title: SARS-CoV-2 genomic and subgenomic RNAs in diagnostic samples are not an indicator of active replication

text: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in China in late December 2019 and has spread worldwide. Coronaviruses are enveloped, positive sense, single-stranded RNA viruses and employ a complicated pattern of virus genome length RNA replication as well as transcription of genome length and leader containing subgenomic RNAs. Although not fully understood, both replication and transcription are thought to take place in so-called double-membrane vesicles in the cytoplasm of infected cells. We here describe detection of SARS-CoV-2 subgenomic RNAs in diagnostic samples up to 17 days after initial detection of infection, and provide a likely explanation not only for extended PCR positivity of such samples, but also for discrepancies in results of different PCR methods described by others. Overall, we present evidence that subgenomic RNAs may not be an indicator of active coronavirus replication/infection, but that these RNAs, similar to the virus genome RNA, may be rather stable, and thus detectable for an extended period, most likely due to their close association with cellular membranes.


title: Performance and health economic evaluation of the Mount Sinai COVID-19 serological assay identifies modification of thresholding as necessary to maximise specificity of the assay

text: We evaluated the FDA approved SARS-CoV-2 immunoassay (developed at Mount Sinai, by Krammer and colleagues) for the identification of COVID-19 seroconversion and potential cross-reactivity of the assay in a United Kingdom (UK) National Health Service (NHS) hospital setting. In our "set up" cohort we found that the SARS-CoV-2 IgG was detectable in 100% of patients tested 14 days post positive COVID-19 nucleic acid test. Serum samples taken from pregnant women in 2018 were used as a negative control group with zero false positives. We also analysed samples from patients with non-COVID-19 viral infections, paraproteinaemia or autoantibodies and found false positive results in 6/179. Modification of the sensitivity threshold to five standard deviations from the mean of the control group eliminated all false positive result in the set up cohort. We confirmed the validity of the test with a revised threshold on an independent prospective "validation cohort" of patient samples. Taking data from both cohorts we report a sensitivity of the Mount Sinai assay of 96.6% (28/29) and specificity of 100% (299/299) using a revised threshold cut-off, at a time point at least 14 days since the diagnostic antigen test. Finally, we conducted a health economic probabilistic sensitivity analysis (PSA) on the costs of producing the tests, and the mean cost we estimate to be 13.63 pounds sterling (95%CI 9.63 - 18.40), allowing its cost effectiveness to be tested against other antibody tests. In summary, we report that the Mount Sinai IgG ELISA assay is highly sensitive test for SARS-Cov-2 infection, however modification of thresholding was required to minimise false positive results.


title: Efficacy of remdesivir in COVID-19 patients with a simulated two-arm controlled study

text: While the recent study on the compassionate use of remdesivir for COVID-19 patients has shown a 68% clinical improvement7 it is a one-arm study that renders the evaluation of the efficacy in reducing death and the length of stay of hospitalization intractable due to a lacking of the control group. We came up with a two-arm controlled study design to simulate the treated and the untreated (control group) group by applying two respective transition models to the empirical data on dynamics of the disease severity (Figure 2 of the original article7) that are classified into low- (no and low oxygen supplement), medium- (non-invasive ventilator and high oxygen supplement), and high-(ECMO and invasive ventilator) from enrolment until discharge, death or the end of follow-up. By using a simulated two-arm controlled study, the remdesivir treatment group as opposed to the control group led to a statistically significantly 29% (95% CI: 22-35%) reduction of death from COVID-19. The treated group also revealed a 33% (95% CI 28-38%) significantly higher odds of discharge than the control group. The median time to discharge for the treated group (5.5 days, 16.5 days, and 29.5 days for low-, medium-, and high-risk state, respectively) was around half of those of the control arm. Our results with a simulated two-arm controlled study have not only corroborated the efficacy of remdesivir but also made great contribution to designing a further large-scale randomized controlled trial. They have significant implications for reducing transmission probability and infectious time of COVID-19 patients when contacting with susceptible health care workers during hospitalization.


Management and Clinical Characteristics in Children with SARS-CoV-2 Infection: Experience in a highly complex public hospital in the city of Sao Paulo


title: Proceedings Eighth Workshop on Mathematically Structured Functional Programming

text: This volume contains the proceedings of the Eighth Workshop on Mathematically Structured Functional Programming (MSFP 2020). The meeting was originally scheduled to take place in Dublin, Ireland on the 25th of April as a satellite event of the European Joint Conferences on Theory&Practice of Software (ETAPS 2020). Due to the COVID-19 pandemic, ETAPS 2020, and consequently MSFP 2020, has been postponed to a date yet to be determined. The MSFP workshop highlights applications of mathematical structures to programming applications. We promote the use of category theory, type theory, and formal language semantics to the development of simple and reasonable programs. This year's papers cover a variety of topics ranging from array programming to dependent types to effects.


Information about the new coronavirus disease (COVID-19)


title: ViralLink: An integrated workflow to investigate the effect of SARS-CoV-2 on intracellular signalling and regulatory pathways

text: The SARS-CoV-2 pandemic of 2020 has mobilised scientists around the globe to research all aspects of the coronavirus virus and its infection. For fruitful and rapid investigation of viral pathomechanisms, a collaborative and interdisciplinary approach is required. Therefore, we have developed ViralLink: a systems biology workflow which reconstructs and analyses networks representing the effect of viruses on intracellular signalling. These networks trace the flow of signal from intracellular viral proteins through their human binding proteins and downstream signalling pathways, ending with transcription factors regulating genes differentially expressed upon viral exposure. In this way, the workflow provides a mechanistic insight from previously identified knowledge of virally infected cells. By default, the workflow is set up to analyse the intracellular effects of SARS-CoV-2, requiring only transcriptomics counts data as input from the user: thus, encouraging and enabling rapid multidisciplinary research. However, the wide-ranging applicability and modularity of the workflow facilitates customisation of viral context, a priori interactions and analysis methods. Through a case study of SARS-CoV-2 infected bronchial/tracheal epithelial cells, we evidence the functionality of the workflow and its ability to identify key pathways and proteins in the cellular response to infection. The application of ViralLink to different viral infections in a cell-type specific manner using different available transcriptomics datasets will uncover key mechanisms in viral pathogenesis. The workflow is available on GitHub (https://github.com/korcsmarosgroup/ViralLink) in an easily accessible Python wrapper script, or as customisable modular R and Python scripts. Author summary Collaborative and multidisciplinary science provides increased value for experimental datasets and speeds the process of discovery. Such ways of working are especially important at present due to the urgency of the SARS-CoV-2 pandemic. Here, we present a systems biology workflow which models the effect of viral proteins on the infected host cell, to aid collaborative and multidisciplinary research. Through integration of gene expression datasets with context-specific and context-agnostic molecular interaction datasets, the workflow can be easily applied to different datasets as they are made available. Application to diverse SARS-CoV-2 datasets will increase our understanding of the mechanistic details of the infection at a cell type specific level, aid drug target discovery and help explain the variety of clinical manifestations of the infection.


title: Sentinel Coronavirus Environmental Monitoring Can Contribute to Detecting Asymptomatic SARS-CoV-2 Virus Spreaders and Can Verify Effectiveness of Workplace COVID-19 Controls

text: Detecting all workplace asymptomatic COVID-19 virus spreaders would require daily testing of employees, which is not practical. Over a two week period, nine workplace locations were chosen to test employees for SARS-CoV-2 infection (841 tests) and high-frequency-touch point environmental surfaces (5,500 tests) for Coronavirus using Eurofins COVID-19 SentinelTM RT-PCR methods. Of the 9 locations, 3 had one or employees infected with SARS-CoV-2, neither of whom had symptoms at the time of testing nor developed symptoms. Locations with Coronavirus contaminated surfaces were 10 times more likely to have clinically positive employees than locations with no or very few positive surfaces. Break room chairs, workbenches, and door handles were the most frequently contaminated surfaces. Coronavirus RNA was detected at very low concentrations (RT-PCR 34 to 38 Cq). Environmental monitoring can be used to validate intervention strategies and be useful to verify the effectiveness of such strategies on a regular basis.


title: SARS-CoV-2 infection and replication in human fetal and pediatric gastric organoids

text: Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global public health emergency. COVID-19 typically manifests as a respiratory illness but an increasing number of clinical reports describe gastrointestinal (GI) symptoms. This is particularly true in children in whom GI symptoms are frequent and viral shedding outlasts viral clearance from the respiratory system. By contrast, fetuses seem to be rarely affected by COVID-19, although the virus has been detected in placentas of affected women. These observations raise the question of whether the virus can infect and replicate within the stomach once ingested. Moreover, it is not yet clear whether active replication of SARS-CoV-2 is possible in the stomach of children or in fetuses at different developmental stages. Here we show the novel derivation of fetal gastric organoids from 8-21 post-conception week (PCW) fetuses, and from pediatric biopsies, to be used as an in vitro model for SARS-CoV-2 gastric infection. Gastric organoids recapitulate human stomach with linear increase of gastric mucin 5AC along developmental stages, and expression of gastric markers pepsinogen, somatostatin, gastrin and chromogranin A. In order to investigate SARS-CoV-2 infection with minimal perturbation and under steady-state conditions, we induced a reversed polarity in the gastric organoids (RP-GOs) in suspension. In this condition of exposed apical polarity, the virus can easily access viral receptor angiotensin-converting enzyme 2 (ACE2). The pediatric RP-GOs are fully susceptible to infection with SARS-CoV-2, where viral nucleoprotein is expressed in cells undergoing programmed cell death, while the efficiency of infection is significantly lower in fetal organoids. The RP-GOs derived from pediatric patients show sustained robust viral replication of SARS-CoV-2, compared with organoids derived from fetal stomachs. Transcriptomic analysis shows a moderate innate antiviral response and the lack of differentially expressed genes belonging to the interferon family. Collectively, we established the first expandable human gastric organoid culture across fetal developmental stages, and we support the hypothesis that fetal tissue seems to be less susceptible to SARS-CoV-2 infection, especially in early stages of development. However, the virus can efficiently infect gastric epithelium in pediatric patients, suggesting that the stomach might have an active role in fecal-oral transmission of SARS-CoV-2.


title: The reproductive index from SEIR model of Covid-19 epidemic in Asean

text: As we calculate analytic to link the coefficient of third-order polynomial equations from raw data of an Asean to the SEIR model. The Reproductive index depending on the average incubation period and the average infection period and the coefficient polynomial equations fitted from raw are derived . We also consider the difference of the average incubation period as 5 days and 3 days with the average infection period as 10 day of an Asean. We find that the value of are Indonesia (7.97), Singapore (6.22), Malaysia (3.86), Thailand (2.48), respectively. And we also find that Singapore has 2 values of as 1.54 (16 Feb to 37 March) and 6.22 (31 March-4 April).The peak of infection rate are not found for Singapore and Indonesia at the time of consideration. The model of external stimulus is added into raw data of Singapore and Indonesia to find the maximum rate of infection. We find that Singapore need more magnitude of external stimulus than Indonesia. And the external stimulus for 14 days can stimulate to occur the peak of infected daily case of both country.


