title: Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection

text: COVID-19 is a global pandemic caused by the SARS-CoV-2 coronavirus. T cell response is a critical part of both individual and herd immunity to SARS-CoV-2 and the efficacy of developed vaccines. However neither the dynamics and cross-reactivity of the SARS-CoV-2-specific T cell response nor the diversity of resulting immune memory are well understood. In this study we use longitudinal high-throughput T cell receptor sequencing to track changes in the T cell repertoire following two mild cases of COVID-19 infection. In both donors we identified SARS-CoV-2-responding CD4+ and CD8+ T cell clones. We describe characteristic motifs in TCR sequences of COVID-19-reactive clones, suggesting the existence of immunodominant epitopes. We show that in both donors the majority of infection-reactive clonotypes acquire memory phenotypes. Certain CD4+ clones were detected in the memory fraction at the pre-infection timepoint, suggesting participation of pre-existing cross-reactive memory T cells in the immune response to SARS-CoV-2.


Cancer Care in “Covid” Times—Indian Solutions to Universal Problems


title: Oncology and COVID-19: Perspectives on Cancer Patients and Oncologists in Africa

text: Abstract The global communities have been grappling with health pandemics for months since the outbreak of COVID-19, which has been flagged a global health emergency by World Health Organization, WHO. While the entire health sector has been overburdened, cancer patients are also at a high risk of getting infected during this COVID-19 pandemic, hence there is a great concern for these patients because there are little to no data to support their management with the current health care structure in Africa. This article outlines the challenges frontline health workers face in the management of cancer patients, as all the entire health sector calls for effective policy formulation and implementation by the government in their role in ensuring the sound health of their citizenry.


title: Is a 14-day quarantine period optimal for effectively controlling coronavirus disease 2019 (COVID-19)?

text: Background The outbreak of a new coronavirus (SARS-CoV-2) disease (Covid-19) has become pandemic. To be more effectively controlling the disease, it is critical to set up an optimal quarantine period so that about 95% of the cases developing symptoms will be retained for isolation. At the moment, the WHO-established quarantine period is 14 days based on previous reports which had studied small sizes of hospitalized cases (10 and ~100, respectively), however, over 80% of adult- and 95% of child-cases were not necessary to stay in hospitals, and therefore, had not been hospitalized. Therefore, we are questioning if the current-inferred median incubation time is representative for the whole Covid-19 population, and if the current quarantine period is optimal. Methods We compiled and analyzed the patient-level information of 2015 laboratory-confirmed Covid-19 cases including 99 children in 28 Chinese provinces. This cohort represents a wide-range spectrum of Covid-19 disease with both hospitalized and non-hospitalized cases. Results The full range of incubation periods of the Covid-19 cases ranged from 0 to 33 days among 2015 cases. There were 6 (0.13%) symptom-free cases including 4 females with a median age of 25.5 years and 2 males with a median age of 36 years. The median incubation period of both male and female adults was similar (7-day) but significantly shorter than that (9-day) of child cases (P=0.02). This cohort contained 4 transmission generations, and incubation periods of the cases between generations were not significantly different, suggesting that the virus has not been rapidly adapted to human beings. Interestingly, incubation periods of 233 cases (11.6%) were longer than the WHO-established quarantine period (14 days). Data modeling suggested that if adults take an extra 4-day or 7-day of isolation (i.e., a quarantine period of 18 or 21 days), 96.2% or 98.3%, respectively, of the people who are developing symptoms will be more effectively quarantined. Patients transmitted via lunch/dinner parties (i.e., gastrointestinal tract infection through oral transmission) had a significantly longer incubation period (9-day) than other adults transmitted via respiratory droplets or contaminated surfaces and objects (P<0.004). Conclusions The whole Covid-19 population including both hospitalized and non-hospitalized cases had a median incubation period of 7-day for adults, which is 1.8-day longer than the hospitalized cases reported previously. An extension of the adult quarantine period to 18 days or 21 days could be more effective in preventing virus-spreading and controlling the disease. The cases transmitted by lunch/dinner parties could be infected first in the gastrointestinal tract through oral transmission and then infected in the respiratory system so that they had a longer incubation period.


title: Presence of Live SARS-CoV-2 Virus in Feces of Coronavirus Disease 2019 (COVID-19) Patients: A Rapid Review

text: Coronavirus disease 2019 (COVID-19) is a rapidly escalating pandemic that has spread to many parts of the world. The disease has already affected over 6 million individuals, with over 400,000 fatalities. Recent studies have confirmed the presence of SARS-CoV-2 nucleic acids in feces of Coronavirus disease 2019 (COVID-19) patients using RT-PCR tests. It is however, still unclear as to whether or not live SARS-CoV-2 virus is actually present in feces of these patients. In this rapid review, we systematically analyzed literature to establish any evidence of live SARS-CoV-2 virus in fecal samples of COVID-19 patients. We identified 4 studies (one case report, 2 case series and 1 cohort study) where the SARS-CoV-2 was successfully isolated from fecal samples of COVID-19 patients using culture techniques. Therefore, there is some evidence COVID-19 could shed live SARS-CoV-2 virus via the gastro-intestinal tract. Larger studies are needed to corroborate these findings, as well as to determine its potential for disease transmission and infection, and possible implications for COVID-19 discharge and isolation policies.


title: Quantitative intravital imaging of Plasmodium falciparum sporozoites: A novel platform to test malaria intervention strategies

text: Malaria infection starts with the injection of motile Plasmodium sporozoites into the host’s skin during a mosquito bite. Previous studies using the rodent malaria model indicate that the dermal inoculation site may be where sporozoites are most vulnerable to antibodies, yet, functional in vivo assays with human malaria parasites are lacking. Here, we present the first characterization of P. falciparum sporozoites in the skin, comparing their motility to two rodent malaria species and investigating whether the environment of its natural host influences P. falciparum sporozoite motility using a human skin xenograft model. The combined data suggest that in contrast to the liver and blood stages, the skin is not a species-specific barrier for Plasmodium. We observe that P. falciparum sporozoites inoculated into mouse skin move with similar speed, displacement and duration, and enter blood vessels in similar numbers as the rodent parasites. Thus, interventions targeting P. falciparum sporozoite migration can be tested in the murine dermis. Importantly, to streamline quantification of sporozoite motility, we developed a toolbox allowing for automated detection and tracking of sporozoites in intravital microscopy videos. This establishes a platform to test vaccine candidates, immunization protocols, monoclonal antibodies and drug candidates for their impact on human malaria sporozoites in vivo. Screening of intervention strategies for in vivo efficacy against Pf sporozoites using this new platform will have the potential to validate targets prior to expensive clinical trials.


title: SCALE19: A scalable and cost-efficient method for testing Covid-19 based on hierarchical group testing

text: Containment of Covid-19 requires an extensive testing of the affected population. Some propose global testing to effectively contain Covid-19. Current tests for Covid-19 are administered individually. These tests for Covid-19 are expensive and are limited due to the lack of resources and time. We propose a simple and efficient group testing method for Covid-19. We propose a group testing method where test subjects are grouped and tested. Depending on the result of the group test, subsequent sub groups are formed and tested recursively based on a quartery search algorithm. We designed and built an evaluation model that simulates test subject population, infected test subjects according to available Covid-19 statistics, and the group testing processes in SCALE19. We considered several population models including USA and the world. Our results show that we can significantly reduce the required number of tests up to 89% without sacrificing the accuracy of the individual test of the entire population. For USA, up to 280 million tests can be reduced from the total US population of 331 million and it would be equivalent saving of $28 billion assuming a cost of $100 per test. For the world, 6.96 billion tests can be reduced from the total population of 7.8 billion and it would be equivalent to saving $696 billion. We propose SCALE19 can significantly reduce the total required number of tests compared to individual tests of the entire population. We believe SCALE19 is efficient and simple to be deployed in containment of Covid-19.


title: Searching the Sigmoid-type trend in Lock Down period covid19 data of India and its different states

text: We have worked on imported covid19 cases of India, detected after declaration of lock down. They are marked as hidden travelers, who are detected later during 1-2 weeks period of lock down. We have investigated the impact of those travelers on selective 15 states, having large number cases. Among them 5 states have faced a noticeable effect on their data profile, although its overall effect in country level is quite negligible. Searching the Sigmoid trends of all 15 states, we have identified 3 categories depending upon latest data of new case with respect to the peak value of Sigmoid functions. Based on our optimistic predicted curves, ongoing lock down period might be enough for getting marginal values of new cases for KL, HR, JK, TN and AP but the reamining of 15 states might need a third phase of lock down or alternative preventive measures.


Coronavirus Disease Pandemic Is a Real Challenge for Brazil


title: Suppression and Mitigation Strategies for Control of COVID-19 in New Zealand

text: A standard SEIR-type compartment model, parameterised for New Zealand, was used to simulate the spread of Covid19 in New Zealand and to test the effectiveness of various control strategies. Control aims can be broadly categorised as either suppression or mitigation. Suppression aims to keep cases to an absolute minimum for as long as possible. Mitigation aims to allow a controlled outbreak to occur, with the aim of preventing significant overloads on healthcare systems and gradually allowing the population to develop herd immunity. Both types of strategy are fraught with uncertainty. Suppression strategies can succeed in delaying an outbreak, but only for as long as such control measures can be sustained. Once controls are eased or restricted, an epidemic is likely to follow as no herd immunity has been acquired. The success or failure of mitigation strategies can depend sensitively on the timing and efficacy of control measures, and require the ability to bring rapidly growing outbreaks under immediate control when needed. This is as yet untested even for a combination of national interventions including case isolation, household quarantine, population-wide social distancing and closure of schools and universities. Although there are disadvantages to both types of approach, suppression has the advantage of buying time until a vaccine and/or treatment become available and allowing NZ to learn from rapidly unfolding events in other countries. A combination of successful suppression, strong border measures, and widespread contact tracing and testing resulting in containment could allow periods when control measures can be relaxed, but only if cases are reduced to a handful.


