title: Treatment with Arbidol and Moxifloxacin in Ordinary and Severe Adult Patients Infected with COVID-19

text: Background An outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely spread. We aim to investigate the therapeutic effect of arbidol and moxifloxacin in patients infected with SARS-CoV-2. Methods We collected and analyzed data on 94 patients with COVID-19 including 27 severe patients at the Intensive Care Unit (ICU) and 74 ordinary patients at general isolation ward in Wuhan Xiehe Hospital, from February 15, 2020 to March 15, 2020. All patients were treated with arbidol (100mg each time, three times a day for 14 days) and moxifloxacin (0.4g each time, once a day for 7-14 days). Other data was also collected including demographic data, symptoms, laboratory findings, treatments and clinical outcomes. Results In basic characteristics, compared with the ordinary patients, the severe patients were older (median age was 63.0 years V.S 57.0 years, p=0.03), had higher proportion of hypertension (30% V.S 9%, p=0.03), higher possibility of getting fatigue and/or myalgia (26% V.S 6%, p=0.03), and had more obvious dyspnea symptom (26% V.S 3%, p=0.006). In regarding to laboratory results, we found the severe patients have higher white blood cell counts (p=0.003), neutrophil counts (p=0.007), higher levels of D-dimer (p<0.001), ALT (p<0.001) and AST (p=0.013) than the ordinary patients. After treatment of arbidol and moxifloxacin for one week, the rates of SARS-CoV-2 nucleic acid turning negative were 69.2% in the severe group and 77.8% in the ordinary group. A peculiar phenomenon was that IL-6 stands out among the cytokines in both groups, and higher in severe group than the ordinary one (p=0.011). After treating with arbidol and moxifloxacin for one week, IL-6 decreased significantly in severe group (p=0.023). Conclusion In summary, we proved the treatment of arbidol and moxifloxacin could be helpful in reducing viral load and inflammation during SARS-CoV2 infection, especially for negatively regulating fatal inflammation in severe COVID-19 patients. However, more evidence awaits further clinical verification.


title: Hydroxychloroquine inhibits trained immunity - implications for COVID-19

text: SARS-CoV-2 infection can cause severe disease for which currently no specific therapy is available. The use of hydroxychloroquine to prevent or treat SARS-CoV-2 infection is controversial and its mode of action poorly understood. We demonstrate that hydroxychloroquine inhibits trained immunity at the functional and epigenetic level and is accompanied by profound changes in the cellular lipidome as well as reduced expression of interferon-stimulated genes. Trained immunity comprises a functional adaptation induced by epigenetic reprogramming which facilitates the anti-viral innate immune response. Our findings therefore suggest that hydroxychloroquine may not have a beneficial effect on the anti-viral immune response to SARS-CoV-2.


title: Current strategies and approaches in combating SARS-CoV-2 virus that causes COVID-19

text: The pandemic spread of severe acute respiratory syndrome coronavirus (SARS-CoV-2) that causes COVID-19 calls for global health emergency with wide prevalence across 94 countries, and around 3073 deaths reported in china on 7thMarch 2020 which created red alert zone in the country. It was further noticed other than China, countries like the republic of Korea ranked first with 6767 cases, Italy with 4747 and Iran with 3513 cases. The spread of COVID-19 made a historical transition between December 2019 to March 2020 by extending the paradigm to a newer territory every day with the highest predicted reproductive number <2. Hence, while combating the epidemic spread, there are spectra of strategies that require crucial validation, some of which include drug repurposing, enzyme inhibition, target drug delivery etc. Among these, the category of drugs called enzyme inhibitors has a unique opportunity in the process of new drug discovery as these enzymes possess structural versatility starting from the host viral interface and up to the release of a new virus. Drugs entrapped within liposomes are highly effective against intracellular microorganisms as per published observations. Regulatory authorities like World Health Organization (WHO) and Centre for disease control and prevention (CDC) strongly recommend the need for the PPE’s like N95 respirator to avoid person to person contact. In this context, Electrospun Nanofiber Technology (ENT) offers ultrathin fibres (20-200nm) with close proximity of 99.97% of high efficient air filtration. Fabrication of ultrafine nano mask by utilizing electospun technology will surely benefit millions of people in a time-dependent manner.


Breaking News: A COVID-19 Success Story, Full of Hope


title: Functional and Genetic Analysis of Viral Receptor ACE2 Orthologs Reveals a Broad Potential Host Range of SARS-CoV-2

text: The pandemic of Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major global health threat. Epidemiological studies suggest that bats are the natural zoonotic reservoir for SARS-CoV-2. However, the host range of SARS-CoV-2 and intermediate hosts that facilitate its transmission to humans remain unknown. The interaction of coronavirus with its host receptor is a key genetic determinant of host range and cross-species transmission. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as the receptor to enter host cells in a species-dependent manner. It has been shown that human, palm civet, pig and bat ACE2 can support virus entry, while the murine ortholog cannot. In this study, we characterized the ability of ACE2 from diverse species to support viral entry. We found that ACE2 is expressed in a wide range of species, with especially high conservation in mammals. By analyzing amino acid residues of ACE2 critical for virus entry, based on structure of SARS-CoV spike protein interaction with human, bat, palm civet, pig and ferret ACE2, we identified approximately eighty ACE2 proteins from mammals that could potentially mediate SARS-CoV-2 entry. Functional assays showed that 44 of these mammalian ACE2 orthologs, including those of domestic animals, pets, livestock, and animals commonly found in zoos and aquaria, could bind SARS-CoV-2 spike protein and support viral entry. In contrast, New World monkey ACE2 orthologs could not bind SARS-CoV-2 spike protein and support viral entry. We further identified the genetic determinant of New World monkey ACE2 that restricts viral entry using genetic and functional analyses. In summary, our study demonstrates that ACE2 from a remarkably broad range of species can facilitate SARS-CoV-2 entry. These findings highlight a potentially broad host tropism of SARS-CoV-2 and suggest that SARS-CoV-2 might be distributed much more widely than previously recognized, underscoring the necessity to monitor susceptible hosts to prevent future outbreaks.


title: Retrospective Clinical Evaluation of Four Lateral Flow Assays for the Detection of SARS-CoV-2 Antibodies

text: Coronavirus disease 2019 (COVID-19) is a potentially life-threatening respiratory infection caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), for which numerous serologic assays are available. In a CLIA laboratory setting, we used a retrospective sample set (n = 457) to evaluate two lateral flow immunoassays (LFIAs; two iterations of Rapid Response COVID-19 Test Cassette, BTNX Inc.) and a subset of to evaluate SARS-COV-2 IgG/IgM Rapid Test, ACON Laboratories (n = 200); and Standard Q COVID-19 IgM/IgG Duo, SD BIOSENSOR (n = 155) for their capacity to detect of SARS-CoV-2 IgG. In a cohort of primarily hospitalized patients with RT-PCR confirmed COVID-19, the BTNX assays demonstrated 95% and 92% agreement with the Abbott SARS-CoV-2 IgG assay and sensitivity was highest at [≥] 14 days from symptom onset [BTNX kit 1, 95%; BTNX kit 2, 91%]. ACON and SD assays demonstrated 99% and 100% agreement with the Abbott assay at [≥] 14 days from symptom onset. Specificity was measured using 74 specimens collected prior to SARS-CoV-2 circulation in the United States and 31 cross-reactivity challenge specimens, including those from patients with a history of seasonal coronavirus infection and was 98% for BTNX kit 1 and ACON and 100% for BTNX kit 2 and SD. Taken with data from EUA assays, these results suggest that LFIAs may provide adequate results for rapid detection of SARS-CoV-2. Replicating these results in fingerstick blood in outpatient populations, would further support the possibility that LFIAs may be useful to increase access to serologic testing.


title: Oral epithelial expression of angiotensin converting enzyme-2: Implications for COVID-19 diagnosis and prognosis

text: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) uses the angiotensin converting enzyme (ACE)-2 as the host receptor for target cell entry. The extent and distribution of ACE-2 has been associated with the clinical symptoms of coronavirus disease (COVID)-19. Here we show by immunofluorescence analysis that the ACE2 is abundantly expressed in oral mucosa, particularly in the surface epithelial cells suggesting that these cells could represent sites of entry for SARS-CoV-2. Further, together with the reports on ACE2 ectodomain shedding, we discuss the rationale for the hypothesis that the ACE-2 measurement in saliva could be a marker for COVID-19 infection during early phase following SARS-CoV-2 exposure.


title: Clinical and Radiological Evaluations of COVID-19 Patients with Anosmia: Preliminary Report.

text: Objective: To investigate clinical and radiological features of olfactory clefts of patients with mild coronavirus disease 2019 (COVID-19). Methods: Sixteen COVID-19 patients were recruited. The epidemiological and clinical data were extracted. Nasal complaints were assessed through the sino-nasal outcome test 22 (SNOT-22). Patients underwent psychophysical olfactory testing, olfactory cleft examination and CT-scan. Results: Sixteen anosmic patients were included. The mean Sniffin Sticks score was 4.6+/-1.7. The majority of patients had no endoscopical abnormality, with a mean olfactory cleft endoscopy score of 0.6+/-0.9. The olfactory clefts were opacified in 3 patients on the CT-scan. The mean radiological olfactory cleft score was 0.7+/-0.8. There were no significant correlations between clinical, radiological and psychophysical olfactory testing. Conclusion: The olfactory cleft of anosmic COVID-19 patients is free regarding endoscopic examination and imaging. The anosmia etiology would be not related to edema of the olfactory cleft.