Covid-19 and Children with Immune Thrombocytopenia: Emerging Issues


title: The COVID-19 RNA-synthesizing machine

text: Coronavirus The COVID-19 RNA-synthesizing machine Valda Vinson Many in the scientific community have mobilized to understand the virus that is causing the global coronavirus disease 2019 (COVID-19) pandemic


title: The evolutionary history of ACE2 usage within the coronavirus subgenus Sarbecovirus

text: SARS-CoV-1 and SARS-CoV-2 are not phylogenetically closely related; however, both use the ACE2 receptor in humans for cell entry. This is not a universal sarbecovirus trait; for example, many known sarbecoviruses related to SARS-CoV-1 have two deletions in the receptor binding domain of the spike protein that render them incapable of using human ACE2. Here, we report three novel sarbecoviruses from Rwanda and Uganda which are phylogenetically intermediate to SARS-CoV-1 and SARS-CoV-2 and demonstrate via in vitro studies that they are also unable to utilize human ACE2. Furthermore, we show that the observed pattern of ACE2 usage among sarbecoviruses is most likely due to recombination. We show that the lineage that includes SARS-CoV-2 is most likely the ancestral ACE2-using lineage, and that recombination with at least one virus from this group conferred ACE2 usage to the progenitor of SARS-CoV-1 at some time in the past. We argue that alternative scenarios such as convergent evolution are much less parsimonious; we show that biogeography and patterns of host tropism support the plausibility of a recombination scenario; and we propose a competitive release hypothesis to explain how this recombination event could have occurred and why it is evolutionarily advantageous. The findings provide important insights into the natural history of ACE2 usage for both SARS-CoV-1 and SARS-CoV-2, and a greater understanding of the evolutionary mechanisms that shape zoonotic potential of coronaviruses. This study also underscores the need for increased surveillance for sarbecoviruses in southwestern China, where most ACE2-using viruses have been found to date, as well as other regions including Africa, where these viruses have only recently been discovered.


title: Identification of severity zones for mitigation strategy assessment COVID-19 outbreak in Malaysia

text: The objective of this research is to identify severity zones for the COVID-19 outbreak in Malaysia. The technique employed for the purpose is fuzzy graph that can accommodate scarcity, quantity, and availability of data set. Two published sets of data by the Ministry of Health of Malaysia are used to implement the technique. The obtained results can offer descriptive insight, reflection, assessment, and strategizing actions in combating the pandemic.


title: Decreased serum levels of inflammaging marker miR-146a are associated with clinical response to tocilizumab in COVID-19 patients

text: Background. Current COVID-19 pandemic poses an unprecedented threat to global health and healthcare systems. At least in western countries, the most amount of the death toll is accounted by old people affected by age-related diseases. In this regard, we proposed that COVID-19 severity may be tightly related to inflammaging, i.e. the age-related onset of inflammation, which is responsible for age-related diseases. It has been reported that systemic hyper-inflammation may turn to be detrimental in COVID-19 patients. Objective. Here, we exploited a recently closed clinical trial (NCT04315480) on the anti-IL-6 drug tocilizumab to assess whether microRNAs regulating inflammaging can be assessed as biomarkers of drug response and outcome. Methods. Serum levels of miR-146a-5p, -21-5p, and -126-3p were quantified by RT-PCR and Droplet Digital PCR by two independent laboratories on 30 patients with virologically confirmed COVID-19, characterized by multifocal interstitial pneumonia confirmed by CT-scan and requiring oxygen therapy, and 29 age- and gender-matched healthy control subjects. COVID-19 patients were treated with a single-dose intravenous infusion of 8 mg/kg tocilizumab and categorized into responders and non-responders. Results. We showed that COVID-19 patients who did not respond to tocilizumab have lower serum levels of miR-146a-5p after the treatment (p=0.007). Moreover, among non-responders, those with the lowest serum levels of miR-146a-5p experienced the most adverse outcome (p=0.008). Conclusion. Our data show that blood-based biomarkers, such as miR-146a-5p, can provide a molecular link between inflammaging and COVID-19 clinical course, thus allowing to enlarge the drug armory against this worldwide health threat.


title: The lower COVID-19 related mortality and incidence rates in Eastern European countries are associated with delayed start of community circulation

text: Background: The purpose of this analysis was to assess the variations in COVID-19 related mortality and incidence rates in relation to the time differences in the commencement of virus circulation and containment measures in different countries of the European Region. Methods: The data for the current analysis (N=50 countries) were retrieved from the John Hopkins University dataset on the 7th of May 2020, with countries as study units. A piecewise regression analysis was conducted with mortality and cumulative incidence rates introduced as dependent variables and time interval (days from the 22nd of January to the date when 100 first cases were reported) as the main predictor. The country average life expectancy at birth was statistically adjusted for in the regression model. Results: Mortality and incidence were strongly and inversely intercorrelated with days from January 22, respectively -0.83 (p<.0001) and -0.73 (p<.0001). Adjusting for average life expectancy, between days 33 to 50 from the 22th of the January, the average mortality rate decreased by 30.4/million per day (95% CI: 23.2, 37.1, p<0.0001). During interval 51 to 73 days, the change in mortality was no longer statistically significant but still showed a decreasing trend. A similar relationship with time interval was found in incidence. Life expectancy was not associated with mortality rate. Conclusion: Countries in Europe which observed the earliest COVID-19 circulation, suffered the worst consequences in terms of health outcomes, specifically mortality. The drastic social isolation measures, undertaken especially in Eastern European countries, where community circulation started after March 11th, may have been timely. This may explain their significantly lower COVID-related mortality compared with the Western European countries.


title: COVID-19 Lockdown in a Kenyan Informal Settlement: Impacts on Household Energy and Food Security

text: A COVID-19 lockdown may impact household fuel use and food security for ~700 million sub-Saharan Africans who rely on polluting fuels (e.g. wood, kerosene) for household energy and typically work in the informal economy. In an informal settlement in Nairobi, surveys administered before (n=474) and after (n=194) a mandatory COVID-19-related community lockdown documented socioeconomic/household energy impacts. During lockdown, 95% of participants indicated income decline or cessation and 88% reported being food insecure. Three quarters of participants cooked less frequently and half altered their diet. One quarter (27%) of households primarily using liquefied petroleum gas (LPG) for cooking before lockdown switched to kerosene (14%) or wood (13%). These results indicate the livelihoods of urban Kenyan families were deleteriously affected by COVID-19 lockdown, with a likely rise in household air pollution from community-level increases in polluting fuel use. To safeguard public health, policies should prioritize enhancing clean fuel and food access among the urban poor.


title: How Did Chinese Government Implement Unconventional Measures Against COVID-19 Pneumonia

text: In recent years, respiratory infectious diseases had continued to attack China, the recent outbreak of COVID-19 pneumonia had attracted worldwide attention. Through studying the literature, interpreting official documents, analyzing medical and social management data, we summarized and compared some powerful measures taken by the Chinese government, such as declaring emergency state, blocking down the epidemic center, prohibiting crowd gathering activities, forcing residents to wear masks, and mobilizing medical staff and products. We found that these unconventional measures, on the one hand, controlled the spread of the epidemic in China, and on the other hand, exposed some of China’s shortcomings in biosafety, food safety, public health input, and emergency system construction. This paper also recommends that other countries should take strict isolation measures as early as possible when fighting COVID-19 epidemics, and also mobilize citizens to strengthen self-protection.


title: COVID-19 infodemic: More retweets for science-based information on coronavirus than for false information

text: The World Health Organization has not only signaled the health risks of COVID-19, but also labeled the situation as infodemic, due to the amount of information, true and false, circulating around this topic. Research shows that, in social media, falsehood is shared far more than evidence-based information. However, there is less research analyzing the circulation of false and evidence-based information during health emergencies. Thus, the present study aims at shedding new light on the type of tweets that circulated on Twitter around the COVID-19 outbreak for two days, in order to analyze how false and true information was shared. To that end, 1000 tweets have been analyzed. Results show that false information is tweeted more but retweeted less than science-based evidence or fact-checking tweets, while science-based evidence and fact-checking tweets capture more engagement than mere facts. These findings bring relevant insights to inform public health policies.


title: Forecasting virus diffusion with simple Bayesian forecast combination

text: There are various diffusion models for S shaped processes like virus diffusion and these models are typically not nested. In this note it is proposed to combine the forecasts using a simple Bayesian forecast combination algorithm. An illustration to daily data on cumulative Covid-19 cases in the Netherlands shows the ease of use of the algorithm and the accuracy of the thus combined forecasts.


