory manifestations, yet conspicuous, affecting nearly over a third of hospitalized individuals. These may be classified in to early – headache, dizziness, hyposmia and hypogeusia and late – encephalopathy. Rarely but surely, a very small proportion of infected individuals might present with stroke. Certain neurological conditions, including cerebrovascular disease in both China and Italy and dementia in Italy predispose to infection and more severe manifestations, requiring intensive care unit admission. There is no convincing evidence that the manifestations, course and outcome of various neurological disorders is impacted by 2019 nCoV infection. Concerns of an increased risk of febrile seizures offset by a reduced frequency of infection in the paediatric age group. Individuals with multiple sclerosis might potentially experience both true and pseudorelapses. Besides a direct effect, 2019 nCoV has tremendously affected neurological care by disrupting the continuity of care and the availability of neurological medicines worldwide. Neurologists should respond to this challenge by developing and sustaining innovative methods of providing care as well as alerting the society at large to adopt measures to contain the spread of 2019 nCoV.


title: Cell studies follow up on previous SARS-CoV-2 studyCell studies follow up on previous SARS-CoV-2 study

text: In March, a team of scientists reported that they had run and analyzed a computational screen that helped them pinpoint 69 compounds that might treat COVID-19, the disease caused by the novel coronavirus, SARS-CoV-2 They now have new data from lab experiments showing that some of those compounds can stop the virus from replicating in cells The hits include a cancer drug currently in clinical trials, an over-the-counter antihistamine, and a compound that’s never been tested in humans but outperformed hydroxychloroquine in the cell studies (Nature 2020, DOI: 10 1038/s41586-020-2286-9) The international group, led by molecular biologist Nevan Krogan of the University of California, San Francisco, identified the original 69 compounds by running a screen to look for human proteins that might interact with the virus’s proteins The program then searched for molecules that could disrupt those potential interactions


title: Modelling the impact of COVID-19 in Australia to inform transmission reducing measures and health system preparedness

text: Background The ability of global health systems to cope with increasing numbers of COVID-19 cases is of major concern. In readiness for this challenge, Australia has drawn on clinical pathway models developed over many years in preparation for influenza pandemics. These models have been used to estimate health care requirements for COVID-19 patients, in the context of broader public health measures. Methods An age and risk stratified transmission model of COVID-19 infection was used to simulate an unmitigated epidemic with parameter ranges reflecting uncertainty in current estimates of transmissibility and severity. Overlaid public health measures included case isolation and quarantine of contacts, and broadly applied social distancing. Clinical presentations and patient flows through the Australian health care system were simulated, including expansion of available intensive care capacity and alternative clinical assessment pathways. Findings An unmitigated COVID-19 epidemic would dramatically exceed the capacity of the Australian health system, over a prolonged period. Case isolation and contact quarantine alone will be insufficient to constrain case presentations within a feasible level of expansion of health sector capacity. Overlaid social restrictions will need to be applied at some level over the course of the epidemic to ensure that systems do not become overwhelmed, and that essential health sector functions, including care of COVID-19 patients, can be maintained. Attention to the full pathway of clinical care is needed to ensure access to critical care. Interpretation Reducing COVID-19 morbidity and mortality will rely on a combination of measures to strengthen and extend public health and clinical capacity, along with reduction of overall infection transmission in the community. Ongoing attention to maintaining and strengthening the capacity of health care systems and workers to manage cases is needed.


title: Post lockdown COVID-19 seroprevalence and circulation at the time of delivery, France

text: Background To fight the COVID-19 pandemic, lockdown has been decreed in many countries worldwide. The impact of pregnancy as a severity risk factor is still debated, but strict lockdown measures have been recommended for pregnant women. Objectives To evaluate the impact of the COVID-19 pandemic and lockdown on the seroprevalence and circulation of SARS-CoV-2 in a maternity ward in an area that has been significantly affected by the virus. Study design Prospective study at the Antoine Beclere Hospital maternity ward (Paris area, France) from May 4 (one week before the end of lockdown) to May 31, 2020 (three weeks after the end of lockdown). All patients admitted to the delivery room during this period were offered a SARS-CoV-2 serology test as well concomitant SARS-CoV-2 RT-PCR on a nasopharyngeal sample. Results A total of 249 women were included. Seroprevalence of SARS-CoV-2 was 8%. The RT-PCR positive rate was 0.5%. 47.4% of the SARS-CoV-2-IgG-positive pregnant women never experienced any symptoms. A history of symptoms during the epidemic, such as fever, myalgia and anosmia, was suggestive of previous infection. Conclusions Three weeks after the end of lockdown, SARS-CoV-2 infections were scarce in our region. A high proportion of SARS-CoV-2-IgG-negative pregnant women must be taken into consideration in the event of a resurgence of the pandemic in order to adapt public health measures to reduce exposure to the virus, such as social distancing and teleworking for this specific population.


title: The effect of multiple interventions to balance healthcare demand for controlling COVID-19 outbreaks: a modelling study