title: Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, double-blinded, phase IIb clinical trial (CloroCovid-19 Study)

text: Background There is no specific antiviral therapy recommended for the disease caused by SARS-CoV-2 (COVID-19). Recent publications have drawn attention to the possible benefit of chloroquine (CQ). Our study aimed to comprehensively evaluate the safety and efficacy of two different CQ dosages in patients with established severe COVID-19. Methods We performed a parallel, double-blinded, randomized, phase IIb clinical trial, aiming to assess safety and efficacy of two different CQ dosages as adjunctive therapy of hospitalized patients with SARS in Manaus, Brazilian Amazon. Eligible participants were allocated to receive orally or via nasogastric tube high dose CQ (600mg CQ twice daily for 10 days or total dose 12g); or low dose CQ (450mg for 5 days, twice daily only on the first day, or total dose 2.7g). In addition, all patients received ceftriaxone and azithromycin. This study was registered with ClinicalTrials.gov, number NCT04323527. Findings Out of a pre-defined 440 patients sample size, 81 patients were enrolled. The high dose CQ arm presented more QTc>500ms (25%), and a trend toward higher lethality (17%) than the lower dosage. Fatality rate was 13.5% (95%CI=6.9-23.0%), overlapping with the CI of historical data from similar patients not using CQ (95%CI=14.5-19.2%). In 14 patients with paired samples, respiratory secretion at day 4 was negative in only one patient. Interpretation Preliminary findings suggest that the higher CQ dosage (10-day regimen) should not be recommended for COVID-19 treatment because of its potential safety hazards. Such results forced us to prematurely halt patient recruitment to this arm. Given the enormous global push for the use of CQ for COVID-19, results such as the ones found in this trial can provide robust evidence for updated COVID-19 patient management recommendations.


title: Efficacy and Safety of Lopinavir/Ritonavir for Treatment of COVID-19: A Systematic Review and Meta-Analysis

text: Background Since the emergence of COVID-19, the world has been desperate to find effective therapeutics and vaccinations to treat hundreds of thousands of affected patients and to suppress the spread of this global pandemic. Lopinavir-ritonavir (LPV/RTV) is an HIV antiviral combination that has been considered for treatment of this disease. Aim of the study This systematic review and meta-analysis aimed to assess the efficacy and safety of lopinavir/ritonavir in COVID-19 patients in the extant published research. A systematic review protocol was developed based on PRISMA-P and the PRISMA statement. Published English and non-English articles written since December 1, 2019 were selected for review from 8 electronic databases. Readily accessible full articles (cohort studies and clinical trials) which specifically mentioned lopinavir/ritonavir and patients with lab-confirmed SARS-CoV-2 or COVOID-19 of any age were included. Three researchers separately evaluated the bias in the reported articles. We conducted a systematic review and meta-analysis with the objective of evaluation of the safety and efficacy of LPV/RTV alone or in combination with other drugs with regard to time to becoming PCR negative, time to body temperature normalization and cough relief, radiological progression, and safety. Review Manager (RevMan) was used to conduct all statistical analyses and generate the forest plots. Meta-analyses were performed using the Mantel Hazel method or the inverse variance method for dichotomous data and continuous data respectively. Results Non-duplicate articles (n=76) were evaluated for possible inclusion. A consensus was reached to select 29 articles for full-text screening, only 11 articles comprised 1,192 patients were included in this study, and six of which were included for meta-analysis. In terms of virological cure (PCR negative), three studies reported less time in days to achieve a virological cure for LPV/RTV arm relative to no antiviral therapy (conventional) (mean difference = -0.81 day; 95% CI, -4.44 to 2.81; P = 0.007, I2 = 80%). However, the overall effect was not significant (P = 0.66). When comparing LPV/RTV arm to umifenovir arm, a favorable affect was observed for umifenovir arm, but not statically significant (mean difference = 0.95 day; 95% CI, -1.11 to 3.01; P = 0.09, I2 = 58%). In terms of time to body normalization and cough relief (clinical cure), two studies reported on time to temperature normalization with no significant effect of LPV/RTV (n = 93) versus umifenovir (n = 71) arm), (OR = 0.87 day; 95% CI, 0.42 to 1.78; (P = 0.70), I2 = 0%), or alleviation of cough duration (p = 0.69). In terms of CT evidence of radiological progression of pneumonia/lung damage, treatment with lopinavir/ritonavir resulted in no significant decrease in the radiological progression (OR = 0.80; 95% CI, 0.42 to 1.54; P = 0.59, I2 = 81%), In terms of safety, a greater number of adverse events were reported for lopinavir/ritonavir (n=45) relative to the umifenovir arm (n=14) and conventional treatments (n=10 ), P = 0.004, 0,0007, respectively Conclusions The small number of studies included in this systematic review and meta-analysis study did not reveal any statistically significant advantage in efficacy of lopinavir-ritonavir in COVID-19 patients, over conventional or other antiviral treatments. This result might not reflect the actual evidence.


title: The potential role of miR-21-3p in coronavirus-host interplay

text: Host miRNAs are known as important regulators of virus replication and pathogenesis. They can interact with various viruses by several possible mechanisms including direct binding the viral RNA. Identification of human miRNAs involved in coronavirus-host interplay is becoming important due to the ongoing COVID-19 pandemic. In this work we performed computational prediction of high-confidence direct interactions between miRNAs and seven human coronavirus RNAs. In order to uncover the entire miRNA-virus interplay we further analyzed lungs miRNome of SARS-CoV infected mice using publicly available miRNA sequencing data. We found that miRNA miR-21-3p has the largest probability of binding the human coronavirus RNAs and being dramatically up-regulated in mouse lungs during infection induced by SARS-CoV. Further bioinformatic analysis of binding sites revealed high conservativity of miR-21-3p binding regions within RNAs of human coronaviruses and their strains.


title: Correlation between hypophosphatemia and the severity of Corona Virus Disease 2019 patients

text: Objective: Retrospectively analyze the clinical data of Corona Virus Disease 2019 (COVID-19) patients and explore the value of serum phosphorus level in evaluating the severity and prognosis of the disease. Methods: COVID-19 patients transferred from the first emergency ward of Taiyuan fourth people's Hospital from February 8 to March 3, 2020 were selected. The information of general conditions, clinical manifestations, laboratory indexes, nucleic acid detection and treatment were collected. The changes of blood phosphorus level and absolute value of lymphocytes in ordinary and severe/critical patients were recorded and compared. Results: A total of 32 patients with COVID-19 were collected, including 12 cases of common type and 20 cases of severe/critical type. Before treatment, the serum phosphorus levels of the two groups were significantly lower than the normal level, and the serum phosphorus levels of the severe/critical patients were lower than those of the common type patients (t = 2.767, P < 0.010). After treatment, the serum phosphorus levels of the two groups reached normal, and there was no significant difference between the two groups (t = 0.231, P > 0.819). The level of lymphocytes in severe/critical patients was lower than that in normal patients (t = 4.636, P < 0.001) before treatment. After treatment, the absolute value of lymphocytes in the two groups reached normal, and there was no significant difference between the two groups (t=1.208, P=0.237). There was a positive correlation between lymphocytes and serum phosphorus, and the correlation coefficient was 0.479. Conclusion: hypophosphatemia is related to the severity of COVID-19, and strengthening the monitoring of serum phosphorus level of COVID-19's severe/critical patients and correcting hypophosphatemia in time are of significance to improve the prognosis.


title: The FDA-approved drug Nelfinavir inhibits lytic cell-free transmission of human adenoviruses

text: Adenoviruses (AdVs) are prevalent and give rise to chronic and recurrent disease. The human AdV (HAdV) species B and C, such as HAdV-C2, C5 and B14, cause respiratory disease, and constitute a health threat for immuno-compromised individuals. HAdV-Cs are well known for lysing cells, owing to the E3 CR1-β-encoded adenovirus death protein (ADP). We previously reported a high-throughput image-based screening framework and identified an inhibitor of HAdV-C2 multi-round infection, Nelfinavir Mesylate. Nelfinavir is the active ingredient of Viracept, an FDA-approved inhibitor of the human immuno-deficiency virus (HIV) aspartyl protease, and used to treat acquired immunodeficiency syndrome (AIDS). It is not effective against single round HAdV infections. Here, we show that Nelfinavir inhibits the lytic cell-free transmission of HAdV, indicated by the suppression of comet-shaped infection foci in cell culture. Comet-shaped foci occur upon convection-based transmission of cell-free viral particles from an infected cell to neighbouring uninfected cells. HAdV lacking ADP was insensitive to Nelfinavir, but gave rise to comet-shaped foci indicating that ADP enhances but is not required for cell lysis. This was supported by the notion that HAdV-B14 and B14p1 lacking ADP were highly sensitive to Nelfinavir, although HAdV-A31, B3, B7, B11, B16, B21, D8, D30 or D37 were less sensitive. Conspicuously, Nelfinavir uncovered slow-growing round-shaped HAdV-C2 foci, independent of neutralizing antibodies in the medium, indicative of non-lytic cell-to-cell transmission. Our study demonstrates the repurposing potential of Nelfinavir with post-exposure efficacy against different HAdVs, and describes an alternative non-lytic cell-to-cell transmission mode of HAdV. Graphical Abstract Figure 1.


title: COVID-19 infection during pregnancy: A systematic review to summarize possible symptoms, treatments, and pregnancy outcomes

text: Abstract Background: With the exponential increase in coronavirus disease 2019 (COVID-19) worldwide, an increasing proportion of pregnant women are now infected during their pregnancy. The aims of this systematic review were to summarize the possible symptoms, treatments, and pregnancy outcomes of women infected with COVID-19 during their pregnancy. Methods: Four databases (Medline, Web of Science, Scopus, and CINAHL) were searched on March 25, 2020, using the following keywords: 'COVID-19', 'nCoV-2019', and 'coronavirus'. Articles included if they reported either the symptoms, treatments for the women who had been infected with the COVID-19 during their pregnancy or pregnancy outcomes. The selected articles' results were summarized employing a narrative synthesis approach. Results: A total of nine studies were selected for this study, comprising 101 infected pregnant women. Other than the infected general population, infected pregnant women reported different symptoms; however, fever (66.7%), cough (39.4%), fatigue (15.2%), and breathing difficulties (14.1%) were common. Infected pregnant women were given different treatments than the general infected population. The C-section was a common (83.9%) mode of delivery among infected pregnant women, and a higher proportion of births were preterm births (30.4%) and low birth weight (17.9%). Conclusions: Pregnant infected women had different symptoms, and they were given dissimilar treatments than the general infected population. Healthcare providers may have appropriately informed about these symptoms and treatments. They, therefore, would be able to handle infection during pregnancy effectively, which would reduce common adverse consequences among infected pregnant women.