title: Similar incidence of Coronavirus Disease 2019 (COVID-19) in patients with rheumatic diseases with and without hydroxychloroquine therapy

text: Background: Hydroxychloroquine is currently being tested as post-exposure prophylaxis against coronavirus disease 2019 (COVID-19) in several ongoing clinical trials. Objective: To compare the incidence of COVID-19 in Spanish patients with autoimmune rheumatic diseases treated with and without hydroxychloroquine. Methods: Retrospective electronic record review, from February 27th to April 16th, of patients with autoimmune inflammatory diseases followed at two academic tertiary care hospitals in Seville, Spain. The cumulative incidence of COVID-19, confirmed or suspected, was compared between patients with and without hydroxychloroquine as part of their treatment of autoimmune inflammatory diseases. Results: Among 722 included subjects, 290 (40%) were receiving hydroxychloroquine. During the seven-week study period, five (1.7% [95% CI: 0.5%-4.0%] cases of COVID-19 were registered among patients with hydroxychloroquine and five (1.2% [0.4%-2.7%]) (p=0.523) in without hydroxychloroquine. COVID-19 was confirmed by PCR in one (0.3%, 95% CI 0.008-1.9%) patient with hydroxychloroquine and two (0.5%, 95% CI 0.05%-1.6%) without hydroxychloroquine (p=1.0). One patient on hydroxychloroquine and two subjects without hydroxychloroquine were admitted to the hospital, none of them required to be transferred to the intensive care unit and no patient died during the episode. Conclusions: The incidence and severity of COVID-19 among patients with autoimmune rheumatic diseases with and without hydroxychloroquine was not significantly different. Hydroxychloroquine does not seem to be an appropriate therapy for post-exposure prophylaxis against COVID-19.


title: A guide to the coronavirus job retention scheme

text: The government, in light of the pressures being placed on businesses across the country, has put together a package of assistance for employers and employees, in an effort to keep as many people in employment as possible during the current Covid-19 emergency.


title: Assessing the Hospital Surge Capacity of the Kenyan Health System in the Face of the COVID-19 Pandemic

text: Introduction The COVID-19 pandemic will test the capacity of health systems worldwide. Health systems will need surge capacity to absorb acute increases in caseload due to the pandemic. We assessed the capacity of the Kenyan health system to absorb surges in the number of people that will need hospitalization and critical care because of the COVID-19. Methods We assumed that 2% of the Kenyan population get symptomatic infection by SARS-Cov-2 based on modelled estimates for Kenya and determined the health system surge capacity for COVID-19 under three transmission curve scenarios, 6, 12, and 18 months. We estimated four measures of hospital surge capacity namely: 1) hospital bed surge capacity 2) ICU bed surge capacity 3) Hospital bed tipping point, and 5) ICU bed tipping point. We computed this nationally and for all the 47 county governments. Results The capacity of Kenyan hospitals to absorb increases in caseload due to COVID-19 is constrained by the availability of oxygen, with only 58% of hospital beds in hospitals with oxygen supply. There is substantial variation in hospital bed surge capacity across counties. For example, under the 6 months transmission scenario, the percentage of available general hospital beds that would be taken up by COVID-19 cases varied from 12% Tharaka Nithi county, to 145% in Trans Nzoia county. Kenya faces substantial gaps in ICU beds and ventilator capacity. Only 22 out of the 47 counties have at least 1 ICU unit. Kenya will need an additional 1,511 ICU beds and 1,609 ventilators (6 months transmission curve) to 374 ICU beds and 472 ventilators (18 months transmission curve) to absorb caseloads due to COVID-19.


title: The COVID-19 pandemic: how can risk science help?

text: This paper reflects on how risk science, with its concepts, principles, approaches, methods and models, can support the actual assessments, communication and handling of the vulnerabilities and risks related to the Coronavirus (Covid-19) pandemic. We highlight the importance of acknowledging uncertainty as a main component of risk, in order to properly characterize and communicate risk, as well as to understand the difference between professional risk judgements and risk perception. We challenge the use of the commonly referred to phrase that the policies adopted are science-based, in a situation like this characterized by fundamental uncertainties about the underlying phenomena and the effects of possible interventions. Arguments are provided for a ‘balanced’ use of precaution, combined with adaptive management and learning.


title: Type and frequency of ocular and other known symptoms experienced by people who self diagnosed as suffering from COVID-19 in the UK

text: Background: Recent literature suggests that ocular manifestations present in people suffering from COVID-19. However, the prevalence and the type of ocular symptoms varies substantially, and most studies report retrospective data from patients suffering from more serious versions of the disease. Little is known of exactly which ocular symptoms manifest in people with milder forms of COVID-19. Methods: An online questionnaire obtained self-report data from people in the community, who reported to be inflicted with COVID-19. The type and frequency of different symptoms suffered during COVID-19 were obtained. Details of any pre-existing ocular conditions and the duration of symptoms of COVID-19 were ascertained. Results: Data from 132 participants showed that the four most reported COVID-19 symptoms were Dry Cough (63%), Fever (67%), Fatigue (83%), and loss of Smell/Taste (63%). 56% of the participants reported to having experienced an eye symptom, 46% reported to having a new or different eye symptom compared to pre-COVID-19 state. Three ocular symptoms (watery eyes, sore eyes, sensitivity to light) were significantly different from Pre-COVID-19 state (p<0.05). Logistic regression showed a significant association of eye symptoms with Fever (p=0.035). Conclusion: Nearly half of the sample of people studied experienced ocular symptoms. The significant ocular symptoms, indicative of viral conjunctivitis, might have been missed in patients with more serious manifestations of the disease. It is also important to differentiate between the types of ocular manifestation, as symptoms of bacterial conjunctivitis (i.e. mucous discharge, gritty eyes) were not significant. Possible mechanisms for SARS-CoV-2 infection within the eye are discussed.


title: Covid-19 and women's triple burden: Vignettes from Sri Lanka, Malaysia, Vietnam and Australia

text: During disease outbreaks, women endure additional burdens associated with paid and unpaid work, often without consideration or the alleviation of other life responsibilities. This paper draws on the concept of the triple burden in theorizing the gender divisions in productive and reproductive work and community activities in the context of disaster. Events that include famine, war, natural disaster or disease outbreak are all well documented as increasing women's vulnerability to a worsening of gendered burdens. In the case of the Covid-19 coronavirus pandemic, this is no different. Focussing on Sri Lanka, Malaysia, Vietnam and Australia, the four vignettes in this paper serve to highlight the intersections between Covid-19 and gendered burdens, particularly in frontline work, unpaid care work and community activities. While pre-disaster gender burdens are well established as strong, our analysis during the early months of the pandemic indicates that women's burdens are escalating. We estimate that women will endure a worsening of their burdens until the pandemic is well under control, and for a long time after. Public policy and health efforts have not sufficiently acknowledged the issues concerned with the associations between gender and disease outbreaks.


title: Thyroid function abnormalities in COVID-19 patients

text: Background: The novel coronavirus COVID-19, has caused a worldwide pandemic, impairing several human organs and systems. Whether COVID-19 affects human thyroid function remains unknown. Methods: 84 hospitalized COVID-19 patients in the First Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou, China) were respectively enrolled in this study. In addition, 73 other patients with pneumonia and 819 healthy subjects were included as controls. Results: We found that the levels of TT3 and TSH were lower in COVID-19 patients than control groups (p<0.001). Within the group of COVID-19 patients, 61.9% patients (52/84) presented with thyroid function abnormalities. We found a larger proportion of patients in severe condition exhibited thyroid dysfunction than mild/moderate cases (90.4% vs. 50.0%, p < 0.001). Patients with thyroid dysfunction tended to have increased interval time for negative conversion of viral nucleic acid (14.1 {+/-} 9.4 vs. 10.6 {+/-} 8.3 days, p = 0.088). To note, thyroid dysfunction was also associated with decreased lymphocytes (p < 0.001) and increased CRP (p = 0.002). In 7 patients with dynamic changes of thyroid function, we observed the levels of TT3 and TSH gradually increased and reached normal range without thyroid hormone replacement at Day 30 post-admission. The correlation between TT3 and TSH level seemed to be positive rather than negative in the early stage, and gradually turned to be negatively related over time. Conclusions: Thyroid function abnormalities are common in COVID-19 patients, especially in severe cases. This might be caused by virus attack and damage to the thyroid-pituitary axis. Therefore, more attention should be paid to thyroid function during treatment of COVID-19, and close follow-up is also needed after discharge.


title: Use of siltuximab in patients with COVID-19 pneumonia requiring ventilatory support

text: COVID-19 is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SAR-CoV-2), resulting in symptoms, such as fever, cough, and shortness of breath. The SARS-CoV-2 virus has also been suggested to initiate a cytokine storm in patients with COVID-19 evidenced by elevated cytokines, such as interleukin-6 (IL-6) and C-reactive protein (CRP). We report preliminary data from 21 patients with COVID-19 who developed pneumonia/acute respiratory distress syndrome (ARDS) and participated in a compassionate-use program at Papa Giovanni XXIII hospital in Bergamo, Italy. All 21 patients received intravenous siltuximab, a chimeric mAb that binds to and blocks the effect of IL-6, at a dose ranging between 700 to 1,200 mg (median 900 mg). The median age of patients treated was 64 years, and all patients were followed for a median of eight days. Serum CRP levels reduced in all 16 patients with available data following treatment. An improvement in the clinical condition was observed in 33% (7/21) of patients, 43% (9/21) of patients stabilized as evidenced by no clinically relevant change in their condition, and 24% (5/21) experienced a worsening in their condition. Of those patients who experienced a worsening in their condition, one patient died, and one patient experienced a cerebrovascular event. This analysis is presented to inform the medical community of the potential role of siltuximab in treating patients with ARDS secondary to SARS-CoV-2 infection, and a cohort study with patients treated with standard therapy in our hospital is ongoing, and will report the 30-day mortality rates upon completion.