title: Risk Factors for COVID-19 versus non-COVID-19 related in-hospital and community deaths by Local Authority District in Great Britain

text: Objectives: To undertake a preliminary hypothesis-generating analysis exploring putative risk factors for coronavirus diseae 2019 (COVID-19) population-adjusted deaths, compared with non-COVID-19 related deaths, at a local authority district (LAD) level in hospital, care homes and at home. Design: Ecological retrospective cohort study Setting Local authority districts (LADs) in England, Scotland and Wales (Great Britain (GB)). Participants All LAD deaths registered by week 16 of 2020. Main Outcome Measures Death registration where COVID-19 is mentioned as a contributing factor per 100,000 people in all settings, and in i) cares homes, ii) hospitals or iii) home only, in comparison to non-COVID-19 related deaths. Results Across GB by week 16 of 2020, 20,684 deaths had been registered mentioning COVID-19, equivalent to 25.6 per 100,000 people. Significant risk factors for LAD COVID-19 death in comparison to non-COVID-19 related death were air pollution and proportion of the population who were female. Significant protective factors were higher air temperature and proportion of the population who were ex-smokers. Conversely, for all COVID-19 unrelated deaths in comparison to COVID-19 deaths, higher rates of communal living, higher population rates of chronic kidney disease, chronic obstructive pulmonary disease, cerebrovascular disease deaths under 75 and dementia were predictive of death, whereas, higher rates of flight passengers was protective. Looking at individual setttings, the most notable findings in care homes was Scotland being a significant risk factor for COVID-19 related deaths compared to England. For hospital setting, the proportion of the population who were from black and Asian minority ethnic (BAME) groups significantly predicted COVID-19 related death. Conclusions This is the first study within GB to assess COVID-19 related deaths in comparison to COVID-19 unrelated deaths across hospital, care homes and home combined. As an ecological study, the results cannot be directly extrapolated to individuals. However, the analysis may be informative for public health policy and protective measures. From our hypothesis-generating analysis, we propose that air pollution is a significant risk factor and high temperature a significant protective factor for COVID-19 related deaths. These factors cannot readily be modelled at an individual level. Scottish local authorities and local authorities with a higher proportion of individuals of BAME origin are potential risk factors for COVID-19 related deaths in care homes and in hospitals, respectively. Altogether, this analysis shows the benefits of access to high quality open data for public information, public health policy and further research.


title: Successful contact tracing systems for COVID-19 rely on effective quarantine and isolation

text: Contact tracing is a key tool in the fight against COVID-19. Its effectiveness depends on the ability of traced contacts to quarantine and then isolate on symptom onset. We show that these factors crucially affect the reduction in the effective transmission number, but make it difficult to measure the effectiveness of the system using routinely collected data. This implies that provision of universal support systems to enable people to quarantine and isolate effectively, coupled with investment in trained public health professionals to undertake contact tracing, are crucial to success. We predict that a high-quality, rapid contact tracing system with strong support structures in place, combined with moderate social distancing measures, is required to contain the spread of COVID-19.


title: Lattice Model of Mitigated Epidemic

text: We study a statistical lattice model of a mitigated epidemic. The level of mitigation, defined by measures to slow down the spread of the infection, is characterized by the infection transmissivity. It is determined by people's mobility, frequency of contacts, and probability to catch the virus from a contact. In the absence of testing the infected people are isolated for a finite period of time during which they are symptomatic. In the presence of testing, people become isolated a soon as they are tested positive. We compute time dependence of daily new infections as a function of transmissivity, initial infection, and testing. The duration of the epidemic increases rapidly with the increased level of mitigation while the number of people falling sick daily decreases. Testing, regardless of the level, has little effect on the duration of the epidemic. The total number of people who contract the disease over the lifetime of the epidemic depends weakly on its duration. It does not change significantly for the homogeneous testing of the population at the level below 10% daily.


title: Sensitivity evaluation of 2019 novel coronavirus (SARS-CoV-2) RT-PCR detection kits and strategy to reduce false negative

text: An ongoing outbreak of pneumonia associated with SARS-CoV-2 has now been confirmed globally. In absence of effective vaccines, infection prevention and control through diagnostic testing and quarantine is critical. Early detection and differential diagnosis of respiratory infections increases the chances for successful control of COVID-19 disease. The nucleic acid RT-PCR test is regarded as the current standard for molecular diagnosis with high sensitivity. However, the highest specificity confirmation target ORF1ab gene is considered to be less sensitive than other targets in clinical application. In addition, a large amount of recent evidence indicates that the initial missed diagnosis of asymptomatic patients with SARS-CoV-2 and discharged patients with "re-examination positive" may be due to low viral load, and the ability of rapid mutation of coronavirus also increases the rate of false negative results. We aimed to evaluate the sensitivity of different nucleic acid detection kits so as to make recommendations for the selection of validation kit, and amplify the suspicious result to be reportable positive by means of simple continuous amplification, which is of great significance for the prevention and control of the current epidemic and the discharge criteria of low viral load patients.


title: Fast and easy disinfection of coronavirus-contaminated face masks using ozone gas produced by a dielectric barrier discharge plasma generator

text: Face masks are one of the currently available options for preventing the transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has caused the 2019 pandemic. However, with the increasing demand for protection, face masks are becoming limited in stock, and the concerned individuals and healthcare workers from many countries are now facing the issue of the reuse of potentially contaminated masks. Although various technologies already exist for the sterilization of medical equipment, most of them are not applicable for eliminating virus from face masks. Thus, there is an urgent need to develop a fast and easy method of disinfecting contaminated face masks. In this study, using a human coronavirus (HCoV-229E) as a surrogate for SARS-CoV-2 contamination on face masks, we show that the virus loses its infectivity to a human cell line (MRC-5) when exposed for a short period of time (1 min) to ozone gas produced by a dielectric barrier discharge plasma generator. Scanning electron microscopy and particulate filtration efficiency (PFE) tests revealed that there was no structural or functional deterioration observed in the face masks even after they underwent excessive exposure to ozone (five 1-minute exposures). Interestingly, for face masks exposed to ozone gas for 5 min, the amplification of HCoV-229E RNA by reverse transcription polymerase chain reaction suggested a loss of infectivity under the effect of ozone, primarily owing to the damage caused to viral envelopes or envelope proteins. Ozone gas is a strong oxidizing agent with the ability to kill viruses on hard-to-reach surfaces, including the fabric structure of face masks. These results suggest that it may be possible to rapidly disinfect contaminated face masks using a plasma generator in a well-ventilated place.


title: A Versatile Platform to Incorporate Viral Trimeric Antigens into Self-Assembling Nanoparticle Immunogens

text: Antigens displayed on self-assembling nanoparticles can stimulate strong immune responses and have been playing an increasingly prominent role in structure-based vaccines. However, the development of such immunogens may be complicated by inefficiencies in their production, especially with the metastable glycosylated trimeric type 1 fusion machines that are prevalent viral vaccine targets. To alleviate this issue, we developed a plug-and-play platform using the spontaneous isopeptide-bond formation of the SpyTag:SpyCatcher system to display trimeric antigens on self-assembling nanoparticles, including the 60-subunit Aquifex aeolicus lumazine synthase (LuS) and the 24-subunit Helicobacter pylori ferritin. LuS and ferritin coupled to SpyTag expressed well in a mammalian expression system when an N-linked glycan was added to the nanoparticle surface. Respiratory syncytial virus fusion (F) glycoprotein trimer – stabilized in the prefusion conformation by multiple disulfides and fused with SpyCatcher – could be efficiently conjugated to LuS-SpyTag or to ferritin-SpyTag, enabling multivalent display of F trimers with prefusion antigenicity. Similarly, F-glycoprotein trimers from human parainfluenza virus-type 3 and spike-glycoprotein trimers from SARS-CoV-2 could be displayed on LuS nanoparticles with decent yield and antigenicity. The versatile platform described here thus allows for multivalent plug-and-play presentation on self-assembling nanoparticles of trimeric antigens from viral respiratory pathogens, including the recently identified SARS-CoV-2.


title: Doctoring in the Time of COVID-19

text: I have always known that I have exceptional residents. I have had the privilege of working with the emergency medicine (EM) residents at Sinai-Grace Hospital in Detroit since 2015, first as their Associate Program Director and now as their Vice Chair of Education. Detroit is a tough city and of the four academic emergency departments (EDs) in Detroit, of which I have worked at three, Sinai-Grace is arguably the toughest. Underlying general health in the communities surrounding Sinai-Grace is poor, access to primary healthcare is difficult, violence is high. The average life expectancy in some of the neighborhoods surrounding Sinai-Grace is sixteen years less than the state average for Michigan. 1You don’t choose to do a residency at Sinai-Grace if you’re looking for a cakewalk. Our residents knowingly sign up for a difficult residency that will make them exceptional attending physicians.


title: Pericyte-specific vascular expression of SARS-CoV-2 receptor ACE2 – implications for microvascular inflammation and hypercoagulopathy in COVID-19 patients

text: Accumulating clinical observations suggest pathogenesis beyond viral pneumonia and its secondary consequences in COVID-19 patients. In particular, many patients develop profound hyperinflammation and hypercoagulopathy with disseminated thrombogenesis and thromboembolism, which we observe also in a Swedish COVID-19 intensive care patient cohort. To understand these vascular manifestations, it is important to establish the potential vascular entry point(s) of the SARS-CoV-2 virus, i.e. which vascular cell types express the SARS-CoV-2 receptor ACE2. We present data that ACE2 is specifically and highly expressed in microvascular pericytes, but absent from endothelial cells, perivascular macrophages and fibroblasts. Mice with pericyte ablation show increased expression and release of Von Willebrand Factor from microvascular endothelial cells, suggesting that pericytes orchestrate thrombogenic responses in neighboring endothelial cells. Identifying pericytes rather than endothelial cells as the ACE2-expressing cells in the vasculature may explain why hypertension, diabetes and obesity are risk factors for severe COVID-19 patients, as these conditions are characterized by an impaired endothelial barrier function, allowing SARS-CoV-2 to reach and infect the pericytes that are normally shielded from the blood behind an intact endothelial barrier. This novel COVID-19-pericyte hypothesis is testable, offers explanations for some of the most enigmatic and lethal aspects of COVID-19 and calls for further investigations into the possible benefits of preventive anticoagulant therapy.


Work Better From Home During the Coronavirus Quarantine


The 2019 Novel Coronavirus: A Crown Jewel of Pandemics?