title: COVID-19 and its ramifications for cancer patients in low-resource settings: Ghana as a case study

text: The impact of COVID-19 on healthcare in low- and middle-income countries (LMICs) is a major challenge requiring urgent measures. Cancer care in LMICs, including Ghana, is faced with inadequate numbers of skilled healthcare professionals and essential material resources which negatively impacts the quality of healthcare and wellbeing of patients. In the face of COVID-19, cancer patients are likely to be affected in three key ways: access to healthcare, increased financial toxicity and increased mental health burden as a consequence of strict measures being implemented to contain the virus in Ghana, including partial lockdowns and social distancing. Some cultural beliefs regarding COVID-19 and its influence on the health and wellbeing of cancer patients have also been discussed. Measures by the government to lessen the burden on citizens and health workers are highlighted with possible recommendations for improvement in cancer care in Ghana and other LMICs during this pandemic.


title: Network pharmacology for treatment of COVID-19 with Renshen Baidu Powder based on cytokines/ 基于细胞因子的人参败毒散治疗新型冠状病毒肺炎（COVID-19）的网络药理学研究

text: Objective: To investigate the multi compound-target-pathway mechanism of Renshen Baidu Powder (RSBDS) in the treatment of COVID-19 from cytokine perspective. Methods: The active compounds of RSBDS were collected by TCMSP and the cytokine storm related targets were collected by the drug target database. The interaction network of RSBDS on single drug-active compounds-targets was established by Cytoscape. The interaction network, GO function and KEGG pathway of the targets were analyzed by String and DAVID databases. Results: The interaction network of RSBDS on single drug-active compounds-targets included 10 kinds of medicinal materials, 211 active compounds and 151 disease targets. Interaction network showed that the targets related to the inhibition to cytokine storm of RSBDS on COVID-19 might include STAT3, MAPK1, NFκB1, PIK3CA, MAPK3, TNF, CXCR4, VEGFA, IL-6, IL-2, etc. GO function showed that above targets in biological function involved chemotaxis and steroid metabolism; Molecular function entries involved heme binding, iron ion binding and oxygen binding; Cell composition entries involved cell surface and cell membrane. KEGG pathway showed that above targets participated in the regulation of Chagas disease, HIF-1 signaling pathway, TNF signaling pathway, etc. Conclusion: The multi compound-target-pathways effect of RSBDS on COVID-19 was realized by inhibiting cytokine storm, which through regulating chemotaxis, increasing blood oxygen saturation, inhibiting STAT, MAPK, NFκB, PIK3K and IL-6 signal pathways.


title: Broad-spectrum antivirals of protoporphyrins inhibit the entry of highly pathogenic emerging viruses

text: Severe emerging and re-emerging viral infections such as Lassa fever, Avian influenza (AI), and COVID-19 caused by SARS-CoV-2 urgently call for new strategies for the development of broad-spectrum antivirals targeting conserved components in the virus life cycle. Viral lipids are essential components, and viral-cell membrane fusion is the required entry step for most unrelated enveloped viruses. In this paper, we identified a porphyrin derivative of protoporphyrin IX (PPIX) that showed broad antiviral activities in vitro against a panel of enveloped pathogenic viruses including Lassa virus (LASV), Machupo virus (MACV), and SARS-CoV-2 as well as various subtypes of influenza A viral strains with IC50 values ranging from 0.91±0.25 μM to 1.88±0.34 μM. A mechanistic study using influenza A/Puerto Rico/8/34 (H1N1) as a testing strain showed that PPIX inhibits the infection in the early stage of virus entry through biophysically interacting with the hydrophobic lipids of enveloped virions, thereby inhibiting the formation of the negative curvature required for fusion and blocking the entry of enveloped viruses into host cells. In addition, the preliminary antiviral activities of PPIX were further assessed by testing mice infected with the influenza A/Puerto Rico/8/34 (H1N1) virus. The results showed that compared with the control group without drug treatment, the survival rate and mean survival time of the mice treated with PPIX were apparently prolonged. These data encourage us to conduct further investigations using PPIX as a lead compound for the rational design of lipid-targeting antivirals for the treatment of infection with enveloped viruses.


title: Mega-phylogeny sheds light on SARS-CoV-2 spatial phylogenetic structure

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent RNA virus that spread around the planet in about 4 months. The consequences of this rapid spread on the virus evolution are under investigation. In this work, we analyzed ca. 9,000 SARS-CoV-2 genomes from Africa, America, Asia, Europe, and Oceania. We show that the virus is a complex of slightly different genetic variants that are unevenly distributed on Earth. Furthermore, we demonstrate that SARS-CoV-2 phylogeny is spatially structured. We hypothesize this could be the result of founder effects occurring as a consequence of, and local evolution occurring after, long-distance dispersal. In light of our results, we discuss how dispersal may constitute an opportunity for the virus to fix otherwise rare, and/or develop new, mutations. Based on previous studies, the possibility that this could significantly affect the virus phenotype is not remote. Relevance A cluster of pneumonia cases of unknown etiology was reported in December 2019 in Wuhan, Hubei province, China. Since then, hundreds of thousands of people have died all around the planet. Quickly after the pandemic onset, metagenomic studies showed the causative agent, now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), belonged to the Betacoronavirus genus, responsible for spillover events in 2002 and 2012 (severe acute respiratory syndrome and Middle East respiratory syndrome, respectively). The zoonotic origins of these viruses (possibly bats, camelids, pangolins and/or palm civets) have received much attention. However, other evolutionary aspects, such as spatial variation, have received comparatively little attention. This study shows that SARS-CoV-2 variants, which we call virotypes, are heterogeneously distributed on Earth and demonstrates that the virus phylogeny is geographically structured. We explain how this may be due to founder effects combined with high mutation rates.


title: Resurgent natures? More-than-human perspectives on COVID-19

text: Stories of nature’s resurgence during quarantine have been dangerously conflated with an alarming narrative contending ‘Earth is healing, we are the virus’. Deploying a more-than-human perspective, we show how this discourse arises from biocultural decontextualisation that assumes nature has an inherent capacity to resurge. Such fetishisations distract from the need for urgent environmental action and obscure what resurgence actually is: a multispecies endeavour requiring cultivation and nurture.


title: Oral administration of a single anti-CfaE nanobody provides broadly cross-protective immunity against major pathogenic Enterotoxigenic Escherichia coli strains

text: Enterotoxigenic Escherichia coli (ETEC) is estimated to cause approximately 380,000 deaths annually during sporadic or epidemic outbreaks worldwide. There is currently no vaccine licensed to prevent ETEC. Development of prophylaxis against ETEC is challenging due to the vast heterogeneity of the ETEC strains. The discovery of nanobodies has emerged as a successful new biologics in treating mucosal infectious disease as nanobodies can recognize conserved epitopes on hypervariable pathogens. In this study, we performed large screens using immunized llamas and a naïve nanobody yeast display library against adhesins of colonization factors. Cross-protective nanobodies were selected with in vitro activities inhibiting mannose-resistant hemagglutination (MRHA) against all eleven major pathogenic ETEC strains. Oral administration of nanobodies led to significant reduction of bacterial colonization in animals challenged with multiple ETEC strains. Structural analysis revealed novel conserved epitopes as critical structural features for pan-ETEC vaccine design. Two of the lead nanobodies, 2R215 and 1D7, were further engineered as trimer or fused with human IgA Fc-fragments as fusionbodies. Oral administration of the trimers or fusionbodies protected mice from infection at a much lower dose compared to the monomeric format. Importantly, fusionbodies prevented infection as a pre-treatment when administrated 2 hours before ETEC challenge to the animals. Together, our study provides the first proof of concept that oral administration of a single nanobody could confer broad protection against major pathogenic ETEC strains. Technological advances in large-scale manufacturing of biological proteins in plants and microorganisms will make nanobody-based immunotherapy a potent and cost-effective prophylaxis or treatment for ETEC.


title: Potential impact of seasonal forcing on a SARS-CoV-2 pandemic

text: A novel coronavirus (SARS-CoV-2) first detected in Wuhan, China, has spread rapidly since December 2019, causing more than 80,000 confirmed infections and 2,700 fatalities (as of Feb 27, 2020). Imported cases and transmission clusters of various sizes have been reported globally suggesting a pandemic is likely. Here, we explore how seasonal variation in transmissibility could modulate a SARS-CoV-2 pandemic. Data from routine diagnostics show a strong and consistent seasonal variation of the four endemic coronaviruses (229E, HKU1, NL63, OC43) and we parameterize our model for SARS-CoV-2 using these data. The model allows for many subpopulations of different size with variable parameters. Simulations of different scenarios show that plausible parameters result in a small peak in early 2020 in temperate regions of the Northern Hemisphere and a larger peak in winter 2020/2021. Variation in transmission and migration rates can result in substantial variation in prevalence between regions. While the uncertainty in parameters is large, the scenarios we explore show that transient reductions in the incidence rate might be due to a combination of seasonal variation and infection control efforts but do not necessarily mean the epidemic is contained. Seasonal forcing on SARS-CoV-2 should thus be taken into account in the further monitoring of the global transmission. The likely aggregated effect of seasonal variation, infection control measures and transmission rate variation is a prolonged pandemic wave with lower prevalence at any given time, thereby providing a window of opportunity for better preparation of health care systems.