title: Network Pharmacology Integrated Molecular Docking Reveals the Anti-COVID-19 Mechanism of Qing-Fei-Da-Yuan Granules

text: Coronavirus disease (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a highly infectious viral disease Clinical observations have shown that Qing-Fei-Da-Yuan (QFDY) granules have good anti-COVID-19 effects, but the underlying molecular mechanisms are unclear In this study, we explored the potential mechanism of QFDY with regard to its anti-COVID-19 effect We first screened the active chemical constituents of QFDY based on the pharmacodynamic activity parameters, followed by screening with the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform The Uniprot database was used for querying the corresponding genes of the target, and Cyoscape 3 6 1 software was used to construct the network of herb-compound-target Protein interaction analysis, target gene function enrichment analysis, and signal pathway analysis were performed via STRING database, Database for Annotation, Visualization, and Integrated Discovery, and KEGG Pathway database Molecular docking was used to predict the binding capacity of the core compound with COVID-19 hydrolase 3CL and angiotensin converting enzyme 2 (ACE2) The results showed that a network of herb-compound-target was successfully constructed, with key targets involving PTGS2, HSP90AA1, CAMKK2, NCOA2, and ESR1 Major metabolic pathways affected were those in cancer, procancer, nonsmall cell lung cancer, and apoptosis The core compounds, such as quercetin, luteolin, and naringenin, showed a strong binding ability with COVID-19 3CL hydrolase;compounds such as anemasaponin C and medicocarpin showed a strong binding ability with ACE2 Thus, it is predicted that QFDY has the characteristics for multicomponent, multitarget, and multichannel overall control The mechanism of action of QFDY in the treatment of COVID-19 may be associated with the regulation of genes co-expressed with ACE2, the regulation of inflammation and immune-related signaling pathways, and the influence of COVID-19 3CL hydrolase and ACE2 binding ability


title: The Easter and Passover Blip in New York City

text: Abstract and Executive Summary - When it comes to pandemics such as the currently present COVID-19 [1], various issues and problems arise for infrastructures and institutions. Due to possible extreme effects, such as hospitals potentially running out of beds or medical equipment, it is essential to lower the infection rate to create enough space to attend to the affected people and allow enough time for a vaccine to be developed. Unfortunately, this requires that measures put into place are upheld long enough to reduce the infection rate sufficiently. In this paper, we describe research simulating the influences of the contact rate on the spread of the pandemic using New York City as an example (Section IV) and especially already observed effects of contact rate increases during holidays [2-4] (Section V). In multiple simulations scenarios for Passover and Easter holidays, we evaluated 25%, 50%, 75%, and 100% temporary increases in contact rates using a scenario close to the currently reported numbers as reference and contact rates based on bioterrorism research as a 'normal' baseline for NYC. The first general finding from the simulations is that singular events of increased visits/contacts amplify each other disproportionately if they are happening in close proximity (time intervals) together. The second general observation was that contact rate spikes leave a permanently increased and devastating infection rate behind, even after the contact rate returns to the reduced one. In case of a temporary sustained increase of contact rate for just three days in a row, the aftermath results in an increase of infection rate up to 40%, which causes double the fatalities in the long run. In numbers, given that increases of 25% and 50% seem to be most likely given the data seen in Germany for the Easter weekend for example [2, 3], our simulations show the following increases (compared to the realistic reference run): for a temporary 25% surge in contact rate, the total cases grew by 215,880, the maximum of required hospitalizations over time increased to 63,063, and the total fatalities climbed by 8,844 accumulated over 90 days. As for the 50% surge, we saw the total number of cases rise by 461,090, the maximum number of required hospitalizations increase to 79,733, and the total number of fatalities climb by 19,125 over 90 days in NYC. All in all, we conclude that even very short, temporary increases in contact rates can have disproportionate effects and result in unrecoverable phenomena that can hardly be reversed or managed later. The numbers show possible phenomena before they might develop effects in reality. This is important because phenomena such as the described blip can impact the hospitals in reality. Therefore, we warn that a wave of infections due to increased contact rates during Passover/Easter might come as a result!


title: Risk and severity of COVID-19 and ABO blood group in transcatheter aortic valve patients

text: Background: Although cardiovascular disease has been associated with an increased risk of coronavirus disease 2019 (COVID-19), no studies have reported its clinical course in patients with aortic stenosis who had undergone transcatheter aortic valve replacement (TAVR). Several observational studies have found an association between the A blood group and an increased susceptibility to SARS-CoV-2 infection, whereas the O blood group appears to be protective. Objective: To investigate the frequency and clinical course of COVID-19 in a large sample of patients who had undergone TAVR and to determine the associations of the ABO blood group with disease occurrence and outcomes. Methods: Patients who had undergone TAVR between 2010 and 2019 were included in this study and followed-up through the recent COVID-19 outbreak. The main outcomes were the occurrence and severity (hospitalization and/or death) of COVID-19 and their association with the ABO blood group. Results: Of the 1125 patients who had undergone TAVR, 403 (36%) died before January 1, 2020, and 20 (1.8%) were lost to follow-up. The study sample therefore consisted of 702 patients. Among them, we identified 22 cases (3.1%) with COVID-19. Fourteen patients (63.6%) were hospitalized or died of disease. Multivariate analysis identified the A blood group (versus others) as the only independent predictor of COVID-19 in patients who had undergone TAVR (odds ratio [OR] = 6.32; 95% confidence interval [CI] = 2.11-18.92; p=0.001). The A blood group (versus others; OR = 8.27; 95% CI = 1.83-37.43, p=0.006) and a history of cancer (OR = 4.99; 95% CI = 1.64-15.27, p = 0.005) were significantly and independently associated with disease severity (hospitalization and/or death). Conclusions: Patients who had undergone TAVR are vulnerable to COVID-19. The subgroup with the A blood group was especially prone to develop the disease and showed unfavorable outcomes.


title: An effect assessment of Airborne particulate matter pollution on COVID-19: A multi-city Study in China

text: Objective: Coronavirus disease 2019 (COVID-19) is a serious infectious disease, which has caused great number of deaths and health problems worldwide. This study aims to examine the effects of airborne particulate matter (PM) pollution on COVID-19 across China. Methods: In this study, we obtained confirmed cases of COVID-19, the data of airborne ambient PM with aerodynamic diameter [≤] 2.5 m (PM2.5) and [≤] 10 m (PM10), ambient temperature (AT), absolute humidity (AH) and migration scale index (MSI) in 72 cities of China (excluded Wuhan city) on a daily basis, each of which confirmed more than 50 cases from January 20th to March 2nd, 2020. We applied a two-stage analysis. Generalized additive models with quasi-Poisson distribution was first fitted to estimate city-specific effects of PM10 and PM2.5 on daily confirmed COVID-19 cases while controlling AT, AH and MSI. Then, we used meta-analysis to generate the pooled effect estimates from city-specific results. Results: During the study period, there were a total of 24 939 COVID-19 cases, most of which were reported in Hubei Province. In our meta-analysis, we found each 10 g/m3 increase in concentration of PM2.5 and PM10 in single day lag (from lag 0 to lag 7 and lag 14) were positively associated with confirmed cases of COVID-19, not including PM10 at lag 5, lag 6 and lag 7, and PM2.5 at lag 5, lag 6. Similar trend was also found in different cumulative lag days (from lag 01 to lag 07 and lag 014). The effects of PM2.5 and PM10 on daily COVID-19 confirmed cases are statistically significant for three cumulative lag periods over 3, 7 and 14 days with the greatest effect over 14 days. The estimated RRs of which were 1.64 (95% CIs: 1.47, 1.82) and 1.47 (95% CIs: 1.34, 1.61) with each 10 g/m3 increase in concentrations of PM2.5 and PM10, respectively. In addition, we found that the effects of PM2.5 on daily confirmed cases were greater than PM10 in all included lag days. Conclusions: This nationwide study suggests that airborne PM pollution likely increases the risk of getting COVID-19 in China.


Planting Critical Ideas: Artists Reconfiguring the Environmental Crisis


title: The transcriptomic profiling of COVID-19 compared to SARS, MERS, Ebola, and H1N1

text: COVID-19 pandemic is a global crisis that threatens our way of life. As of April 29, 2020, COVID-19 has claimed more than 200,000 lives, with a global mortality rate of ~7% and recovery rate of ~30%. Understanding the interaction of cellular targets to the SARS-CoV2 infection is crucial for therapeutic development. Therefore, the aim of this study was to perform a comparative analysis of transcriptomic signatures of infection of COVID-19 compared to different respiratory viruses (Ebola, H1N1, MERS-CoV, and SARS-CoV), to determine unique anti-COVID1-19 gene signature. We identified for the first time molecular pathways for Heparin-binding, RAGE, miRNA, and PLA2 inhibitors, to be associated with SARS-CoV2 infection. The NRCAM and SAA2 that are involved in severe inflammatory response, and FGF1 and FOXO1 genes, which are associated with immune regulation, were found to be associated with a cellular gene response to COVID-19 infection. Moreover, several cytokines, most significantly the IL-8, IL-6, demonstrated key associations with COVID-19 infection. Interestingly, the only response gene that was shared between the five viral infections was SERPINB1. The PPI study sheds light on genes with high interaction activity that COVID-19 shares with other viral infections. The findings showed that the genetic pathways associated with Rheumatoid arthritis, AGE-RAGE signaling system, Malaria, Hepatitis B, and Influenza A were of high significance. We found that the virogenomic transcriptome of infection, gene modulation of host antiviral responses, and GO terms of both COVID-19 and Ebola are more similar compared to SARS, H1N1, and MERS. This work compares the virogenomic signatures of highly pathogenic viruses and provides valid targets for potential therapy against COVID-19.


title: A cross-sectional study of patients presenting for hospital-based screening for COVID-19: risk of disease, and healthcare access preferences.