Practice of Interventional Radiology during the COVID-19 Pandemic


title: Assessment of impact of COVID-19 outbreak & lockdown on mental health status & its associated risk and protective factors in adult Indian population

text: Nationwide lockdown to tackle the COVID-19 outbreak in India is anticipated to have psychological impact on the population. Our study aims to study the effect of the outbreak & lockdown on mental health status of adult Indian population along with identifying high risk groups. An online survey was conducted during 3rd phase of lockdown gathering details about sociodemographic variables, precautionary measures, awareness and concerns regarding COVID-19 and mental health status through DASS21 questionnaire from 873 adults. The prevalence of depression, anxiety and stress were 18.56%, 25.66%, and 21.99% respectively with majority being mild depression (15.1%) and stress (14.5%) and moderate anxiety (16.3%). Female gender, age <25 years, unemployment, self-business, employed in private sector, lack of formal education, larger household size, parenthood (>2 kids) were associated with increased likelihood of negative mental health. Confidence in physician's ability to diagnose COVID-19 infection, decreased self-perceived likelihood of contracting COVID-19, lesser frequency of checking for information on COVID-19 and satisfaction of information received were protective against negative mental health. This landmark study identified the protective and risk factors of mental health during COVID-19 pandemic, to help authorities and mental health workers to strategize and deliver interventional methods to maintain psychosocial wellbeing of the population.


title: Estimating the infection fatality risk of COVID-19 in New York City, March 1-May 16, 2020

text: During March 1-May 16, 2020, 191,392 laboratory-confirmed COVID-19 cases were diagnosed and reported and 20,141 confirmed and probable COVID-19 deaths occurred among New York City (NYC) residents. We applied a network model-inference system developed to support the City's pandemic response to estimate underlying SARS-CoV-2 infection rates. Based on these estimates, we further estimated the infection fatality risk (IFR) for 5 age groups (i.e. <25, 25-44, 45-64, 65-74, and 75+ years) and all ages overall, during March 1-May 16, 2020. We estimated an overall IFR of 1.45% (95% Credible Interval: 1.09-1.87%) in NYC. In particular, weekly IFR was estimated as high as 6.1% for 65-74 year-olds and 17.0% for 75+ year-olds. These results are based on more complete ascertainment of COVID-19-related deaths in NYC and thus likely more accurately reflect the true, higher burden of death due to COVID-19 than previously reported elsewhere. It is thus crucial that officials account for and closely monitor the infection rate and population health outcomes and enact prompt public health responses accordingly as the pandemic unfolds.


title: Simulating the infected population and spread trend of 2019-nCov under different policy by EIR model

text: Chinese government has taken strong measures in response to the epidemic of new coronavirus (2019-nCoV) from Jan.23, 2020. The number of confirmed infected individuals are still increasing rapidly. Estimating the accurate infected population and the future trend of epidemic spreading under control measures is significant and urgent. There have been reports external icon of spread from an infected patient with no symptoms to a close contact, which means the incubation individuals may has the possibility of infectiousness. However, the traditional transmission model, Susceptible-Exposed-Infectious-Recovered (SEIR) model, assumes that the exposed individual is being infected but without infectiousness. Thus, the estimating infected populations based on SEIR model from the existing literatures seems too far more than the official reported data. Here, we inferred that the epidemic could be spread by exposed (incubation) individuals. Then, we provide a new Exposed-identified-Recovered (EIR) model, and simulated the epidemic spreading processes from free propagation phase to extremely control phase. Then, we estimate of the size of the epidemic and forecast the future development of the epidemics under strong prevention interventions. According to the spread characters of 2019-nCov, we construct a novel EIR compartment system dynamics model. This model integrates two phases of the epidemic spreading: before intervention and after intervention. We assume that 2019-nCov is firstly spread without intervention then the government started to take strong quarantine measures. Use the latest reported official data, we estimate the basic parameters of the model and the basic reproduction number of 2019-nCov. Then, based on this model, we simulate the future spread of the epidemics. Both the infected population and the spreading trend of 2019-nCov under different prevention policy scenarios are estimated. The epidemic spreading trends under different quarantine rate and action starting date of prevention policy are simulated and compared.


title: Coronametrics: The UK turns the corner

text: There are many ways of analyzing the progress of an epidemic, but when it comes to short term forecasting, it is very hard to beat a simple time series regression model. These are good at allowing for the noise in day to day observations, extracting the trend and projecting it forward. We develop regression models to exploit this, using the daily statistics released by PHE and NHSE. These strongly suggest that the tide has turned and that taking one day with the next, the national figures for deaths from this virus will now fall back noticeably, easing the pressure on the NHS and its staff.


title: COVID 19: Real-time Forecasts of Confirmed Cases, Active Cases, and Health Infrastructure Requirements for India and its Majorly Affected States using the ARIMA model.

text: Background: COVID-19 is an emerging infectious disease which has been declared a Pandemic by the World Health Organization (WHO) on March 11 2020. This pandemic has spread over the world in more than 200 countries. India is also adversely affected by this pandemic, and there are no signs of slowing down of the virus in coming time. The absence of a vaccine for COVID-19 is making the situation worse for the already overstretched Indian public health care system. Objective: This study is forecasting the confirmed and active cases for COVID-19 until June, using time series ARIMA model. In further analysis, based on predicted active cases, we estimated the requirement of isolation beds, ICU beds and ventilators for COVID-19 patients until June. Methods: We used ARIMA model, and Auto ARIMA model for forecasting confirmed and active cases till the end of June month using time series data of COVID-19 cases in India from March 14, 2020, to May 3 2020. We estimated requirement of ICU beds as 10%, Ventilators as 5% and isolation beds as 85% of the active cases predicted from our calculations. Results: We expect that India will be having 441896 confirmed cases (95% CI: 210240, 673552), 124712 active cases (95% CI: 68481, 180944) at the end of June based on our forecasts. Maharashtra, Punjab, Gujarat and Delhi (UT) will be the most affected states, having the highest number of active and confirmed cases at the end of June while Kerala is expected to have less than 1000 confirmed cases and no active cases at the end of June. We expect that India has to prepare 106006 isolation beds (95% CI: 58209, 153802), 12471 ICU beds (95% CI: 6848,18094) and 6236 ventilators (95% CI: 3424,9047) to accommodate the patients at the end of June. Discussion and Conclusion: Our forecasts show a very alarming situation for India in coming days and, the actual numbers can go higher than our estimates of confirmed cases as India is observing partial lockdown currently. In future, lockdown might be lifted, and in that case, there will be a surge in the number of daily confirmed and active cases. The requirement of isolation beds, ICUs and ventilators will also be increased in that scenario. Migrants returning to their homes due to loss of livelihood and income in the lockdown period may lead to a rise in the number of cases, which could not be accounted for in our projections. We suggest a Public-Private Partnership (PPP) model in the health sector to accommodate COVID-19 patients adequately and reduce the burden of the already overstretched Indian public health care system.


title: Intestinal receptor of SARS-CoV-2 in inflamed IBD tissue is downregulated by HNF4A in ileum and upregulated by interferon regulating factors in colon

text: Patients with IBD are considered immunosuppressed, but do not seem more vulnerable for COVID-19. Nevertheless, intestinal inflammation has shown an important risk factor for SARS-CoV-2 infection and prognosis. Therefore, we investigated the effect of intestinal inflammation on the viral intestinal entry mechanisms, including ACE2, in IBD. We collected (un)inflamed mucosal biopsies from CD (n=193) and UC (n=158) patients, and 51 matched non-IBD controls for RNA sequencing, differential gene expression and co-expression analysis. Organoids from UC patients were subjected to an inflammatory mix and processed for RNA sequencing. Transmural ileal biopsies were processed for single-cell (sc) sequencing. Publicly available colonic sc-RNA sequencing data, and microarrays from tissue pre/post anti-TNF therapy, were analyzed. In inflamed CD ileum, ACE2 was significantly decreased compared to control ileum (p=4.6E-07), whereas colonic ACE2 expression was higher in inflamed colon of CD/UC compared to control (p=8.3E-03; p=1.9E-03). Sc-RNA sequencing confirmed this ACE2 dysregulation, and exclusive epithelial ACE2 expression. Network analyses highlighted HNF4A as key regulator of ileal ACE2, while pro-inflammatory cytokines and interferon regulating factors regulated colonic ACE2. Inflammatory stimuli upregulated ACE2 in UC organoids (p=1.7E-02), not in non-IBD controls (p=9.1E-01). Anti-TNF therapy restored colonic ACE2 dysregulation in responders. Intestinal inflammation alters SARS-CoV-2 coreceptors in the intestine, with opposing effects in ileum and colon. HNF4A, an IBD susceptibility gene, is an important upstream regulator of ACE2 in ileum, whereas interferon signaling dominates in colon. Our data support the importance of adequate control of IBD in order to reduce risk of (complicated) COVID-19.


title: Identifying impacts of covid-19mixed-methodspandemicapproachon vulnerable populations: A mixed-methods appro

text: As the Corona-Crisis unfolds, scholars around the world realize that the social contexts in which its transmission occurs deserve special attention. In this context, one of the main con-cepts social scientists should consider to help tackling this crisis is vulnerability. This paper proposes a methodology to study vulnerable populations during the COVID-19 pandemic in the city of Curitiba, one of the main Brazilian metropolises. The proposed methodology encompasses three different strategies, in a mixed-methods approach: i. In-depth telephone interviews with vulnerable people and community leaders who work with them; ii. Online surveys with the city’s general population; iii. Focus groups coupled with alternative scenarios methods involving key actors in the community life of the city. In addition to the research findings themselves, our methodology also envisages fostering initiatives by public authorities and civil society to mitigate the effects of the pandemic over vulnerable populations.


title: ROX Index Predicts Intubation in Patients with COVID-19 Pneumonia and Moderate to Severe Hypoxemic Respiratory Failure Receiving High Flow Nasal Therapy.

text: Introduction Use of high flow nasal therapy (HFNT) to treat COVID-19 pneumonia has been greatly debated around the world due to concern for increased healthcare worker transmission and delays in invasive mechanical Ventilation (IMV). Methods A retrospective analysis of consecutive patients admitted to Temple University Hospital in Philadelphia, Pennsylvania, from March 10, 2020, to May 17, 2020 with moderate to severe respiratory failure treated with High Flow nasal therapy (HFNT). HFNT patients were divided into two groups: HFNT only and HFNT progressed to IMV. The primary outcome was the ability of the ROX index to predict the need of IMV. Results Of the 837 patients with COVID-19, 129 met inclusion criteria. The mean age was 60.8 ({+/-}13.6) years, BMI 32.6 ({+/-}8), 58 (45 %) were female, 72 (55.8%) were African American, 40 (31%) Hispanic. 48 (37.2%) were smokers. Mean time to intubation was 2.5 days ({+/-} 3.3). ROX index of less than 5 at HFNT initiation was predictive of progression to IMV (OR = 2.137, p = 0,052). Any decrease in ROX index after HFNT initiation was predictive of intubation (OR= 14.67, p <0.0001). {Delta}ROX (<=0 versus >0), peak D-dimer >4000 and admission GFR < 60 ml/min were very strongly predictive of need for IMV (ROC = 0.86, p=). Mortality was 11.2% in HFNT only group versus 47.5% in the HFNT progressed to IMV group (p,0.0001). Mortality and need for pulmonary vasodilators were higher in the HNFT progressed to IMV group. Conclusion ROX index is a valuable, noninvasive tool to evaluate patients with moderate to severe hypoxemic respiratory failure in COVID-19 treated with HFNT. ROX helps predicts need for IMV and thus limiting morbidity and mortality associated with IMV.