text: Background Recent outbreak of a novel coronavirus disease 2019 (COVID-19) has led a rapid global spread around the world. For controlling COVID-19 outbreaks, many countries have implemented two non-pharmaceutical interventions: suppression like immediate lock-downsin cities at epicentre of outbreak; or mitigation that slows down but not stopping epidemic for reducing peak healthcare demand. Both interventions have apparent pros and cons; the effectiveness of any one intervention in isolation is limited. It is crucial but hard to know how and when to take which level of interventions tailored to the specific situation in each country. We aimed to conduct a feasibility study for robustly accessing the effect of multiple interventions to control the number and distribution of infections, growth of deaths, peaks and lengths of COVID-19 breakouts in the UK and other European countries, accounting for balance of healthcare demand. Methods We developed a model to attempt to infer the impact of mitigation, suppression and multiple rolling interventions for controlling COVID-19 outbreaks in the UK. Our model assumed that each intervention has equivalent effect on the reproduction number R across countries and over time; where its intensity was presented by average-number contacts with susceptible individuals as infectious individuals; early immediate intensive intervention led to increased health need and social anxiety. We considered two important features: direct link between Exposed and Recovered population, and practical healthcare demand by separation of infections into mild, moderate and critical cases. Our model was fitted and calibrated with date on cases of COVID-19 in Wuhan to estimate how suppression intervention impacted on the number and distribution of infections, growth of deaths over time during January 2020, and April 2020. We combined the calibrated model with data on the cases of COVID-19 in London and non-London regions in the UK during February 2020 and April 2020 to estimate the number and distribution of infections, growth of deaths, and healthcare demand by using multiple interventions. We applied the calibrated model to the prediction of infection and healthcare resource changes in other 6 European countries based on actual measures they have implemented during this period. Findings We estimated given that 1) By the date (5th March 2020) of the first report death in the UK, around 7499 people would have already been infected with the virus. After taking suppression on 23rd March, the peak of infection in the UK would have occurred between 28th March and 4th April 2020; the peak of death would have occurred between 18th April and 24th April 2020. 2) By 29th April, no significant collapse of health system in the UK have occurred, where there have been sufficient hospital beds for severe and critical cases. But in the Europe, Italy, Spain and France have experienced a 3 weeks period of shortage of hospital beds for severe and critical cases, leading to many deaths outside hospitals. 3) One optimal strategy to control COVID-19 outbreaks in the UK is to take region-level specific intervention. If taking suppression with very high intensity in London from 23rd March 2020 for 100 days, and 3 weeks rolling intervention between very high intensity and high intensity in non-London regions. The total infections and deaths in the UK were limited to 9.3 million and 143 thousand; the peak time of healthcare demand was due to the 96th day (12th May, 2020), where it needs hospital beds for 68.9 thousand severe and critical cases. 4) If taking a simultaneous 3 weeks rolling intervention between very high intensity and high intensity in all regions of the UK, the total infections and deaths increased slightly to 10 million and 154 thousand; the peak time of healthcare occurs at the 97th day (13th May, 2020), where it needs equivalent hospital beds for severe and critical cases of 73.5 thousand. 5) If too early releasing intervention intensity above moderate level and simultaneously implemented them in all regions of the UK, there would be a risk of second wave, where the total infections and deaths in the UK possibly reached to 23.4 million and 897 thousand. Interpretation: Considering social and economic costs in controlling COVID-19 outbreaks, long-term suppression is not economically viable. Our finding suggests that rolling intervention is an optimal strategy to effectively and efficiently control COVID-19 outbreaks in the UK and potential other countries for balancing healthcare demand and morality ratio. As for huge difference of population density and social distancing between different regions in the UK, it is more appropriate to implement regional level specific intervention with varied intensities and maintenance periods. We suggest an intervention strategy to the UK that take a consistent suppression in London for 100 days and 3 weeks rolling intervention in other regions. This strategy would reduce the overall infections and deaths of COVID-19 outbreaks, and balance healthcare demand in the UK.


title: One enzyme reverse transcription qPCR using Taq DNA polymerase

text: Taq DNA polymerase, one of the first thermostable DNA polymerases to be discovered, has been typecast as a DNA-dependent DNA polymerase commonly employed for PCR. However, Taq polymerase belongs to the same DNA polymerase superfamily as the Molony murine leukemia virus reverse transcriptase and has in the past been shown to possess reverse transcriptase activity. We report optimized buffer and salt compositions that promote the reverse transcriptase activity of Taq DNA polymerase, and thereby allow it to be used as the sole enzyme in TaqMan RT-qPCR reactions. We demonstrate the utility of Taq-alone RT-qPCR reactions by executing CDC SARS-CoV-2 N1, N2, and N3 TaqMan RT-qPCR assays that could detect as few as 2 copies/µL of input viral genomic RNA.


title: COVID-19 Variants Database: A repository for Human SARS-CoV-2 Polymorphism Data

text: COVID-19 is a newly communicable disease with a catastrophe outbreak that affects all over the world. We retrieved about 8,781 nucleotide fragments and complete genomes of SARS-CoV-2 reported from sixty-four countries. The CoV-2 reference genome was obtained from the National Genomics Data Center (NGDC), GISAID, and NCBI Genbank. All the sequences were aligned against reference genomes using Clustal Omega and variants were called using in-house built Python script. We intend to establish a user-friendly online resource to visualize the variants in the viral genome along with the Primer Infopedia. After analyzing and filtering the data globally, it was made available to the public. The detail of data available to the public includes mutations from 5688 SARS-CoV-2 sequences curated from 91 regions. This database incorporated 39920 mutations over 3990 unique positions. According to the translational impact, these mutations include 11829 synonymous mutations including 681 synonymous frameshifts and 21701 nonsynonymous mutations including 10 nonsynonymous frameshifts. Development of SARS-CoV-2 mutation genome browsers is a fundamental step obliging towards the virus surveillance, viral detection, and development of vaccine and therapeutic drugs. The SARS-COV-2 mutation browser is available at http://covid-19.dnageography.com.


title: External location of touch is constructed post-hoc based on limb choice

text: When humans indicate on which hand a tactile stimulus occurred, they often err when their hands are crossed. This finding seemingly supports the view that the automatically determined touch location in external space affects limb assignment: the crossed right hand is localized in left space, and this conflict presumably provokes hand assignment errors. Here, participants judged on which hand the first of two stimuli, presented during a bimanual movement, had occurred, and then indicated its external location by a reach-to-point movement. When participants incorrectly chose the hand stimulated second, they pointed to where that hand had been at the correct, first time point, though no stimulus had occurred at that location. This behavior suggests that stimulus localization depended on hand assignment, not vice versa. It is, thus, incompatible with the notion of automatic computation of external stimulus location upon occurrence. Instead, humans construct external touch location post-hoc and on demand.


title: Association of radiologic findings with mortality of patients infected with 2019 novel coronavirus in Wuhan, China

text: Radiologic characteristics of 2019 novel coronavirus (2019-nCoV) infected pneumonia (NCIP) which had not been fully understood are especially important for diagnosing and predicting prognosis. We retrospective studied 27 consecutive patients who were confirmed NCIP, the clinical characteristics and CT image findings were collected, and the association of radiologic findings with mortality of patients was evaluated. 27 patients included 12 men and 15 women, with median age of 60 years (IQR 47-69). 17 patients discharged in recovered condition and 10 patients died in hospital. The median age of mortality group was higher compared to survival group (68 (IQR 63-73) vs 55 (IQR 35-60), P = 0.003). The comorbidity rate in mortality group was significantly higher than in survival group (80% vs 29%, P = 0.018). The predominant CT characteristics consisted of ground glass opacity (67%), bilateral sides involved (86%), both peripheral and central distribution (74%), and lower zone involvement (96%). The median CT score of mortality group was higher compared to survival group (30 (IQR 7-13) vs 12 (IQR 11-43), P = 0.021), with more frequency of consolidation (40% vs 6%, P = 0.047) and air bronchogram (60% vs 12%, P = 0.025). An optimal cutoff value of a CT score of 24.5 had a sensitivity of 85.6% and a specificity of 84.5% for the prediction of mortality. 2019-nCoV was more likely to infect elderly people with chronic comorbidities. CT findings of NCIP were featured by predominant ground glass opacities mixed with consolidations, mainly peripheral or combined peripheral and central distributions, bilateral and lower lung zones being mostly involved. A simple CT scoring method was capable to predict mortality.