text: Introduction: Early during the SARS-CoV-2 pandemic, Australian emergency departments (EDs) have experienced an unprecedented surge in patients seeking screening for COVID-19. Understanding what proportion of these patients require screening, who can be safely screened in community based models of care, and who requires an emergency departments to care for them is critical for workforce and infrastructure planning across the healthcare system, as well as public messaging campaigns. Methods: In this cross-sectional survey, we screened patients presenting to a SARS-CoV-2 screening clinic in a tertiary hospital Emergency Department in Melbourne, Australia. We assessed the proportion of patients who met screening criteria; self-reported symptom severity; reasons why they came to the ED for screening; views on community-based models of care; and sources of information accessed about COVID-19. Results: We included findings from 1846 patients who presented to the Emergency Department (ED) for COVID-19 screening from 18th to 30th March 2020. Most patients (55.3%) did not meet criteria for screening and most (57.6%) had mild or no (13.4%) symptoms. The main reason for coming to the ED was being referred by a telephone health service (31.3%) and 136 (7.4%) said they tried to contact their GP but could not get an appointment. Only 47 (2.6%) said they thought the disease was too specialized for their GP to manage. Patients accessed numerous information sources, commonly government websites (68.4%) and other websites (51.3%) for COVID-19 information. Conclusions: if we are to ensure that emergency departments can cope with the likely surge in presentations requiring resuscitation or inpatient care COVID-19, we should strengthen access to alternative services to triage patients to prevent unnecessary presentations at health services, and to direct those who are well but require screening away from EDs.


title: Evaluation of the disinfecting capacity of ozone in emergency vehicles.

text: Objective: As a consequence of the health crisis arising from the SARS-CoV-2 coronavirus pandemic, ozone treatments are being applied as disinfectant in emergency vehicles, without objective evidence on its efficacy. Here we evaluate the efficacy of ozone treatment over bacterial strains and virus-like particles. Method: A preparation of a lentiviral vector (lentivector) and dried cultures of two bacterial strains (gram + Staphylococcus aureus and gram - Salmonella enterica ser. Enteritidis) were placed inside an ambulance at two different locations. The interior of the vehicle was subjected to 10 min and 20 min treatments (3 and 6 times the recommended time by the manufacturer). Following the treatments, lentivector preparations were titrated, and viable bacteria (colony forming units, CFUs) counted and compared to pre-treatment titers and infectious CFUs of the same lysates and cultures. Results: None of the treatments significantly reduced either lentivector titer or the number of viable bacteria. Conclusions: At least in the analyzed conditions and for the microorganisms used in this study, it can be concluded that ozone treatment is not advisable for the disinfection of emergency vehicles.


title: Extracellular vesicles containing ACE2 efficiently prevent infection by SARS-CoV-2 Spike protein-containing virus

text: SARS-CoV-2 entry is mediated by binding of the spike protein (S) to the surface receptor ACE2 and subsequent priming by TMPRRS2 allowing membrane fusion. Here, we produced extracellular vesicles (EVs) exposing ACE2 and demonstrate that ACE2-EVs are efficient decoys for SARS-CoV-2 S protein-containing lentivirus. Reduction of infectivity positively correlates with the level of ACE2, is 500 to 1500 times more efficient than with soluble ACE2 and further enhanced by the inclusion of TMPRSS2.


title: Estimation of airborne viral emission: quanta emission rate of SARS-CoV-2 for infection risk assessment

text: Airborne transmission is a pathway of contagion that is still not sufficiently investigated despite the evidence in the scientific literature of the role it can play in the context of an epidemic. While the medical research area dedicates efforts to find cures and remedies to counteract the effects of a virus, the engineering area is involved in providing risk assessments in indoor environments by simulating the airborne transmission of the virus during an epidemic. To this end, virus air emission data are needed. Unfortunately, this information is usually available only after the outbreak, based on specific reverse engineering cases. In this work, a novel approach to estimate the viral load emitted by a contagious subject on the basis of the viral load in the mouth, the type of respiratory activity (e.g. breathing, speaking), respiratory physiological parameters (e.g. inhalation rate), and activity level (e.g. resting, standing, light exercise) is proposed. The estimates of the proposed approach are in good agreement with values of viral loads of well-known diseases from the literature. The quanta emission rates of an asymptomatic SARS-CoV-2 infected subject, with a viral load in the mouth of 108 copies mL-1, were 10.5 quanta h-1 and 320 quanta h-1 for breathing and speaking respiratory activities, respectively, at rest. In the case of light activity, the values would increase to 33.9 quanta h-1 and 1.03×103 quanta h-1, respectively. The findings in terms of quanta emission rates were then adopted in infection risk models to demonstrate its application by evaluating the number of people infected by an asymptomatic SARS-CoV-2 subject in Italian indoor microenvironments before and after the introduction of virus containment measures. The results obtained from the simulations clearly highlight that a key role is played by proper ventilation in containment of the virus in indoor environments.


title: Cost effectiveness of interventions for Post-Traumatic Stress Disorders following major incidents including terrorism and pandemics

text: Background Post-traumatic stress disorder (PTSD) is commonly experienced in the aftermath of major incidents such as terrorism and pandemics. Well-established principles of response include effective and scalable treatment for individuals affected by PTSD. In England, such responses have combined proactive outreach, screening, and evidence-based interventions (a 'screen-and-treat' approach), but little is known about the cost-effectiveness of this approach. Methods A decision modelling analysis was undertaken to estimate the costs per quality adjusted life year (QALY) gained from a screen-and-treat approach compared to treatment-as-usual. Model input variables were drawn from relevant empirical studies in the context of terrorism and the unit costs of health and social care in England. The model was run over a five-year time horizon for a hypothetical cohort of 1,000 exposed adults from the perspective of the National Health Service and Personal Social Services in England. Results The incremental cost per QALY gained was GBP8,297. This would be considered cost-effective 95% of the time at a willingness-to-pay threshold of GBP20,000 per QALY gained, the threshold associated with NICE. Sensitivity analysis confirmed this result was robust. Conclusions A screen-and-treat approach for identifying and treating PTSD in adults following major incidents appears cost-effective in England compared to treatment-as-usual through conventional primary care routes. This finding was in the context of terrorism but can be translatable into other major-incident related scenarios including the current COVID-19 pandemic in lieu of data on the impact of this pandemic.


title: SUBJECT INDEX

text: Unknown


title: Heterogeneity in the response of different subtypes of Drosophila melanogaster enteroendocrine cells to viral infections

text: Single cell RNA sequencing (scRNA-seq) offers the possibility to monitor both host and pathogens transcriptomes at the cellular level. Here, public scRNA-seq data from Drosophila melanogaster have been used to compare the differences in replication strategy and cellular response between two viruses, Thika virus (TV) and D. melanogaster Nora virus (DMelNV) in enteroendocrine cells (EEs). TV and DMelNV exhibited different patterns of replication and for TV, accumulation varied according to cell subtype. Cells infected with TV underwent down-regulation of genes that represent bottlenecks in the fruit fly interactome, while cells infected with DMelNV went through a down-expression of translation-related genes that represent both hubs and bottlenecks in the host interactome. In contrast, flies infected with DMelNV show only a systemic level down-regulation of bottleneck genes. Here, we use scRNA-seq to highlight the differences and commonalities between cellular response to TV and DMelNV and between cellular and systemic response to DMelNV.


title: A statistical forecast of LOW mortality (< 400,000 deaths) due to COVID-19, for the whole WORLD.

text: OBJECTIVE: To forecast the death toll of COVID-19 in the whole world by fitting the time series of reported deaths with a parametric equation (integrated Gaussian equation) related to Farr s law. DATA: The time series of cumulative deaths due to COVID-19 produced by John Hopkins University and stored in a github repository. RESULTS: The projected total death toll will be 261680 (392520 to 183176) which represents the 0.003 % of world population. This number amounts to 0.054 deaths per 1000, while the mean in the world (all causes) is 7.7. The daily peak of deaths (7270 (+/-500)) happened the 15 (+/- 3) of April, meaning that we are in descending curve of the pandemic. The outbreak will end completely the 23th (+/-3) of June. However, already on 9th (+/- 3) of May, 2 sigma; (95.45%) of the deaths will have be occured. The projected death toll is much lower (5-10 times) than those forecasted by the Imperial College Group (ICG) even considering the best scenario of total suppression of virus transmission. Using actual mortality rates it is possible to back calculate which number of infected individuals would produce such mortality. The death toll arises from a number of infected individuals between 53 (worst case) and 3.3 million. The calculated number of infected individuals is significantly lower than that calculated by ICG (227.5 millions) with suppression.


title: Process Mechanics Based Uncertainty Modeling for Cutting Force Prediction in High Speed Micromilling of Ti6Al4V

text: Abstract High speed machining is essential to counter the low flexural rigidity of micro-end mill in micromilling process. High speed machining can excite the higher frequency modes and in addition, run-out is also amplified. These effects in high speed micromachining induces the uncertainty in cutting forces. The estimation of cutting coefficients without inclusion of uncertainty cannot give accurate values and hence, the predicted cutting force and machining stability using these cutting coefficient may not be accurate. In the present work, cutting coefficients have been determined using the Bayesian inference which includes the uncertainty in estimated cutting coefficients. Note that, estimated cutting coefficient independent of chip load and cutting velocity does not include the high speed micromachining mechanics like size effect. The cutting coefficients have been estimated as a function of cutting velocity and chip load in the present work. The segmented cutting coefficients for different ranges of cutting speed varying from 10000 rpm to 110000 rpm has been obtained as a non-liner function of chip load. Bayesian inference modelling for cutting coefficients has been carried out using the Metropolis-Hastings (MH) algorithm Markov Chain Monte Carlo (MCMC) method. The convergence of prior and posterior distribution has been verified using correlation and trace of samples used for sampling. The posterior distribution shows that there is a good fitting, which accurately predicts the mean of the cutting coefficients. Finally, predicted cutting coefficients have been compared with cutting coefficients obtained from the deterministic approach using least square method. The experimentally estimated cutting coefficients are found to be lying within the upper and lower limit of predicted cutting coefficients with Bayesian inference approach. The predicted cutting coefficients using Bayesian inference shows the deviation of 0.89% and 8.4% at 40000 rpm from experimentally obtained cutting coefficients for tangential and radial cutting coefficients, respectively. The experimental cutting force is found to be lying within the upper and lower limit of predicted cutting force with Bayesian inference based cutting coefficients fitting at 105000 rpm.