title: First Clinical Study Using HCV Protease Inhibitor Danoprevir to Treat Naive and Experienced COVID-19 Patients

text: As coronavirus disease 2019 (COVID-19) outbreak, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), started in China in January, 2020, repurposing approved drugs is emerging as important therapeutic options. We reported here the first clinical study using hepatitis C virus (HCV) protease inhibitor, danoprevir, to treat COVID-19 patients. Danoprevir (Ganovo) is a potent HCV protease (NS3/4A) inhibitor (IC50 = 0.29 nM), which was approved and marketed in China since 2018 to treat chronic hepatitis C patients. Ritonavir is a CYP3A4 inhibitor to enhance plasma concentration of danoprevir while it also acts as a human immunodeficiency virus (HIV) protease inhibitor at high doses. The chymotrypsin-like protease of SARS-CoV-2 shares structure similarity with HCV and HIV proteases. In the current clinical study (NCT04291729) conducted at the Nineth Hospital of Nanchang, we evaluated therapeutic effects of danoprevir, boosted by ritonavir, on treatment naive and experienced COVID-19 patients. The data from this small-sample clinical study showed that danoprevir boosted by ritonavir is safe and well tolerated in all patients. After 4 to 12-day treatment of danoprevir boosted by ritonavir, all eleven patients enrolled, two naive and nine experienced, were discharged from the hospital as they met all four conditions as follows: (1) normal body temperature for at least 3 days; (2) significantly improved respiratory symptoms; (3) lung imaging shows obvious absorption and recovery of acute exudative lesion; and (4) two consecutive RT-PCR negative tests of SARS-CoV-2 nucleotide acid (respiratory track sampling with interval at least one day). Our findings suggest that repurposing danoprevir for COVID-19 is a promising therapeutic option.


title: Validation and Comparison of a Modified CDC Assay with two Commercially Available Assays for the Detection of SARS-CoV-2 in Respiratory Specimen

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), has spread rapidly around the globe since it was first identified in December of 2019 in Wuhan, China. In a race to contain the infection, researchers and healthcare officials have developed several assays to help diagnose individuals with COVID-19. To help laboratories in deciding what assay to bring into testing lines, factors such as assay availability, cost, throughput, and TAT should be considered. Here we validated a modified version of the CDC assay and used it as a reference to evaluate the performance of the NeuMoDx™ SARS-CoV-2 and DiaSorin Simplexa™ Covid-19 Direct assays. In silico analysis and clinical sample testing showed that the primesr/probes designed by the CDC were specific to the SARS-CoV-2 as they accurately detected all reactive samples with an assay LoD of 200 copies/ml. The performance of the three assays were analyzed using 161 nasopharyngeal swabs specimen tested within 24 hours or 5 days from routine testing. A 100% agreement was observed between the commercial assays and the modified CDC SARS-CoV-2 assay. A deeper look at the Ct values showed no significant difference between NeuMoDx and the modified CDC SARS-CoV-2 assay, whereas DiaSorin had lower overall Ct values than the modified CDC SARS-CoV-2 assay. NeuMoDx and DiaSorin workflows were much easier to perform. NeuMoDx has the highest throughput and shortest TAT, whereas although the modified CDC SARS-CoV-2 assay has comparable throughput to DiaSorin, it has the longest hands-on time, and highest TAT.


title: Pharmacists and COVID-19

text: In the fight against COVID-19, frontline health workers have been vital to keeping the pandemic at bay, but recognition of individual professions’ efforts have been inconsistent at all levels. Pharmacists around the world have continued to provide direct patient care and perform frontline duties for their communities during this pandemic, but are often relegated to the background and overlooked when frontline workers are heralded. Community pharmacists are the most accessible healthcare practitioners, which is further proven during the pandemic as they continued to provide direct patient care despite restrictions imposed by the government due to the pandemic. Due to the inaccessibility of other healthcare practitioners during this time, community pharmacists have reduced the burden on the healthcare system by diverting the influx of patients away from hospitals through triaging and screening patients. Community pharmacists have played various roles in supporting the healthcare system during COVID-19: delivering medications to patients, educating patients on telehealth services, assessing patients for renewal of chronic medications, performing consultations on minor ailments, clarifying misconceptions about COVID-19 treatments, and contributing to COVID-19 screening. Alongside ICU nurses, physicians, and respiratory therapists, hospital pharmacists have been part of the COVID-19 efforts and their roles include management of drug shortages, development of treatment protocols, participation of patient rounds, interpretation of lab results for COVID-19, participant recruitment for clinical trials, exploration of new drugs, medication management advice, and antimicrobial stewardship. Further support from pharmacists will be needed once a vaccine is launched in order to reach population-wide coverage. Amid COVID-19, pharmacists have not stopped working as frontline workers and they should be recognized as such.


title: Whole genome sequencing of human enteroviruses from clinical samples by nanopore direct RNA sequencing

text: Enteroviruses are small RNA viruses that affect millions of people each year by causing an important burden of disease with a broad spectrum of symptoms. In routine diagnostic laboratories, those viruses are identified by PCR based methods, often combined with partial sequencing for genotyping. In this proof-of-principle study, we assessed direct RNA sequencing (DRS) using nanopore sequencing technology for fast whole-genome sequencing of viruses directly from clinical samples. Results of the approach were complemented with those obtained by sequencing the corresponding viral cDNA via Illumina MiSeq sequencing. DRS of total RNA extracted from three different enterovirus-positive stool samples produced long RNA fragments, covering between 59% to 99.6 % of the best reference genomes. The identification of the enterovirus sequences in the sample was confirmed by the short-read cDNA sequencing. Sequence identity between DRS and Illumina MiSeq enterovirus consensus sequences ranged between 94-97%. Here we show that nanopore DRS can be used to correctly identify the genotypes of enteroviruses from patient stool samples with high viral load.


title: COVID-19 Global Pandemic Planning: Decontamination and Reuse Processes for N95 Respirators

text: Coronavirus disease 2019 (COVID-19) is an illness caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease was first identified as a cluster of respiratory illness in Wuhan City, Hubei Province, China in December 2019, and has rapidly spread across the globe to greater than 200 countries. Healthcare providers are at an increased risk for contracting the disease due to occupational exposure and require appropriate personal protective equipment (PPE), including N95 respirators. The rapid worldwide spread of high numbers of COVID-19 cases has facilitated the need for a substantial supply of PPE that is largely unavailable in many settings, thereby creating critical shortages. Creative solutions for the decontamination and safe reuse of PPE to protect our frontline healthcare personnel are essential. Here, we describe the development of a process that began in late February 2020 for selecting and implementing the use of hydrogen peroxide vapor (HPV) as viable method to reprocess N95 respirators. Since pre-existing HPV decontamination chambers were not available, we optimized the sterilization process in an operating room after experiencing initial challenges in other environments. Details are provided about the prioritization and implementation of processes for collection and storage, pre-processing, HPV decontamination, and post-processing of filtering facepiece respirators (FFRs). Important lessons learned from this experience include, developing an adequate reserve of PPE for effective reprocessing and distribution, and identifying a suitable location with optimal environmental controls (i.e., operating room). Collectively, information presented here provides a framework for other institutions considering decontamination procedures for N95 respirators.


title: Impact of COVID-19 pandemic on lung cancer treatment scheduling

text: Objective: Current pandemic of coronavirus disease 2019 (COVID-19) is associated with a heavy burden on the mental and physical health of patients, regional healthcare resources, and global economic activity. Many patients with lung cancer are thought to be affected by this situation. Therefore, we aimed to evaluate the impact of COVID-19 pandemic on lung cancer treatment scheduling. Study design: We retrospectively reviewed the medical records of lung cancer patients who were undergoing anti-cancer treatment at the National Hospital Organization Kyoto Medical Center (600 beds) in Kyoto, Japan, between March 1, 2020 and May 31, 2020. Methods: After the medical records were reviewed, the patients were assigned to one of two groups, depending on whether their lung cancer treatment schedule was delayed. We assessed the characteristics, types of histopathology and treatment, and the reason for the delay. Results: A total 15 (9.1%) patients experienced the delay of lung cancer treatment during COVID-19 pandemic. Patients with treatment delay received significantly more ICIs monotherapy than patients without treatment delay (p=0.0057). On the contrary, no patients receiving molecular target agents experienced treatment delay during COVID-19 pandemic period (p=0.0027). The treatments of most of the patients were delayed per their request. Conclusion: We revealed 9.1% lung cancer patients suffered anxiety and requested treatment delay during COVID-19 pandemic. Oncologists should keep in mind that patient with cancer have more anxiety than we expected under special occasions such as COVID-19 pandemic.


title: Scalable In-hospital Decontamination of N95 Filtering Facepiece Respirator with a Peracetic Acid Room Disinfection System

text: Abstract Background: Critical shortages of personal protective equipment (PPE) especially N95 respirators, during the SARS-CoV-2 pandemic continues to be a source of great concern among health care workers (HCWs). Novel methods of N95 filtering facepiece respirator (FFR) decontamination that can be scaled-up for in-hospital use can help address this concern and keep HCWs safe. Methods: A multidisciplinary pragmatic study was conducted to evaluate the use of an ultrasonic room high-level disinfection system (HLDS) that generates aerosolized peracetic acid (PAA) and hydrogen peroxide for decontamination of large numbers of N95 respirators. A cycle duration that consistently achieved disinfection of N95 respirators (defined as >6 log10 reductions in bacteriophage MS2 and Geobacillus stearothermophilus spores inoculated onto respirators) was identified. The treated masks were then assessed for changes to their hydrophobicity, material structure, strap elasticity, and filtration efficiency (FE). Assessment of PAA off-gassing from a treated mask was also performed. Results: The PAA room HLDS was effective for disinfection of N95 respirators in a 2447 cubic feet room with deploy and dwell times of 16 and 32 minutes respectively, and a total cycle time of 1 hour and 16 minutes. After 5 treatment cycles, no adverse effects were detected on filtration efficiency, structural integrity, or strap elasticity. There was no detectable off-gassing of PAA from the treated masks. Conclusion: The PAA room disinfection system provides a rapidly scalable solution for in-hospital decontamination of large numbers of N95 respirators to meet the needs of HCWs during the SARS-CoV-2 pandemic.