Contact tracing: Can ‘Big tech’ come to the rescue, and if so, at what cost?


title: Predictive Modeling for Epidemic Outbreaks: A New Approach and COVID-19 Case Study

text: Since the onset of the COVID-19 outbreak in Wuhan, China, numerous forecasting models have been proposed to project the trajectory of coronavirus infection cases. Most of these forecasts are based on epidemiology models that utilize deterministic differential equations and have resulted in widely varying predictions. We propose a new discrete-Time Markov chain model that directly incorporates stochastic behavior and for which parameter estimation is straightforward from available data. Using such data from China's Hubei province (for which Wuhan is the provincial capital city and which accounted for approximately 82% of the total reported COVID-19 cases in the entire country), the model is shown to be flexible, robust, and accurate. As a result, it has been adopted by the first Shanghai assistance medical team in Wuhan's Jinyintan Hospital, which was the first designated hospital to take COVID-19 patients in the world. The forecast has been used for preparing medical staff, intensive care unit (ICU) beds, ventilators, and other critical care medical resources and for supporting real-Time medical management decisions.


title: Efficacy and Safety of Remdesivir for COVID-19 Treatment: An Analysis of Randomized, Double-Blind, Placebo-Controlled Trials

text: BACKGROUND Remdesivir, an inhibitor of viral RNA-dependent RNA polymerases, has been identified as a candidate for COVID-19 treatment. However, the therapeutic effect of remdesivir is controversial. METHODS We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials, from inception to June 11, 2020 for randomized controlled trials on the clinical efficacy of remdesivir. The main outcomes were discharge rate, mortality, and adverse events. This study is registered at INPLASY (INPLASY202060046). RESULTS Data of 1075 subjects showed that remdesivir significantly increased the discharge rate of patients with COVID-19 compared with the placebo (50.4% vs. 45.29%; relative risk [RR] 1.19 [95% confidence interval [CI], 1.05-1.34], I2 = 0.0%, P = 0.754). It also significantly decreased mortality (8.18% vs. 12.70%; RR 0.64 [95% CI, 0.44-0.92], I2 = 45.7%, P = 0.175) compared to the placebo. Data of 1296 subjects showed that remdesivir significantly decreased the occurrence of serious adverse events (RR 0.77 [95% CI, 0.63-0.94], I2 = 0.0%, P = 0.716). CONCLUSION Remdesivir is efficacious and safe for the treatment of COVID-19. TRIAL REGISTRATION NUMBER This study is registered at the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY202060046).


Covid-19 and heart disease


title: Upper arm length along with mid-upper arm circumference to enhance wasting prevalence estimation and diagnosis : sensitivity and specificity in 6 to 59 month-old children.

text: Objective: To evaluate the added value of the use of upper arm length (UAL) along with MUAC (mid-upper arm circumference) to diagnose and estimate the prevalence of wasting in comparison to current WHO standard and others MUAC based methods. Design: We included UAL to usual anthropometric measurements during a Mauritanian national 6-59-month-old cross-sectional nutritional survey. Children were classified into 3 groups UALG1, UALG2 and UALG3 according to the following UAL limits: [≤] 150 mm, 151-180, and > 180mm respectively. We used a Receiver Operating Characteristic curve to determine the best MUAC cut-off for each group with weight-for-height Z score as a reference standard. We compared the wasting prevalence, sensitivity, and specificity, of all diagnostic methods. Findings: In total, 12 619 children were included in the study. Wasting prevalence was 16.1%, 5.0% and 12.5% when diagnosed by WHZ < -2, MUAC < 125 mm and MUAC-UALG methods respectively. Using the MUAC-UALG method increased the sensitivity for wasting diagnosis from 17.98 % with MUAC < 125 mm to 39.43% with MUAC-UALG. The specificity decreased from 97.49% with MUAC < 125 to 92.71% with MUAC-UALG. With MUAC-height Z score and MUAC < 138 mm, sensitivity was 26.04% and 69.76%and specificity were 97.40%and 75.64% respectively. Conclusion: This alternative method using MUAC measuring tape to measure UAL increases the wasting diagnosis accuracy and allows for a better estimation of wasting prevalence. This method could be used as a potential alternative method for quick surveys in emergency settings such as Corona virus disease 2019 context.


title: The psychology of coronavirus fear: Are healthcare professionals suffering from corona-phobia?

text: Background: Coronaviruses are a category of associated viruses that trigger diseases, including severe acute respiratory syndrome-related coronavirus (SARS-CoV) in 2003, human coronavirus NL63 (HCoV NL63) in 2004, human coronavirus HKU1 (HKU1) in 2005, Middle East respiratory syndrome-related coronavirus (MERS-CoV) in 2012, and severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) in December 2019. Objective: This study used a qualitative and quantitative approach to measure Covid-19 pandamic’s impact on psychological well-being. At the moment, the world is fearing from this widespread pandemic, its outbreak and has no idea how it is leaving psychological effects on human well-being. Method: This study designed questionnaires to judge the psychological health of healthcare professionals those are directly treating quarantined patients within the hospital. We asked questions from 250-healthcare professionals (including doctors, nurses, and paramedical staff) who are treating quarantined patients at different hospitals of Lahore, Pakistan. Results: This study concludes that corona-phobia persist in healthcare professionals and cause various psychological symptoms on their mental health. Conclusion & Policy Implication: This study suggests the government need to provide medical facilities/equipment with those healthcare professionals who are frontline soldiers in treating quarantine patients.


title: Interferon-a2b treatment for COVID-19

text: Summary Background The global pandemic of COVID-19 cases caused by infection with SARS-CoV-2 is ongoing. We describe here the clinical course of COVID-19 in a cohort of confirmed cases in Wuhan, China, treated with the repurposed potential experimental therapeutics IFN-α2b, arbidol or a combination of IFN-α2b plus arbidol. Methods 77 adults with confirmed COVID-19 were treated with either nebulized IFN-α2b (5mU,b.i.d.), arbidol (200mg dispersible tablet, t.i.d.) or a combination of IFN-α2b plus arbidol. Serial SARS-CoV-2 testing along with hematological measurements, including cell counts and blood biochemistry, serum cytokine levels, temperature and blood oxygen saturation levels were recorded for each patient during their hospital stay. Findings Treatment with IFN-α2b with or without arbidol significantly reduced the duration of detectable virus in the upper respiratory tract and in parallel reduced duration of elevated blood levels for the inflammatory markers IL-6 and CRP. Interpretation IFN-α2b should be investigated as therapy in COVID-19 cases.


title: Increased travel times to United States SARS-CoV-2 testing sites: a spatial modeling study

text: Importance: Access to testing is key to a successful response to the COVID-19 pandemic. Objective: To determine the geographic accessibility to SARS-CoV-2 testing sites in the United States, as quantified by travel time. Design: Cross-sectional analysis of SARS-CoV-2 testing sites as of April 7, 2020 in relation to travel time. Setting: United States COVID-19 pandemic. Participants: The United States, including the 48 contiguous states and the District of Columbia. Exposures: Population density, percent minority, percent uninsured, and median income by county from the 2018 American Community Survey demographic data. Main Outcome: SARS-CoV-2 testing sites identified in two national databases (Carbon Health and CodersAgainstCovid), geocoded by address. Median county 1 km2 gridded friction surface of travel times, as a measure of geographic accessibility to SARS-CoV-2 testing sites. Results: 6,236 unique SARS-CoV-2 testing sites in 3,108 United States counties were identified. Thirty percent of the U.S. population live in a county (N = 1,920) with a median travel time over 20 minutes. This was geographically heterogeneous; 86% of the Mountain division population versus 5% of the Middle Atlantic population lived in counties with median travel times over 20 min. Generalized Linear Models showed population density, percent minority, percent uninsured and median income were predictors of median travel time to testing sites. For example, higher percent uninsured was associated with longer travel time (B= 0.41 min/percent, 95% confidence interval 0.3-0.53, p = 1.2x10-12), adjusting for population density. Conclusions and Relevance: Geographic accessibility to SARS-Cov-2 testing sites is reduced in counties with lower population density and higher percent of minority and uninsured, which are also risk factors for worse healthcare access and outcomes. Geographic barriers to SARS-Cov-2 testing may exacerbate health inequalities and bias county-specific transmission estimates. Geographic accessibility should be considered when planning the location of future testing sites and interpreting epidemiological data.


title: The novel coronavirus and its possible treatment by vaccines, therapeutics and drug delivery systems: Current status and future perspectives

text: In the mid-end of December 2019, several cases of pneumonia outbreak of unknown cause and etiology were identified in Wuhan City of Hubei province in China, a city with a population of over 11 million. Till date(April 2020) around 1,051,635 confirmed cases of coronavirus disease 2019(COVID-19) and 56,985 confirmed deaths have been reported according to COVID-19 Situation Report – 75 by WHO. On 7th January 2020, the causative agent was iden-tified and named consequently as Severe Acute Respiratory Syndrome Coron-avirus 2 (SARS-CoV-2) by the Chinese Centre for Disease Control and Prevention (CCDC) from throat swab samples. Later, on 12th January 2020, this coro-navirus was named as 2019-novel coronavirus (2019-nCoV) by World Health Organization (WHO) and in 11th February 2020,it has been declared the epidemic disease caused by SARS-CoV-2 as Corona Virus Disease 2019(COVID-19) as it is spreading rapidly from its origin in Wuhan City to the rest of the world. In this context, the current review provides a landscape of the novel Corona Virus including its origin, transmission, epidemiology, drugs and vaccines in clinical trials for better understanding to the reads and peoples the status and future perspectives of this pandemic disease.


title: Relations of parameters for describing the epidemic of COVID―19 by the Kermack―McKendrick model

text: In order to quantitatively characterize the epidemic of COVID―19, useful relations among parameters describing an epidemic in general are derived based on the Kermack-McKendrick model. The first relation is 1/τgrow=1/τtrans−1/τinf, where τgrow is the time constant of the exponential growth of an epidemic, τtrans is the time for a pathogen to be transmitted from one patient to uninfected person, and the infectious time τinf is the time during which the pathogen keeps its power of transmission. The second relation p(∞) ≈1−exp(−(R0−1)/0.60) is the relation between p(∞), the final size of the disaster defined by the ratio of the total infected people to the population of the society,and the basic reproduction number, R0, which is the number of persons infected by the transmission of the pathogen from one infected person during the infectious time. The third relation 1/τend=1/τinf−(1−p(∞))/τtrans gives the decay time constant τend at the ending stage of the epidemic. Derived relations are applied to influenza in Japan in 2019 for characterizing the epidemic.


title: A data-driven method to detect the flattening of the COVID-19 pandemic curve and estimating its ending life-cycle using only the time-series of new cases per day.