Note From the Editor: Clade X, Coronavirus, and the Challenges of Global Health Security


title: Predicting the impacts of epidemic outbreaks on global supply chains: A simulation-based analysis on the coronavirus outbreak (COVID-19/SARS-CoV-2) case

text: Abstract Epidemic outbreaks are a special case of supply chain (SC) risks which is distinctively characterized by a long-term disruption existence, disruption propagations (i.e., the ripple effect), and high uncertainty. We present the results of a simulation study that opens some new research tensions on the impact of COVID-19 (SARS-CoV-2) on the global SCs. First, we articulate the specific features that frame epidemic outbreaks as a unique type of SC disruption risks. Second, we demonstrate how simulation-based methodology can be used to examine and predict the impacts of epidemic outbreaks on the SC performance using the example of coronavirus COVID-19 and anyLogistix simulation and optimization software. We offer an analysis for observing and predicting both short-term and long-term impacts of epidemic outbreaks on the SCs along with managerial insights. A set of sensitivity experiments for different scenarios allows illustrating the model’s behavior and its value for decision-makers. The major observation from the simulation experiments is that the timing of the closing and opening of the facilities at different echelons might become a major factor that determines the epidemic outbreak impact on the SC performance rather than an upstream disruption duration or the speed of epidemic propagation. Other important factors are lead-time, speed of epidemic propagation, and the upstream and downstream disruption durations in the SC. The outcomes of this research can be used by decision-makers to predict the operative and long-term impacts of epidemic outbreaks on the SCs and develop pandemic SC plans. Our approach can also help to identify the successful and wrong elements of risk mitigation/preparedness and recovery policies in case of epidemic outbreaks. The paper is concluded by summarizing the most important insights and outlining future research agenda.


title: Gilead and Moderna lead on coronavirus treatments

text: wo US biotech firms have positioned themselves as front-runners fighting the novel coronavirus, called SARS-CoV-2 On Feb 25, the US National Institutes of Health (NIH) said it had begun a Phase II clinical trial of remdesivir, an experimental small-molecule drug made by Gilead Sciences, for treatment of those infected with SARS-CoV-2 On the same day, Moderna said it had shipped its experimental coronavirus vaccine to the NIH, which will conduct a Phase I trial to assess its safety The entire process—from vaccine design, to manufacturing, to shipment—took only 7 weeks The news came just as the US Centers for Disease Control and Prevention warned that US communities should brace for “disruption to everyday life ” Gilead was able to move quickly because it had previously developed remdesivir to treat the Ebola virus The firm is now launching two of its own Phase III clinical trials of remdesivir, in addition to the [truncated]


title: “We've Cared for the Dead since We Started Caring”: COVID‐19 and Our Relationship to Public and Private Deathcare

text: The COVID‐19 pandemic has highlighted public organizations’ challenges related to deathcare Within the emergency management literature, and specifically within public administration, there is a gap when it comes to planning past death Using data from interviews with 35 municipal cemetery managers throughout the United States, I show how our unwillingness to talk about or plan for death, coupled with cemetery managers who are underfunded and often left out of emergency management planning processes, needs increased attention While many deathcare best practices were deployed to respond to the virus, cemetery managers often are not part of the planning process


title: A Hemodialysis Patient with Severe COVID-19 Pneumonia

text: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a novel coronavirus that has spread rapidly, resulting in a worldwide pandemic. Even though end-stage renal disease (ESRD) patients are particularly susceptible to COVID-19 infection and can develop severe to critical disease, there are limited studies and case reports about COVID-19 in ESRD patients. We report a case of a 63-year-old gentleman with ESRD on regular hemodialysis. We describe the clinical presentation of this patient, the diagnostic process, the laboratory and imaging investigations, as well as the course of treatment. He positively responded to a 14-day course of Lopinavir-Ritonavir, Ribavirin, Azithromycin, and Hydroxychloroquine.


title: Fighting COVID‐19 with Agility, Transparency, and Participation: Wicked Policy Problems and New Governance Challenges

text: Governments are being put to the test as they struggle with the fast and wide spread of COVID‐19. This article discusses the compelling challenges posed by the COVID‐19 pandemic by examining how this wicked problem has been managed by the South Korean government with agile‐adaptive, transparent actions to mitigate the surge of COVID‐19. Unlike many Western countries, South Korea has been able to contain the spread of COVID‐19 without a harsh forced lockdown of the epicenter of the virus. This essay argues that an agile‐adaptive approach, a policy of transparency in communicating risk, and citizens’ voluntary cooperation are critical factors. It also suggests that the South Korean government learned costly lessons from the MERS failure of 2015. This essay suggests ways that Western countries can manage future wicked problems such as COVID‐19 without paying too much cost and maintaining quality of life in open and free societies.


title: Feature Extraction Approaches for Biological Sequences: A Comparative Study of Mathematical Models

text: The number of available biological sequences has increased significantly in recent years due to various genomic sequencing projects, creating a huge volume of data. Consequently, new computational methods are needed to analyze and extract information from these sequences. Machine learning methods have shown broad applicability in computational biology and bioinformatics. The utilization of machine learning methods has helped to extract relevant information from various biological datasets. However, there are still several problems that motivate new algorithms and pipeline proposals, mainly involving feature extraction problems, in which extracting significant discriminatory information from a biological set is challenging. Considering this, our work proposes to study and analyze a feature extraction pipeline based on mathematical models (Numerical Mapping, Fourier, Entropy, and Complex Networks). As a case study, we analyze Long Non-Coding RNA sequences. Moreover, we divided this work into two studies, e.g., (I) we assessed our proposal with the most addressed problem in our review, e.g., lncRNA vs. mRNA; (II) we tested its generalization on different classification problems, e.g., circRNA vs. lncRNA. The experimental results demonstrated three main contributions: (1) An in-depth study of several mathematical models; (2) a new feature extraction pipeline and (3) its generalization and robustness for distinct biological sequence classification.