title: COVID-19: Spatial Analysis of Hospital Case-Fatality Rate in France

text: When the population risk factors and reporting systems are similar, the assessment of the case-fatality (or lethality) rate (ratio of cases to deaths) represents a perfect tool for analyzing, understanding and improving the overall efficiency of the health system. The objective of this article is to estimate the influence of the hospital care system on lethality in metropolitan France during the inception of the COVID-19 epidemic, by analyzing the spatial variability of the hospital case-fatality rate between French districts. The results show that the higher case-fatality rates observed in certain districts are mostly related to the level of morbidity in the district, therefore to the overwhelming of the healthcare systems during the acute phases of the epidemic. However, the magnitude of this increase of case-fatality rate represents less than 10 per cent of the average case-fatality rate and cannot explain the magnitude of the variations in case-fatality rate reported by country by international organizations or information sites. These differences can only be explained by the systems for reporting cases and deaths, which, indeed, vary greatly from country to country, and not attributed to the care or treatment of patients, even during hospital stress due to epidemic peaks.


title: Origin of imported SARS-CoV-2 strains in The Gambia identified from Whole Genome Sequences

text: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a positive-sense single stranded RNA virus with high human transmissibility. This study generated Whole Genome data to determine the origin and pattern of transmission of SARS-CoV-2 from the first six cases tested in The Gambia. Total RNA from SARS-CoV-2 was extracted from inactivated nasopharyngeal-oropharyngeal swabs of six cases and converted to cDNA following the ARTIC COVID-19 sequencing protocol. Libraries were constructed with the NEBNext ultra II DNA library prep kit for Illumina and Oxford Nanopore Ligation sequencing kit and sequenced on Illumina MiSeq and Nanopore GridION, respectively. Sequencing reads were mapped to the Wuhan reference genome and compared to eleven other SARS-CoV-2 strains of Asian, European and American origins. A phylogenetic tree was constructed with the consensus genomes for local and non-African strains. Three of the Gambian strains had a European origin (UK and Spain), two strains were of Asian origin (Japan). In The Gambia, Nanopore and Illumina sequencers were successfully used to identify the sources of SARS-CoV-2 infection in COVID-19 cases.


title: Non-Linear fitting of Sigmoidal Growth Curves to predict a maximum limit to the total number of COVID-19 cases in the United States.

text: In the present work is used non-linear fitting of the "Gompert" and "Logistic" growth models to the number of total COVID-19 cases from the United States as a country and individually by states. The methodology allowed us to estimate that the maximum limit for the total number of cases of COVID-19 patients such as those registered with the World Health Organization will be approximately one million and one hundred thousand cases to the United States. Up to 04/19/20 the models indicate that United States reached 70% of this maximum number of "total cases" and the United States will reach 95% of this limit by 05/14/2020. The application of the nonlinear fitting of growth curves to the individual data of each American state showed that only 25% of them did not reach, on 04/19/20, the percentage of 59% of the maximum limit of "total cases" and that 17 of the 50 states still will not have reached 95% of that limit on 05/14/20.


title: Mining Implicit Relevance Feedback from User Behavior for Web Question Answering

text: Training and refreshing a web-scale Question Answering (QA) system for a multi-lingual commercial search engine often requires a huge amount of training examples. One principled idea is to mine implicit relevance feedback from user behavior recorded in search engine logs. All previous works on mining implicit relevance feedback target at relevance of web documents rather than passages. Due to several unique characteristics of QA tasks, the existing user behavior models for web documents cannot be applied to infer passage relevance. In this paper, we make the first study to explore the correlation between user behavior and passage relevance, and propose a novel approach for mining training data for Web QA. We conduct extensive experiments on four test datasets and the results show our approach significantly improves the accuracy of passage ranking without extra human labeled data. In practice, this work has proved effective to substantially reduce the human labeling cost for the QA service in a global commercial search engine, especially for languages with low resources. Our techniques have been deployed in multi-language services.


title: Novel Coronavirus (COVID-19) Knowledge and Perceptions: A Survey of Healthcare Workers

text: Background: During the first week of March, the surge of coronavirus disease 2019 (COVID-19) cases reached over 100 countries with more than 100,000 cases. Healthcare authorities have already initiated awareness and preparedness activities beyond borders. A poor understanding of the disease among healthcare workers (HCWs) may result in delayed treatment and the rapid spread of infection. This study aimed to investigate the knowledge and perceptions of HCWs about COVID-19. Methods: A cross-sectional, web-based study was conducted among HCWs about COVID-19 during the first week of March 2020. A 23-item survey instrument was developed and distributed randomly to HCWs using social media; it required 5 minutes to complete. A chi-square test was used to investigate the level of association among variables at the significance level of p<0.05. Results: Of 529 participants, a total of 453 HCWs completed the survey (response rate: 85.6%); 51.6% were males, 32.1% were aged 25-34 years, and most were doctors (30.2%) and medical students (29.6%). Regarding COVID-19, most of the participants used social media to obtain information (61%), and a significant proportion of HCWs had poor knowledge of its transmission (61%) and symptom onset (63.6%) and showed positive perceptions of COVID-19 prevention and control. Factors such as age and profession were associated with inadequate knowledge and poor perception of COVID-19. Conclusion: As the global threat of COVID-19 continues to emerge, it is critical to improve the knowledge and perceptions of HCWs. Educational interventions are urgently needed to reach HCWs beyond borders, and further studies are warranted.


Fitness during the COVID-19 Pandemic


title: OpenSAFELY: factors associated with COVID-19-related hospital death in the linked electronic health records of 17 million adult NHS patients.

text: Background Establishing who is at risk from a novel rapidly arising cause of death, and why, requires a new approach to epidemiological research with very large datasets and timely data. Working on behalf of NHS England we therefore set out to deliver a secure and pseudonymised analytics platform inside the data centre of a major primary care electronic health records vendor establishing coverage across detailed primary care records for a substantial proportion of all patients in England. The following results are preliminary. Data sources Primary care electronic health records managed by the electronic health record vendor TPP, pseudonymously linked to patient-level data from the COVID-19 Patient Notification System (CPNS) for death of hospital inpatients with confirmed COVID-19, using the new OpenSAFELY platform. Population 17,425,445 adults. Time period 1st Feb 2020 to 25th April 2020. Primary outcome Death in hospital among people with confirmed COVID-19. Methods Cohort study analysed by Cox-regression to generate hazard ratios: age and sex adjusted, and multiply adjusted for co-variates selected prospectively on the basis of clinical interest and prior findings. Results There were 5683 deaths attributed to COVID-19. In summary after full adjustment, death from COVID-19 was strongly associated with: being male (hazard ratio 1.99, 95%CI 1.88-2.10); older age and deprivation (both with a strong gradient); uncontrolled diabetes (HR 2.36 95% CI 2.18-2.56); severe asthma (HR 1.25 CI 1.08-1.44); and various other prior medical conditions. Compared to people with ethnicity recorded as white, black people were at higher risk of death, with only partial attenuation in hazard ratios from the fully adjusted model (age-sex adjusted HR 2.17 95% CI 1.84-2.57; fully adjusted HR 1.71 95% CI 1.44-2.02); with similar findings for Asian people (age-sex adjusted HR 1.95 95% CI 1.73-2.18; fully adjusted HR 1.62 95% CI 1.43-1.82). Conclusions We have quantified a range of clinical risk factors for death from COVID-19, some of which were not previously well characterised, in the largest cohort study conducted by any country to date. People from Asian and black groups are at markedly increased risk of in-hospital death from COVID-19, and contrary to some prior speculation this is only partially attributable to pre-existing clinical risk factors or deprivation; further research into the drivers of this association is therefore urgently required. Deprivation is also a major risk factor with, again, little of the excess risk explained by co-morbidity or other risk factors. The findings for clinical risk factors are concordant with policies in the UK for protecting those at highest risk. Our OpenSAFELY platform is rapidly adding further NHS patients' records; we will update and extend these results regularly. Keywords COVID-19, risk factors, ethnicity, deprivation, death, informatics.


title: The science of social distancing and total lock down: Does it work? whom does it benefit?

text: COVID-19 is spiralling like wild fire and has caused a global mayhem. Many lives have already been lost, and the global economy is at stake. In the absence of vaccine, social distancing and total lock down is the current mainstay in efforts to mitigate and flatten the epidemic curves. Several countries across the globe are currently implementing social distancing and total lock downs. However, what is social distancing and lock down? Does it work? Whom does it benefit? We expound on these questions and conclude that social distancing and lock down benefit the local and international community alike. Moreover, we hypothesis that evacuations may facilitate international spread of a highly contagious disease of pandemic potential.


Little Pharma


title: From Postmodernism to Posthumanism: Theorizing Ethos in an Age of Pandemic

text: This essay expands on the previous discussion, “Positioning Ethos” (Baumlin and Meyer 2018), which outlined a theory of ethos for the 21st century There, my coauthor and I observed the dialectic between ethics and ethotics, grounding subjectivity within a sociology of rhetoric: Contemporary ethos, thus, explores the physical embodiment (with its “markers of identity”), positionality, and “cultural dress” of speakers There as here, we looked to Heidegger for an expanded definition, one reaching beyond a speaker’s self-image to bring all aspects of our lifeworld—cultural, technological, biological, planetary—into a dynamic unity And, there as here, we observed the dialectic between speaker and audience: Within this transactional model, ethos marks the “space between” speaker and audience—a socially- and linguistically-constructed meeting ground (or, perhaps better, playground) where meanings can be negotiated Crucial to this transactional model is the skeptron, as described by Bourdieu: To possess the skeptron is to claim the cultural authority, expertise, trust, and means to speak and to be heard—indeed, to be seen—in one’s speaking To our previous essay’s ethics and ethotics, this present essay adds the dialectic arising between bios and technê We “dwell” in memory, in language, in history, in culture: All speakers in all cultural moments can claim as much But, writing in an age of postmodernism, we acknowledge the heightened roles of technology, “expert systems,” and urbanization in our lifeworld today What we had described as the cultural “habitus” of ethos is here supplemented by an ethos of scientific technoculture;similarly, what we had described as the existentialist “embodied self” is here supplemented by the postmodern—indeed, posthuman—ethos of the cyborg, a biotechnic “assemblage” part cybernetic machine and part living organism, simultaneously personal and collective in identity This posthuman con/fusion of bios and technê is not a transcendence of (human) nature;rather, it acknowledges our immersion within an interspecies biology while expanding our habitus from the polis to the planet It’s these aspects of our lifeworld—insterspecies biology, bodily health as self-identity, postmodern technology, and urban lifestyle—that COVID-19 pressures and threatens today In the current struggle between science-based medicine and conservative politics, the skeptron assumes life-and-death importance: Who speaks on behalf of medical science, the coronavirus victim, and community health?