text: The novel Coronavirus-19 disease (COVID-19) has emerged as a pandemic and has presented itself as an unprecedented challenge to the majority of countries worldwide. The containment measures for this disease such as the requirement of health care facilities greatly rely on estimating the future dynamics and flattening of the COVID-19 curve. However, it is always challenging to estimate the future trends and flattening of the COVID-19 curve due to the involvement of many real-life variables. Recently, traditional methods based on SIR and SEIR have been presented for predictive monitoring and detection of flattening of the COVID-19 curve. In this paper, a novel method for detection of flattening of the COVID-19 curve and its ending life-cycle using only the time-series of new cases per day is presented. Simulation results are compared to the SIR based methods in three different scenarios using COVID-19 curves for South Korea, the United States of America, and India. In this study, simulations, performed on the 26th April 2020 show that the peak of the COVID-19 curve in the USA has already arrived and situated on the 14th of April 2020, while the peak of the COVID-19 curve for India has yet to arrive.


docid: hipujblu

title: Adoption and impact of non-pharmaceutical interventions for COVID-19

text: Background: Several non-pharmaceutical interventions (NPIs) have been implemented across the world to control the coronavirus disease (COVID-19) pandemic. Social distancing (SD) interventions applied so far have included school closures, remote working and quarantine. These measures have been shown to have large impacts on pandemic influenza transmission. However, there has been comparatively little examination of such measures for COVID-19. Methods: We examined the existing literature, and collated data, on implementation of NPIs to examine their effects on the COVID-19 pandemic so far. Data on NPIs were collected from official government websites as well as from media sources. Results: Measures such as travel restrictions have been implemented in multiple countries and appears to have slowed the geographic spread of COVID-19 and reduced initial case numbers. We find that, due to the relatively sparse information on the differences with and without interventions, it is difficult to quantitatively assess the efficacy of many interventions. Similarly, whilst the comparison to other pandemic diseases such as influenza can be helpful, there are key differences that could affect the efficacy of similar NPIs. Conclusions: The timely implementation of control measures is key to their success and must strike a balance between early enough application to reduce the peak of the epidemic and ensuring that they can be feasibly maintained for an appropriate duration. Such measures can have large societal impacts and they need to be appropriately justified to the population. As the pandemic of COVID-19 progresses, quantifying the impact of interventions will be a vital consideration for the appropriate use of mitigation strategies.


title: Procedural knowledge and function blocks for smart process planning

text: Abstract In the age of digital manufacturing there is a need to elicit and transfer procedural knowledge between humans and machines. Having proper knowledge is essential in decision-making. The more the knowledge, the better decisions are made. To capture experiences and turn them into knowledge is fundamental in learning processes and knowledge development. Knowledge engineering and knowledge management have been subject for research for decades and several concepts about knowledge and knowledge transfer have been introduced, but a functional approach to exploit knowledge efficiently in manufacturing is still missing. In the era of Industry 4.0, humans and machines must be able to collaborate in such way that both can exploit the best abilities of each other in a manufacturing process. This paper introduces a procedural knowledge process (PKP) approach to capturing and defining unexpected events, while a process step is able to perform its required functions and transfer that information as machine-understandable knowledge about a failure mode. Function blocks (FBs), as per the IEC-61499 standard, have been proposed as a way to achieve distributed process planning in which the manufacturing process can adapt itself to runtime conditions, e.g. machine availability, etc. However, FBs are event-driven systems and the approach is limited to work under well-known runtime conditions, e.g. machine configurations and states, or deviations which are impossible to foresee in advance, for instance the outcome of a process failure mode effects analysis (PFMEA). The PKP introduced in this paper, aims at bridging this gap by integrating at runtime an expert operator’s solution based on root cause analysis (RCA) in an FB architecture, making the FB knowledge-driven systems, for further executions of the same without redesigning it. Natural language representations of procedural knowledge blocks (PKBs) allow to transfer procedural knowledge to human operators, i.e. explain the process flow of a machine decision, while machine representations of PKBs allow to embed procedural knowledge that is elicited from expert operators upon unexpected events into the FBs process. The resulting PKP enhances the FBs for smart industrial applications, such as the process planning use case described in this paper.


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title: Respiratory Failure in Covid19 is associated with increased monocyte expression of complement receptor 3

text: A key question in COVID-19 infection is why some previously healthy patients develop severe pulmonary failure and some ultimately die. Initial pulmonary failure does not exhibit classical features of ARDS; hypercoagulability is a common laboratory feature, and pulmonary thrombotic microangiopathy has been reported post mortem1,2,3. Biomarkers cannot robustly identify such patients pre-emptively and no specific interventions exist to mitigate clinical deterioration. Mononuclear phagocytic cells are key immune cells and bind fibrinogen through the CD11b/CD18 dimer CR3, whose activated form can initiate microthrombus formation. Accordingly, we profiled circulating monocyte CD11b/CD18 cell surface density from COVID-19 infected adults who were (i) symptomatic but breathless, (ii) requiring ventilatory support, and (iii) recovering following ICU care for hypoxia.


title: Vaccines and Drug Therapeutics to Lock Down Novel Coronavirus Disease 2019 (COVID-19): A Systematic Review of Clinical Trials

text: The ongoing novel coronavirus disease 2019 (COVID-19) pandemic has been responsible for millions of infections and hundreds of thousands of deaths. To date, there is no approved targeted treatment, and many investigational therapeutic agents and vaccine candidates are being considered for the treatment of COVID-19. To extract and summarize information on potential vaccines and therapeutic agents against COVID-19 at different stages of clinical trials from January to March 2020, we reviewed major clinical trial databases such as ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP), and other primary registries between January and March 15, 2020. Interventional studies at different phases under the COVID-19 pipeline were included. A total of 249 clinical trials were identified between January to March 15, 2020. After filtering observational studies (194 studies), a total of 56 interventional trials were considered. The majority of clinical trials have been conducted on chloroquine (n=10) and traditional Chinese medications (TCMs; n=10), followed by antivirals (n=8), anti-inflammatory/immunosuppressants (n=9), cellular therapies (n=4), combinations of different antivirals therapies (n=3), antibacterial (n=1), and other therapies (n=5). Five vaccines are under phase I, and there are a couple of phase III trials on the Bacillus Calmette-Guérin (BCG) vaccine under investigation among healthcare workers. Many novel compounds and vaccines against COVID-19 are currently under investigation. Some candidates have been tested for other viral infections and are listed for clinical trials against the COVID-19 pipeline. Currently, there are no effective specific antivirals or drug combinations available for the treatment of COVID-19.


Comments on the publication by Yerramilli et al titled “Palliative Radiotherapy for Oncologic emergencies in the setting of COVID-19: Approaches to Balancing Risks and Benefits.”


title: Coronavirus Disease 2019 (COVID-19) Complicated by Acute Respiratory Distress Syndrome: An Internist’s Perspective

text: A pandemic outbreak of a novel coronavirus disease (COVID-19) that began in Wuhan, China, in December 2019 has spread rapidly to multiple countries. In the United States, the first confirmed case was reported on January 20, 2020, and since then, the number of cases is rising exponentially on a daily basis. We report a case of COVID-19 infection that presented with symptoms suggestive of pneumonia. Due to the major backlog with an immense number of pending tests, it took 48 hours for the result to come back positive, while the patient went into acute respiratory distress syndrome. We provide an internist’s perspective of the difficulties encountered in terms of the available management options, as the patient progressively deteriorated on the regular medical floor prompting transfer to the intensive care unit.


title: Modelling and simulation of COVID-19 propagation in a large population with specific reference to India

text: Deterministic mathematical models (called Compartmental models) of disease propagation such as the SIR model and its variants (MSIR, Carrier state, SEIR, SEIS, MSEIR, MSEIRS models) are used to study the propagation of COVID19 in a large population with specific reference to India.


title: Multiscale dynamics of COVID-19 and model-based recommendations for 105 countries

text: We analyse the dynamics of COVID-19 using computational modelling at multiple scales. For large scale analysis, we propose a 2-scale lattice extension of the classical SIR-type compartmental model with spatial interactions called the Lattice-SIRQL model. Computational simulations show that global quantifiers are not completely representative of the actual dynamics of the disease especially when mitigation measures such as quarantine and lockdown are applied. Furthermore, using real data of confirmed COVID-19 cases, we calibrate the Lattice-SIRQL model for 105 countries. The calibrated model is used to make country specific recommendations for lockdown relaxation and lockdown continuation. Finally, using an agent-based model we analyse the influence of cluster level relaxation rate and lockdown duration on the spread of the disease.


title: He who defends everything, defends nothing: proactivity in organizational resilience

text: Organisational resilience is most often defined as the ability to function during a shock and then return to normal function; consequently, it has been studied from the perspective of organisational disciplines closely related to crisis and crisis-recovery, such as supply-chain management and risk management. However, increasing complexity and the volume, variety and velocity of shocks has created an environment where the organisation must proactively and continuously demonstrate resilience, through the cultivation of anticipatory innovation.


title: The knowledge and practice towards COVID-19 pandemic prevention among residents of Ethiopia: An Online Cross-Sectional Study

text: Background The Novel coronavirus disease-2019 (COVID-19) is now the international concerns and a pandemic, since the World Health Organization declared as the outbreaks. The objective of this study to assess the prevention knowledge and practices towards the COVID-19 among the residents of Ethiopia. Methods An online cross-sectional study was conducted among the sample of Ethiopian residents via social platforms of the author’s network with the popular media such as Facebook, in Ethiopia from the April 15-22, 2020 and successfully recruited 341 responses. The snowball sampling was employed to recruit the participants. The data were analyzed using STATA version 14. Descriptive statistics were used to summarize the level of knowledge and practices. Results The majority of the respondents (80.35%) were male. The overall prevention knowledge of the participants towards the novel coronavirus (COVID-19) was high. About 91.2% of the participant was heard about the novel coronavirus disease and Social Medias’ were the main source of the information. About 90% of the participants had a good prevention knowledge of maintaining social distance and frequent hand washing. The practices of the participants towards the COVID-19 prevention were very low. Out of 341 participants, only 61% and 84% of the participants were practicing social distance and frequent hand washing, respectively. Conclusions Majority of the participants had knew the ways of protecting themselves from the novel coronavirus. But, there was deficiencies of changing these prevention knowledge to practice. This indicates that there was gap between knowledge and implementation of prevention strategies in the community. The concerned body should focus on providing education for the community regarding the implementation of the prevention knowledge to practice.