Covid-19: A wake-up call


title: CCAPP: Number of deaths from untreated addiction may rival those from COVID-19

text: In a far-reaching clarion call for attention to addiction in the midst of the COVID-19 pandemic, Pete Nielsen, CEO of the California Consortium of Addiction Professionals and Programs (CCAPP), urges policymakers to recognize that the isolation required in shelter-in-place will fuel even more deaths from alcohol, drugs and suicide In The Disease of Addiction Thrives on Isolation, released this month, Nielsen warns that these deaths were already ?on track to break records in the number of victims in our state this year,? and goes on to say that those ?who survive this year will face a second wave of death due to tobacco related diseases and or relapse to drug of choice unless tobacco is routinely treated in substance use disorder ?


title: BCG protects against COVID-19? A word of caution

text: The COVID-19 pandemic, caused by type 2 Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), puts all of us to the test. Epidemiologic observations could critically aid the development of protective measures to combat this devastating viral outbreak. A recent publication, linked nation based universal Bacillus Calmette-Guerin (BCG) vaccination to potential protection against morbidity and mortality from SARS-CoV-2, and received much attention in public media, even before its peer review. We wished to validate the findings by examining the association between daily rates of COVID-19 case fatality (i.e. Death Per Case /Days of the endemic [dpc/d]) and the presence of universal BCG vaccination before 1980, or the year of the establishment of universal vaccination. There was no significant association in either analysis. In this work we emphasize caution amidst the publication surge on COVID-19, and highlight the political/economical-, arbitrary selection-, and fear/anxiety related biases, which may obscure scientific rigor. It is underscored that physical (social) distancing (i.e. quarantine) and use of personal protective equipment (PPE) are the only epidemiologic measures (Iceland being a great example, where universal BCG vaccination policy was never in place), which consistently associate with successful counteraction of morbidity and mortality during the pandemic.


title: The SARS-CoV-2 exerts a distinctive strategy for interacting with the ACE2 human receptor

text: The COVID-19 disease has plagued over 110 countries and has resulted in over 4,000 deaths within 10 weeks. We compare the interaction between the human ACE2 receptor and the SARS-CoV-2 spike protein with that of other pathogenic coronaviruses using molecular dynamics simulations. SARS-CoV, SARS-CoV-2, and HCoV-NL63 recognize ACE2 as the natural receptor but present a distinct binding interface to ACE2 and a different network of residue-residue contacts. SARS-CoV and SARS-CoV-2 have comparable binding affinities achieved by balancing energetics and dynamics. The SARS-CoV-2–ACE2 complex contains a higher number of contacts, a larger interface area, and decreased interface residue fluctuations relative to SARS-CoV. These findings expose an exceptional evolutionary exploration exerted by coronaviruses toward host recognition. We postulate that the versatility of cell receptor binding strategies has immediate implications on therapeutic strategies. One Sentence Summary Molecular dynamics simulations reveal a temporal dimension of coronaviruses interactions with the host receptor.


title: Editor’s introduction: Our public service manifesto during pandemic

text: In this Editor's Introduction, we write during the COVID-19 pandemic response this manifesto for public service.


title: Synthetic antibodies neutralize SARS-CoV-2 infection of mammalian cells

text: Coronaviruses (CoV) are a large family of enveloped, RNA viruses that circulate in mammals and birds. Three highly pathogenic strains have caused zoonotic infections in humans that result in severe respiratory syndromes including the Middle East Respiratory Syndrome CoV (MERS), Severe Acute Respiratory Syndrome CoV (SARS), and the ongoing Coronavirus Disease 2019 (COVID-19) pandemic. Here, we describe a panel of synthetic monoclonal antibodies, built on a human IgG framework, that bind to the spike protein of SARS-CoV-2 (the causative agent of COVID-19), compete for ACE2 binding, and potently inhibit SARS-CoV-2. All antibodies that exhibited neutralization potencies at sub-nanomolar concentrations against SARS-CoV-2/USA/WA1 in Vero E6 cells, also bound to the receptor binding domain (RBD), suggesting competition for the host receptor ACE2. These antibodies represent strong immunotherapeutic candidates for treatment of COVID-19.


title: The Post: A token woman leader's transformation

text: In this precarious time of staying at home due to the Covid-19 pandemic, people often ask around what movies are worth watching. I recommend the movie, The Post, directed by Steven Spielberg in 2017. In this review, I am going to provide a rationale for why I keep returning to the movie: it gave me opportunities to ponder what it means to be a token woman leader who began as a housewife and became a transformational leader in U.S. history. I present here select notable scenes that are memorable and inspiring. To that end, I capture the scenes first and then add my own reviews from the lens of women's leadership. My conclusion: we need to hear more transformational women leaders' voices that will help inspire women in the next generation.


COVID-19: fear, explanation, action, unity and ingenuity and World Hand Hygiene Day


title: Four ways researchers are responding to the COVID-19 outbreak

text: How did researchers react so quickly to the SARS-CoV-2 epidemic? Nature Medicine has asked some key experts How did researchers react so quickly to the SARS-CoV-2 epidemic? Nature Medicine has asked some key experts


title: Early Short Course Corticosteroids in Hospitalized Patients with COVID-19

text: Background: There is no proven antiviral or immunomodulatory therapy for COVID-19. The disease progression associated with the pro-inflammatory host response prompted us to examine the role of early corticosteroid therapy in patients with moderate to severe COVID-19. Methods: We conducted a single pre-test, single post-test quasi-experiment in a multi-center health system in Michigan from March 12 to March 27, 2020. Adult patients with confirmed moderate to severe COVID were included. A protocol was implemented on March 20, 2020 using early, short-course, methylprednisolone 0.5 to 1 mg/kg/day divided in 2 intravenous doses for 3 days. Outcomes of pre- and post-corticosteroid groups were evaluated. A composite endpoint of escalation of care from ward to ICU, new requirement for mechanical ventilation, and mortality was the primary outcome measure. All patients had at least 14 days of follow-up. Results: We analyzed 213 eligible subjects, 81 (38%) and 132 (62%) in pre-and post-corticosteroid groups, respectively. The composite endpoint occurred at a significantly lower rate in post-corticosteroid group compared to pre-corticosteroid group (34.9% vs. 54.3%, p=0.005). This treatment effect was observed within each individual component of the composite endpoint. Significant reduction in median hospital length of stay was observed in the post-corticosteroid group (8 vs. 5 days, p < 0.001). Multivariate regression analysis demonstrated an independent reduction in the composite endpoint at 14-days controlling for other factors (aOR: 0.45; 95% CI [0.25-0.81]). Conclusion: An early short course of methylprednisolone in patients with moderate to severe COVID-19 reduced escalation of care and improved clinical outcomes.


title: Building an International Consortium for Tracking Coronavirus Health Status

text: Information is the most potent protective weapon we have to combat a pandemic, at both the individual and global level. For individuals, information can help us make personal decisions and provide a sense of security. For the global community, information can inform policy decisions and offer critical insights into the epidemic of COVID-19 disease. Fully leveraging the power of information, however, requires large amounts of data and access to it. To achieve this, we are making steps to form an international consortium, Coronavirus Census Collective (CCC, coronaviruscensuscollective.org), that will serve as a hub for integrating information from multiple data sources that can be utilized to understand, monitor, predict, and combat global pandemics. These sources may include self-reported health status through surveys (including mobile apps), results of diagnostic laboratory tests, and other static and real-time geospatial data. This collective effort to track and share information will be invaluable in predicting hotspots of disease outbreak, identifying which factors control the rate of spreading, informing immediate policy decisions, evaluating the effectiveness of measures taken by health organizations on pandemic control, and providing critical insight on the etiology of COVID-19. It will also help individuals stay informed on this rapidly evolving situation and contribute to other global efforts to slow the spread of disease. In the past few weeks, several initiatives across the globe have surfaced to use daily self-reported symptoms as a means to track disease spread, predict outbreak locations, guide population measures and help in the allocation of healthcare resources. The aim of this paper is to put out a call to standardize these efforts and spark a collaborative effort to maximize the global gain while protecting participant privacy.


Risk Governance for Systemic Risks, Not Measures for Infectious Diseases


title: Enhanced comparisons of COVID-19 mortality across populations

text: Background The reported crude case fatality rate (CFR) for COVID-19 varies considerably across countries. Crude CFRs could by biased by larger proportions of older COVID-19 cases in population data, who are also at increased mortality risk. Such distorted age case structures are a common feature of selective COVID 19 testing strategies in many countries, and they potentially mask underlying differences arising from other important factors such as health system burden. Methods We used the method of direct case-age standardisation to evaluate the effects of age variations on CFRs. Data on cases and death by age from Italy, Spain, China, Australia and South Korea were analysed to derive standardised CFRs. Findings were compared across different case age distribution references as standards. Results Using the South Korean case age distribution as a standard, the fivefold higher crude CFR for Italy is reduced to less than two-fold after adjustment, while the crude CFR difference for Spain is virtually eliminated. The adjusted CFR for Australia is the lowest among all countries. Discussion Mortality differences based on crude CFRs are exaggerated by age structures, which are effectively controlled by case age standardization. Residual CFR differences could be attributed to health and health system factors. The South Korean case age distribution is an appropriate reference standard, given its robust case detection and contact tracing program. Till reliable population level indicators of incidence and mortality are available, the age-standardized CFR could be a viable option for international comparison of the impact of the COVID 19 epidemic.