title: Disinfecting handheld electronic devices with UV-C in a healthcare setting.

text: Handheld Electronic Devices (HEDs) play a central role in the current hospital environment. However, HEDs can be a potential vehicle for transmitting (pathogenic) microorganisms. We conducted a study to assess whether disinfection with UV-C light is successful in disinfecting three different handheld electronic devices in a clinical operational setting. More than half of the baseline measurements were moderately (>10CFU) or highly (>50 CFU) contaminated. Post-disinfection the CFU was 0 in 87% of measurements. We conclude that the UV-Smart D25 can successfully be used to disinfect non-critical handheld electronic devices in the clinical healthcare.


title: Biophysical modeling of the SARS-CoV-2 viral cycle reveals ideal antiviral targets

text: Effective therapies for COVID-19 are urgently needed. Presently there are more than 800 COVID-19 clinical trials globally, many with drug combinations, resulting in an empirical process with an enormous number of possible combinations. To identify the most promising potential therapies, we developed a biophysical model for the SARS-CoV-2 viral cycle and performed a sensitivity analysis for individual model parameters and all possible pairwise parameter changes (162 = 256 possibilities). We found that model-predicted virion production is fairly insensitive to changes in most viral entry, assembly, and release parameters, but highly sensitive to some viral transcription and translation parameters. Furthermore, we found a cooperative benefit to pairwise targeting of transcription and translation, predicting that combined targeting of these processes will be especially effective in inhibiting viral production.


title: Estimation of Undetected Symptomatic and Asymptomatic cases of COVID-19 Infection and prediction of its spread in USA

text: The reported COVID-19 cases in the USA have crossed over 2 million, and a large number of infected cases are undetected whose estimation can be done if country-wide antibody testing is performed. In this work, we estimate this undetected fraction of the population by modeling and simulation approach. We propose a new epidemic model SIPHERD in which three categories of infection carriers Symptomatic, Purely Asymptomatic, and Exposed are considered with different transmission rates that are taken dependent on the lockdown conditions, and the detection rate of the infected carriers is taken dependent on the tests done per day. The model is first validated for Germany and South Korea and then applied for prediction of total number of confirmed, active and death, and daily new positive cases in the United States. Our study also demonstrates the possibility of a second wave of the infection if social distancing regulations are relaxed to a large extent. We estimate that around 12.7 million people are already infected, and in the absence of any vaccine, 17.7 million (range: 16.3-19.2) people, or 5.3% (range: 4.9-5.8) of the population will be infected by when the disease spread ends in the USA. We find the Infection to Fatality Ratio to be 0.93% (range: 0.85-1.01).


title: Geospatial Correlation Between COVID-19 Health Misinformation on Social Media and Poisoning with Household Cleaners

text: Prolific social media activity has accompanied the COVID-19 pandemic. Health misinformation on social media may lead to harm from using toxic substances, especially in a pandemic where few vetted therapies exist. Here we show that social media activity on Twitter precedes increased exposure to bleach and other cleaning products. We analyzed tweets from the Greater Boston Area and compared them to calls to the Massachusetts and Rhode Island Poison Control Center. Social media activity accounted for 30-40% spikes in calls to poison control centers 2-3 days later. The time-lagged cross-correlation was only significant for tweets geotagged as from the Greater Boston area, strengthening the specificity of this relationship.


title: Early phase of the COVID-19 outbreak in Hungary and post-lockdown scenarios

text: COVID-19 epidemic has been suppressed in Hungary due to timely non-pharmaceutical interventions, prompting a huge reduction in the number of contacts and transmission of the virus. This strategy was effective in preventing epidemic growth and reducing the incidence of COVID-19 to low levels. In this report, we present the first epidemiological and statistical analysis of the early phase of the COVID-19 outbreak in Hungary. Then, we establish an age-structured compartmental model to explore alternative post-lockdown scenarios. We incorporate various factors, such as age-specific measures, seasonal effects, and spatial heterogeneity to project the possible peak size and disease burden of a COVID-19 epidemic wave after the current measures are relaxed.


title: 2019 Novel Coronavirus Disease Outbreak and Molecular Genetic Characteristics of Severe Acute Respiratory Syndrome-coronavirus-2

text: The 2019 novel coronavirus disease (COVID-19) outbreaks that emerged in Wuhan city, Hubei province, have led to a formidable number of confirmed cases that resulted in >5,700 deaths globally, including 143 countries in all 6 continents. The World Health Organization declared a Public Health Emergency of International Concern with a very high level of global risk assessment. Severe acute respiratory syndrome (SARS)-coronavirus-2 (SARS-CoV-2), the agent of COVID-19, has >79% nucleotide sequence homology to SARS-CoV; therefore, both belong to the genus betacoronavirus and subgenus sarbecovirus. The S1 domains of the two appeared to share the cellular receptor ACE2, but revealed a much higher S1-ACE2 binding affinity. As seen in many other human coronaviruses, SARS-CoV-2 also shows respiratory infection, but the basic reproductive number (R0) in transmission and the clinical latency are quite dissimilar from those of SARS-or MERS-CoVs. Many scientists infer that the time point of cross-barrier transfer from bats to mediate animals or to humans should be a rather recent event based on the full-length genome analyses obtained from the very first patients. Copy-choice polymerization, which often leads to a significant genome recombination rate in most coronaviruses, predicts the continued emergence of novel coronaviruses.


title: Generation of human bronchial organoids for SARS-CoV-2 research

text: Coronavirus disease 2019 (COVID-19) is a disease that causes fatal disorders including severe pneumonia. To develop a therapeutic drug for COVID-19, a model that can reproduce the viral life cycle and evaluate the drug efficacy of anti-viral drugs is essential. In this study, we established a method to generate human bronchial organoids (hBO) from commercially available cryopreserved human bronchial epithelial cells and examined whether they could be used as a model for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) research. Our hBO contain basal, club, ciliated, and goblet cells. Angiotensin-converting enzyme 2 (ACE2), which is a receptor for SARS-CoV-2, and transmembrane serine proteinase 2 (TMPRSS2), which is an essential serine protease for priming spike (S) protein of SARS-CoV-2, were highly expressed. After SARS-CoV-2 infection, not only the intracellular viral genome, but also progeny virus, cytotoxicity, pyknotic cells, and moderate increases of the type I interferon signal could be observed. Treatment with camostat, an inhibitor of TMPRSS2, reduced the viral copy number to 2% of the control group. Furthermore, the gene expression profile in SARS-CoV-2-infected hBO was obtained by performing RNA-seq analysis. In conclusion, we succeeded in generating hBO that can be used for SARS-CoV-2 research and COVID-19 drug discovery. Graphical abstract


title: Long-term potentiation prevents ketamine-induced aberrant neurophysiological dynamics in the hippocampus-prefrontal cortex pathway in vivo

text: N-methyl-D-aspartate receptor (NMDAr) antagonists such as ketamine (KET) produce psychotic-like behavior in both humans and animal models. NMDAr hypofunction affects normal oscillatory dynamics and synaptic plasticity in key brain regions related with schizophrenia, particularly in the hippocampus and the prefrontal cortex. In contrast, long-term potentiation (LTP) induction is known to increase glutamatergic transmission. Thus, we hypothesized that LTP could mitigate the electrophysiological changes promoted by KET. We recorded HPC-PFC local field potentials and evoked responses in urethane anesthetized rats, before and after KET administration, preceded or not by LTP induction. Our results show that KET promotes an aberrant delta-high-gamma crossfrequency coupling in the PFC and an enhancement in HPC-PFC evoked responses. LTP induction prior to KET attenuates changes in synaptic efficiency and prevents the increase in cortical gamma amplitude comodulation. These findings are consistent with evidence that increased efficiency of glutamatergic receptors attenuates cognitive impairment in animal models of psychosis. Therefore, high-frequency stimulation in HPC may be a useful tool to better understand how to prevent NMDAr hypofunction effects on synaptic plasticity and oscillatory coordination in cortico-limbic circuits.


title: On spatial molecular arrangements of SARS-CoV2 genomes of Indian patients

text: A pandemic caused by the SARS-CoV2 is being experienced by the whole world since December, 2019. A thorough understanding beyond just sequential similarities among the protein coding genes of SARS-CoV2 is important in order to differentiate or relate to the other known CoVs of the same genus. In this study, we compare three genomes namely MT012098 (India-Kerala), MT050493 (India-Kerala), MT358637 (India-Gujrat) from India with NC_045512 (China-Wuhan) to view the spatial as well as molecular arrangements of nucleotide bases of all the genes embedded in these four genomes. Based on different features extracted for each gene embedded in these genomes, corresponding phylogenetic relationships have been built up. Differences in phylogenetic tree arrangement with individual gene suggest that three genomes of Indian origin have come from three different origins or the evolution of viral genome is very fast process. This study would also help to understand the virulence factors, disease pathogenicity, origin and transmission of the SARS-CoV2.