title: Potent human neutralizing antibodies elicited by SARS-CoV-2 infection

text: The pandemic caused by emerging coronavirus SARS-CoV-2 presents a serious global public health emergency in urgent need of prophylactic and therapeutic interventions. SARS-CoV-2 cellular entry depends on binding between the viral Spike protein receptor-binding domain (RBD) and the angiotensin converting enzyme 2 (ACE2) target cell receptor. Here, we report on the isolation and characterization of 206 RBD-specific monoclonal antibodies (mAbs) derived from single B cells of eight SARS-CoV-2 infected individuals. These mAbs come from diverse families of antibody heavy and light chains without apparent enrichment for particular families in the repertoire. In samples from one patient selected for further analyses, we found coexistence of germline and germline divergent clones. Both clone types demonstrated impressive binding and neutralizing activity against pseudovirus and live SARS-CoV-2. However, the antibody neutralizing potency is determined by competition with ACE2 receptor for RBD binding. Surprisingly, none of the SARS-CoV-2 antibodies nor the infected plasma cross-reacted with RBDs from either SARS-CoV or MERS-CoV although substantial plasma cross-reactivity to the trimeric Spike proteins from SARS-CoV and MERS-CoV was found. These results suggest that antibody response to RBDs is viral species-specific while that cross-recognition target regions outside the RBD. The specificity and neutralizing characteristics of this plasma cross-reactivity requires further investigation. Nevertheless, the diverse and potent neutralizing antibodies identified here are promising candidates for prophylactic and therapeutic SARS-CoV-2 interventions.


title: Evaluating aerosol and splatter following dental procedures: addressing new challenges for oral healthcare and rehabilitation

text: Background Dental procedures often produce aerosol and splatter which are potentially high risk for spreading pathogens such as SARS-CoV-2. The existing literature is limited. Objective(s) To develop a robust, reliable and valid methodology to evaluate distribution and persistence of dental aerosol and splatter, including the evaluation of clinical procedures. Methods Fluorescein was introduced into the irrigation reservoirs of a high-speed air-turbine, ultrasonic scaler and 3-in-1 spray and procedures performed on a mannequin in triplicate. Filter papers were placed in the immediate environment. The impact of dental suction and assistant presence were also evaluated. Samples were analysed using photographic image analysis, and spectrofluorometric analysis. Descriptive statistics were calculated and Pearson’s correlation for comparison of analytic methods. Results All procedures were aerosol and splatter generating. Contamination was highest closest to the source, remaining high to 1-1.5 m. Contamination was detectable at the maximum distance measured (4 m) for high-speed air-turbine with maximum relative fluorescence units (RFU) being: 46,091 at 0.5 m, 3,541 at 1.0 m, and 1,695 at 4 m. There was uneven spatial distribution with highest levels of contamination opposite the operator. Very low levels of contamination (≤0.1% of original) were detected at 30 and 60 minutes post procedure. Suction reduced contamination by 67-75% at 0.5-1.5 m. Mannequin and operator were heavily contaminated. The two analytic methods showed good correlation (r=0.930, n=244, p<0.001). Conclusion Dental procedures have potential to deposit aerosol and splatter at some distance from the source, being effectively cleared by 30 minutes in our setting.


The Second Neurologist President of the AHA: His Vision, Goals, and Work in the Time of COVID-19


COVID -19 pandemic and paediatric population with special reference to congenital heart disease


title: Characterizing super-spreading events and age-specific infectivity of COVID-19 transmission in Georgia, USA

text: As the current COVID-19 pandemic continues to impact countries around the globe, refining our understanding of its transmission dynamics and the effectiveness of interventions is imperative. In particular, it is essential to obtain a firmer grasp on the effect of social distancing, potential individual-level heterogeneities in transmission such as age-specific infectivity, and impact of super-spreading. To this end, it is important to exploit multiple data streams that are becoming abundantly available during the pandemic. In this paper, we formulate an individual-level spatio-temporal mechanistic framework to statistically integrate case data with geo-location data and aggregate mobility data, enabling a more granular understanding of the transmission dynamics of COVID-19. We analyze reported cases from surveillance data, between March and early May 2020, in five (urban and rural) counties in the State of Georgia USA. We estimate natural history parameters of COVID-19 and infer unobserved quantities including infection times and transmission paths using Bayesian data-augmentation techniques. First, our results show that the overall median reproductive number was 2.88 (with 95% C.I. [1.85, 4.9]) before the state-wide shelter-in-place order issued in early April, and the effective reproductive number was reduced to below 1 about two weeks by the order. Super-spreading appears to be widespread across space and time, and it may have a particularly important role in driving the outbreak in the rural area and increasing importance towards later stages of outbreaks in both urban and rural settings. Overall, about 2% of cases may have directly infected 20% of all infections. We estimate that the infected children and younger adults (<60 years old) may be 2.38 [1.30, 3.51] times more transmissible than infected elderly (>=60), and the former may be the main driver of super-spreading. Through the synthesis of multiple data streams using our transmission modelling framework, our results enforce and improve our understanding of the natural history and transmission dynamics of COVID-19. More importantly, we reveal the roles of age-specific infectivity and characterize systematic variations and associated risk factors of super-spreading. These have important implications for the planning of relaxing social distancing and, more generally, designing optimal control measures.


title: Machine Learning Approach for Confirmation of COVID-19 Cases: Positive, Negative, Death and Release

text: In recent days, Covid-19 coronavirus has been an immense impact on social, economic fields in the world. The objective of this study determines if it is feasible to use machine learning method to evaluate how much prediction results are close to original data related to Confirmed-Negative-Released-Death cases of Covid-19. For this purpose, a verification method is proposed in this paper that uses the concept of Deep-learning Neural Network. In this framework, Long short-term memory (LSTM) and Gated Recurrent Unit (GRU) are also assimilated finally for training the dataset and the prediction results are tally with the results predicted by clinical doctors. The prediction results are validated against the original data based on some predefined metric. The experimental results showcase that the proposed approach is useful in generating suitable results based on the critical disease outbreak. It also helps doctors to recheck further verification of virus by the proposed method. The outbreak of Coronavirus has the nature of exponential growth and so it is difficult to control with limited clinical persons for handling a huge number of patients with in a reasonable time. So it is necessary to build an automated model, based on machine learning approach, for corrective measure after the decision of clinical doctors. It could be a promising supplementary confirmation method for frontline clinical doctors. The proposed method has a high prediction rate and works fast for probable accurate identification of the disease. The performance analysis shows that a high rate of accuracy is obtained by the proposed method.


Oncology's Telehealth Growth in the COVID-19 Pandemic


title: A New Three-Parameter Discrete Distribution with Associated INAR(1) Process and Applications

text: The aim of this article is to propose a new three-parameter discrete Lindley distribution. A wide range of its structural properties are investigated. This includes the shape of the probability mass function, hazard rate function, moments, skewness, kurtosis, index of dispersion, mean residual life, mean past life and stress-strength reliability. These properties are expressed in explicit forms. The maximum likelihood approach is used to estimate the model parameters. A detailed simulation study is carried out to examine the bias and mean square error of the estimators. Using the proposed distribution, a new first-order integer-valued autoregressive process is introduced for the over-dispersed, equi-dispersed and under-dispersed time series of counts. To demonstrate the importance of the proposed distribution, three data sets on coronavirus, length of stay at psychiatric ward and monthly counts of larceny calls are analyzed.


title: Spatial variability in the risk of death from COVID-19 in Italy, 2020

text: Objectives: Italy is bearing the brunt of the COVID-19 pandemic, as the death toll there has already surpassed that in Wuhan, the city in China where the coronavirus emerged in December 2019. Here we employ statistical methods to assess the severity of COVID-19 pandemic across different regions of Italy. Method: We manually retrieved the daily cumulative numbers of laboratory-confirmed cases and deaths attributed to COVID-19 stratified by region in Italy. We estimated both the crude and time-delay adjusted case fatality ratio across five geographic regions of Italy. Results: The Northwest that includes Lombardy exhibited the highest time-delay-adjusted CFR at 23.0% followed by the Northeast (14.2%), the Center region (11.6%) and the South region (12.1%). The Island region has exhibited the lowest CFR (9.6%). Conclusion: Our estimates in the Northwest and the Northeast are higher than those reported from most affected areas in China. The CFR in Northwest Italy is 1.9-fold higher than that in Wuhan. Our finding reflects the need of urgent medical support in the Northwest region and the appropriate planning and supplies procurement in other regions of Italy focusing on medical care delivery to those who are at the highest risk of poorer outcomes due to COVID-19.


COVID‐19 and new‐onset arrhythmia


title: A novel biparatopic antibody-ACE2 fusion that blocks SARS-CoV-2 infection: implications for therapy

text: In the absence of a proven effective vaccine preventing infection by SARS-CoV-2, or a proven drug to treat COVID-19, the positive results of passive immune therapy using convalescent serum provides a strong lead. We have developed a new class of tetravalent, biparatopic therapy, 89C8-ACE2. It combines the specificity of a monoclonal antibody (89C8) that recognizes the relatively conserved N-terminal domain (NTD) of the viral S glycoprotein, and the ectodomain of ACE2, which binds to the receptor-binding domain (RBD) of S. This molecule shows exceptional performance in vitro, inhibiting the interaction of recombinant S1 to ACE2 and transduction of ACE2-overexpressing cells by S-pseudotyped lentivirus with IC50s substantially below 100 pM, and with potency approximately 100-fold greater than ACE2-Fc itself. Moreover, 89C8-ACE2 was able to neutralize authentic virus infection in a standard assay at low nanomolar concentrations, making this class of molecule a promising lead for therapeutic applications.


title: Viral Kinetics and Antibody Responses in Patients with COVID-19

text: Background A pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading over the world. However, the viral dynamics, host serologic responses, and their associations with clinical manifestations, have not been well described in prospective cohort. Methods We conducted a prospective cohort and enrolled 67 COVID-19 patients admitting between Jan 26 and Feb 5, 2020. Clinical specimens including nasopharyngeal swab, sputum, blood, urine and stool were tested periodically according to standardized case report form with final follow-up on February 27. The routes and duration of viral shedding, antibody response, and their associations with disease severity and clinical manifestations were systematically evaluated. Coronaviral particles in clinical specimens were observed by transmission electron microscopy (TEM). Results The median duration of SARS-CoV-2 RNA shedding were 12 (3-38), 19 (5-37), and 18 (7-26) days in nasopharyngeal swabs, sputum and stools, respectively. Only 13 urines (5.6%) and 12 plasmas (5.7%) were viral positive. Prolonged viral shedding was observed in severe patients than that of non-severe patients. Cough but not fever, aligned with viral shedding in clinical respiratory specimens, meanwhile the positive stool-RNA appeared to align with the proportion who concurrently had cough and sputum production, but not diarrhea. Typical coronaviral particles could be found directly in sputum by TEM. The anti-nucleocapsid-protein IgM started on day 7 and positive rate peaked on day 28, while that of IgG was on day 10 and day 49 after illness onset. IgM and IgG appear earlier, and their titers are significantly higher in severe patients than non-severe patients (p<0.05). The weak responders for IgG had a significantly higher viral clearance rate than that of strong responders (p= 0.011). Conclusions Nasopharyngeal, sputum and stools rather than blood and urine, were the major shedding routes for SARS-CoV-2, and meanwhile sputum had a prolonged viral shedding. Symptom cough seems to be aligned with viral shedding in clinical respiratory and fecal specimens. Stronger antibody response was associated with delayed viral clearance and disease severity.