title: Clinical and Paraclinical Characteristics of COVID-19 patients: A systematic review and meta-analysis

text: Introduction: Recently, a new strain of coronaviruses, which originated from Wuhan City, Hubei Province, China has been identified. According to the high prevalence of new coronavirus, further investigation on the clinical and paraclinical features of this disease seems essential. Hence, we carried out this systematic review and meta-analysis to figure out the unknown features. Methods: This study was performed using databases of Web of Science, Scopus and PubMed. We considered English cross-sectional and case-series papers which reported clinical, radiological, and laboratory characteristics of patients with COVID-19. We used STATA v.11 and random effect model for data analysis. Results: In the present meta-analysis, 32 papers including 49504 COVID-19 patients were studied. The most common clinical symptoms were fever (84%), cough (65%) and fatigue (42%), respectively. The most common radiological and paraclinical features were bilateral pneumonia (61%), ground-glass opacity (50%), thrombocytopenia (36%) and lymphocytopenia (34%). The study also showed that the frequency of comorbidities and early symptoms was higher in critically severe patients. Moreover, we found the overall mortality rate of three percent. Conclusion: According to that there are many cases without Computed Tomography Scan findings or clear clinical symptoms, it is recommended to use other confirming methods such RNA sequencing in order to identification of suspicious undiagnosed patients. Moreover, while there is no access to clinical and paraclinical facilities in in public places such as airports and border crossings, it is recommended to consider factors such as fever, cough, sputum and fatigue.


title: A modified SEIR meta-population transmission based Modeling and Forecasting of the COVID-19 pandemic in Pakistan

text: The coronavirus disease 2019 (COVID-19) started from China at the end of 2019, has now spread across the globe. Modeling and simulation of the - outspread is significant for timely and effective measures to be taken. Scientists around the world are using various epidemiological models to help policymakers to plan and determine what interventions and resources will be needed in case of a surge and to estimate the potential future burden on health care system. Pakistan is also among the affected countries with 18th highest number of total detected number of cases, as of 3rd of June, 2020. A modified time-dependent Susceptible-Exposed-Infected-Recovered (SEIR) metapopulation transmission model is used in the Global Epidemic and Mobility Model (GLEaM) for this simulation. The simulation assumes the index case in Wuhan, China and models the global spread of SARS- COV-2 with reasonable results for several countries within the 95% confidence interval. This model was then tuned with parameters for Pakistan to predict the outspread of COVID-19 in Pakistan. The impact of Non-Drug Interventions on flattening the curve are also incorporated in the simulation and the results are further extended to find the peak of the pandemic and future predictions. It has been observed that in the current scenario, the epidemic trend of COVID-19 spread in Pakistan would attain a peak in the second decade of month of June with approximately (3600-4200) daily cases. The current wave of SARS-COV-2 in Pakistan with is estimated to cause some (210,000 - 226,000) cumulative cases and (4400 - 4750) cumulative lost lives by the end of August when the epidemic is reduced by 99%. However, the disease is controllable in the likely future if inclusive and strict control measures are taken.


title: EVALUATION OF THE ROCHE ELECSYS ANTI-SARS-COV-2 ASSAY.

text: Background: Little is known about the performance of the Roche novel severe acute respiratory syndrome coronavirus 2 antibody (anti-SARS-CoV-2) assay. We provide an extensive evaluation of this fully automated assay on the Cobas e801/e602 immunoassay analysers. Methods: We assessed the linearity, precision, and throughput of the Roche anti-SARS-CoV-2 assay. Sensitivity was calculated from 349 SARS-CoV-2 polymerase chain reaction (PCR) positive samples; specificity was determined from 714 coronavirus disease 2019 (COVID-19)-naive samples. We examined cross-reactivity against other antibody positive samples (syphilis, RF, ANA, ds-DNA, influenza, dengue, HBV, HCV) and the anti-SARS-CoV-2 kinetics. Results: The assay cut-off index (COI) was linear up to 90.7. The inter-assay precision was 2.9% for a negative control (COI=0.1) and 5.1% for a positive control (COI=3.0). Assay time is 18min and results are available 1 minute later; throughput for 300 samples was 76 minutes. No cross-reactivity was observed with other antibody positive samples; specificity was 100%. The assay has a sensitivity of 97.1% 14 days after PCR positivity (POS) and 100% at [≥]21 days POS; 48.2% of cases had anti-SARS-CoV-2 within 6 days POS. In 11 subjects in whom serum was available prior to a positive antibody signal (COI [≥]1.0) the interval between the last negative and first positive COI (time to sero-conversion) on average is 3 days (range 1-6 days) and 4 more days (range 1-7) for the anti-SARS-CoV-2 to plateau. Conclusion: The Roche anti-SARS-CoV-2 assay shows excellent performance with minimal cross-reactivity from other viral and confounding antibodies. Antibody development and sero-conversion appears quite early.


title: Insights on early mutational events in SARS-CoV-2 virus reveal founder effects across geographical regions

text: Here we aim to describe early mutational events across samples from publicly available SARS-CoV-2 sequences from the sequence read archive repository. Up until March 27, 2020, we downloaded 53 illumina datasets, mostly from China, USA (Washington DC) and Australia (Victoria). Of 30 high quality datasets, 27 datasets (90%) contain at least a single founder mutation and most of the variants are missense (over 63%). Five-point mutations with clonal (founder) effect were found in USA sequencing samples. Sequencing samples from USA in GenBank present this signature with 50% allele frequencies among samples. Australian mutation signatures were more diverse than USA samples, but still, clonal events were found in those samples. Mutations in the helicase and orf1a coding regions from SARS-CoV-2 were predominant, among others, suggesting that these proteins are prone to evolve by natural selection. Finally, we firmly urge that primer sets for diagnosis be carefully designed, since rapidly occurring variants would affect the performance of the reverse transcribed quantitative PCR (RT-qPCR) based viral testing.


title: Human agency and infection rates: implications for social distancing during epidemics

text: Social distancing is an important measure in controlling epidemics. This paper presents a simple theoretical model focussed on the implications of the wide range in interaction rates between individuals, both within the workplace and in the social setting. The model is based on well-mixed populations and so is not intended for studying geographic spread. The model shows that epidemic growth rate is largely determined by the upper interactivity quantiles of society, implying that the most efficient methods of epidemic control are interaction capping approaches rather than overall reductions in interaction. The theoretical model can also be applied to look at the dynamics of epidemic progression under various scenarios. The theoretical model suggests that with no intervention herd immunity would be achieved with a lower overall infection rate than if variation in interaction rate is ignored, because by this stage almost all the most interactive members of society would have had the infection; however the overall mortality with such an approach is very high. Scenarios for mitigation and suppression suggest that, by using interactivity capping, it should be possible to control an epidemic without extreme sanctions on the majority of the population if R0 of the uncontrolled infection is 2.4. However to control the infection rate to a specific level will always require the switching on and off of measures and for this reason eradication is likely to be a less costly policy in the long run. While social distancing alone can be used for eradication it is not be a good mechanism on its own to prevent reinfection. The use of robust testing, quarantining, and contact tracing would strengthen any social distancing measures, speed up eradication, and be a better tool for prevention of infection or reinfection.


title: Total and Stroke Related Imaging Utilization Patterns During the COVID-19 Pandemic

text: During the COVID-19 pandemic, radiology practices are reporting a decrease in imaging volumes. We review total imaging volume, CTA head and neck volume, critical results rate, and stroke intervention rates before and during the COVID-19 pandemic. Total imaging volume as well as CTA head and neck imaging fell approximately 60% since the beginning of the pandemic. Critical results fell 60-70% for total imaging as well as for CTA head and neck. Compared to the same time frame a year prior, the number of stroke codes at the early impact of the pandemic had decreased approximately 50%. Proportional reductions in total imaging volume, stroke-related imaging, and associated critical result reports during the COVID-19 pandemic raise concern for missed stroke diagnoses in our population.


title: Multi-parametric disease dynamics study and analysis of the COVID-19 epidemic and implementation of population-wide intrusions: The Indian perspective

text: The outbreak of COVID-19 had spread at a deadly rate since its onset at Wuhan, China and is now spread across 216 countries and has affected more than 6 million people all over the world. The global response throughout the world has been primarily the implementation of lockdown measures, testing and contact tracing to minimise the spread of the disease. The aim of the present study was to predict the COVID-19 prevalence and disease progression rate in Indian scenario in order to provide an analysis that can shed light on comprehending the trends of the outbreak and outline an impression of the epidemiological stage for each state of a diverse country like India. In addition, the forecast of COVID-19 incidence trends of these states can help take safety measures and policy design for this epidemic in the days to come. In order to achieve the same, we have utilized an approach where we test modelling choices of the spatially unambiguous kind, proposed by the wave of infections spreading from the initial slow progression to a higher curve. We have estimated the parameters of an individual state using factors like population density and mobility. The findings can also be used to strategize the testing and quarantine processes to manipulate the spread of the disease in the future. This is especially important for a country like India that has several limitations about healthcare infrastructure, diversity in socioeconomic status, high population density, housing conditions, health care coverage that can be important determinants for the overall impact of the pandemic. The results of our 5-phase model depict a projection of the state wise infections/disease over time. The model can generate live graphs as per the change in the data values as the values are automatically being fetched from the crowd-sourced database.