title: What Has Been the Impact of Covid-19 on Safety Culture?

text: Introduction Covid-19 has placed an unprecedented demand on healthcare systems worldwide. A positive safety culture is associated with improved patient safety and in turn patient outcomes. To date, no study has evaluated the impact of Covid-19 on safety culture. Methods The Safety Attitudes Questionnaire (SAQ) was used to investigate safety culture during Covid-19 at a large UK teaching hospital. Findings were compared with baseline data from 2017. Incident reporting from the year preceding the pandemic was also examined. Results Significant increases were seen in SAQ score for doctors and AHPs (p value) from baseline (p value). A decrease in SAQ was found in the nursing group. Largely due to perception of management and safety climate subscales. During Covid-19, on univariate regression analysis, female gender (p<0.001), age 40-49 years (p<0.01), non-white ethnicity (p<0.001), nursing job role (p<0.001) were all associated with lower SAQ scores. Training (p<0.001) and support (p<0.001) for redeployment were associated with higher SAQ scores. On multivariate analysis, non-disclosed gender (-0.13, -0.26-0.00), non-disclosed ethnicity (-0.11, -0.22-0.00), nursing role (-0.15, -0.24-0.06), and support (0.24, 0.07-0.4) persisted to significance. A significant decrease (p<0.003) was seen in error reporting after the onset of the Covid-19 pandemic. Discussion Differences in reported safety culture may reflect perception of risk due to: occupational exposure, job function, or access to support services. Reductions in incident reporting may be due to increased workload, change in nature of work, or changing safety attitudes. Targeted high-quality support for redeployed staff may help improve safety during future pandemics.


title: A systematic, unbiased mapping of CD8+ and CD4+ T cell epitopes in Yellow Fever vaccinees

text: Examining CD8+ and CD4+ T cell responses after primary Yellow Fever vaccination in a cohort of 210 volunteers, we have identified and tetramer-validated 92 CD8+ and 50 CD4+ T cell epitopes, many inducing strong and prevalent (i.e. immunodominant) T cell responses. Restricted by 40 and 14 HLA-class I and II allotypes, respectively, these responses have wide population coverage and might be of considerable academic, diagnostic and therapeutic interest. The broad coverage of epitopes and HLA overcame the otherwise confounding effects of HLA diversity and non-HLA background providing the first evidence of T cell immunodomination in humans. Also, double-staining of CD4+ T cells with tetramers representing the same HLA-binding core, albeit with different flanking regions, demonstrated an extensive diversification of the specificities of many CD4+ T cell responses. We suggest that this could reduce the risk of pathogen escape, and that multi-tetramer staining is required to reveal the true magnitude and diversity of CD4+ T cell responses. Our T cell epitope discovery approach uses a combination of 1) overlapping peptides representing the entire Yellow Fever virus proteome to search for peptides containing CD4+ and/or CD8+ T cell epitopes, 2) predictors of peptide-HLA binding to suggest epitopes and their restricting HLA allotypes, 3) generation of peptide-HLA tetramers to identify T cell epitopes, and 4) analysis of ex vivo T cell responses to validate the same. This approach is systematic, exhaustive, and can be done in any individual of any HLA haplotype. It is all-inclusive in the sense that it includes all protein antigens and peptide epitopes, and encompasses both CD4+ and CD8+ T cell epitopes. It is efficient and, importantly, reduces the false discovery rate. The unbiased nature of the T cell epitope discovery approach presented here should support the refinement of future peptide-HLA class I and II predictors and tetramer technologies, which eventually should cover all HLA class I and II isotypes. We believe that future investigations of emerging pathogens (e.g. SARS-CoV-2) should include population-wide T cell epitope discovery using blood samples from patients, convalescents and/or long-term survivors, who might all hold important information on T cell epitopes and responses.


title: Temporal and spatial characteristics of the spread of COVID-19 in Rio de Janeiro state and city

text: From the first cases detected in Wuhan, China, of infections by the disease of the new coronavirus, COVID-19, until the present moment of this pandemic, millions of people have already been infected and hundreds of thousands have died worldwide. The way in which the virus has been dispersed in Brazil, and more specifically in Rio de Janeiro, is the motivation of the present work. Our studies consist of analyzing temporal and spatial characteristics of the spread of COVID-19 in the municipalities of the state of Rio de Janeiro and in the neighborhoods of the state capital, based on open data published by the Health Departments of Governments of the State of RJ and the Municipality of Rio de Janeiro, covering the period from February 27, 2020 to April 27, 2020. For that, we use analysis of time evolution graphs and mappings of spatial distributions and statistics analysis of spatial correlation. Our results suggest that the initial stages of spreading the virus across the state occur exponentially, with specific regions with a higher concentration of rates of cases, deaths and recovered people. In addition, our qualitative and quantitative results, for the data considered, point out that the regions with the highest income average per capita have higher rates of confirmed cases and recovered people, however, the regions of higher lethality do not are found in these places, with several of these regions of high lethality in places of low income per capita. Our results reinforce the idea of creating specific and strategic plans for policies to combat the spread of COVID-19 in the various localities in Rio de Janeiro.


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title: Estimating the effective reproduction number of the 2019-nCoV in China

text: We estimate the effective reproduction number for 2019-nCoV based on the daily reported cases from China CDC. The results indicate that 2019-nCoV has a higher effective reproduction number than SARS with a comparable fatality rate.


title: Comparative Analysis of SARS-CoV2 with Special Emphasis on Genome Sequences

text: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus - 2 (SARS-CoV-2), was declared a global pandemic on 11th March, 2020 by World Health Organization As of now,27th May,2020, there are about 54,88,825 infected cases and 3,49,095 deaths globally Coronavirus samples collected from all the countries have been sequenced for advanced studies in a bid to understand the structure and functioning of the virus In our study we have tried working on every available sequence to setup both comparisons and co-relations There is no such available study as of now for reference and hence it can become a pioneer stone in this direction The mortality rate calculated turns out to be 9 19%,34 37% and 6 29% for SARS-2003, MERS-2012 and COVID-19 respectively The basic reproduction rate R0 was 2-5 for SARS-2003, 0 3-0 8 for MERS-2012 and 1 4-5 7 for COVID-19 We found out the relation between number of mutations and mortality as well as phylogenetic relations High number of mutations corresponded to higher mortality rate as in countries like Italy and Spain Alpha and Beta-coronaviruses show a common ancestor from which they descended Brazil and Iran have shown similar phylogenetic descent explaining their mortality rate India however showed a distant relation from the common ancestor of other genome sequences This study highlights the mutations of the SARS-CoV2 virus as well as sets up a comparison with the previous outbreaks Similar type of studies should be conducted when more genome samples are present These results can also contribute towards making an effective anti-viral therapy and vaccines