Preparing teachers to teach in complex settings: opportunities for professional learning and development


title: Attitude, practice, behavior, and mental health impact of COVID-19 on doctors

text: Background: COVID-19, like every other pandemic, has imposed an unprecedented threat to doctors' physical and mental health. Literature in this area is sparse. The present study has been done to explore the knowledge, attitude, and behavior of doctors regarding this pandemic and how it influences their depression, anxiety, and stress level. Materials and Methods: This online survey has been done for 10 days. Data were collected on background characteristics, knowledge, attitude, and behavior of the respondents in a semi-structured pro forma, and psychiatric morbidity was measured by the Depression, Anxiety, and Stress Scale-21. A total of 152 complete responses have been received. The data were assessed using SPSS software. Results: Out of 152 study participants, 34.9% were depressed and 39.5% and 32.9% were having anxiety and stress, respectively. Significant predictors for psychiatric morbidities were experience in health sector, duty hours, use of protective measures, and altruistic coping. Multivariable logistic regression showed most of the factors to be significantly associated with depression, anxiety, and stress level. Discussion: Doctors who were working during COVID pandemic have a high prevalence of psychiatric morbidity. Age and having multiple comorbidities are significant predictive factors. Adequate protective measures should be warranted. Altruistic coping and a sense of greater goal are significant among the doctor community, in this pressing time. The doctors are pushing themselves to the best of their capacity and also protecting their patients' best interest. A large-scale, multicentric study will probably give a larger picture and will guide us for better service planning and delivery.


Covid‐19 coronavirus: Closing carbon age, but opening hydrogen age


title: Estimating the infection and case fatality ratio for COVID-19 using age-adjusted data from the outbreak on the Diamond Princess cruise ship

text: Adjusting for delay from confirmation-to-death, we estimated case and infection fatality ratios (CFR, IFR) for COVID-19 on the Diamond Princess ship as 2.3% (0.75%-5.3%) and 1.2% (0.38-2.7%). Comparing deaths onboard with expected deaths based on naive CFR estimates using China data, we estimate IFR and CFR in China to be 0.5% (95% CI: 0.2-1.2%) and 1.1% (95% CI: 0.3-2.4%) respectively.


title: The epidemic consequences of virulence and free-living survival relationships in models of emerging outbreaks

text: The relationship between parasite virulence and transmission is a pillar of evolutionary theory that has specific implications for public health. Part of this canon involves the idea that virulence and free-living survival (a key component of transmission) may have different relationships in different host-parasite systems. Most examinations of the evolution of virulence-transmission relationships—theoretical or empirical in nature—tend to focus on the evolution of virulence, with transmission a secondary consideration. In virus evolution, recent studies have examined how the evolution of free-living survival can influence other traits. However, few studies have examined the epidemic-scale consequences of evolution across the different virulence-survival relationships, and specifically, of increased free-living survival. In this study, we utilize a mathematical model motivated by aspects of SARS-CoV-2 natural history to investigate how evolutionary changes in survival traits, and their subsequent relationship to virulence traits, may influence several aspects of disease dynamics. Specifically, we examine how each of two different hypothesized relationships between virulence and survival, one deemed “the Curse of the Pharaoh hypothesis” and the other more classically referred to as the “tradeoff hypothesis.” Across virulence-survival frameworks, we found that small changes (5% above and below the nominal value) in survival can have a meaningful effect on certain outbreak features, including the R0, and the size of the infectious peak in the population. These results highlight the importance of properly understanding the relationship between virulence and parasite survival, as they offer considerably different predictions for how the evolution of free-living survival will influence the trajectory of an emerging epidemic.


title: A model simulation study on effects of intervention measures in Wuhan COVID-19 epidemic

text: Background: In the beginning of January 2020, new unknown virus pneumonia cases started to emerge in local hospitals in Wuhan, China. This virus epidemic quickly became a public health emergency of international concern by the WHO. Enormous amount of medical supplies as well as healthcare personals from other provinces were mobilized to support Wuhan. This current work tent to help people understanding how infectious disease spread and the purpose and consequences of various efforts based on simulation model. Method: a simulation model was created using known parameters. R0 set to 3 and mean incubation time to be 7.5days. the epidemic was divided to 3 periods. Simulation would run 50 times to mimic different patient0 status. Personal activity index was used to mimic different level of control measures. 141427709 simulated patients were created. Cumulation number of patients at the end of period 1 (day50) is 2868.7 ± 1739.0. Total infected patients could be 913396.5 ± 559099.9 by the end of period 2 (day70) in free transmission state. And at day90, total patients number is 913396.5 ± 559099.9. Conclusion: COVID-19 is a novel severe respiratory disease. This will put great burden on the shoulder of healthcare workers as well as on medical hardware and supplements. Current strict control measures help to contain disease from spreading. An early detecting, reporting and fast reacting system needs to be setup to prevent future unknown infectious disease.


title: Importations of COVID-19 into African countries and risk of onward spread

text: Background The emergence of a novel coronavirus (SARS-CoV-2) in Wuhan, China, at the end of 2019 has caused widespread transmission around the world. As new epicentres in Europe and America have arisen, of particular concern is the increased number of imported coronavirus disease 2019 (COVID-19) cases in Africa, where the impact of the pandemic could be more severe. We aim to estimate the number of COVID-19 cases imported from 12 major epicentres in Europe and America to each African country, as well as the probability of reaching 10,000 infections in total by the end of March, April, and May following viral introduction. Methods We used the reported number of cases imported from the 12 major epicentres in Europe and America to Singapore, as well as flight data, to estimate the number of imported cases in each African country. Under the assumption that Singapore has detected all the imported cases, the estimates for Africa were thus conservative. We then propagated the uncertainty in the imported case count estimates to simulate the onward spread of the virus, until 10,000 infections are reached or the end of May, whichever is earlier. Specifically, 1,000 simulations were run separately under two scenarios, where the reproduction number under the stay-at-home order was assumed to be 1.5 and 1.0 respectively. Findings We estimated Morocco, Algeria, South Africa, Egypt, Tunisia, and Nigeria as having the largest number of COVID-19 cases imported from the 12 major epicentres. Based on our 1,000 simulation runs, Morocco and Algeria's estimated probability of reaching 10,000 infections by end of March was close to 100% under both scenarios. In particular, we identified countries with less than 100 cases in total reported by end of April whilst the estimated probability of reaching 10,000 infections by then was higher than 50% even under the more optimistic scenario. Conclusion Our study highlights particular countries that are likely to reach (or have reached) 10,000 infections far earlier than the reported data suggest, calling for the prioritization of resources to mitigate the further spread of the epidemic.


title: Social stigma during COVID-19 and its impact on HCWs outcomes

text: The COVID-19 emergency has significantly transformed the working environment and job demands. Providing care was emotionally difficult for healthcare workers. Uncertainty, stigmatisation, and potentially exposing their families to infection were prominent themes for healthcare workers (HCWs) during the crisis, which first broke out in China at the end of 2019, and then in Italy in early 2020. This study examined the effects of stigma, job demands, and self-esteem, and the consequences of working as a "frontline care provider" with patients infected with the coronavirus (COVID-19). A correlational design study involved 260 healthcare workers (HCWs) working in a large hospital in southern Italy. The following questionnaires were administered: (1) the Job Content Questionnaire (JCQ), for assessing psychological and physical demands; (2) the Professional Quality of Life Scale (ProQOL) to measure the quality individuals feel in relation to their work as "frontline care providers", through three dimensions: compassion fatigue (CF), burnout (BO), and compassion satisfaction (CS); (3) the Rosenberg Self-Esteem Scale, for evaluating individual self-esteem; (4) a self-administered multiple-choice questionnaire developed by See et al. about attitudes of discrimination, acceptance, and fear towards HCWs exposed to COVID-19. The findings suggest that stigma has a high impact on workers' outcomes. Stigma may influence worker compliance and can guide management communication strategies relating to pandemic risk for HCWs.


title: Regional Difference in Seroprevalence of SARS-CoV-2 in Tokyo: Results from the community point-of-care antibody testing

text: The serosurvey is an alternative way to know the magnitude of the population infected by coronavirus disease 2019 (COVID-19) since the expansion of capacity of the polymerase chain reaction (PCR) to detect the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was delayed. We herein report seroprevalence of COVID-19 accessed in the two community clinics in Tokyo. The point-of-care immunodiagnostic test was implemented to detect the SARS-CoV-2 specific IgG antibody in the peripheral capillary blood. The overall positive percentage of SARS-CoV-2 IgG antibody is 3.83% (95% confidence interval: 2.76-5.16) for the entire cohort (n =1,071). The central Tokyo of 23 special wards exhibited a significantly higher prevalence compared to the other area of Tokyo (p =0.02, 4.68% [95%CI: 3.08-6.79] versus 1.83 [0.68-3.95] in central and suburban Tokyo, respectively). The seroprevalence of the cohort surveyed in this study is low for herd immunity, which suggests the need for robust disease control and prevention. A community-based approach, rather than state or prefectural levels, is of importance to figure out profiles of the SARS-COV-2 outbreak.