COVID-19 en América Latina: Retos y oportunidades/ COVID-19 in Latin America: Challenges and opportunities


title: Molecular docking reveals the potential of Salvadora persica flavonoids to inhibit COVID-19 virus main protease

text: In December 2019, an outbreak of coronavirus disease 2019 (COVID-19) commenced in Wuhan, China and affected around 210 countries and territories in a matter of weeks It has a phylogenetic similarity to SARS-CoV and it was named coronavirus 2 (SARS-CoV-2) and caused severe acute respiratory syndrome that could lead to death One of the promising therapeutic strategies for virus infection is the search for enzyme inhibitors among natural compounds using molecular docking in order to obtain products with minimal side effects COVID-19 virus main protease plays a vital role in mediating viral transcription and replication, introducing it as an attractive antiviral agent target Metabolic profiling of the aqueous extract of Salvadora persica L (Salvadoraceae) aerial parts dereplicated eleven known flavonol glycosides using LC-HRESIMS All the annotated flavonoids exhibited significant binding stability at the N3 binding site to different degrees, except isorhamnetin-3-O-beta-d-glucopyranoside, when compared with the currently used COVID-19 main protease inhibitor, darunavir Structural similarity between the identified flavonoids enabled the study of the relationship between their structure and interactions with the receptor in the N3 binding site of the COVID-19 main protease The results indicate that the basic flavonol nucleus possesses activity itself Moreover, the presence of a rutinose moiety at the 3 position of ring C and absence of an O-methyl group in ring B of the flavonol structure could increase the binding stability This study provides a scientific basis for the health benefits of the regular use of S persica as it leaches bioactive flavonoids in the aqueous saliva


title: Ecological grief generates desire for environmental healing in tourism after COVID-19

text: Tourism research is starting to take interest in the psychology of environmental distress, particularly as it relates to climate change. For both the COVID-19 pandemic of 2020 and the climate change movement that dominated international media in 2019, psychological parallels exist in terms of our experience of loss. As the world grapples with the pandemic and tourism grinds to a halt, stories on social media are surfacing that claim wildlife is returning to quarantined cities and that the Earth is healing itself. Much of the implicit critique of these stories is directed at the tourism industry, with two viral posts in particular supposedly documenting the ‘rewilding’ of Venice, that infamous icon of overtourism. While the popular media have been concerned primarily with the factual accuracy of these claims, what has gone largely unexplored is the apparent desire for environmental reparation that they express. The fixation on environmental healing evidenced in tourist social media can be interpreted as a response to widely-felt ‘ecological grief’, triggered by the events of COVID-19. In this context, animal reclamation of urban spaces can be identified as a motif of environmental hope that symbolises life, regeneration and resilience, the understanding of which may contribute to the project of hopeful tourism in the post-COVID-19 era.


title: 2019-nCoV - Towards a 4th generation vaccine

text: The first report of the unusual manifestation of pneumonia-like symptoms in Wuhan City, China was made on 31 December 2019. Within one week, the Chinese authorities reported that they had identified the causative agent as a new member of the Coronavirus family, the same family of that was responsible for MERS and SARS not so many years ago. The new virus was called Novel Coronavirus 2019 (2019-nCoV). Three weeks later, the World Health Organization declared that 2019-nCoV was capable of direct human-to-human transmission, the virus had spread across several countries in three continents, and had infected close to two thousand people, of whom at least 1 in 5 quite severely. The number of fatalities was fast rising. Yet, the World Health Organization officially announced that there is still at present no recommended anti-nCoV vaccine for subject at-risk, nor treatment for patients with suspected or confirmed nCoV, let alone 2019-nCov. It is therefore timely and critical to propose new possible and practical approaches for preventive interventions for subjects at-risk, and for treatment of patients afflicted with 2019-nCov-induced disease (Corona Virus Disease 2019; COVID-19) before the present situation explodes into a worldwide pandemic. One such potential clinical protocol is proposed as a hypothesis.


title: Leveraging Deep Learning to Simulate Coronavirus Spike proteins has the potential to predict future Zoonotic sequences

text: Motivation Coronaviridae are a family of positive-sense RNA viruses capable of infecting humans and animals. These viruses usually cause a mild to moderate upper respiratory tract infection, however, they can also cause more severe symptoms, gastrointestinal and central nervous system diseases. These viruses are capable of flexibly adapting to new environments, hence health threats from coronavirus are constant and long-term. Immunogenic spike proteins are glyco-proteins found on the surface of Coronaviridae particles that mediate entry to host cells. The aim of this study was to train deep learning neural networks to produce simulated spike protein sequences, which may be able to aid in knowledge and/or vaccine design by creating alternative possible spike sequences that could arise from zoonotic sources in future. Results Here we have trained deep learning recurrent neural networks (RNN) to provide computer-simulated coronavirus spike protein sequences in the style of previously known sequences and examine their characteristics. Training used a dataset of alpha, beta, gamma and delta coronavirus spike sequences. In a test set of 100 simulated sequences, all 100 had most significant BLAST matches to Spike proteins in searches against NCBI non-redundant dataset (NR) and also possessed concomitant Pfam domain matches. Conclusions Simulated sequences from the neural network may be able to guide us in future with prospective targets for vaccine discovery in advance of a potential novel zoonosis. We may effectively be able to fast-forward through evolution using neural networks to investigate sequences that could arise.


title: Effects of home confinement on mental health and lifestyle behaviours during the COVID-19 outbreak: Insight from the "ECLB-COVID19" multi countries survey

text: Background: Although recognised as effective measures to curb the spread of the COVID-19 outbreak, social distancing and self-isolation, have been suggested to generate burden throughout the population. To provide scientific data to help identify risk-factors for the psychosocial strain during the COVID-19 outbreak, an international cross-disciplinary online survey was circulated in April 2020. This report outlines the mental, emotional and behavioural consequences of COVID-19 home confinement. Method: Thirty-five research organisations from four continents promoted the survey through their networks to the general society, in Ten different languages. Questions were presented in a differential format with questions related to responses before and during confinement period. Results: 1047 replies (54% women) from Western-Asia (36%), North-Africa (40%), Europe (21%) and other countries (3%) were analysed. The COVID-19 home confinement evoked a negative effect on mental wellbeing and emotional status (P < 0.001; 0.43 [≤] d [≤] 0.65) with a greater proportion of individuals experiencing psychosocial and emotional disorders (10% to 16.5%). These psychosocial tolls were associated with unhealthy lifestyle behaviours with a greater proportion of individuals experiencing (i) physical (+15.2%) and social (71.2%) inactivity, (ii) poor sleep quality (12.8%), (iii) unhealthy diet behaviours (10%), and (iv) unemployment (6%). Conversely, participants demonstrated a greater use (15%) of technology solutions during the confinement period. Conclusion: These findings elucidate the risk of psychosocial strain during the current home confinement period and provide a clear remit for the urgent implementation of technology-based intervention to foster an Active and Healthy Confinement Lifestyle (AHCL).


title: Children behind closed doors due to covid-19 isolation: Abuse, neglect and domestic violence/ Djeca iza zatvorenih vrata covid-19 izolacije: Zlostavljanje, zanemarivanje i nasilje u obitelji

text: Abuse and neglect of children is a public health issue at a global, European, and Croatian level, with significant rates of morbidity and mortality. Actual circumstances of a health crisis generate and aggravate a series of risk factors for child abuse and neglect at the level of the child and parent characteristics, family dy-namics and the wider social environment. Isolation and quarantine possibly leading to social exclusion, rep-resent a serious risk for child abuse and neglect, possibly also being the reason for fewer reports. This paper reviews clinical and empirical studies related to the rates of abuse and neglect of children during health and other crises in other countries. It also analyses trends of recent data of the Ministry of Interior with practical guidelines for improved child protection in this period.


title: An analysis of SARS-CoV-2 viral load by patient age

text: As children are under-represented in current studies aiming to analyse transmission of SARS-coronavirus 2 (SARS-CoV-2), their contribution to transmission is unclear. Viral load, as measured by RT-PCR, can inform considerations regarding transmission, especially if existing knowledge of viral load in other respiratory diseases is taken into account. RT-PCR threshold cycle data from 3303 patients who tested positive for SARS-CoV-2 (out of 77,996 persons tested in total, drawn from across Germany) were analysed to examine the relationship between patient age and estimated viral load. Two PCR systems were used. In data from the PCR system predominantly used for community and cluster screening during the early phase of the epidemic (Roche LightCycler 480 II), when such screening was frequent practice, viral loads do not differ significantly in three comparisons between young and old age groups (differences in log10 viral loads between young and old estimated from raw viral load data and a Bayesian mixture model of gamma distributions collectively range between -0.11 and -0.43). Data from a second type of PCR system (Roche cobas 6800/8800), introduced into diagnostic testing on March 16, 2020 and used during the time when household and other contact testing was reduced, show a credible but small difference in the three comparisons between young and old age groups (differences, measured as above, collectively range between -0.43 and -0.83). This small difference may be due to differential patterns of PCR instrument utilization rather than to an actual difference in viral load. Considering household transmission data on influenza, which has a similar viral load kinetic to SARS-CoV-2, the viral load differences between age groups observed in this study are likely to be of limited relevance. Combined data from both PCR instruments show that viral loads of at least 250,000 copies, a threshold we previously established for the isolation of infectious virus in cell culture at more than 5% probability, were present across the study period in 29.0% of kindergarten-aged patients 0-6 years old (n=38), 37.3% of those aged 0-19 (n=150), and in 51.4% of those aged 20 and above (n=3153). The differences in these fractions may also be due to differences in test utilization. We conclude that a considerable percentage of infected people in all age groups, including those who are pre- or mild-symptomatic, carry viral loads likely to represent infectivity. Based on these results and uncertainty about the remaining incidence, we recommend caution and careful monitoring during gradual lifting of non-pharmaceutical interventions. In particular, there is little evidence from the present study to support suggestions that children may not be as infectious as adults.


title: BCG vaccination and socioeconomic variables vs Covid-19 global features: clearing up a controversial issue

text: Background: The Covid-19 pandemic is characterized by extreme variability in the outcome distribution and mortality rates across different countries. Some recent studies suggested an inverse correlation with BCG vaccination at population level, while others denied this hypothesis. In order to address this controversial issue, we performed a strict epidemiological study collecting data available on a global scale, considering additional variables such as cultural-political factors and adherence to other vaccination coverages. Methods: Data on 121 countries, accounting for about 99% of Covid-19 cases and deaths globally, were from John's Hopkins Coronavirus Resource Center, World Bank, International Monetary Fund, United Nations, Human Freedom Report, and BCG Atlas. Statistical models used were Ordinary Least Squares, Tobit and Fractional Probit, implemented on Stata/MP16 software. Results: Based on our results, countries where BCG vaccination is or has been mandated in the last decades have seen a drastic reduction in Covid-19 diffusion (-80% on average) and mortality (-50% on average), even controlling for relative wealth of countries and their governmental health expenditure. A significant contribution to this reduction (respectively -50% and -13% on average) was also associated to the outbreak onset during summer, suggesting a possible influence of seasonality. Other variables turned out to be associated, though to a lesser extent. Conclusions: Relying on a very large dataset and a wide array of control variables, our study confirms a strong and robust association between Covid-19 diffusion and mortality with BCG vaccination and a set socio-economic factors, opening new perspectives for clinical speculations and public health policies.