Bronchoalveolar specimen can help detect COVID-19 in suspicious case with negative PCR for nasopharyngeal specimen test


title: A single dose of ChAdOx1 MERS provides broad protective immunity against a variety of MERS-CoV strains

text: Middle East respiratory syndrome coronavirus (MERS-CoV) continues to infect humans via the dromedary camel reservoir and can transmit between humans, most commonly via nosocomial transmission. Currently, no licensed vaccine is available. Previously we showed that vaccination of transgenic mice with ChAdOx1 MERS, encoding the MERS S protein, prevented disease upon lethal challenge. In the current study we show that rhesus macaques seroconverted rapidly after a single intramuscular vaccination with ChAdOx1 MERS. Upon MERS-CoV challenge vaccinated animals were protected against respiratory injury and pneumonia and had a reduction in viral load in lung tissue of several logs. Furthermore, we did not detect MERS-CoV replication in type I and II pneumocytes of ChAdOx1 MERS vaccinated animals. A prime-boost regimen of ChAdOx1 MERS boosted antibody titers, and viral replication was completely absent from the respiratory tract tissue of these rhesus macaques. Finally, we investigated the ability of ChAdOx1 MERS to protect against six different MERS-CoV strains, isolated between 2012 to 2018, from dromedary camels and humans in the Middle East and Africa. Antibodies elicited by ChAdOx1 MERS in rhesus macaques were able to neutralize all MERS-CoV strains. Vaccination of transgenic hDPP4 mice with ChAdOx1 MERS completely protected the animals against disease and lethality for all different MERS-CoV strains. The data support further clinical development of ChAdOx1 MERS supported by CEPI. One Sentence Summary Prime-only vaccination with ChAdOx1 MERS provides protective immunity against HCoV-EMC/2012 replication in rhesus macaques, and a wide variety of MERS-CoV strains in mice.


title: WeChat, a Chinese social media, may early detect the SARS-CoV-2 outbreak in 2019

text: We plotted daily data on the frequencies of keywords related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from WeChat, a Chinese social media. Using 'Feidian', Chinese abbreviation for SARS, may detect the SARS-CoV-2 outbreak in 2019 two weeks earlier. WeChat offered a new approach to early detect disease outbreaks.


title: Sequence variation among SARS-CoV-2 isolates in Taiwan

text: Taiwan experienced two waves of imported cases of coronavirus disease 2019 (COVID-19), first from China in January to late February, followed by those from other countries starting in early March. Additionally, several cases could not be traced to any imported cases and were suspected as sporadic local transmission. Twelve full viral genomes were determined in this study by Illumina sequencing either from virus isolates or directly from specimens, among which 5 originated from clustered infections. Phylogenetic tree analysis revealed that these sequences were in different clades, indicating that no major strain has been circulating in Taiwan. A deletion in open reading frame 8 was found in one isolate. Only a 4-nucleotide difference was observed among the 5 genomes from clustered infections.


title: Interfacial Water Molecules Make RBD of SPIKE Protein and Human ACE2 to Stick Together

text: A novel coronavirus (SARS-CoV-2; COVID-19) that initially originates from Wuhan province in China has emerged as a global pandemic, an outbreak that started at the end of 2019 which claims 431,192 (Date: 15th June 2020 (https://covid19.who.in) life till now. Since then scientists all over the world are engaged in developing new vaccines, antibodies, or drug molecules to combat this new threat. Here in this work, we performed an in-silico analysis on the protein-protein interactions between the receptor-binding (RBD) domain of viral SPIKE protein and human angiotensin-converting enzyme 2 (hACE2) receptor to highlight the key alteration that happened from SARS-CoV to SARS-CoV-2. We analyzed and compared the molecular differences between these two viruses by using various computational approaches such as binding affinity calculations, computational alanine, and molecular dynamics simulations. The binding affinity calculations show SARS-CoV-2 binds little more firmly to the hACE2 receptor than that of SARS-CoV. Analysis of simulation trajectories reveals that enhanced hydrophobic contacts or the van der Waals interaction play a major role in stabilizing the protein-protein interface. The major finding obtained from molecular dynamics simulations is that the RBD-ACE2 interface is populated with water molecules and interacts strongly with both RBD and ACE2 interfacial residues during the simulation periods. We also emphasize that the interfacial water molecules play a critical role in binding and maintaining the stability of the RBD/hACE2 complex. The water-mediated hydrogen bond by the bridge water molecules is crucial for stabilizing the RBD and ACE2 domains. The structural and dynamical features presented here may serve as a guide for developing new drug molecules, vaccines, or antibodies to combat the COVID-19 pandemic.


title: Complexity in SARS-CoV-2 genome data: Price theory of mutant isolates

text: SARS-CoV-2 is a highly virulent and deadly RNA virus causing the Covid-19 pandemic and several deaths across the world. The pandemic is so fast that any concrete theory of sudden widespread of this disease is still not known. In this work, we studied and analyzed a large number of publicly available SARS-CoV-2 genomes across the world using the multifractal approach. The mutation events in the isolates obey the Markov process and exhibit very high mutational rates, which occur in six specific genes and highest in orf1ab gene, leading to virulent nature. f (α) analysis indicated that the isolates are highly asymmetric (left-skewed), revealing the richness of complexity and dominance by large fluctuations in genome structure organization. The values of Hq and Dq are found to be significantly large, showing heterogeneous genome structure self-organization, strong positive correlation in organizing the isolates, and quite sensitive to fluctuations in and around it. We then present multiple-isolates hosts-virus interaction models, and derived Price equation for the model. The phase plane analysis of the model showed asymptotic stability type bifurcation. The competition among the mutant isolates drives the trade-off of the dominant mutant isolates, otherwise confined to the present hosts.