title: Mathematical modelling for coronavirus disease (COVID-19) in predicting future behaviours and sensitivity analysis

text: Nowadays, there are a variety of descriptive studies of available clinical data for coronavirus disease (COVID-19) Mathematical modelling and computational simulations are effective tools that help global efforts to estimate key transmission parameters The model equations often require computational tools and dynamical analysis that play an important role in controlling the disease This work reviews some models for coronavirus first, that can address important questions about the global health care and suggest important notes Then, we model the disease as a system of differential equations We develop previous models for the coronavirus, some key computational simulations and sensitivity analysis are added Accordingly, the local sensitivities for each model state with respect to the model parameters are computed using three different techniques: non-normalizations, half normalizations and full normalizations Results based on sensitivity analysis show that almost all model parameters may have role on spreading this virus among susceptible, exposed and quarantined susceptible people More specifically, communicate rate person-to-person, quarantined exposed rate and transition rate of exposed individuals have an effective role in spreading this disease One possible solution suggests that healthcare programs should pay more attention to intervention strategies, and people need to self-quarantine that can effectively reduce the disease


title: Hydroxychloroquine and Azithromycin as a treatment of COVID-19: preliminary results of an open-label non-randomized clinical trial

text: Background Chloroquine and Hydroxychloroquine have been found to be efficient on COV-19, and reported to be efficient in Chinese patients infected by this virus. We evaluate the role of Hydroxychloroquine on respiratory viral loads. Patients and methods Patients were included in a single arm protocol to receive 600mg of hydroxychloroquine daily and their viral load in nasal swabs was tested daily. Depending on their clinical presentation azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative control. Presence and absence of virus at Day-6 was considered the end point. Results Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D-6 compared to controls, and much lower than reported average carrying duration of untreated patients in the literature. Azithromycin added to Hydroxychloroquine was significantly more efficient for virus elimination. Conclusion : Hydroxychloroquine is significantly associated with viral load reduction/disappearance in patients with COVID-19 and its effect is reinforced by Azithromycin.


title: Age Associated Coronavirus Disease 2019 Incubation Period: Impact on Quarantine Policy

text: A unified 14-day quarantine may not effectively contain the spread of COVID-19. With the current recommendation of a uniform 14-day quarantine, up to 9.2% of patients 42 or younger and 18.6% of patients older than 42 years could develop symptoms after the end of the period.


title: Superconducting Nanowire Single-Photon Detectors for Quantum Information

text: The superconducting nanowire single-photon detector (SNSPD) is a quantum-limit superconducting optical detector based on the Cooper-pair breaking effect by a single photon, which exhibits a higher detection efficiency, lower dark count rate, higher counting rate, and lower timing jitter when compared with those exhibited by its counterparts. SNSPDs have been extensively applied in quantum information processing, including quantum key distribution and optical quantum computation. In this review, we present the requirements of single-photon detectors from quantum information, as well as the principle, key metrics, latest performance issues and other issues associated with SNSPD. The representative applications of SNSPDs with respect to quantum information will also be covered.


title: Understanding the Incidence of Covid-19 among the police force in Maharashtra through a mixed approach

text: Abstract Background: The study tries to understand the incidence of COVID-19 among police officials along with the challenges they face and their preparedness during the pandemic response in Maharashtra. Method: The study analyzed the daily trends of confirmed, active, recovered, and deceased cases for Maharashtra and police professional. Ten telephonic in-depth interviews and a descriptive survey were conducted to obtain experiences of police regarding their combat against Covid-19. Results: PPR (0.01 to 1.12), CRR (0 to 39.22) and CFR (0 to 1.07) have consistently increased and CRR found lower among police than the general population. The qualitative data by analyzing several indicators suggests that there is a higher individual efficacy over collective efficacy among the police force. Further, the long-time fight against Covid-19 had drained police force mentally and physically and this put them in higher risk. Conclusion: Immediate priority interventions like provision of protective gears need to be provided by the government to control the risk of infection among police. Holistic support and recovery system from all stakeholders of society needed for the well-being of the police force so that they can soldier on to avert such a crisis in future. Keywords: COVID-19, Police force, Efficacy


title: Simplified model of the number of Covid-19 patients in the ICU: update April 6, 2020

text: INTRODUCTION: Predicting the number of Covid19 patients in the Intensive Care Units (ICU) could be useful to avoid the breaking point. We attempted to deduce a formula in order to model the number of the ICU patients in France from the official data and patient turnover in the ICU. METHODS: The Covid19 ICU patient turnover was calculated using a recurrence relation from the internal data provided by Hospices Civils de Lyon. The number of new Covid19 cases detected daily was modelized to fit with the last known data in France and extrapolated for the coming days using two scenarios following the existing data in China (best scenario) and Italy (worst scenario). The number of daily admissions in ICU was calculated as the sum of 13.7% of the new Covid19 cases detected on a given day and 7.8% of the average of the total new Covid-19 cases recorded in the last week. Approximately 39.7% of patients admitted to the ICU were non-intubated with an average ICU length of stay of 4 days. Conversely, 60.3% of patients were intubated and for those who died among them (14.44%) the ICU length of stay was of 4 days for 78.3% of them and of 15 days for 21.7% of them. For the intubated patients that were discharged alive, the ICU length of stay was of 6 days for 44.4% of them and of 20 days for 55.6% of them. RESULTS: We predict a peak of between 7072 and 8043 patients for the overall French territory. CONCUSION: Despite a simplified mathematical model, the strength of our study is a narrow possible range of predicted total number of ICU patients.


title: Diagnostic Indexes of a Rapid IgG/IgM Combined Antibody Test for SARS-CoV-2

text: [Abstract]Objective Coronavirus disease 2019 has become pandemic in the world. The need for IgG/IgM combined antibody test is booming, but data on diagnostic indexes evaluation was inadequate. The aim of this study was to evaluate diagnostic indexes of a rapid IgG/IgM combined antibody test for SARS-CoV-2. Methods A total of 179 patients were enrolled. Serum were collected for IgG-IgM combined antibody test and corresponding nasal and pharyngeal swab specimens were collected for SARS-CoV-2 RT-PCR. According to SARS-CoV-2 RT-PCR results, patients under study were categorized as PCR positive group in 90 patients and PCR negative group in 89 patients. Results 1. Of the 90 PCR positive samples, 77 were tested positive by SARS-CoV-2 IgG-IgM test kit, yielding a sensitivity of 85.6%. Meanwhile, of the 89 PCR negative sample, 8 samples were detected positive, resulting in a specificity of 91%. Positive predictive value, negative predictive value and accuracy of this test kit was 95.1%, 82.7%, and 88.3%, respectively. Kappa efficiency between IgG/IgM test kit and RT-PCR were 0.75. 2. Accuracy in mild/common and severe/critical subgroup were 73.9% and 97.7%, respectively. Accuracy in clinical confirmed, suspected cases and other disease subgroups were 70%, 60%, and 100%, respectively. 3. Patients were further divided into 0-7, 8-15 and >= 16 groups according to the time from illness onset to sample collection. Sensitivity, specificity and accuracy in these three groups were 18.8%, 77.8% and 40%; 100%, 50% and 87.5%; 100%, 64.3%, and 93.9, respectively. Conclusion The sensitivity and specificity of this ease-of-use IgG/IgM combined test kit were adequate, plus short turnaround time, no specific requirements for additional equipment or skilled technicians, all of these collectively contributed to its competence for mass testing. At the current stage, it cannot take the place of SARA-CoV-2 nucleic acid RT-PCR, but can be served as a complementary option for RT-PCR. The combination of RT-PCR and IgG-IgM combined test kit could provide further insight into SARS-CoV-2 infection diagnosis.


title: The role of remdesivir in South Africa: preventing COVID-19 deaths through increasing ICU capacity

text: Countries such as South Africa have limited intensive care unit (ICU) capacity to handle the expected number of COVID-19 patients requiring ICU care. Remdesivir can prevent deaths in countries such as South Africa by decreasing the number of days people spend in ICU, therefore freeing up ICU bed capacity.


title: Eruption of COVID-19 like illness in a remote village in Papua (Indonesia)

text: Background The COVID-19 pandemic is creating significant challenges for healthcare infrastructure for countries of all development and resource levels. Low-and-middle resource countries face even larger challenges, as their resources are stretched and often insufficient under normal circumstances. A village in the Papuan highlands of Indonesia; small, isolated, accessed only by small plane or trekking has experienced an outbreak typical of COVID-19. Methodology/Principal Findings This description was compiled from patient care records by lay healthcare workers in M20 (a pseudonym) during and after an outbreak and from medical doctors responding to online requests for help. We assume that, for reasons given, the outbreak that has been described was COVID-19. The dense social structure of the village resulted in a rapid infection of 90-95% of the population. Physical distancing and isolation measures were used, but probably implemented suboptimal and too late, and their effect on the illness course was unclear. The relatively young population, with a majority of women, probably influenced the impact of the epidemic, resulting in only two deaths so far. Conclusions/Significance This outbreak pattern of suspected SARS-CoV-2 in a village in the highlands of Papua (Indonesia) presents a unique report of the infection of an entire village population over five weeks. The age distribution, common in Papuan highland villages may have reduced case fatality rate (CFR) in this context and that might be the case in similar remote areas since survival to old age is already very limited and CFR among younger people is lower.


title: COVID-19 most vulnerable Mexican cities lack the public health infrastructure to face the pandemic: a new temporally-explicit model

text: Recently, a wide array of epidemiological models has been developed to guide public health actors in containing the rapid dissemination of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), cause of COVID-19. Despite their usefulness, many epidemiological models recently developed to understand the spread of SARS-CoV-2 and infection rates of COVID-19 fall short as they ignore human mobility, limiting our understanding of the spread of the disease, together with the vulnerability of population centers in a broad scale. We developed a new temporally-explicit model and simulated several social distancing scenarios to predict the vulnerability to COVID-19 of 50 Mexican cities that are interconnected by their air transportation network. Additionally, we assessed the sufficiency of the public health infrastructure in the focal cities to face the pandemic over time. Based on our model, we show that the most important cities within the Mexican air transportation network are the most vulnerable to COVID-19, with all assessed public health infrastructure being insufficient to face the modeled scenario for the pandemic after 100 days. Despite these alarming findings, our results show that social distancing could dramatically decrease the total number of infected people (77% drop-off for the 45% distancing scenario when contrasted with no distancing), flattening the growth of infection rate. Thus, we consider that this study provides useful information that may help decision-makers to timely implement health policies to anticipate and lessen the impact of the current pandemic in Mexico.