title: SARS-CoV-2 Viral Load Predicts COVID-19 Mortality

text: The need for reliable and widely available SARS-CoV-2 testing is well recognized, but it will be equally necessary to develop quantitative methods that determine viral load in order to guide patient triage and medical decision making. We are the first to report that SARS-CoV-2 viral load at the time of presentation is an independent predictor of COVID-19 mortality in a large patient cohort (n=1,145). Viral loads should be used to identify higher-risk patients that may require more aggressive care and should be included as a key biomarker in the development of predictive algorithms.


title: Protection after Quarantine: Insights from a Q-SEIR Model with Nonlinear Incidence Rates Applied to COVID-19

text: Community quarantine has been resorted to by various governments to address the current COVID-19 pandemic; however, this is not the only non-therapeutic method of effectively controlling the spread of the infection. We study an SEIR model with nonlinear incidence rates, and introduce two parameters, and {varepsilon}, which mimics the effect of quarantine (Q). We compare this with the Q-SEIR model, recently developed, and demonstrate the control of COVID-19 without the stringent conditions of community quarantine. We analyzed the sensitivity and elasticity indices of the parameters with respect to the reproduction number. Results suggest that a control strategy that involves maximizing and {varepsilon} is likely to be successful, although quarantine is still more effective in limiting the spread of the virus. Release from quarantine depends on continuance and strict adherence to recommended social and health-promoting behaviors. Furthermore, maximizing and {varepsilon} is equivalent to a 50% successful quarantine in disease-free equilibrium (DFE). This model reduced the infectious in Quezon City by 3.45% and Iloilo Province by 3.88%; however, earlier peaking by nine and 17 days, respectively, when compared with the results of Q-SEIR.


title: Protein interaction with dendrimer monolayers: Energy and surface topology

text: Protein interaction with polymers layers is a keystone in designing bio-nano devices. Polyamidoamines (PAMAMs) are well-known polymers. Zero aromatic core dendrimers (ZAC) are molecules with no proven toxic effect in cultured cells. When coating nanodevices with enzymatic systems, active sites are disturbed by an interaction with the biosystem surface. Computational methods were used in order to simulate, characterize, and quantify protein-polymer interaction. Protein corona, i.e., surface proteins disposed on a viral membrane or nanodevice outer surface, are crucial in interactions with a potential pharmacological target or receptor. Corona symmetry has been observed in the Middle East respiratory syndrome-related coronavirus (MERS-CoV), severe acute respiratory syndromecoronavirus (SARS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As a protein alpha 1 antitrypsin's a crystallographic structure was chosen. Protein-mono dendrimer layer systems were generated using in silico methods in order to simulate their interaction. Interactions were quantified using topological and quantum mechanical strategies. Results showed that PAMAM and ZAC interact differently with alpha 1 antitrypsin. Energy and topological surfaces of protein vary accordingly with the dendrimer monolayer. Topological surfaces have a higher sensibility in describing the interactions.


title: Lung epithelial stem cells express SARS-CoV-2 entry factors: implications for COVID-19

text: SARS-CoV-2 can infiltrate the lower respiratory tract, resulting in severe respiratory failure and a high death rate. Normally, the airway and alveolar epithelium can be rapidly reconstituted by multipotent stem cells after episodes of infection. Here, we analyzed published RNA-seq datasets and demonstrated that cells of four different lung epithelial stem cell types express SARS-CoV-2 entry factors, including Ace2. Thus, stem cells can be infected by SARS-CoV-2, which can lead to defects in regeneration capacity and account for the severity of SARS-CoV-2 infection and its consequences.


title: Wuhan and Hubei COVID-19 mortality analysis reveals the critical role of timely supply of medical resources

text: We report that COVID-19 mortality and recovery rates in Hubei Province, China exponentially decays (R2>0.93) and grows (R2>0.95), respectively. A great number of newly supplied medical resources (health workers and beds) enabled overwhelming patients to be treated effectively. This may help other countries to deal with the coming COVID-19 outbreaks.


title: COVID-19 Propagation and Mortality in a Two-Part Population

text: There has recently emerged a striking consistency to the mortality from SARS-CoV-2, as a fraction of population, across many nations. We have constructed a model for the spread of the virus that reproduces this phenomenon via inclusion of two (or more) categories of susceptibility to the virus. In the simplest case, the population is given a smaller fraction of 10-20% with higher susceptibility and the balance of 80-90% with lower susceptibility. Susceptibility is taken to include the level of immunity to the virus combined with the societal circumstances of certain smaller groups within a population. This is programmed numerically by considering a realistic random rate of contacts, together with an assumed constant viral genome. The remaining major variable is the societal response of nations to the outbreak, with earlier or later application of various degrees of lockdown, tracing and sanitation. China, South Korea and other nations, including Germany, have stopped or greatly slowed the spread of the disease before it could run its course through a whole population. Using this model the extent of progress toward herd immunity is discussed, with an in-principle estimate of the remaining toll to be experienced.


title: Eurofins Covid-19 Sentinel TM Wastewater Test Provide Early Warning of a potential COVID-19 outbreak

text: The Eurofins Covid-19 SentinelTM program was developed to monitor the evolution of the pandemic and for early detection of outbreaks. The study objective was to develop a wastewater testing method to analyze SARS-CoV-2 as an indicator of community infection rate resurgence of COVID-19 or in well-defined sites such as production facilities or nursing homes. Eurofins performed >700 tests on 78 unique samples from 18 sites in Denmark, France and Belgium. Ten variant test protocols were trialed. Protocol variations trialed included centrifugation, precipitation of the SARS-CoV-2 RNA, agitation prior to precipitation, cooling, and pasteurization of the samples. A method was succesfully developed and reliability was supported by stability, reproducibility, and dilution & linearity studies. Results obtained showed a direct link to number of RNA copies in the sample using a calibration curve with synthetic SARS-CoV-2. Analysis was performed on both the liquid phase and solid phase of wastewater samples, with virus RNA detected in both phases but more frequently in the liquid phase. The virus was present in a sample from a Danish community wastewater treatment plant collected on February 24, 3 days before the first COVID-19 case was officially reported in the country. The greatest concentration of virus detected corresponded to when the COVID-19 crisis was at its peak in Denmark. Based on studies carried out in a Danish hospital, the wastewater testing method is expected to be able to detect a community COVID-19 prevalence rate as low as a 0,02%-0,1% (i.e. between 2 virus shedders per 10000 and 1 virus shedder per 1000). The wastewater testing method was used to monitor a Danish Community after a COVID-19 outbreak and it was shown that the method can be used as a semi-quantitative method to monitor the development of an outbreak.


Limiting fatality in COVID-19 patients


title: Contact

text: In korte periode heb ik veel nieuwe woorden geleerd. Tot dan wist ik niets over een coronavirus COVID-19. De vele artikelen in de krant, de persconferenties, de talkshows weten van geen ophouden om ons goed te informeren. Het blijft niet bij de coronacrisis, want het virus heeft effect op vele aspecten van het leven. Op de gezondheidszorg, op de economie, op de financiële markt, de woningmarkt, de energiemarkt, de internationale verhoudingen, noem maar op. Ineens leven we via een intelligente lockdown in een anderhalve-meter-samenleving. Social distancing is de belangrijkste omgangsvorm en behoort tot ‘het nieuwe normaal’. En die afstand tussen mensen, dat niet aanraken van elkaar, kan zelfs leiden tot huidhonger!


title: Modelling the potential impact of social distancing on the COVID-19 epidemic in South Africa

text: The novel coronavirus (COVID-19) pandemic continues to be a global health problem whose impact has been significantly felt in South Africa. Social distancing has been touted as the best form of response in managing a rapid increase in the number of infected cases. In this paper, we present a deterministic model to model the impact of social distancing on the transmission dynamics of COVID-19 in South Africa. The model is fitted to the currently available data on the cumulative number of infected cases and a scenario analysis on different levels of social distancing are presented. The results show a continued rise in the number of cases in the lock down period with the current levels of social distancing albeit at a lower rate. The model shows that the number of cases will rise to above 4000 cases by the end of the lockdown. The model also looks at the impact of relaxing the social distancing measures after the initial announcement of the lock down measures. A relaxation of the social distancing by 2% can result in a 23% rise in the number of cumulative cases while on the other hand increasing the levels of social distancing by 2% would reduce the number of cumulative cases by about 18%. These results have implications on the management and policy direction in the early phases of the epidemic.


title: COVID-19 :Determinants of Hospitalization, ICU and Death among 20,293 reported cases in Portugal

text: Introduction Determinants of hospitalization, intensive care unit (ICU) admission and death are still unclear for Covid-19 and only a few studies have adjusted for confounding for different clinical outcomes including all reported cases in a country in the analysis. We used routine surveillance data from Portugal to identify risk factors for COVID-19 outcomes, in order to support risk stratification, clinical and public health interventions, and to improve scenarios to plan health care resources. Methods We conducted a retrospective cohort study including 20,293 laboratory confirmed cases of COVID-19 in Portugal to 28 April 2020, electronically through the National Epidemic Surveillance System of the Directorate-General of Health(DGS). We calculated absolute risks, relative risks (RR) and adjusted relative risks (aRR) to identify demographic and clinical factors associated with hospitalization, admission to ICU and death using Poisson regressions. Results Increasing age after 60 years was the greatest determinant for all outcomes. Assuming 0-50 years as reference, being aged 80-89 years was the strongest determinant of hospital admission (aRR-5.7), 70-79 years for ICU(aRR-10.4) and >90 years for death(aRR-226.8) with an aRR of 112.7 in those 70-79 . Among comorbidites, Immunodeficiency, cardiac disease, kidney disease, and neurologic disease were independent risk factors for hospitalization (aRR 1.83, 1.79, 1.56, 1.82), for ICU these were cardiac, Immunodeficiency, kidney and lung disease (aRR 4.33, 2.76, 2.43, 2.04), and for death they were kidney, cardiac and chronic neurological disease (aRR: 2.9, 2.6, 2.0) Male gender was a risk factor for all outcomes. There were statistically significant differences for the 3 outcomes between regions. Discussion and Conclusions Older age stands out as the strongest risk factor for all outcomes specially for death as absolute is risk was small for those younger than 50. These findings have implications in terms of risk stratified public health measures that should prioritize protecting older people. Epidemiologic scenarios and clinical guidelines may consider the estimated risks, even though under-ascertainment of mild and asymptomatic cases should be considered in different age groups.