title: Gene expression and in situ protein profiling of candidate SARS-CoV-2 receptors in human airway epithelial cells and lung tissue

text: In December 2019, SARS-CoV-2 emerged causing the COVID-19 pandemic. SARS-CoV, the agent responsible for the 2003 SARS outbreak, utilizes ACE2 and TMPRSS2 host molecules for viral entry. ACE2 and TMPRSS2 have recently been implicated in SARS-CoV-2 viral infection. Additional host molecules including ADAM17, cathepsin L, CD147, and GRP78 may also function as receptors for SARS-CoV-2. To determine the expression and in situ localization of candidate SARS-CoV-2 receptors in the respiratory mucosa, we analyzed gene expression datasets from airway epithelial cells of 515 healthy subjects, gene promoter activity analysis using the FANTOM5 dataset containing 120 distinct sample types, single cell RNA sequencing (scRNAseq) of 10 healthy subjects, immunoblots on multiple airway epithelial cell types, and immunohistochemistry on 98 human lung samples. We demonstrate absent to low ACE2 promoter activity in a variety of lung epithelial cell samples and low ACE2 gene expression in both microarray and scRNAseq datasets of epithelial cell populations. Consistent with gene expression, rare ACE2 protein expression was observed in the airway epithelium and alveoli of human lung. We present confirmatory evidence for the presence of TMPRSS2, CD147, and GRP78 protein in vitro in airway epithelial cells and confirm broad in situ protein expression of CD147 in the respiratory mucosa. Collectively, our data suggest the presence of a mechanism dynamically regulating ACE2 expression in human lung, perhaps in periods of SARS-CoV-2 infection, and also suggest that alternate receptors for SARS-CoV-2 exist to facilitate initial host cell infection.


title: Serum SARS-COV-2 Nucleocapsid Proteinï¼A Sensitivity and Specificity Early Diagnostic Marker for SARS-COV-2 Infection

text: Objective: This study aimed to explore the diagnostic value of serum severe acute respiratory syndrome coronavirus 2 (SARSCoV2) nucleocapsid(N) protein assay in the early stage of SARSCOV2 infection. Method: Serum N protein in SARSCOV2 infected patients and non SARSCOV2 infected population was measured by enzyme-linked immunosorbent assay (ELISA) double antibody sandwich assay. Colloidal gold immunochromatography assay is used to detect serum N protein antibodies in the above population. Results: 50 cases of SARSCoV2 nucleic acid positive and SARSCoV2 antibody negative patients had a serum N protein positive rate of 76%, including 2% with a concentration of 10.00~49.99 pg / mL, 8% with a concentration of 50.00~99.99 pg / mL, 22% with a concentration of 100.00 ~299.99 pg/mL, and 44% with a concentration [≥]300.00 pg / mL. 37 samples of patients with serum SARSCoV2 antibody positive after infection had a serum SARSCoV2 N protein positive rate of 2.7%, of which 2.7% had the concentration of 10.00~49.99 pg / mL and 0% had the concentration of 50.00~99.99 pg / mL, 100.00 ~299.99 pg / mL, and [≥]300.00 pg / mL. Serum N protein test results of 633 non SARSCOV2 infected patients including pregnant women, other respiratory infections, and increased rheumatoid factor were all negative, having a serum N protein concentration less than 10.00 pg/mL, with a specificity of 100%. Using SPSS 19.0 to calculate the receiver operating characteristic curve, the area under the curve was 0.9756 (95% confidence interval 0.9485~1.000, p <0.0001), sensitivity and specificity were 92% (95% confidence interval 81.16% to 96.85%) and 96.84% (95% confidence interval 95.17% to 97.15%). The best CUTOFF value is 1.850 pg / mL. Conclusion: The measurement of SARSCOV2 serum N protein has a high diagnostic value for the infected patients before the antibody appears, and shortens the window period of serological diagnosis. The laboratory needs to establish an individual CUTOFF value according to purpose of the application.


title: A COVID-19 Infection Risk Model for Frontline Health Care Workers

text: The number of confirmed COVID-19 cases admitted in hospitals is continuously increasing in the Philippines. Frontline health care workers are faced with imminent risks of getting infected. In this study, we formulate a theoretical model to calculate the risk of being infected in health care facilities considering the following factors: the average number of encounters with a suspected COVID-19 patient per hour; interaction time for each encounter; work shift duration or exposure time; crowd density, which may depend on the amount of space available in a given location; and availability and effectiveness of protective gears and facilities provided for the frontline health care workers. Based on the simulation results, we recommend the following: (i) decrease the rate of patient encounter per frontline health care worker, e.g., maximum of three encounters per hour in a 12-hour work shift duration; (ii) decrease the interaction time between the frontline health care worker and the patients, e.g., less than 40 minutes for the whole day; (iii) increase the clean and safe space for social distancing, e.g., maximum of 10% crowd density, and if possible, implement compartmentalization of patients; and/or (iv) provide effective protective gears and facilities, e.g., 95% effective, that the frontline health care workers can use during their shift. Moreover, the formulated model can be used for other similar scenarios, such as identifying infection risk in public transportation, school classroom settings, offices, and mass gatherings.


title: Strict Physical Distancing May Be More Efficient: A Mathematical Argument for Making Lockdowns Count

text: COVID-19 created a global public health and economic emergency. Policymakers acted quickly and decisively to contain the spread of disease through physical distancing measures. However, these measures also impact physical, mental and economic well-being, creating difficult trade-offs. Here we use a simple mathematical model to explore the balance between public health measures and their associated social and economic costs. Across a range of cost-functions and model structures, commitment to intermittent and strict social distancing measures (lockdowns) leads to better overall outcomes than temporally consistent implementation of moderate physical distancing measures. With regard to the trade-offs that policy makers may soon face, our results emphasize that economic and health out comes do not exist in full competition. Compared to consistent moderation, intermittently strict policies can better mitigate the impact of the pandemic on both of these priorities for a range of plausible utility functions.