title: Impact of anti-androgenic therapies on COVID-19: an observational study in male population from a COVID-19 regional centre of Lombardy (Italy)

text: There are gender differences in susceptibility and vulnerability to the Coronavirus disease 2019 (COVID-19). The S protein of coronaviruses facilitates viral entry into target cells and employs the host cellular serine protease TMPRSS2 for S protein priming. The TMPRSS2 gene expression is responsive to androgen stimulation and it could partially explain gender differences. We tested the hypothesis that men who received 5-Alpha reductase inhibitors (5ARIs) or androgen deprivation therapy (ADT) for prostate cancer could have a different susceptibility to COVID-19. We carried out an observational study on patients who were referred to our COVID-19 regional centre in Lombardy from 1st to 31st March 2020. Data from 421 patients, 137 women (32.54%) and 284 men (67.44%) with laboratory-confirmed COVID-19, were included in this report. Overall 84 patients died: 28 women (33.33%) and 56 men (66.67%). Among men, 12 patients (4.22%) reported assuming 5ARI treatment, and 6 were under ADT. Over 12 patients under 5ARIs, 3 (25%) died; 2 deaths (33%) were reported in patients under ADT. Our findings showed that only 4.22% of the overall population received 5ARI anti-androgen therapy, a percentage, which revealed to be significantly lower (P<0.0001) than what observed in Italian men aged more than 40 years (14.97%).


title: Leveraging community engaged research partnerships for crisis and emergency risk communication to vulnerable populations in the COVID-19 pandemic

text: Community engagement is important for reaching vulnerable populations in the COVID-19pandemic A risk communication framework was implemented by a community-engagedresearch (CenR) partnership in Southeast Minnesota to address COVID-19 prevention,testing, and socioeconomic impacts Bidirectional communication between CommunicationLeaders and community members within their social networks were used by the partnershipto refine messages, leverage resources, and advise policy makers Over 14 days, messageswere delivered by 24 Communication Leaders in 6 languages across 9 electronic platforms to9,882 individuals within their networks CEnR partnerships may effectively implement crisisand emergency risk communication to vulnerable populations in a pandemic


title: Atazanavir inhibits SARS-CoV-2 replication and pro-inflammatory cytokine production

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is already responsible for far more deaths than previous pathogenic coronaviruses (CoVs) from 2002 and 2012. The identification of clinically approved drugs to be repurposed to combat 2019 CoV disease (COVID-19) would allow the rapid implementation of potentially life-saving procedures. The major protease (Mpro) of SARS-CoV-2 is considered a promising target, based on previous results from related CoVs with lopinavir (LPV), an HIV protease inhibitor. However, limited evidence exists for other clinically approved antiretroviral protease inhibitors, such as atazanavir (ATV). ATV is of high interest because of its bioavailability within the respiratory tract. Our results show that ATV could dock in the active site of SARS-CoV-2 Mpro, with greater strength than LPV. ATV blocked Mpro activity. We confirmed that ATV inhibits SARS-CoV-2 replication, alone or in combination with ritonavir (RTV) in Vero cells, human pulmonary epithelial cell line and primary monocytes, impairing virus-induced enhancement of IL-6 and TNF-α levels. Together, our data strongly suggest that ATV and ATV/RTV should be considered among the candidate repurposed drugs undergoing clinical trials in the fight against COVID-19.


docid: yaapimwn

title: Evaluating efficiency of pooling specimens for PCR-based detection of COVID-19

text: In the age of a pandemic, such as the ongoing one caused by SARS-CoV-2, the world faces limited supply of tests, PPE and reagents, and factories are struggling to meet the growing demands. This study aimed to evaluate the efficacy of pooling specimen for testing of SARS-CoV-2 virus, to determine whether costs and resource savings could be achieved without impacting the sensitivity of the testing. Ten specimens were pooled for testing, containing either one or two known positive specimen of varying viral concentrations. Pooling specimens did not affect the sensitivity of detecting SARS-CoV-2, and the PCR cycle threshold (Ct) between testing of pooling specimen and subsequent individual testing was not significantly different using paired t-test. This study also identified cost savings garnered from pooling of specimen for testing at 4 differing prevalence rates, ranging from 0.1-10%. Pooling specimens to test for COVID-19 infection in low prevalence areas or in low risk population can dramatically decrease the resources burden on lab operations by up to 80%. This paves the possibility for large-scale population screening, allowing for assured policy decisions by governmental bodies to ease lockdown restrictions in areas with low incidence of infection, or with lower risk populations.


title: Evaluation of the EUROIMMUN Anti-SARS-CoV-2 ELISA Assay for detection of IgA and IgG antibodies

text: As the Coronavirus 2019 (COVID-19) pandemic evolves, the development of immunoassays to help determine exposure and potentially predict immunity has become a pressing priority. In this report we present the performance of the EUROIMMUN enzyme-linked immunosorbent assay (ELISA) for semi-quantitative detection of IgA and IgG antibodies in serum and plasma samples using recombinant S1 domain of the SARS-CoV-2 spike protein as antigen. Specimens from patients, with and without COVID-19 infection, were tested at the University of Chicago Clinical Microbiology and Immunology Laboratory. Of 57 samples from COVID-19 PCR-negative patients, including 28 samples positive for common human coronavirus strains, 53 tested negative and 4 tested positive for IgA (93.0% agreement) while 56 tested negative and 1 tested positive for IgG (98.2% agreement). For COVID-19 PCR-positive patients, 29 of 30 (96.7%) samples collected ≥3 days after positive PCR were positive for IgA, and 28 of 28 samples collected ≥4 days after positive PCR were positive for IgG. The EUROIMMUN Anti-SARS-CoV-2 ELISA Assay demonstrates excellent sensitivity for detection of IgA and IgG antibodies from samples collected ≥3 days and ≥4 days, respectively, after COVID-19 diagnosis by PCR. This assay did not demonstrate cross reaction in any of the 28 samples from patients with common human coronaviruses, including types HKU1, NL63, CV229E, and OC43.


title: Mandated Bacillus Calmette-Guérin (BCG) vaccination predicts flattened curves for the spread of COVID-19

text: Prior work suggests that BCG vaccination reduces the risk of different infectious diseases. BCG vaccination may thus serve as a protective factor against COVID-19. Here, we drew on day-by-day reports of both confirmed cases and deaths and analyzed growth curves in countries that mandate BCG policies versus countries that do not. Linear mixed models revealed that the presence of mandated BCG policies was associated with a significant flattening of the exponential increase in both confirmed cases and deaths during the first 30-day period of country-wise outbreaks. This effect held after controlling for median age, gross domestic product per capita, population density, population size, net migration rate, and various cultural dimensions (e.g., individualism and the tightness vs. looseness of social norms). Our analysis suggests that mandated BCG vaccination can be effective in the fight against COVID-19.


title: Identification of a super-spreading chain of transmission associated with COVID-19

text: Background: Super-spreading events were associated with the outbreaks of SARS and MERS, but their association with the outbreak of COVID-19 remains unknown. Here, we report a super-spreading transmission chain of SARS-CoV-2 involving an index patient, seven cancer patients, 40 health care workers and four family members. Methods: We conducted a retrospective study to identify the index patient and the exposed individuals linked to a chain of transmission associated with COVID-19. We collected and analyzed the data on demographic features, exposure history, clinical presentation, laboratory investigation, radiological examination, and disease outcome of these patients. Results: We identified the index patient and another presumptive super-spreader, who initiated and amplified a super-spreading transmission chain associated with COVID-19, respectively. There were 31 female and 21 male patients in this cohort, and the median age was 37 years (range: 22-79 years). Each of them had an exposure history with the index patient or his close contacts. Approximately 87% (45/52) of the patients had fever or other symptoms, 96% (50/52) had abnormal chest CT-scan findings, 86% of the tested patients (39/45) were positive for SARS-CoV-2 in the nasopharyngeal or throat swab specimen, 85% of the tested patients (29/34) were positive for SARS-CoV-2-specific IgM and/or IgG, 15% of the RT-PCR positive patients were tested negative for the specific IgM and/or IgG at the convalescent phase, and 15% of the RT-PCR negative patients were tested positive for the specific IgM and/or IgG. The severe patients experienced a significant decrease in oximetry saturation, lymphocyte, and platelet counts, along with a significant increase in C-reactive protein, D-dimer, and lactate dehydrogenase. All six fatal cases had comorbidities and five of the seven cancer patients (71%) died within 2-20 days of the disease onset. Conclusions: The super-spreading events were associated with the outbreak of COVID-19 in Wuhan and its impact on disease transmission warrants further investigation. Cancer patients appeared highly vulnerable to COVID-19. The finding that a significant portion of SARS-CoV-2 infected patients were tested negative for the serum specific IgM and IgG at the convalescent phase should be addressed by additional studies.


title: Relational Modeling for Robust and Efficient Pulmonary Lobe Segmentation in CT Scans

text: Pulmonary lobe segmentation in computed tomography scans is essential for regional assessment of pulmonary diseases. Recent works based on convolution neural networks have achieved good performance for this task. However, they are still limited in capturing structured relationships due to the nature of convolution. The shape of the pulmonary lobes affect each other and their borders relate to the appearance of other structures, such as vessels, airways, and the pleural wall. We argue that such structural relationships play a critical role in the accurate delineation of pulmonary lobes when the lungs are affected by diseases such as COVID-19 or COPD. In this paper, we propose a relational approach (RTSU-Net) that leverages structured relationships by introducing a novel non-local neural network module. The proposed module learns both visual and geometric relationships among all convolution features to produce self-attention weights. With a limited amount of training data available from COVID-19 subjects, we initially train and validate RTSU-Net on a cohort of 5000 subjects from the COPDGene study (4000 for training and 1000 for evaluation). Using models pre-trained on COPDGene, we apply transfer learning to retrain and evaluate RTSU-Net on 470 COVID-19 suspects (370 for retraining and 100 for evaluation). Experimental results show that RTSU-Net outperforms three baselines and performs robustly on cases with severe lung infection due to COVID-19.


Anesthetic management of a COVID 19 suspected patient for mastectomy