docid: fwquzrmo

title: Evaluation of Sample Pooling for Screening of SARS-CoV-2

text: Background: The coronavirus disease (COVID-19) pandemic has revealed the global public health importance of robust diagnostic testing. To overcome the challenge of nucleic acid (NA) extraction and testing kit availability efficient method is urgently needed. Objectives: To establish an efficient, time and resource-saving and cost-effective methods, and to propose an ad hoc pooling approach for mass screening of SARS-CoV-2 Methods: Direct clinical sample and NA pooling approach was used for the standard reverse transcriptase polymerase chain reaction (RT-PCR) test of the SARS CoV-2 targeting the envelop (E) and open reading frame (ORF1ab) genomic region of the virus. In this approach, experimental pools were created using SARS CoV-2 positive clinical samples spiked with up to 9 negative samples prior to NA extraction step to have a final extraction volume of 200L (maximum dilution factor of 10). Viral NA was also subsequently extracted from each pool and tested using the SARS CoV-2 RT-PCR assay. Results: We found that a single positive sample can be amplified and detected in pools of up to 7 samples depending on the ct value of the original sample, corresponding to high, medium, and low SARS CoV-2 viral copies/reaction. However, to minimize false negativity of the assay with pooling strategies and with unknown false negativity rate of the assay under validation, we recommend poling of 4 in 1 using the standard protocols of the assay, reagents and equipment. The predictive algorithm indicated a pooling ratio of 4 in 1 was expected to retain accuracy of the test irrespective of the ct value (relative RNA copy number) of the sample spiked and result in a 237% increase in testing efficiency. Conclusions: The approaches showed its concept in easily customized and resource-saving manner and would allow expanding of current screening capacities and enable the expansion of detection in the community.


title: Covid-19 infection and attributable mortality in UK Long Term Care Facilities: Cohort study using active surveillance and electronic records (March-June 2020)

text: Background: Rates of Covid-19 infection have declined in many countries, but outbreaks persist in residents of long-term care facilities (LTCFs) who are at high risk of severe outcomes. Epidemiological data from LTCFs are scarce. We used population-level active surveillance to estimate incidence of, and risk factors for Covid-19, and attributable mortality in elderly residents of LTCFs. Methods: Cohort study using individual-level electronic health records from 8,713 residents and daily counts of infection for 9,339 residents and 11,604 staff across 179 UK LTCFs. We modelled risk factors for infection and mortality using Cox proportional hazards and estimated attributable fractions. Findings: 2,075/9,339 residents developed Covid-19 symptoms (22.2% [95% confidence interval: 21.4%; 23.1%]), while 951 residents (10.2% [9.6%; 10.8%]) and 585 staff (5.0% [4.7%; 5.5%]) had laboratory confirmed infections. Confirmed infection incidence in residents and staff respectively was 152.6 [143.1; 162.6] and 62.3 [57.3; 67.5] per 100,000 person-days. 121/179 (67.6%) LTCFs had at least one Covid-19 infection or death. Lower staffing ratios and higher occupancy rates were independent risk factors for infection. 1,694 all-cause deaths occurred in 8,713 (19.4% [18.6%; 20.3%]) residents. 217 deaths occurred in 607 residents with confirmed infection (case-fatality rate: 35.7% [31.9%; 39.7%]). 567/1694 (33.5%) of all-cause deaths were attributable to Covid-19, 28.0% of which occurred in residents with laboratory-confirmed infection. The remainder of excess deaths occurred in asymptomatic or symptomatic residents in the context of limited testing for infection, suggesting substantial under-ascertainment. Interpretation: 1 in 5 residents had symptoms of infection during the pandemic, but many cases were not tested. Higher occupancy and lower staffing levels increase infection risk. Disease control measures should integrate active surveillance and testing with fundamental changes in staffing and care home occupancy to protect staff and residents from infection. Funding: Economic and Social Research Council [ES/V003887/1].


title: A burning question: Can natural climate solutions and carbon financing save the lion from extinction?

text: Lions (Panthera leo) in Africa have lost nearly half their population in just the last two decades, and effective management of the protected areas where lions live will cost an estimated USD $1 B/year in new funding. We explore the potential for natural climate solutions to fill this funding gap by introducing early dry season fire management programs to generate carbon credits. Potential carbon revenue from a single method (avoided emissions) or from multiple sequestration methods could provide annual revenue of USD $59.6-$655.9 M (at USD $5/ton) or USD $155.0 M–$1.7 B (at USD $13/ton). The top twenty PAs with lions and the greatest PCR could generate annually between USD $2.0–$57.5 M per PA, and PAs with the greatest potential for lion numbers between USD $1.5–$44.4 M per PA. We highlight priorities for investments and pilot projects to realize this potential in Africa.


title: CEPI commits $384 million to Novavax’s COVID-19 vaccine

text: The Coalition for Epidemic Preparedness Innovations (CEPI) will commit up to $384 million for manufacturing and clinical testing of Novavax’s nanoparticle-based COVID-19 vaccine Novavax was one of the first companies to disclose that it was working on a COVID-19 vaccine in January, and a Phase I clinical trial on the safety of that experimental vaccine will begin in Australia this month That trial will make it one of the first 10 vaccines to enter clinical testing since the pandemic began CEPI, a nonprofit organization that funds infectious disease vaccine development, counts at least 115 vaccine programs underway for COVID-19 CEPI has so far provided funding to nine of them Before now, the coalition had invested $58 million across all its COVID-19 vaccine efforts, including an initial $4 million for Novavax The new, $384 million commitment to Novavax is the largest single investment CEPI has ever made in a vaccine


title: A Network-Based Stochastic Epidemic Simulator: Controlling COVID-19 with Region-Specific Policies

text: In this work, we present an open-source stochastic epidemic simulator, calibrated with extant epidemic experience of COVID-19. Our simulator incorporates information ranging from population demographics and mobility data to health care resource capacity, by region, with interactive controls of system variables to allow dynamic and interactive modeling of events. The simulator can be generalized to model the propagation of any disease, in any territory, but for this experiment was customized to model the spread of COVID-19 in the Republic of Kazakhstan, and estimate outcomes of policy options to inform deliberations on governmental interdiction policies.


title: Comparative analyses revealed reduced spread of COVID-19 in malaria endemic countries

text: In late 2019, SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection started in Hubei province of China and now it has spread like a wildfire in almost all parts of the world except some. WHO named the disease caused by SARS-CoV-2 as COVID-19 (CoronaVirus Disease-2019). It is very intriguing to see a mild trend of infection in some countries which could be attributed to mitigation efforts, lockdown strategies, health infrastructure, demographics and cultural habits. However, the lower rate of infection and death rates in mostly developing countries, which are not placed at higher levels in terms of healthcare facilities, is a very surprising observation. To address this issue, we hypothesize that this lower rate of infection is majorly been observed in countries which have a higher transmission/prevalence of protozoan parasite borne disease, malaria. We compared the COVID-19 spread and malaria endemicity of 108 countries which have shown at least 200 cases of COVID-19 till 18th April 2020. We found that the number of COVID-19 cases per million population correlates negatively with the malaria endemicity of respective countries. The malaria free countries not only have higher density of COVID-19 infections but also the higher case fatality rates as compared to highly malaria endemic countries. We also postulate that this phenomenon is due to natural immune response against malaria infection, which is providing a heterologous protection against the virus. Unfortunately, there is no licensed vaccine against SARS-CoV-2 yet, but this information will be helpful in design of future strategies against fast spreading COVID-19 disease.


Corticosteroid therapy for severe COVID-19 pneumonia: optimal dose and duration of administration


title: Self-collection: an appropriate alternative during the SARS-CoV-2 pandemic

text: BACKGROUND Swabs for SARS-CoV-2 are routinely collected by health care workers, putting them at risk of infection and requiring use of personal protective equipment (PPE). Self-collected swabs offer many advantages provided detection rate of SARS-CoV-2 and other respiratory viruses is not compromised. METHODS In a prospective study, patients attending dedicated COVID-19 collection clinics were offered the option to first self-collect (SC) nasal and throat swabs prior to health worker collection (HC). Two different laboratory services participated, with HC at Site 1 collecting nasal and throat swabs and at Site 2 nasopharyngeal (NP) and throat swabs. Samples were analysed for SARS-CoV-2 as well as common respiratory viruses. Concordance of results between methods was assessed using Cohens kappa (κ). RESULTS Of 236 patients sampled by HC and SC, 25 had COVID-19 (24 by HC and 25 by SC) and 63 had other respiratory viruses (56 by HC and 58 by SC). SC was highly concordant with HC (κ = 0.890) for all viruses including SARS-CoV-2 and more concordant than HC to positive results by any method (κ = 0.959 vs 0.933). CONCLUSIONS Self-collection of throat and nasal swabs offers a reliable alternative to health worker collection for the diagnosis of SARS-CoV-2 and other common respiratory viruses. High viral load of SARS-CoV-2 throughout the respiratory tract and sensitive molecular methods may explain these findings. Self-collection also provides patients with easier access to testing, reduces the exposure of the community and health workers to those undergoing testing and reduces the requirement for PPE.


title: High seroreactivity against SARS-CoV-2 Spike epitopes in a pre SARS-CoV-2 cohort: implications for antibody testing and vaccine design

text: Little is known about the quality of polyclonal antibody responses in COVID-19 patients, and how it correlates with disease severity or patients' prior exposure to other pathogens. The whole polyclonal antibody repertoire in a retrospective cohort of 538 individuals was mapped against SARS-CoV-2 spike (S) glycoprotein, the main target of antibody immune responses in SARS-CoV-2 infection. Bioinformatic predictions identified 15 major B cell epitopes for S of SARS-CoV-2. Several epitopes localised in RBD of S including those spanning the ACE2-binding site, the highly conserved cryptic epitope of the neutralizing antibody of SARS-CoV, and fusion/entry domains of HR1 and HR2 of S protein of SARS-CoV-2. Intriguingly, some of these epitopes have cross-reactivity to antigens of common pathogens, potentially affecting SARS-CoV-2 infection outcome. High level of anti-Spike SARS-CoV-2 seroreactivity in populations with no history of exposure to SARS-CoV-2 is of clinical relevance and could underpin better understanding of COVID-19 pathophysiology in different populations and provide a blueprint for design of effective vaccines and developing better strategies for antibody testing.


title: The Heritage of Pathogen Pressures and Ancient Demography in the Human Innate-Immunity CD209/CD209L Region

text: The innate immunity system constitutes the first line of host defense against pathogens. Two closely related innate immunity genes, CD209 and CD209L, are particularly interesting because they directly recognize a plethora of pathogens, including bacteria, viruses, and parasites. Both genes, which result from an ancient duplication, possess a neck region, made up of seven repeats of 23 amino acids each, known to play a major role in the pathogen-binding properties of these proteins. To explore the extent to which pathogens have exerted selective pressures on these innate immunity genes, we resequenced them in a group of samples from sub-Saharan Africa, Europe, and East Asia. Moreover, variation in the number of repeats of the neck region was defined in the entire Human Genome Diversity Panel for both genes. Our results, which are based on diversity levels, neutrality tests, population genetic distances, and neck-region length variation, provide genetic evidence that CD209 has been under a strong selective constraint that prevents accumulation of any amino acid changes, whereas CD209L variability has most likely been shaped by the action of balancing selection in non-African populations. In addition, our data point to the neck region as the functional target of such selective pressures: CD209 presents a constant size in the neck region populationwide, whereas CD209L presents an excess of length variation, particularly in non-African populations. An additional interesting observation came from the coalescent-based CD209 gene tree, whose binary topology and time depth (∼2.8 million years ago) are compatible with an ancestral population structure in Africa. Altogether, our study has revealed that even a short segment of the human genome can uncover an extraordinarily complex evolutionary history, including different pathogen pressures on host genes as well as traces of admixture among archaic hominid populations.


title: Early cases of COVID-19 in Tokyo and occupational health

text: The coronavirus disease 2019 (COVID-19) has spread rapidly across the globe, presenting severe challenges to societies Gaining a better understanding of patient demographics is essential to develop measures to counteract such spreading In this context, from a viewpoint of occupational health, we analyzed the publicly available data on patients diagnosed with COVID-19 in Tokyo, which reported the highest number of cases in Japan A total of 243 cases aged 20 years or older (excluding students) were recorded between January 14 and March 27, 2020 Of 233 cases excluding 10 cases of the first cluster, 162 were men and 176 were of working age (20 to 69 years) Of 203 cases with valid information on employment status, 151 (74%) were workers: 114 employees, 31 self-employed, and 6 medical staff Of the working patients, the majority were male: 72% in employed and 87% in self-employed These data suggest the importance of occupational health in controlling the spread of COVID-19 In April 2020, a state of emergency was declared in response to a surge in the number of cases, especially in metropolitan areas A working schedule associated with lower risks of infection, including telework and flexible working hours, should be rigorously promoted to minimize human-to-human contact Such policies, along with the implementation of effective measures to protect essential workers from infection, overwork, and stigma, would ensure the smooth running of society amidst the present crisis